Compounds are provided according to Formula (I) or Formula (II) and pharmaceutically acceptable salts, hydrates, solvates, prodrugs, tautomers and stereoisomers, as well as pharmaceutical compositions, wherein Ring A, Ring B, Ring C, Ring C1, Ring D. Rc, Rc' and L are as defined herein. The compounds disclosed herein are contemplated to be useful for the prevention and treatment of a variety of conditions.
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 475/10 - Heterocyclic compounds containing pteridine ring systems with a nitrogen atom directly attached in position 4 with an aromatic or hetero-aromatic ring directly attached in position 2
Use of a treatment regime comprising: three components: a) fostroxacitabine bralpamide; b) an immune checkpoint inhibitor which is an anti-PD-L1 antibody or an anti-PD-1 antibody; and c) a VEGF antagonist, with the proviso that component c) is not sorafenib, regorafenib or donafenib in the treatment of hepatocellular cancer, wherein the respective components are administered simultaneously or sequentially.
Compounds of the formula I
Compounds of the formula I
Compounds of the formula I
wherein X is a bond or —CH2, and pharmaceutically acceptable salts thereof are useful in the parenteral treatment of leukemia, myelodysplastic syndrome or lymphoma, especially in patients presenting with cytarabine resistance and/or over 60 years of age.
C07F 9/6558 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
A61P 35/02 - Antineoplastic agents specific for leukemia
The compound of the formula (I) (I) or a pharmaceutically acceptable salt thereof which shows utility in the treatment of Legg Calvé Perthes Disease (LCPD) in children and juvenile animals.
A61P 19/08 - Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
A61K 31/09 - Ethers or acetals having an ether linkage to aromatic ring nuclear carbon having two or more such linkages
A61K 31/167 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen atom of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
A61K 31/343 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
A61K 31/381 - Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
A61K 31/403 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
C07D 491/048 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
Compounds are provided according to Formula (I)
Compounds are provided according to Formula (I)
Compounds are provided according to Formula (I)
and pharmaceutically acceptable salts, hydrates, solvates, prodrugs, tautomers and stereoisomers, as well as pharmaceutical compositions, wherein Ring B, Ring A, RA, Rb, Rc, Rc′, R1, R2, R6, m and n are as defined herein. The compounds disclosed herein are contemplated to be useful for the prevention and treatment of a variety of conditions.
Use of lenvatinib, or a pharmaceutically acceptable salt thereof in combination with a compound of the formula MIV-818:
Use of lenvatinib, or a pharmaceutically acceptable salt thereof in combination with a compound of the formula MIV-818:
Use of lenvatinib, or a pharmaceutically acceptable salt thereof in combination with a compound of the formula MIV-818:
or pharmaceutically acceptable salt thereof, in the treatment of liver cancer or liver metastases. The respective dosage regimes of the compounds can be delivered concurrently or alternately.
A61K 31/688 - Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols both hydroxy compounds having nitrogen atoms, e.g. sphingomyelins
The invention provides compounds of the formula:
The invention provides compounds of the formula:
R1 is OR11, or NR5R5′;
R2 is H or F;
R5 is H, C1-C6alkyl, OH, C(═O)R6, O(C═O)R6 or O(C═O)OR6;
R5′ is H or C1-C6alkyl;
R6 is C1-C6alkyl or C3-C7cycloalkyl;
R13 is H, phenyl, pyridyl, benzyl, indolyl or naphthyl wherein the phenyl, pyridyl, benzyl, indolyl and naphthyl is optionally substituted with 1, 2 or 3 R22;
and the other variables are as defined in the claims,
which are of use in the treatment of cancer, and related aspects.
C07F 9/6558 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
C07D 405/04 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
Provided herein is a specific crystalline form of the anti-cancer drug birinapant, designated Form H. Compositions comprising Form H are disclosed, as well as methods of use thereof. Methods of preparation of the specific crystalline form are also provided. Form H is suitable for manufacturing drug product under GMP guidelines. Birinapant is a peptidomimetic of second mitochondrial-derived activator of caspases (SMAC), and inhibits proteins of the IAP (Inhibitor of Apoptosis Protein) family.
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
A pharmaceutical composition, comprising a therapeutically effective amount of an active pharmaceutical ingredient (API) compound represented by the following structural formula
A pharmaceutical composition, comprising a therapeutically effective amount of an active pharmaceutical ingredient (API) compound represented by the following structural formula
at least one acidifying agent; and a vehicle base comprising at least one pharmaceutically acceptable non-aqueous solvent. Values and preferred values of the variables in structural formula (I) are defined herein.
A61K 47/12 - Carboxylic acidsSalts or anhydrides thereof
A61K 31/222 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
C07C 259/06 - Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
A61P 35/04 - Antineoplastic agents specific for metastasis
C07D 403/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07K 5/02 - Peptides having up to four amino acids in a fully defined sequenceDerivatives thereof containing at least one abnormal peptide link
Compounds of the formula II:
or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as osteoporosis, osteoarthritis, rheumatoid arthritis or bone metastases.
C07D 277/40 - Unsubstituted amino or imino radicals
C07D 491/048 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
Compounds are provided according to Formula (I). Formula (I), and pharmaceutically acceptable salts, hydrates, solvates, prodrugs, tautomers and. stereoisomers, as well as pharmaceutical compositions, wherein Ring B, Ring A, RA, Rb, Rc, Rc', R1, R2, R6, m and n are as defined herein. The compounds disclosed herein are contemplated to be useful for the prevention and treatment of a variety of conditions.
Use of a compound of the formula I:
or a pharmaceutically acceptable salt thereof, in the therapy of a liver cancer in a mammal, characterized by the concurrent or sequential treatment of the mammal with a monoclonal antibody which blocks the binding of PD-L1 and/or PD-L2 to PD-1.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 31/4375 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring hetero atom, e.g. quinolizines, naphthyridines, berberine, vincamine
A61K 31/4353 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
A61K 31/395 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
15.
MIV-818/LENVATINIB COMBINATION THERAPY FOR LIVER CANCER
Use of lenvatinib, or a pharmaceutically acceptable salt thereof in combination with a compound of the formula MIV-818: (MIV-818) or pharmaceutically acceptable salt thereof, in the treatment of liver cancer or liver metastases. The respective dosage regimes of the compounds can be delivered concurrently or alternately.
