05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Pharmaceutical preparations for the treatment of pruritus; Pharmaceutical preparations for the treatment of pain; Pharmaceutical preparations for the treatment of nausea and vomiting
The invention provides formulations for oral delivery of a therapeutic wherein the formulation comprises a kappa opioid receptor agonist, an oligosaccharide stabilizing agent and an optional absorption enhancer. The kappa opioid receptor agonist may be coated with, embedded in or mixed with an oligosaccharide, such as trehalose. Also provided are capsules containing the oral formulations of the kappa opioid receptor agonists, the oligosaccharide and the absorption enhancer of the invention. The invention further provides methods of manufacture of the formulations and methods of their use for the prophylaxis, inhibition and treatment of variety of kappa opioid receptor-associated diseases and conditions such as pain, pruritus and inflammation. The methods of use include administering to the mammal the formulation of the kappa opioid receptor agonist, oligosaccharide and optional absorption enhancers.
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 9/48 - Preparations in capsules, e.g. of gelatin, of chocolate
The invention provides formulations for oral delivery of a therapeutic agent wherein the formulation comprises a kappa opioid receptor agonist and an absorption enhancer, the absorption enhancer includes a medium chain fatty acid or a salt of a medium chain fatty acid; and a medium chain fatty acid glyceride. The kappa opioid receptor agonist may be embedded in an oligosaccharide, such as trehalose. Also provided are capsules containing the oral formulations of the kappa opioid receptor agonists and the absorption enhancer of the invention and methods use of these formulations for the prophylaxis and treatment of variety of kappa opioid receptor-associated diseases and conditions such as pain, pruritus and inflammation; the method comprising administering to the mammal the formulation comprising the kappa opioid receptor agonist and an absorption enhancer.
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
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 9/48 - Preparations in capsules, e.g. of gelatin, of chocolate
Conjugate (KTAC) compounds that include a peptidic kappa opioid receptor agonist linked through a protease-sensitive linker and/or acid-sensitive linker to an antibody molecule are provided. The linker may include spacer regions on either side of the protease sensitive cleavage site. The antibody can be a monoclonal antibody such as a therapeutic monoclonal antibody. The KTAC compounds may be incorporated into pharmaceutical compositions useful for the treatment of diseases and conditions, particularly those that include an inflammatory component.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
6.
ATOPIC DERMATITIS THERAPY WITH KAPPA OPIOID RECEPTOR AGONIST AS ADJUNCT TO TOPICAL CORTICOSTEROID
The invention relates to a method of treatment of atopic dermatitis in a patient, the method includes providing a course of treatment comprising orally administering an effective amount of a kappa opioid receptor agonist (KORA) to the patient and applying an effective amount of a topical corticosteroid (TCS) to an area of the patient affected by the atopic dermatitis.
A61K 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
(1) Pharmaceutical preparations for the treatment of pruritus; pharmaceutical preparations for the treatment of pain; pharmaceutical preparations for the treatment of nausea and vomiting
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Pharmaceutical preparations for the treatment of pruritus; Pharmaceutical preparations for the treatment of pain; Pharmaceutical preparations for the treatment of nausea and vomiting.
10.
KAPPA OPIOID RECEPTOR AGONIST-THERAPEUTIC ANTIGEN BINDING PROTEIN CONJUGATE (KTAC) COMPOUNDS
Conjugate (KTAC) compounds that include a peptidic kappa opioid receptor agonist linked through a protease-sensitive linker and/or acid-sensitive linker to an antibody molecule are provided. The linker may include spacer regions on either side of the protease sensitive cleavage site. The antibody can be a monoclonal antibody such as a therapeutic monoclonal antibody. The KTAC compounds may be incorporated into pharmaceutical compositions useful for the treatment of diseases and conditions, particularly those that include an inflammatory component.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
C07K 5/037 - Peptides having up to four amino acids in a fully defined sequenceDerivatives thereof containing at least one abnormal peptide link the abnormal link being formed by the side chain of an alpha-amino acid, e.g. gamma-Glu, epsilon-Lys, glutathione
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
11.
KAPPA OPIOID RECEPTOR AGONIST-THERAPEUTIC ANTIGEN BINDING PROTEIN CONJUGATE (KTAC) COMPOUNDS
Conjugate (KTAC) compounds that include a peptidic kappa opioid receptor agonist linked through a protease-sensitive linker and/or acid-sensitive linker to an antibody molecule are provided. The linker may include spacer regions on either side of the protease sensitive cleavage site. The antibody can be a monoclonal antibody such as a therapeutic monoclonal antibody. The KTAC compounds may be incorporated into pharmaceutical compositions useful for the treatment of diseases and conditions, particularly those that include an inflammatory component.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 5/107 - Tetrapeptides the side chain of the first amino acid containing carbocyclic rings, e.g. Phe, Tyr
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
12.
Oral formulations of kappa opioid receptor agonists
The invention provides formulations for oral delivery of a therapeutic agent wherein the formulation comprises a kappa opioid receptor agonist and an absorption enhancer, the absorption enhancer includes a medium chain fatty acid or a salt of a medium chain fatty acid; and a medium chain fatty acid glyceride. The kappa opioid receptor agonist may be embedded in an oligosaccharide, such as trehalose. Also provided are capsules containing the oral formulations of the kappa opioid receptor agonists and the absorption enhancer of the invention and methods use of these formulations for the prophylaxis and treatment of variety of kappa opioid receptor-associated diseases and conditions such as pain, pruritus and inflammation; the method comprising administering to the mammal the formulation comprising the kappa opioid receptor agonist and an absorption enhancer.
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
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 31/485 - Morphinan derivatives, e.g. morphine, codeine
A61K 47/14 - Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
A61K 9/48 - Preparations in capsules, e.g. of gelatin, of chocolate
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
13.
OLIGOSACCHARIDE FORMULATIONS OF KAPPA OPIOID RECEPTOR AGONISTS
The invention provides formulations for oral delivery of a therapeutic agent wherein the formulation comprises a kappa opioid receptor agonist, an oligosaccharide stabilizing agent and an optional absorption enhancer. The kappa opioid receptor agonist may be coated with, embedded in or mixed with an oligosaccharide, such as trehalose. Also provided are capsules containing the oral formulations of the kappa opioid receptor agonists, the oligosaccharide and the absorption enhancer of the invention. The invention further provides methods of manufacture of the formulations and methods of their use for the prophylaxis, inhibition and treatment of variety of kappa opioid receptor-associated diseases and conditions such as pain, pruritus and inflammation. The methods of use include administering to the mammal the formulation of the kappa opioid receptor agonist, oligosaccharide and optional absorption enhancers.
The invention provides formulations for oral delivery of a therapeutic agent wherein the formulation comprises a kappa opioid receptor agonist, an oligosaccharide stabilizing agent and an optional absorption enhancer. The kappa opioid receptor agonist may be coated with, embedded in or mixed with an oligosaccharide, such as trehalose. Also provided are capsules containing the oral formulations of the kappa opioid receptor agonists, the oligosaccharide and the absorption enhancer of the invention. The invention further provides methods of manufacture of the formulations and methods of their use for the prophylaxis, inhibition and treatment of variety of kappa opioid receptor-associated diseases and conditions such as pain, pruritus and inflammation. The methods of use include administering to the mammal the formulation of the kappa opioid receptor agonist, oligosaccharide and optional absorption enhancers.
The invention provides formulations for oral delivery of a therapeutic agent wherein the formulation comprises a kappa opioid receptor agonist, an oligosaccharide stabilizing agent and an optional absorption enhancer. The kappa opioid receptor agonist may be coated with, embedded in or mixed with an oligosaccharide, such as trehalose. Also provided are capsules containing the oral formulations of the kappa opioid receptor agonists, the oligosaccharide and the absorption enhancer of the invention. The invention further provides methods of manufacture of the formulations and methods of their use for the prophylaxis, inhibition and treatment of variety of kappa opioid receptor-associated diseases and conditions such as pain, pruritus and inflammation. The methods of use include administering to the mammal the formulation of the kappa opioid receptor agonist, oligosaccharide and optional absorption enhancers.
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 31/485 - Morphinan derivatives, e.g. morphine, codeine
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Medicines and pharmaceutical preparations for the treatment and prevention of kidney diseases; medicines and pharmaceutical preparations for the treatment and prevention of chronic kidney diseases; medicines and pharmaceutical preparations for the treatment of pruritus; medicines and pharmaceutical preparations for the treatment of pain.