A61K 31/513 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
A61K 31/685 - Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
The invention provides compounds of formula (I) wherein R1, R2, R3, R4and R5 are as defined in the specification which are potent inhibitors of the enzyme MALT1 and are useful in the treatment of autoimmune disorders and diseases and as an immunooncology approach to the treatment of cancer, especially bladder cancer, colon cancer, hepatocellular cancer and small cell or non-small cell lung cancer.
C07D 405/04 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07F 9/6558 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
Compounds of the formula II:
or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as osteoporosis, osteoarthritis, rheumatoid arthritis or bone metastases.
C07D 491/048 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
C07D 277/40 - Unsubstituted amino or imino radicals
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 403/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07K 5/02 - Peptides having up to four amino acids in a fully defined sequenceDerivatives thereof containing at least one abnormal peptide link
Use of a compound of the formula (I): or a pharmaceutically acceptable salt thereof, in the therapy of a liver cancer in a mammal, characterized by the concurrent or sequential treatment of the mammal with a monoclonal antibody which blocks the binding of PD-L1 and/or PD-L2 to PD-1.
C07D 405/04 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07F 9/6558 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
Combination therapy with sorafenib or regorafenib and a phosphoramidate prodrug of troxacitabine with the formula:
4alkyl and Z is H or fluoro, or a pharmaceutically acceptable salt thereof, shows surprising utility in the treatment of liver cancer or liver metastasis.
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
A61K 31/685 - Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
A61K 31/513 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
Compounds of the formula II:
or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as osteoporosis, osteoarthritis, rheumatoid arthritis or bone metastases.
C07D 491/048 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
C07F 9/6558 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
C07D 405/04 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
22, and pharmaceutically acceptable salts thereof are useful in the parenteral treatment of leukemia, myelodysplastic syndrome or lymphoma, especially in patients presenting with cytarabine resistance and/or over 60 years of age.
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
C07D 405/04 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
A61P 35/02 - Antineoplastic agents specific for leukemia
27.
CANCER TREATMENT WITH (2,2-BISHYDROXYMETHYL) METHYLENECYCLOPROPANE NUCLEOTIDES
The invention provides a compound of formula (I) wherein B is a nucleobase; U is O or S; Rxis -OC(=O)Ry, -OC(=O)CH(Ry222OC(=O)Ry; Ryis optionally substituted alkyl or alkenyl or the side chain of a natural or unnatural amino acid R1is H, or optionally substituted phenyl, benzyl, naphthyl, pyridyl or indolyl, or Rxand R1together define a bond thus forming a cyclic phosphate; R2and R2'together define the side chain of a natural or unnatural amino acid; R3is optionally substituted alkyl, cycloalkyl, phenyl or benzyl; and pharmaceutically acceptable salts and compositions thereof which are useful in the treatment of cancer, especially leukemias.
C07F 9/6561 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
A61K 31/522 - Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
A61K 31/685 - Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
C07D 239/36 - One oxygen atom as doubly bound oxygen atom or as unsubstituted hydroxy radical
C07D 239/54 - Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
C07D 473/16 - Heterocyclic compounds containing purine ring systems with oxygen, sulfur, or nitrogen atoms directly attached in positions 2 and 6 two nitrogen atoms
C07D 473/18 - Heterocyclic compounds containing purine ring systems with oxygen, sulfur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
C07D 473/30 - Oxygen atom attached in position 6, e.g. hypoxanthine
C07D 473/34 - Nitrogen atom attached in position 6, e.g. adenine
C07D 403/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07K 5/062 - Dipeptides the side chain of the first amino acid being acyclic, e.g. Gly, Ala
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07K 5/02 - Peptides having up to four amino acids in a fully defined sequenceDerivatives thereof containing at least one abnormal peptide link
The invention provides compounds of the formula:
5′;
2 is H or F;
6;
6alkyl;
7cycloalkyl;
22;
and the other variables are as defined in the claims,
which are of use in the treatment of cancer, and related aspects.
C07D 405/04 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07F 9/6558 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
4alkyl and Z is H or fluoro, or a pharmaceutically acceptable salt thereof, shows surprising utility in the treatment of liver cancer or liver metastasis.
A61K 31/513 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
A61K 31/685 - Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
A61K 9/00 - Medicinal preparations characterised by special physical form
The invention provides a compound of formula (I): herein R1, R2 and R3 of series (x), (y) and (z) are as defined in the specification which are potent inhibitors of the enzyme MALT1 and are useful in an immunooncology approach to the treatment of cancer, especially bladder cancer, colon cancer, hepatocellular cancer or small cell or non-small cell lung cancer.
C07D 403/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07K 5/062 - Dipeptides the side chain of the first amino acid being acyclic, e.g. Gly, Ala
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07K 5/02 - Peptides having up to four amino acids in a fully defined sequenceDerivatives thereof containing at least one abnormal peptide link
The present invention relates to novel applications for inhibitors, notably small molecule inhibitors, of the protease in which the inhibitors are used in an immunooncology setting to treat certain cancers. This in turn means that the compounds are directed to immune components and not to the tumour tissue directly.
Compounds of Formula (I): wherein W is NR1A or CR1BR1B; Z is N or CH; R1A is C1-C3alkyl, C1-C3haloalkyl C3-C4cycloalkyl or phenyl wherein cycloalkyl or phenyl is optionally mono-, di- or tri-substituted with substituents each independently selected from C1- C3alkyl, halo, amino and C1-C3alkoxy; the two R1B together with the carbon atom to which they are attached combine and form C3-C6cycloalkyl or heterocyclyl, wherein the cycloalkyl is substituent with C(=O)OR1C, NHC(=O)OR1C or NHS(=O)2R1C, and the heterocyclyl is substituent with C(=O)R1C, C(=O)OR1C, S(=O)2 R1C, C(=O)NH2 or C(=O)NR1CR1C'; n is 0, 1 or 2; n, q, R1C, R1C', R2 and R3 are as defined herein, their use as inhibitors of RSV and related aspects.