05 - Pharmaceutical, veterinary and sanitary products
Goods & Services
Medicines and pharmaceutical preparations for the treatment and prevention of kidney diseases; medicines and pharmaceutical preparations for the treatment and prevention of chronic kidney diseases; medicines and pharmaceutical preparations for the treatment of pruritus; medicines and pharmaceutical preparations for the treatment of pain.
19.
ORAL FORMULATIONS OF KAPPA OPIOID RECEPTOR AGONISTS
The invention provides formulations for oral delivery of a therapeutic agent wherein the formulation comprises a kappa opioid receptor agonist and an absorption enhancer, the absorption enhancer includes a medium chain fatty acid or a salt of a medium chain fatty acid; and a medium chain fatty acid glyceride. The kappa opioid receptor agonist may be embedded in an oligosaccharide, such as trehalose. Also provided are capsules containing the oral formulations of the kappa opioid receptor agonists and the absorption enhancer of the invention and methods use of these formulations for the prophylaxis and treatment of variety of kappa opioid receptor-associated diseases and conditions such as pain, pruritus and inflammation; the method comprising administering to the mammal the formulation comprising the kappa opioid receptor agonist and an absorption enhancer.
The invention provides formulations for oral delivery of a therapeutic agent wherein the formulation comprises a kappa opioid receptor agonist and an absorption enhancer, the absorption enhancer includes a medium chain fatty acid or a salt of a medium chain fatty acid; and a medium chain fatty acid glyceride. The kappa opioid receptor agonist may be embedded in an oligosaccharide, such as trehalose. Also provided are capsules containing the oral formulations of the kappa opioid receptor agonists and the absorption enhancer of the invention and methods use of these formulations for the prophylaxis and treatment of variety of kappa opioid receptor-associated diseases and conditions such as pain, pruritus and inflammation; the method comprising administering to the mammal the formulation comprising the kappa opioid receptor agonist and an absorption enhancer.
A61K 47/36 - PolysaccharidesDerivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 9/52 - Sustained or differential release type
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 31/485 - Morphinan derivatives, e.g. morphine, codeine
The invention provides formulations for oral delivery of a therapeutic agent wherein the formulation comprises a kappa opioid receptor agonist and an absorption enhancer, the absorption enhancer includes a medium chain fatty acid or a salt of a medium chain fatty acid; and a medium chain fatty acid glyceride. The kappa opioid receptor agonist may be embedded in an oligosaccharide, such as trehalose. Also provided are capsules containing the oral formulations of the kappa opioid receptor agonists and the absorption enhancer of the invention and methods use of these formulations for the prophylaxis and treatment of variety of kappa opioid receptor-associated diseases and conditions such as pain, pruritus and inflammation; the method comprising administering to the mammal the formulation comprising the kappa opioid receptor agonist and an absorption enhancer.
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
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 31/485 - Morphinan derivatives, e.g. morphine, codeine
A61K 47/14 - Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
A61K 9/48 - Preparations in capsules, e.g. of gelatin, of chocolate
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K 47/26 - Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharidesDerivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure of formula I:
These compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions.
450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure:
The compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions.
450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure:
The compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions.
450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure of formula I:
Pharmaceutical compositions containing these compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions. Such treatable pain includes visceral pain, neuropathic pain and hyperalgesia. Inflammation associated with conditions such as IBD and IBS, ocular and otic inflammation, other disorders and conditions such as pruritis, edema, hyponatremia, hypokalemia, ileus, tussis and glaucoma are treatable or preventable with the pharmaceutical compositions of the invention.
A method for preventing, inhibiting or treating hard tissue pain in a mammalian subject, the method comprising administering an effective amount of a peripherally-restricted kappa opioid receptor agonist to the subject. The hard tissue pain can be associated with bone, tendons, or cartilage. The peripherally-restricted kappa opioid receptor agonist can be a L-amino acid-containing peptide, a D-amino acid-containing peptide, or a synthetic peptide amide, such as for instance, CR845.
A61K 31/485 - Morphinan derivatives, e.g. morphine, codeine
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
450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure of formula I:
Pharmaceutical compositions containing these compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions. Such treatable pain includes visceral pain, neuropathic pain and hyperalgesia. Inflammation associated with conditions such as IBD and IBS, ocular and otic inflammation, other disorders and conditions such as pruritis, edema, hyponatremia, hypokalemia, ileus, tussis and glaucoma are treatable or preventable with the pharmaceutical compositions of the invention.
The invention relates to methods of use of synthetic peptide amides that are ligands of the kappa opioid receptor in the treatment and prevention of kappa opioid receptor-associated diseases and conditions; and particularly to uses of these agonists in the prophylaxis, inhibition and treatment of pain, inflammation and pruritis associated with a variety of diseases, disorders and conditions. Inflammatory conditions preventable or treatable by the methods of the invention include diseases and conditions associated with elevated levels of a proinflammatory cytokines, such as TNF-α, IL-1β, IL-6, MMP-1 and MMP-3. Such diseases and conditions include cardiovascular inflammation, neurological inflammation, skeletal inflammation, muscular inflammation, gastrointestinal inflammation, ocular inflammation, otic inflammation, inflammation due to insect bites and inflammation due to wound healing; atherosclerosis, ischemia, restenosis and vasculitis; of asthma, Sjogren's syndrome, pulmonary inflammation, chronic airway inflammation and chronic obstructive pulmonary disease (COPD), allergy, psoriasis, psoriatic arthritis, eczema, scleroderma, atopic dermatitis and systemic lupus erythematosus, arthritis, synovitis, osteomyelitis, rheumatoid arthritis, osteoarthritis and ankylosing spondylitis; septicemia and septic shock, diabetes, glucose intolerance, insulin resistance and obesity, colitis, ulcerative colitis, Crohn's disease, IBD and IBS, and the inflammatory diseases and conditions due to tumor proliferation, tumor metastasis or transplantation rejection.
C07K 5/11 - Tetrapeptides the side chain of the first amino acid containing more amino groups than carboxyl groups, or derivatives thereof, e.g. Lys, Arg
A method for preventing, inhibiting or treating nausea and/or vomiting in a mammalian subject, the method comprising administering an effective amount of a peripherally-restricted kappa opioid receptor agonist to the subject. The nausea and/or vomiting can be associated with use of an opioid, such as morphine or fentanyl. The peripherally-restricted kappa opioid receptor agonist can be an L-amino acid-containing peptide, a D-amino acid-containing peptide, or a synthetic peptide amide, such as for instance, D-Phe-D-Phe-D-Leu-D-Lys-[ω(4-aminopiperidine-4-carboxylic acid)] -OH (CR845).
450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure:
The compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions.
A method of treating of a mammalian subject suffering from an inflammatory disease or condition by administering a peripherally-restricted kappa opioid receptor agonist for reducing the inflammation is provided. The peripherally-restricted kappa opioid receptor agonist can include a peptide and the peptide can include D-amino acids. Administration of peripherally- restricted kappa opioid receptor agonists results in lowering of serum levels of pro-inflammatory cytokines and elevation of levels of anti-inflammatory cytokines.
450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure of formula I:
Pharmaceutical compositions containing these compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions. Such treatable pain includes visceral pain, neuropathic pain and hyperalgesia. Inflammation associated with conditions such as IBD and IBS, ocular and otic inflammation, other disorders and conditions such as pruritis, edema, hyponatremia, hypokalemia, ileus, tussis and glaucoma are treatable or preventable with the pharmaceutical compositions of the invention.
450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure of formula I:
Pharmaceutical compositions containing these compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions. Such treatable pain includes visceral pain, neuropathic pain and hyperalgesia. Inflammation associated with conditions such as IBD and IBS, ocular and otic inflammation, other disorders and conditions such as pruritis, edema, hyponatremia, hypokalemia, ileus, tussis and glaucoma are treatable or preventable with the pharmaceutical compositions of the invention.
The present invention provides substituted imidazoheterocycles having the general structure of formula I:
h—. Also provided are pharmaceutically acceptable salts, acid salts, hydrates, solvates and stereoisomers of the compounds of formula I. The compounds are useful as modulators of cannabinoid receptors and for the prophylaxis and treatment of cannabinoid receptor-associated diseases and conditions, such as pain, inflammation and pruritis.