C07D 237/04 - Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having less than three double bonds between ring members or between ring members and non-ring members
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
Compounds of Formula (I): wherein W is NR1A or CR1BR1B; Z is N or CH, R1A is C1-C3alkyl, C1-C3haloalkyl, C3-C4cycloalkyl or phenyl wherein cycloalkyl or phenyl is optionally mono-, di- or tri-substituted with substituents each independently selected from C1- C3alkyl, halo, amino and C1-C3alkoxy; the two R1B together with the carbon atom to which they are attached combine and form C3- C6cycloalkyl or heterocyclyl, wherein the cycloalkyl is substituent with C(=O)OR1C, NHC(=O)OR1C or NHS(=O)2 R1C, and the heterocyclyl is substituent with C(=O)R1C, C(=O)OR1C, S(=O)2 R1C, C(=O)NH2 or C(=O)NR1CR1C'; q, n, R1C, R2 and R3 are as defined herein, their use as inhibitors of RSV and related aspects.
C07D 237/04 - Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having less than three double bonds between ring members or between ring members and non-ring members
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
A pharmaceutical composition, comprising a therapeutically effective amount of an active pharmaceutical ingredient (API) compound represented by the following structural formula
at least one acidifying agent; and a vehicle base comprising at least one pharmaceutically acceptable non-aqueous solvent. Values and preferred values of the variables in structural formula (I) are defined herein.
A61K 31/222 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 31/165 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
C07C 259/06 - Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
38.
Methods for the preparation of diastereomerically pure phosphoramidate prodrugs
Methods for the preparation of diastereomerically pure phosphoramidate prodrugs of nucleosides, and intermediates useful for the preparation are provided. The nucleosides are useful for the treatment of hepatitis C and cancer.
C07H 21/00 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
C07D 405/04 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07F 9/6558 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
40.
COMBINATION THERAPY WITH SORAFENIB OR REGORAFENIB AND A PHOSPHORAMIDATE PRODRUG OF TROXACITABINE
Combination therapy with sorafenib or regorafenib and a phosphoramidate prodrug of troxacitabine with the formula: where Y is C1-C8 straight or branched chain alkyl, X is H, halo, C3-C4cycloalkyl or C1-C4alkyl and Z is H or fluoro, or a pharmaceutically acceptable salt thereof, shows surprising utility in the treatment of liver cancer or liver metastasis.
Compounds of Formula (I): (Formula I), wherein Z1 is NR1A, CHR1A or CR1BR1B; one of Z2 and Z3 is CH or CR1A', the other is N, CH or CR1A'; n is 0, 1 or 2; q is 0, 1 or 2; R1A, R1A', R1B, R2 and R3 are as defined herein, their use as inhibitors of RSV and related aspects.
A61K 31/4725 - Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
C07D 401/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
Molecular mimics of Smac are capable of modulating apoptosis through their interaction with cellular IAPs (inhibitor of apoptosis proteins). The mimetics are based on a monomer or dimer of the N-terminal tetrapeptide of IAP-binding proteins, such as Smac/DIABLO, Hid, Grim and Reaper, which interact with a specific surface groove of IAP. Also disclosed are methods of using these peptidomimetics for therapeutic purposes. In various embodiments of the invention the Smac mimetics of the invention are combined with chemotherapeutic agents, including, but not limited to topoisomerase inhibitors, kinase inhibitors, NSAIDs, taxanes and platinum containing compounds use broader language.
A61K 31/405 - Indole-alkanecarboxylic acidsDerivatives thereof, e.g. tryptophan, indomethacin
C07K 5/078 - Dipeptides the first amino acid being heterocyclic, e.g. Pro, His, Trp
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
Use of a compound represented by formula (1A), or a pharmaceutically acceptable salt thereof, in the therapy of HCV in a mammal or human, wherein the compound of formula 1A is administered in combination with a further HCV antiviral selected from: a) asunaprevir, daclatasvir and/or beclabuvir; or b) simeprevir and/or JNJ56914845; or c) an HCV protease inhibitor selected from paritaprevir or ABT493, and an NS5A inhibitor selected from ombitasvir or ABT-530; or d) alisporavir; or e) EDP-239; or f) odalasvir and/or sovaprevir; or g) grazoprevir and/or elbasvir.
C07H 19/10 - Pyrimidine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
A61K 31/7072 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
Compound 1 with the formula I is an HCV antiviral protide, which is surprisingly soluble in ethanol, thereby facilitating the preparation of pharmaceutical formulations, such as adsorbed mesoporous carriers or SEDDS of Pouton Types III or IV.
A61K 31/7072 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
C07H 19/10 - Pyrimidine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
46.
Form 2 crystalline polymorph of a salt of N-[1-6-(ethynyl-3-oxo-hexahydro-furo[3,2-B]pyrrole-4-carbonyl)-3-methyl-butyl]-4-[5-fluoro-2-(4-methyl-piperazinyl) thiazol-4-yl]-benzamide useful as cysteine protease inhibitor
There is provided Form 2 crystalline polymorph consisting of N-[1-6-(ethynyl-3-oxo-hexahydro-furo[3,2-b]pyrrole-4-carbonyl)-3-methyl-butyl]-4-[5-fluoro-2-(4-methyl-piperazin-1-yl)thiazol-4-yl]-benzamide monohydrochloride and N-[1-6-(ethynyl-3-oxo-hexahydro-furo[3,2-b]pyrrole-4-carbonyl)-3-methyl-butyl]-4-[5-fluoro-2-(4-methyl-piperazin-1-yl)thiazol-4-yl]benzamide hydrate monohydrochloride, its use as a medicament and methods for its preparation.
C07D 491/048 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
47.
METHODS FOR THE PREPARATION OF DIASTEREOMERICALLY PURE PHOSPHORAMIDATE PRODRUGS
Methods for the preparation of diastereomerically pure phosphoramidate prodrugs of nucleosides, and intermediates useful for the preparation are provided. The nucleosides are useful for the treatment of hepatitis C and cancer.
Compounds of the formula II:
or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as osteoporosis, osteoarthritis, rheumatoid arthritis or bone metastases.
C07D 491/048 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
The invention provides compounds of formula (I), wherein: R1 is OR11, or NR5R5'; R2 is H or F; R5 is H, C1-C6alkyl, OH, C(=O)R6, O(C=O)R6 or O(C=O)OR6; R5´ is H or C1-C6alkyl; R6 is C1-C6alkyl or C3-C7cycloalkyl; R13 is H, phenyl, pyridyl, benzyl, indolyl or naphthyl wherein the phenyl, pyridyl, benzyl, indolyl and naphthyl is optionally substituted with 1, 2 or 3 R22; and the other variables are as defined in the claims, which are of use in the treatment of cancer, and related aspects.