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
The present invention provides substituted pyrazolo-heterocycles having the general structure of formula I
c are described in the specification. Also provided are pharmaceutically acceptable salts, acid salts, hydrates, solvates and stereoisomers of the compounds of formula I. The compounds are useful as modulators of cannabinoid receptors and for the prophylaxis, treatment and inhibition of cannabinoid receptor-associated diseases and conditions, such as pain, inflammation and pruritis.
A61K 31/437 - 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 five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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
450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure:
The compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions.
Methods for distinguishing between cotton species by analyzing a sample of mature cotton fibers from raw cotton materials or from textile goods are disclosed. DNA is extracted from the mature cotton fiber sample and subjected to PCR techniques which enable the identification of the species of cotton utilized in the textile or cotton material of interest.
The invention relates to methods of use of synthetic peptide amides that are ligands of the kappa opioid receptor in the treatment and prevention of kappa opioid receptor-associated diseases and conditions; and particularly to uses of these agonists in the prophylaxis, inhibition and treatment of pain, inflammation and pruritis associated with a variety of diseases, disorders and conditions. Inflammatory conditions preventable or treatable by the methods of the invention include diseases and conditions associated with elevated levels of a proinflammatory cytokines, such as TNF-α, IL-β, IL-6, MMP-1 and MMP-3. Such diseases and conditions include cardiovascular inflammation, neurological inflammation, skeletal inflammation, muscular inflammation, gastrointestinal inflammation, ocular inflammation, otic inflammation, inflammation due to insect bites and inflammation due to wound healing; atherosclerosis, ischemia, restenosis and vasculitis; of asthma, Sjogren's syndrome, pulmonary inflammation, chronic airway inflammation and chronic obstructive pulmonary disease (COPD), allergy, psoriasis, psoriatic arthritis, eczema, scleroderma, atopic dermatitis and systemic lupus erythematosus, arthritis, synovitis, osteomyelitis, rheumatoid arthritis, osteoarthritis and ankylosing spondylitis; septicemia and septic shock, diabetes, glucose intolerance, insulin resistance and obesity, colitis, ulcerative colitis, Crohn's disease, IBD and IBS, and the inflammatory diseases and conditions due to tumor proliferation, tumor metastasis or transplantation rejection.
The present invention provides substituted pyrazolo-heterocycles having the general structure of formula I
Also provided are pharmaceutically acceptable salts, acid salts, hydrates, solvates and stereoisomers of the compounds of formula I. The compounds are useful as modulators of cannabinoid receptors and for the prophylaxis and treatment of cannabinoid receptor-associated diseases and conditions, such as pain, inflammation and pruritis.
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 31/35 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
C07D 413/12 - 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 chain containing hetero atoms as chain links
C07D 207/06 - 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 radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms
C07D 311/94 - Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems condensed with rings other than six-membered or with ring systems containing such rings
42.
Synthetic peptide amides and dimeric forms thereof
450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure:
wherein Xaa is a D-amino acid and G is selected from the following three groups:
The compounds are useful in the prophylaxis and treatment of pain, pruritis and inflammation associated with a variety of diseases and conditions.
The present invention provides a method of prophylaxis, treatment or inhibition of a cannabinoid receptor-associated disease, disorder or condition in a mammalian subject, the method comprising administering to the subject a compound having the structure of formula I or a pharmaceutically acceptable salt, acid salt, hydrate or stereoisomer thereof, wherein the cannabinoid receptor-associated disease, disorder or condition is pain or an inflammatory disease, disorder or condition, and wherein formula I is as follows:
c, Z, Y and m are defined in the specification.
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
The present invention provides substituted pyrazolo-heterocycles having the general structure of formula I (I). The structures of rings A and B and substituents R a, R b and R c are described in the specification. Also provided are pharmaceutically acceptable salts, acid salts, hydrates, solvates and stereoisomers of the compounds of formula I. The compounds are useful as modulators of cannabinoid receptors and for the prophylaxis, treatment and inhibition of cannabinoid receptor- associated diseases and conditions, such as pain, inflammation and pruritis.
A61K 31/437 - 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 five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
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
The present invention provides substituted pyrazolo-heterocycles having the general structure of formula I (I). The structures of rings A and B and substituents Ra, Rb and Rc are described in the specification. Also provided are pharmaceutically acceptable salts, acid salts, hydrates, solvates and stereoisomers of the compounds of formula I. The compounds are useful as modulators of cannabinoid receptors and for the prophylaxis, treatment and inhibition of cannabinoid receptor- associated diseases and conditions, such as pain, inflammation and pruritis.