C07D 405/04 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS (Spain)
SWISS TROPICAL AND PUBLIC HEALTH INSTITUTE (Switzerland)
SYNGENE INTERNATIONAL LIMITED PLC (India)
Inventor
Kahnberg, Pia
Johansson, Nils-Gunnar
Gilbert, Ian
Hampton, Shahienaz
Harrison, Justin
Sarkar, Sandipan
Gonzales, Dolores
Abstract
The invention provides compounds of the formula: wherein L1 and L2 are independently selected from O and S; R1 is C3-C6straight or branched alkyl, C3-C7cycloalkyl, C5-C7cycloalkenyl, adamantly, phenyl or saturated heterocyclyl, any of which being optionally substituted; R2 is H, methyl or ethyl; R5 is NRxCORy, NRxRy, CH2COCH3, CH2C≡N, or a 5- or 6-membered heteroaryl group which is optionally substituted; X, Y and Z are independently N or CH; Rx is independently H or C1-C4alkyl; Ry is independently H, CrC4alkyl, phenyl or benzyl, either of which is optionally substituted; n is 0-3; salts, hydrates and N-oxides, wherein the optional substituents are further defined in the claims. The compounds have utility in the prophylaxis or treatment of trypanosomal diseases, such as T. cruzi (Chagas disease).
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 403/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
The invention provides compounds of the formula:
wherein B is a nucleobase selected from the groups (a) to (d):
which are of use in the treatment or prophylaxis of hepatitis C virus infection, and related aspects.
C07H 19/02 - Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radicalNucleosidesMononucleotidesAnhydro derivatives thereof sharing nitrogen
A61K 31/7072 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
52.
QUINAZOLINE BASED RESPIRATORY SYNCYTIAL VIRUS INHIBITORS
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
C07D 401/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 403/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 407/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 413/06 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
C07D 403/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
The invention provides compounds of the formula (I) wherein B is a nucleobase selected from the groups (a) to (d): and the other variables are as defined in the claims, which are of use in the treatment or prophylaxis of hepatitis C virus infection, and related aspects.
A61K 31/7068 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
A61K 31/7072 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
The invention provides compounds of the formula:(I) wherein B is a nucleobase selected from the groups (a) to (d) and the other variables are as defined in the claims, which are of use in the treatment or prophylaxis of hepatitis C virus infection, and related aspects.
FORM 2 CRYSTALLINE POLYMORPH OF A SALT OF N-[1-6-(ETHYNYL-3-OXO-HEXAHYDRO-FURO[3,2-B]PYRROLE-4-CARBONYL)-3-METHYL-BUTYL]-4-[5-FLUORO-2-(4-METHYL-PIPERAZINYL)THIAZOL-4-YL]-BENZAMIDE USEFUL AS CYSTEINE PROTEASE INHIBITOR
There is provided Form 2 crystalline polymorph consisting of N-[1-6-(ethynyl-3-oxo-hexahydro-furo[3,2-b]pyrrole-4-carbonyl)-3-methyl-butyl]-4-[5-fluoro-2-(4-methyl-piperazin-1-yl)thiazol-4-yl]-benzamide monohydrochloride and N-[1-6-(ethynyl-3-oxo-hexahydro-furo[3,2-b]pyrrole-4- carbonyl)-3-methyl-butyl]-4-[5-fluoro-2-(4-methyl-piperazin-1-yl)thiazol-4-yl]-benzamide hydrate monohydrochloride, its use as a medicament and methods for its preparation.
C07D 491/048 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
Molecular mimics of Smac are capable of modulating apoptosis through their interaction with cellular IAPs (inhibitor of apoptosis proteins). The mimetics are based on a monomer or dimer of the N-terminal tetrapeptide of IAP-binding proteins, such as Smac/DIABLO, Hid, Grim and Reaper, which interact with a specific surface groove of IAP. Also disclosed are methods of using these peptidomimetics for therapeutic purposes. In various embodiments of the invention the Smac mimetics of the invention are combined with chemotherapeutic agents, including, but not limited to topoisomerase inhibitors, kinase inhibitors, NSAIDs, taxanes and platinum containing compounds use broader language.
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
C07K 5/062 - Dipeptides the side chain of the first amino acid being acyclic, e.g. Gly, Ala
Compounds of the formula II:
or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as osteoporosis, osteoarthritis, rheumatoid arthritis or bone metastases.
C07D 491/048 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
A01N 43/38 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings condensed with carbocyclic rings
A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
C07K 5/02 - Peptides having up to four amino acids in a fully defined sequenceDerivatives thereof containing at least one abnormal peptide link
C07D 403/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07K 5/062 - Dipeptides the side chain of the first amino acid being acyclic, e.g. Gly, Ala
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
Molecular mimics of Smac are capable of modulating apoptosis through their interaction with cellular IAPs (inhibitor of apoptosis proteins). The mimetics are based on a monomer or dimer of the N-terminal tetrapeptide of IAP-binding proteins, such as Smac/DIABLO, Hid, Grim and Reaper, which interact with a specific surface groove of IAP. Also disclosed are methods of using these peptidomimetics for therapeutic purposes. In various embodiments of the invention the Smac mimetics of the invention are combined with chemotherapeutic agents, including, but not limited to topoisomerase inhibitors, kinase inhibitors, NSAIDs, taxanes and platinum containing compounds use broader language.
Compounds of the formula II:
or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as osteoporosis, osteoarthritis, rheumatoid arthritis or bone metastases.
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A pharmaceutical composition, comprising a therapeutically effective amount of an active pharmaceutical ingredient (API) compound represented by the following structural formula at least one acidifying agent; and a vehicle base comprising at least one pharmaceutically acceptable non-aqueous solvent. Values and preferred values of the variables in structural formula (I) are defined herein.
C07C 259/06 - Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 31/165 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
A61K 31/222 - Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
The invention provides compounds of formula (I): wherein Rings A and A' are independently 5-membered optionally substituted aromatic heterocycles; Q is C(=O)NR1R1' or formula U is C(R4)2, O, S, S(=O)2, C(R4)2C(R4)2, CH2O, OCH2, CH2S, SCH2, CH2S(=O)2, S(=O)CH2 or C=C(Ru )2; X is CH2, CHR12, CR12R12, O, S, S(=O)2 or NRx; m is 0, 1, 2 or 3; n is 0, 1, 2 or 3; the other variables are as defined in the claims, which are of use in the treatment or prophylaxis of hepatitis C virus infection, and related aspects.
C07D 413/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
A61K 31/427 - Thiazoles not condensed and containing further heterocyclic rings
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/4523 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/5386 - 1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged ring systems
A61K 31/553 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and at least one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
C07D 403/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 407/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 409/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
The invention provides compounds of the formula:(I) which are of use in the treatment or prophylaxis of hepatitis C virus infection, and related aspects.
C07H 19/20 - Purine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
A61K 31/7072 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
05 - Pharmaceutical, veterinary and sanitary products
42 - Scientific, technological and industrial services, research and design
Goods & Services
Pharmaceutical and veterinary preparations; Sanitary preparations for medical purposes; Dietetic substances adapted for medical or veterinary use. Research and product development relating to products in the healthcare industry.
A01N 43/38 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings condensed with carbocyclic rings
A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
Compounds of the formula (I) wherein One of A1 and A2 is N-CH3 and the other is CH; R1 is C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl or oxetan-3-yl, wherein C3-C6cycloalkyl is optionally substituted with one, two or three fluoro or with CF3; R2a and R2b are independently selected from H, halo, C1-C4alkyl, C1-C4haloalkyl and C1- C4alkoxy; R3 is CH3 or F; n is 1, 2, 3 or 4; or a pharmaceutically acceptable salt, hydrate or N-oxide thereof for the use in the prophylaxis and/or treatment of a disorder characterised by inappropriate expression or activation of cathepsin S.
C07D 305/08 - Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring atoms
Compounds of the formula I wherein R1 is CrC6alkyl, CrC6haloalkyl, C3-C6cycloalkyl, wherein C3-C6cycloalkyl is optionally substituted with CF3, methyl, ethyl or one or two F; R2a and R2b are independently H, F and CH30; R3 is F or CH3; or a pharmaceutically acceptable salt, hydrate or N-oxide thereof, for the use in the prophylaxis or treatment of a disorder characterised by inappropriate expression or activation of cathepsin S.
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
The present invention concerns the synthesis of substantially anomerically pure 2,3-dideoxy-3- fluoro-5-0-(4-phenylbenzoyl)-a-D-erythropentofuranosyl chloride from an α/β-mixture of the corresponding methyl glycoside. The method of the invention provides the pure a-chloride without the need of anomeric separation. The α-chloride thus achieved is suitable for use as glycosyl donor in the preparation of 2',3'-dideoxy-3'-fluoro nucleosides. In particular, the preparation of 2',3'-dideoxy-3 '-fluoroguanosine, FLG, using an α/β-mixture of the methyl glycoside without the need of anomeric separation is disclosed.
This invention relates to a stereochemically pure uracyl spirooxetane nucleoside phosphoramidate useful in the treatment of patients infected with the hepatitis C virus (HCV).
A61K 31/7072 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
This invention relates to a stereochemically pure uracyl spirooxetane nucleoside phosphoramidate of formula (I) which inhibits the hepatitis C virus (HCV).
A61K 31/7072 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
Compounds of the formula (I) wherein R2a and R2b are independently H, halo, C1-C4alkyl, C1-C4haloalkyl or C1-C4alkoxy, or R2a and R2b together with the carbon atom to which they are attached form a C3-C6cycloalkyl; R3 is a C5-C10 alkyl, optionally substituted with 1-3 substituents independently selected from halo, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy; or R3 is a C2-C4alkyl chain with at least 2 chloro or 3 fluoro substituents; or R3 is C3-C7cycloalkylmethyl, optionally substituted with 1-3 substituents independently selected from C1-C4alkyl, halo, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy; R4 is C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, C1-C6alkylamino, C1- C6dialkylamino or; R4 is Het or Carbocyclyl, either of which is optionally substituted with 1-3 substituents; n is 1, 2 or 3; for the use in the prophylaxis or treatment of a disorder characterised by inappropriate expression or activation of cathepsin S.
C07C 237/14 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being saturated and containing rings
A61P 11/00 - Drugs for disorders of the respiratory system
A61P 37/00 - Drugs for immunological or allergic disorders
C07D 233/58 - Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring nitrogen atoms
Molecular mimics of Smac are capable of modulating apoptosis through their interaction with cellular IAPs (inhibitor of apoptosis proteins). The mimetics are based on a monomer or dimer of the N-terminal tetrapeptide of IAP-binding proteins, such as Smac/DIABLO, Hid, Grim and Reaper, which interact with a specific surface groove of IAP. Also disclosed are methods of using these peptidomimetics for therapeutic purposes. In various embodiments of the invention the Smac mimetics of the invention are combined with chemotherapeutic agents, including, but not limited to topoisomerase inhibitors, kinase inhibitors, NSAIDs, taxanes and platinum containing compounds use broader language.
The present invention relates to a combination of a macrocyclic HCV protease inhibitor, a macrocyclic non-nucleoside HCV polymerase inhibitor and a nucleoside HCV polymerase inhibitor.
A61K 31/427 - Thiazoles not condensed and containing further heterocyclic rings
A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
Compounds of Formula (II) wherein R1a is H; and R1b is C1-C6alkyl, Carbocyclyl or Het; or R1a and R1b together define a saturated cyclic amine with 3-6 ring atoms; R2a and R2b are independently H, halo, C1-C4alkyl, C1-C4haloalkyl or C1-C4alkoxy, or R2a and R2b together with the carbon atom to which they are attached form a C3-C6cycloalkyl; R3 is a branched C5-C10 alkyl chain, C2-C4haloalkyl or -CH2C3-C7 cycloalkyl; R4' is C1-C6alkyl, C1-C6haloalkyl or oxetany-3-yl. for use in the prophylaxis or treatment of a disorder characterised by inappropriate expression or activation of cathepsin S.
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
C07C 271/20 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by nitrogen atoms not being part of nitro or nitroso groups
C07D 277/46 - Acylated amino or imino radicals by carboxylic acids, or sulfur or nitrogen analogues thereof
C07D 405/12 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Compounds of the formula (I) wherein R1a is H; and R1b is C1-C6alkyl, Carbocyclyl or Het; or R1a and R1b together define a saturated cyclic amine with 3-6 ring atoms; R2a and R2b are independently H, halo, C1-C4alkyl, C1-C4haloalkyl or C1-C4alkoxy, or R2a and R2b together with the carbon atom to which they are attached form a C3-C6cycloalkyl; R3 is a branched C5-C10 alkyl chain, C2-C4haloalkyl or -CH2C3-C7 cycloalkyl; R4 is C1-C6alkyl, C1-C6haloalkyl, C1-C6alkylamino or C1-C6dialkylamino; for use in the prophylaxis or treatment of a disorder characterised by inappropriate expression or activation of cathepsin S.