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
A61K 31/437 - 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 five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
The present invention provides substituted pyrazolo-heterocycles having the general structure of formula I
Also provided are pharmaceutically acceptable salts, acid salts, hydrates, solvates and stereoisomers of the compounds of formula I. The compounds are useful as modulators of cannabinoid receptors and for the prophylaxis and treatment of cannabinoid receptor-associated diseases and conditions, such as pain, inflammation and pruritis.
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 31/35 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
C07D 413/12 - 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 chain containing hetero atoms as chain links
C07D 207/06 - 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 radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms
C07D 311/94 - Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems condensed with rings other than six-membered or with ring systems containing such rings
The present invention provides substituted imidazoheterocycles having the general structure of formula (I), wherein Y is chosen from -O-, -OCRgRh-, -CRgRhO-, -CRgRh-, -(CRgRh)2-, -NRi-, -CRgRhNRi- and -NRiCRgRh-. Also provided are pharmaceutically acceptable salts, acid salts, hydrates, solvates and stereoisomers of the compounds of formula I. The compounds are useful as modulators of cannabinoid receptors and for the prophylaxis and treatment of cannabinoid receptor-associated diseases and conditions, such as pain, inflammation and pruritis.
Compounds are provided having the general structure of formula I: In formula I, one member of the group (W, X, Y and Z) is a nitrogen atom and the remaining three members of the group are each independently a carbon atom covalently bonded to a radical, R4. The radicals, R1 R2, R3 and R4 are each defined herein, and n is an integer from 1 to 4. Also provided are stereoisomers, prodrugs, pharmaceutically acceptable salts, hydrates, salt hydrates, acid salt hydrates, and polymorphs of the compounds having the structure of formula I. The compounds bind the prostaglandin D2 receptor and are useful in the prophylaxis and treatment of prostaglandin D2-mediated diseases and conditions, including pain and inflammation, as well as asthma and allergic diseases and conditions.
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
450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure:
wherein Xaa is a D-amino acid and G is selected from the following three groups:
The compounds are useful in the prophylaxis and treatment of pain, pruritus and inflammation associated with a variety of diseases and conditions.
Methods for elevating and stabilizing prolactin levels in a mammal including methods of treating disorders and conditions associated with reduced serum levels of prolactin are provided. Also provided are methods of using certain synthetic tetrapeptide amides which are peripherally selective kappa opioid receptor agonists to elevate or stabilize serum prolactin levels.
450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure:
Pharmaceutical compositions containing these compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions. Such treatable pain includes visceral pain, neuropathic pain and hyperalgesia. Inflammation associated with conditions such as IBD and IBS, ocular and otic inflammation, other disorders and conditions such as pruritis, edema, hyponatremia, hypokalemia, ileus, tussis and glaucoma are treatable or preventable with the pharmaceutical compositions of the invention.
The invention provides compounds having the structure of formula I,
4 are defined in the specification. These compounds can be administered in pharmaceutical formulations to modulate cannabinoid receptor activity for the prevention and treatment of a variety of diseases and conditions, including pain, inflammation and pruritis.
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
A61K 31/5365 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one oxygen as the ring hetero atoms, e.g. 1,2-oxazines ortho- or peri-condensed with heterocyclic ring systems
The invention provides compounds having the structure of formula I, and prodrugs, stereoisomers, racemates, salts, hydrates, solvates, acid salt hydrates and isomorphic crystalline forms thereof, wherein A, Y and the groups R1, R2, R3 and R4 are defined in the specification. These compounds can be administered in pharmaceutical formulations to modulate cannabinoid receptor activity for the prevention and treatment of a variety of diseases and conditions, including pain, inflammation and pruritis.
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 413/02 - 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
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 403/02 - 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
54.
Synthetic peptide amides and dimeric forms thereof
450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure:
wherein Xaa is a D-amino acid and G is selected from the following three groups:
The compounds are useful in the prophylaxis and treatment of pain, pruritis and inflammation associated with a variety of diseases and conditions.