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
C07C 237/14 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being saturated and containing rings
C07D 277/46 - Acylated amino or imino radicals by carboxylic acids, or sulfur or nitrogen analogues thereof
HIV inhibitors of formula (I) wherein R1 is halo, C1-4alkoxy, trifluoromethoxy; R2 is a group of formula (A); R3 is a group of formula (B); R4 is a group of formula (C); n is 0 or 1; A is CH or N; R5 and R6 are hydrogen, C1-4alkyl, halo; R7 and R8 are C1-4alkyl or C1-4alkoxyC1-4alkyl; R9 is C1-4alkyl, cyclopropyl, trifluoromethyl, C1-4alkoxy, or dimethylamino; R10 is hydrogen, C1-4alkyl, cyclopropyl, trifluoromethyl, C1-4alkoxy, or dimethylamino; pharmaceutically acceptable addition salts and solvates thereof; pharmaceutical compositions containing these compounds as active ingredient and processes for preparing said compounds.
C07D 213/64 - One oxygen atom attached in position 2 or 6
C07D 213/74 - Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
C07D 277/30 - Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 405/12 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
Compounds of formula I : including any possible stereoisomers thereof, wherein: R1 is hydrogen, -C(=O)R6 or -C(=O)CHR7-NH2; R2 is hydrogen; or C1-C6alkyl or phenyl, either of which is optionally substituted with 1, 2 or 3 substituents each independently selected from halo, C1-C6alkyl, C2-C6-alkenyl and C1-C6alkoxy, hydroxy or amino, or R2 is naphtyl; or R2 is indolyl, R3 is hydrogen, Ci-C6alkyl, benzyl; R4 is hydrogen, Ci-C6alkyl, benzyl; or R3 and R4 together with the carbon atom to which they are attached form C3-C7Cyclo- alkyl; R5 is C1-C10alkyl, C3-C7-cycloalkyl, benzyl, or phenyl, any of which being optionally substituted with 1, 2 or 3 substituents each independently selected from hydroxy, C1-C6alkoxy, amino, mono- and diC1-C6alkylamino; R6 is C1-C6 alkyl; R7 is C1-C6 alkyl; R8 is hydrogen or halogen; or a pharmaceutically acceptable salt or solvate thereof are useful in the prophylaxis or treatment of HCV infections.
C07H 19/10 - Pyrimidine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
A61K 31/7072 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
Compounds of the formula II:
or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as osteoporosis, osteoarthritis, rheumatoid arthritis or bone metastases.
A01N 43/38 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings condensed with carbocyclic rings
A61K 31/40 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
Compounds of the formula (I) including any possible stereoisomers thereof, wherein: R4 is a monophosphate, diphosphate or triphosphate ester; or R4 is formula (II) or formula (III), R7 is optionally substituted phenyl, optionally substituted naphthyl, or optionally substituted indolyl; R8 and R8 are hydrogen, C1-C6alkyl, benzyl, or phenyl; or R8 and R8 form C3-C7cycloalkyl; R9 is C1-C10alkyl, C3-C7cycloalkyl, phenyl or phenyl-C1-C6alkyl, wherein the phenyl moiety in phenyl or phenyl-C1-C6alkyl is optionally substituted; or a pharmaceutically acceptable salt or solvate thereof; pharmaceutical formulations and the use of compounds I as HCV inhibitors.
C07H 19/10 - Pyrimidine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
A61K 31/7072 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
A compound of formula (I) N-oxides, addition salts, quaternary amines metal complexes stereochemically isomeric forms and metabolites thereof, wherein A is CR1 Or N; formula (A) or formula (B) D is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, G is NR10 or O Q is C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C6Cycloalkyl, aryl or heterocyclyl; W is H, C1-C6alkyl, C3-C6Cycloalkyl, CH2F, CHF2 or CF3; one of X' and X" is H or CH3, the other is C1-C3alkyl, F, OH, NRaRb, CF3 or N3; or X' and X" are both F; Y is NRd or O; Z is O, NRa, CHRd, CF2 or S(=0)r or a bond; the other variables are as defined in the specification. The compounds of the invention are inhibitors of BACE and are among other things useful for the treatment and/or prevention of conditions associated with BACE activity such as Alzheimer's disease.
A61K 31/166 - Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon atom of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/444 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
C07C 237/34 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to an acyclic carbon atom of a hydrocarbon radical substituted by nitrogen atoms not being part of nitro or nitroso groups
C07C 311/08 - Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
C07D 207/08 - Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
C07D 277/28 - Radicals substituted by nitrogen atoms
C07D 401/06 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 417/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a chain containing hetero atoms as chain links
Compounds of the formula I wherein R1a is H; and R1b is C1-C6 alkyl, Carbocyclyl or Het; or R1a and R1b together define a saturated cyclic amine with 3-6 ring atoms; R2a and R2b are H, halo, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy; or R2a and R2b together with the carbon atom to which they are attached form a C3-C6cycloalkyl; R is a branched C5-C10alkyl chain, C2-C4haloalkyl or C3-C7cycloalkylmethyl, R4 is Het, Carbocyclyl, optionally substituted as defined in the specification and pharmaceutically acceptable salts, hydrates and N-oxides thereof; are inhibitors of cathepsin S and have utility in the treatment of psoriasis, autoimmune disorders and other disorders such as asthma, arteriosclerosis, COPD and chronic pain
C07D 295/20 - Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
A61K 31/145 - Amines, e.g. amantadine having sulfur atoms, e.g. thiurams (N—C(S)—S—C(S)—N or N—C(S)—S—S—C(S)—N)Sulfinylamines (—N=SO)Sulfonylamines (—N=SO2)
A61K 31/341 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
A61K 31/343 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
A61P 37/00 - Drugs for immunological or allergic disorders
C07C 215/20 - Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated the carbon skeleton being saturated and containing rings
C07C 235/74 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of a saturated carbon skeleton
C07C 311/21 - Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
C07D 213/71 - Sulfur atoms to which a second hetero atom is attached
C07D 231/12 - Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
C07D 233/64 - Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
C07D 241/12 - Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
C07D 275/03 - Heterocyclic compounds containing 1, 2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
C07D 307/46 - Doubly bound oxygen atoms, or two oxygen atoms singly bound to the same carbon atom
C07D 307/80 - Radicals substituted by oxygen atoms
Compounds of the formula (I) including any possible stereoisomers thereof, wherein: R1 is hydrogen or halo; R4 is a monophosphate, diphosphate or triphosphate ester; or R4 is a group of formula (II) R7 is optionally substituted phenyl; naphthyl; indolyl or N-C1-C6alkyloxycarbonyl- indolyl; R8 is hydrogen, C1-C6alkyl, benzyl; R8' is hydrogen, C1-C6alkyl, benzyl; or R8 and R8' together with the carbon atom to which they are attached form C3-C7cycloalkyl; R9 is C1-C10alkyl, benzyl, or optionally substituted phenyl; or a pharmaceutically acceptable salt or solvate thereof. pharmaceutical formulations and the use of compounds I as HCV inhibitors.
C07H 19/10 - Pyrimidine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
A61K 31/7072 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
A compound of formula (I): N-oxides, addition salts, quaternary amines metal complexes stereochemically isomeric forms and metabolites thereof, wherein A is CR1 or N; D is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl or Q is C2-C6alkenyl, C2-Cealkynyl, aryl or heterocyclyl; W is H, Ci-Cealkyl, C2-C6alkenyl, haloC1-C3alkyl, hydroxyC1-C3alkyl, C3-C6Cy cloalkyl, aryl or heterocyclyl; one of X' and X" is H or CH3, the other is C1-C3alkyl, F, OH, NRaRb, CF3 or N3; or X' and X" are both F; Y is a bond, CH2, NRa, O, CH2CH2, CH2NRa, CH2O or S(=O)r; Z is O, S(=O)r or NRa; the other variables are as defined in the specification. The compounds of the invention are inhibitors of BACE and are among other things useful for the treatment and/or prevention of conditions associated with BACE activity such as Alzheimer's disease.
C07D 213/75 - Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
A61K 31/195 - Carboxylic acids, e.g. valproic acid having an amino group
A61K 31/455 - Nicotinic acid, i.e. niacinDerivatives thereof, e.g. esters, amides
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
C07C 229/38 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino groups bound to acyclic carbon atoms and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
Compounds of the formula II: wherein R1 and R2 are independently H, F or CH3; or R1 forms an ethynyl bond and R2 is H or C3-C6 cycloalkyl which is optionally substituted with one or two substituents independently selected from methyl, CF3, OMe or halo; R3 is C1-C3 alkyl or C3-C6 cycloalkyl, either of which is optionally substituted with one or two methyl and/or a fluoro, trifluoromethyl or methoxy, when R3 is C3-C6 cycloalkyl it may alternatively be gem subsituted with fluoro; R4 is methyl or fluoro; m is 0, 1 or 2; E is a bond, or thiazolyl, optionally substituted with methyl or fluoro; A1 is CH or N, A2 is CR6R7 or NR6, provided at least one Of A1 and A2 comprises N; R6 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkyl-O-C1-C3 alkyl, or when A2 is C, R6 can also be C1-C4 alkoxy or F; R7 is H, C1-C4 alkyl or F or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as osteoporosis, osteoarthritis, rheumatoid arthritis or bone metastases.
C07D 491/048 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
Compounds of the formula II, wherein R3 is C1-C3 alkyl or C3-C6 cycloalkyl, either of which is optionally substituted with one or two methyl and/or a fluoro, trifluoromethyl or methoxy, when R3 is C3-C6 cycloalkyl it may alternatively be gem substituted with fluoro; R4 is methyl or fluoro; m is 0, 1 or 2; E is a bond, or thiazolyl, optionally substituted with methyl or fluoro; A1 is CH or N, A2 is CR6R7 or NR6, provided at least one of A1 and A2 comprises N; n is 0 or 1 such that the ring containing A1 and A2 is a saturated, nitrogen-containing ring of 5 or 6 ring atoms; R6 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkyl-O-C1-C3 alkyl, or when A2 is C, R6 can also be C1-C4 alkoxy or F; R7 is H, C1-C4 alkyl or F; or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as osteoporosis, osteoarthritis, rheumatoid arthritis or bone metastases.
C07D 491/048 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
Compounds of the formula II: wherein R1 forms an ethynyl bond and R2 is H or C3-C6 cycloalkyl which is optionally substituted with one or two substituents independently selected from methyl, CF3, OMe or halo; R3 is C1-C3 alkyl or C3-C6 cycloalkyl, either of which is optionally substituted with one or two methyl and/or a fluoro, trifluoromethyl or methoxy, when R3 is C3-C6 cycloalkyl it may alternatively be gem subsituted with fluoro; R4 is methyl or fluoro; m is 0, 1 or 2; E is a bond, A1 is CH or N, A2 is CR6R7 or NR6, provided at least one of A1 and A2 comprises N; n is 0 or 1 such that the ring containing A1 and A2 is a saturated, nitrogen-containing ring of 5 or 6 ring atoms; R6 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkyl-O-C1-C3 alkyl, or when A2 is C, R6 can also be C1-C4 alkoxy or F; R7 is H, C1-C4 alkyl or F or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as osteoporosis, osteoarthritis, rheumatoid arthritis or bone metastases.
C07D 491/048 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
Molecular mimics of Smac are capable of modulating apoptosis through their interaction with cellular IAPs (inhibitor of apoptosis proteins). The mimetics are based on a monomer or dimer of the N-terminal tetrapeptide of IAP-binding proteins, such as Smac/DIABLO, Hid, Grim and Reaper, which interact with a specific surface groove of IAP. Also disclosed are methods of using these peptidomimetics for therapeutic purposes. In various embodiments of the invention the Smac mimetics of the invention are combined with chemotherapeutic agents, including, but not limited to topoisomerase inhibitors, kinase inhibitors, NSAIDs, taxanes and platinum containing compounds use broader language.