The present invention provides substituted imidazoheterocyclic compounds having the structure of formula I
Also provided are pharmaceutically acceptable salts, acid salts, hydrates, solvates and stereoisomers of the compounds of formula I. The compounds are useful as modulators of cannabinoid receptors and for the prophylaxis and treatment of cannabinoid receptor-associated diseases and conditions, such as pain, inflammation and pruritis.
450 CYP inhibition and low penetration into the brain. An exemplary synthetic tetrapeptide amide of the invention is D-Phe-D-Phe-D-Leu-(ε-Me) D-Lys-[4-Amidinohomopiperazine amide]:
Pharmaceutical compositions containing these compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions. Such treatable pain includes visceral pain, neuropathic pain and hyperalgesia. Inflammation associated with conditions such as IBD and IBS, ocular and otic inflammation, other disorders and conditions such as pruritis, edema, hyponatremia, hypokalemia, ileus, tussis and glaucoma are treatable or preventable with the pharmaceutical compositions of the invention.
The present invention provides benzo-fused heterocyclic compounds having the structure of formula I, as well as prodrugs, stereoisomers, racemates, salts, hydrates, solvates, acid salt hydrates and isomorphic crystalline forms thereof. (I) The compounds directly or indirectly modulate the activity of one or more cannabinoid receptors and can be incorporated into pharmaceutical preparations that are useful for the prevention and treatment of a variety of diseases and conditions, including pain, inflammation and pruritis.
The present invention provides benzo-fused heterocyclic compounds having the structure of formula I, as well as prodrugs, stereoisomers, racemates, salts, hydrates, solvates, acid salt hydrates and isomorphic crystalline forms thereof.
The compounds directly or indirectly modulate the activity of one or more cannabinoid receptors and can be incorporated into pharmaceutical preparations that are useful for the prevention and treatment of a variety of diseases and conditions, including pain, inflammation and pruritis.
C07D 279/16 - 1,4-ThiazinesHydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
A61K 31/5415 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and at least one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
59.
Substituted imidazo[1,5-a][1,4]diazepines and imidazo[1,5-a]pyrazines as cannabinoid receptor agonists for the treatment of pain
The present invention provides substituted imidazoheterocyclic compounds having the structure of formula I
Also provided are pharmaceutically acceptable salts, acid salts, hydrates, solvates and stereoisomers of the compounds of formula I. The compounds are useful as modulators of cannabinoid receptors and for the prophylaxis and treatment of cannabinoid receptor-associated diseases and conditions, such as pain, inflammation and pruritis.
The present invention provides substituted imidazoheterocyclic compounds having the structure of Formula (I) Also provided are pharmaceutically acceptable salts, acid salts, hydrates, solvates and stereoisomers of the compounds of formula I. The compounds are useful as modulators of cannabinoid receptors and for the prophylaxis and treatment of cannabinoid receptor- associated diseases and conditions, such as pain, inflammation and pruritis.
The present invention provides substituted imidazoheterocyclic compounds having the structure of Formula (I) Also provided are pharmaceutically acceptable salts, acid salts, hydrates, solvates and stereoisomers of the compounds of formula I. The compounds are useful as modulators of cannabinoid receptors and for the prophylaxis and treatment of cannabinoid receptor- associated diseases and conditions, such as pain, inflammation and pruritis.
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/551 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogens as ring hetero atoms, e.g. clozapine, dilazep
A61P 25/04 - Centrally acting analgesics, e.g. opioids
C07D 519/00 - Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups or
Bridged phenanthridine compounds having the structure of formula I or of formula II are provided. These compounds are useful as cannabinoid receptor ligands and can be prepared as pharmaceutical compositions for the prophylaxis or treatment of a variety of diseases, disorders and conditions including inflammatory pain, visceral pain, postoperative pain, cancer pain, neuropathic pain, musculoskeletal pain, dysmenorrhea, menstrual pain, migraine, headache as well as inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, Crohn's disease, psoriasis, eczema, multiple sclerosis, diabetes and thyroiditis. The compounds can also be used in the treatment of skin disorders, lung disorders, ophthalmic disorders, gastrointestinal disorders, cardiovascular disorders, as well as neurodegenerative, neuroinflammatory and certain psychiatric disorders.