The invention provides compounds of the formula (I wherein Q is trifluoromethyl, C3-C6cycloalkyl, phenyl, p-fluorophenyl, pyridyl, thiazolyl, furyl, thienyl or C3-C6cycloalkylethynyl; R3 is C1-C6alkyl; R4 is C1-C6alkyl; W is cyano or fluoro; or a pharmaceutically acceptable salt, hydrate or N-oxide thereof. The compounds of the invention are inhibitors of aspartyl proteases such as renin and are among other things useful for the treatment of conditions associated with activities of the RAS, such as hypertension, heart failure and renal insufficiency.
C07C 237/22 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
C07D 213/04 - Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
C07D 275/02 - Heterocyclic compounds containing 1, 2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings
Compounds of formula I: wherein: R2 is hydrogen or C1-C4alkyl; R3 and R4 are hydrogen, -C(=O)R5, or -C(=O)CHR6-NH2; or R3 is hydrogen and R4 is a monophosphate-, diphosphate-, or triphosphate ester; or R3 is hydrogen, -C(=O)CHR5, or -C(=O)CHR6-NH2 and R4 is (formula 2) each R5 is hydrogen, C1-C6alkyl, or C3-C7cycloalkyl; R6 is hydrogen or C1-C6alkyl; R7 is optionally substituted phenyl; naphthyl; or indolyl; R8 and R8 are hydrogen, C3-C7alkyl, benzyl; or R8 and R8 combined form C3-C7cycloalkyl; R9 is C1-C6alkyl, benzyl, or optionally substituted phenyl; provided that R2, R3 and R4 are not all hydrogen; or a pharmaceutically acceptable salt or solvate thereof; pharmaceutical formulations with the compounds I; the use of compounds I, including the compounds of formula I wherein R2, R3 and R4 are all hydrogen, as HCV inhibitors.
A topical antiviral composition comprising acyclovir, penciclovir and/or omaciclovir in a glucocorticoid-free pharmaceutical carrier comprising 15 to 25 weight % propylene glycol and 10 to 25 weight % isopropyl C12-C22 alkanoic ester. The compositions have utility in the treatment or prophylaxis of herpesvirus infections. Clinical results demonstrate that treatment commencing at the prodromal stage can prevent the development of a classic cold sore lesion in a large proportion of patients.
The invention provides compounds of the formula (I) wherein A is selected from the partial structures A1, A2 and A3; Ry and Ry' are both hydrogen, or Ry and Ry' together with the nitrogen atom to which they are attached form a cyclic amine such as morpholine, piperidine, piperazine or pyrrolidine; L is NHNH, CH2NH, O or S; Y is NH, NHNH, NHC(=O), S(=O)2NH, NHS(=O)2, CH2, CH2NH, O, S or S(=0)p; Q is aryl or heterocyclyl; Z is O, S, NRa or S(=0)p; m is O, 1 or 2; n is O, 1, 2 or 3; p is independently 1 or 2; q is 0 or 1; Ra is H or C1-C4alkyl; R1 is hydrogen, C1-C6alkyl, C3-C7cycloalkylC0-C3alkyl, arylC0-C3alkyl or heterocyclylC0-C3alkyl, R4'' is H or C1-C6alkyl; or R4' and R4'' together with the carbon atom to which they are attached define a C3-C6cycloalkyl; W is H, C1-C6alkyl, C3-C7ycycloalkyl, aryl or heterocyclyl; or a pharmaceutically acceptable salt, hydrate or N-oxide thereof. The compounds of the invention are inhibitors of aspartyl proteases such as renin and are among other things useful for the treatment of conditions associated with activities of the RAS, such as hypertension, heart failure and renal insufficiency.
Compounds of the formula II: wherein R2 is the side chain of leucine, isoleucine, cyclohexylglycine, O-methyl threonine, 4- fluoroleucine or 3-methoxyvaline; R3 is H, methyl or F; Rq is thfluoromethyl and Rq' is H or Rq and Rq' define keto; Q is a p-(C1-C6alkylsulphonyl)phenyl- or an optionally substitued 4-(C1- C6alkyl)piperazin-1 -yl-thiazol-4-yl- moiety have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as osteoporosis, osteoarthritis, rheumatoid arthritis or bone metastases.
C07D 491/048 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
A61K 31/407 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with heterocyclic ring systems, e.g. ketorolac, physostigmine
A61P 19/02 - Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
A61P 19/08 - Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
The invention provides compounds of the formula (I) N-oxides, addition salts, quaternary amines, metal complexes, stereochemically isomeric forms and metabolites thereof, wherein G is-O-, -S(=O)r-, -CRdRd or -NRa-; W is H, C1-C6alkyl, C3-C6cycloalkyl, aryl or heterocyclyl; L1 is a bond, methyleneor ethylene; L2 is CHR1;or L1 and L2 together form CH=CH; L3 is a bond, C(=O) or CH2; V1 and V2 are independently a bond, NRa, CRdRd or O; R1 is H, C1-C 6alkyl, C1-C6alkoxy, C1-C4alkoxyC1-C4alkyl, C1-C4alkoxyC1-C4alkoxyC1-C4alkyl, C0-C3alkandiylcarbocyclyl or C0-C3alkandiylheterocyclyl; R2b are both H, or the two R2b together form=O; ring A is a five or six membered saturated, partially unsaturated or aromatic ring; and the other variables are as defined in the specification. The compounds of the invention are inhibitors of BACE and are among other things useful for the treatment and/or prevention of conditions associated with BACE activity such as Alzheimer´s disease.
C07D 267/00 - Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one oxygen atom as the only ring hetero atoms
C07D 313/00 - Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
The invention provides compounds of the formula (I). N-oxides, addition salts, quaternary amines, metal complexes, stereochemically isomeric forms and metabolites thereof, wherein W is H, C1-C6alkyl, C3-C6cycloalkyl, aryl or heterocyclyl; Q is aryl or heterocyclyl; A is a five or six membered saturated, partially unsaturated or aromatic ring; D is formula (II) or formula (III); and the other variables are as defined in the specification. The compounds of the invention are inhibitors of aspartyl proteases such as renin and BACE and are among other things useful for the treatment and/or prophylaxis of conditions associated with activities of the RAS, such as hypertension, heart failure and renal insufficiency and for the treatment and or prophylaxis of conditions associated with BACE activity such as of Alzheimer's disease.
C07C 311/08 - Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
C07C 311/07 - Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring
C07C 255/57 - Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and carboxyl groups, other than cyano groups, bound to the carbon skeleton