C07D 213/06 - 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 containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
C07D 215/02 - Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure of formula I:
Pharmaceutical compositions containing these compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions. Such treatable pain includes visceral pain, neuropathic pain and hyperalgesia. Inflammation associated with conditions such as IBD and IBS, ocular and otic inflammation, other disorders and conditions such as pruritis, edema, hyponatremia, hypokalemia, ileus, tussis and glaucoma are treatable or preventable with the pharmaceutical compositions of the invention.
Tetrahydroquinolinone and tetrahydronaphthyridone cannabinoid receptor ligand compounds and stereoisomers, mixtures of stereoisomers, prodrugs, pharmaceutically acceptable salts, hydrates, solvates, acid salt hydrates, and isomorphic crystalline forms thereof are described. The compounds conform to the structure of formula (I)
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 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
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 409/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms 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
A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
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
The invention relates to synthetic peptide amide ligands of the kappa opioid receptor and particularly to agonists of the kappa opioid receptor that exhibit low P45O CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure: Pharmaceutical compositions containing these compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions. Such treatable pain includes visceral pain, neuropathic pain and hyperalgesia. Inflammation associated with conditions such as IBD and IBS, ocular and otic inflammation, other disorders and conditions such as pruritis, edema, hyponatremia, hypokalemia, ileus, tussis and glaucoma are treatable or preventable with the pharmaceutical compositions of the invention.
The invention relates to synthetic peptide amide ligands of the kappa opioid receptor and particularly to agonists of the kappa opioid receptor that exhibit low P45O CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure: Pharmaceutical compositions containing these compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions. Such treatable pain includes visceral pain, neuropathic pain and hyperalgesia. Inflammation associated with conditions such as IBD and IBS, ocular and otic inflammation, other disorders and conditions such as pruritis, edema, hyponatremia, hypokalemia, ileus, tussis and glaucoma are treatable or preventable with the pharmaceutical compositions of the invention.
The invention relates to synthetic peptide amide dimer ligands of the kappa opioid receptor and particularly to synthetic peptide amide dimer agonists of the kappa opioid receptor that exhibit low P450 CYP inhibition and low penetration into the brain. The synthetic peptide amide dimers of the invention conform to the structure: (See above Formula) wherein G is (See above Formula) The synthetic peptide amide dimer compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions including pain and inflammation.
The invention relates to synthetic peptide amide ligands of the kappa opioid receptor and particularly to agonists of the kappa opioid receptor that exhibit low P450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure of formula I: Pharmaceutical compositions containing these compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions. Such treatable pain includes visceral pain, neuropathic pain and hyperalgesia. Inflammation associated with conditions such as IBD and IBS, ocular and otic inflammation, other disorders and conditions such as pruritis, edema, hyponatremia, hypokalemia, ileus, tussis and glaucoma are treatable or preventable with the pharmaceutical compositions of the invention.
The invention relates to synthetic peptide amide ligands of the kappa opioid receptor and particularly to agonists of the kappa opioid receptor that exhibit low P450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure of formula I: Pharmaceutical compositions containing these compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions. Such treatable pain includes visceral pain, neuropathic pain and hyperalgesia. Inflammation associated with conditions such as IBD and IBS, ocular and otic inflammation, other disorders and conditions such as pruritis, edema, hyponatremia, hypokalemia, ileus, tussis and glaucoma are treatable or preventable with the pharmaceutical compositions of the invention.
Methods for elevating and stabilizing prolactin levels in a mammal including methods of treating disorders and conditions associated with reduced serum levels of prolactin are provided. Also provided are methods of using certain synthetic tetrapeptide amides which are peripherally selective kappa opioid receptor agonists to elevate or stabilize serum prolactin levels.
Certain peptides which exhibit high selectivity for the kappa opioid receptor (KOR) versus the mu opioid receptor and little or no CYP3A4 inhibitory activity including tetrapeptides of four D-isomer amino acid residues having a C-terminus which is an N-oxide-substituted amide such, as H-D-Phe-D-Phe-D-Nle-D-Arg-NH-4- picolyl-N-oxide. A preferred compound, which has an affinity for the KOR at least 1,000 times its affinity for the mu opioid receptor and an IC50 for CYP3 A4 of greater than about 10 micromolar, is H-D-Phe-D-Phe-D-Nle-D-Arg-NH-4-picolyl-N-oxide
