Methods for preparing an inhibitor of dipeptidyl peptidase IV, as well as formulations of such inhibitors of dipeptidyl peptidase IV that have a high degree of stability including under warm, humid storage conditions.
C07D 403/12 - Composés hétérocycliques contenant plusieurs hétérocycles, comportant des atomes d'azote comme uniques hétéro-atomes du cycle, non prévus par le groupe contenant deux hétérocycles liés par une chaîne contenant des hétéro-atomes comme chaînons
The invention provides new, more effective olefin metathesis catalytic systems and catalysts, suitable for catalyzing olefin metathesis reactions. Addition of imidazolium ions to ruthenium-based olefin metathesis catalysts results in higher yields and greater purities of products. The catalysts are useful for the formation of macrocyclic products. Methods are provided for using the catalysts, such as in formation of a key intermediate in the synthesis of a macrocyclic hepatitis C virus protease inhibitor.
The invention provides macrocyclic compounds inhibitory to the Hepatitis C viral protease, compositions and combinations including the compounds, methods of treatment of conditions wherein inhibition of the Hepatitis C viral protease is medically indicated, and methods of treatment of a Hepatitis C viral infection in a human patient.
A01N 55/02 - Biocides, produits repoussant ou attirant les animaux nuisibles ou régulateurs de croissance des végétaux, contenant des composés organiques comportant des éléments autres que le carbone, l'hydrogène, les halogènes, l'oxygène, l'azote et le soufre contenant des atomes de métal
The present invention provides a method of synthesis of a macrocyclic compound known as a potent inhibitor of a protease produced by the hepatitis C virus (HCV). Inhibition of the viral protease blocks assembly of mature viral particles in an infected mammalian host. The method of synthesis involves a ring-closing metathesis step using a ruthenium catalyst. Hydrogenation and boronate deprotection provide the HCV protease-inhibitory product.
A61K 38/00 - Préparations médicinales contenant des peptides
C07D 245/00 - Composés hétérocycliques contenant des cycles de plus de sept chaînons comportant deux atomes d'azote comme uniques hétéro-atomes du cycle
The invention provides compounds inhibitory to the Hepatitis C viral protease, compositions and combinations including the compounds, methods of treatment of conditions wherein inhibition of the Hepatitis C viral protease is medically indicated, and methods of treatment of a Hepatitis C viral infection in a human patient.
A61K 31/585 - Composés contenant des systèmes cycliques du cyclopenta[a]hydrophénanthrèneLeurs dérivés, p. ex. stéroïdes contenant des hétérocycles, p. ex. danazol, stanozolol, pancuronium ou digitogénine contenant des cycles lactone, p. ex. oxandrolone, bufaline
C07H 17/08 - Hétérocycles d'au moins huit chaînons, p. ex. érythromycines
C12P 17/08 - Préparation de composés hétérocycliques comportant O, N, S, Se ou Te comme uniques hétéro-atomes du cycle l'oxygène comme unique hétéro-atome du cycle contenant un hétérocycle d'au moins sept chaînons, p. ex. zéaraléone, aglycones de macrolides
6.
A CRYSTALLINE SYNTHETIC INTERMEDIATE FOR PYRROLIDIN-3-YL-GLYCYLAMINOALKYLBORONATES
The present invention provides compounds and crystalline forms of dicyclohexylammonium 1-benzyloxycarbonylpyrrolidin-3-yl-N-benzyloxycarbonylglycinate, useful as a synthetic intermediate in the preparation of certain boro-proline based selective inhibitors of the enzyme DPP-IV. Methods of preparing the compounds and the crystalline forms, and methods of using the compounds and crystalline forms in the preparation of certain DPP-IV inhibitors are also provided.
A01N 55/08 - Biocides, produits repoussant ou attirant les animaux nuisibles ou régulateurs de croissance des végétaux, contenant des composés organiques comportant des éléments autres que le carbone, l'hydrogène, les halogènes, l'oxygène, l'azote et le soufre contenant du bore
C07D 207/00 - Composés hétérocycliques contenant des cycles à cinq chaînons, non condensés avec d'autres cycles, ne comportant qu'un atome d'azote comme unique hétéro-atome du cycle
7.
STABLE PHARMACEUTICAL FORMULATION OF A DPP-IV INHIBITOR WITH METFORMIN
A dosage form is provided for an anti-diabetic DPP-IV inhibitor of formula (I) as its tartrate salt compound of formula (IT), in combination with a metformin salt, wherein the purity of the active pharmaceutical ingredients are maintained over a prolonged storage period under conditions similar to those likely encountered in home storage of the medication by a diabetic patient. A formulation free of calcium salts such as calcium phosphate, but including, for example, microcrystalline cellulose, copovidone, crospovidone, colloidal silicon dioxide, and magnesium stearate, when compacted into a tablet with the tartrate salt compound of formula (IT) was shown to be more stable than for a tablet formulation including a calcium salt. Methods for preparation of the dosage form, and methods for use of the dosage form, are also provided.
A01N 55/08 - Biocides, produits repoussant ou attirant les animaux nuisibles ou régulateurs de croissance des végétaux, contenant des composés organiques comportant des éléments autres que le carbone, l'hydrogène, les halogènes, l'oxygène, l'azote et le soufre contenant du bore
Compounds inhibiting the bioactivity of the protein tyrosine kinase JAK2 are provided, along with methods of using the compounds in the treatment of malconditions wherein inhibition of JAK2 is medically indicated. Methods of preparation are also provided.
A01N 43/90 - Biocides, produits repoussant ou attirant les animaux nuisibles, ou régulateurs de croissance des végétaux, contenant des composés hétérocycliques comportant plusieurs hétérocycles déterminants condensés entre eux ou avec un système carbocyclique commun
A61K 31/519 - PyrimidinesPyrimidines hydrogénées, p. ex. triméthoprime condensées en ortho ou en péri avec des hétérocycles
9.
A CRYSTALLINE SYNTHETIC INTERMEDIATE FOR PREPARATION OF A DPP-IV INHIBITOR AND METHOD OF PURIFICATION THEREOF
The invention provides a crystalline form of a synthetic intermediate useful in the preparation of a DPP-IV inhibitor, a method for preparing the crystalline form of the intermediate, and a method of using the crystalline form of the intermediate in the preparation of the inhibitor.
A01N 55/08 - Biocides, produits repoussant ou attirant les animaux nuisibles ou régulateurs de croissance des végétaux, contenant des composés organiques comportant des éléments autres que le carbone, l'hydrogène, les halogènes, l'oxygène, l'azote et le soufre contenant du bore
A dosage form is provided for an anti-diabetic DPP-IV inhibitor of formula (I) as its tartarate salt, wherein the purity of the active pharmaceutical ingredient is maintained over a prolonged storage period under conditions similar to those likely encountered in home storage of the medication by a diabetic patient. A formulation free of calcium salts such as calcium phosphate, but including microcrystalline cellulose, copovidone, crospovidone, colloidal silicon dioxide, and magnesium stearate, when compacted into a tablet with the active pharmaceutical ingredient, was shown to be stable for at least six months at 40°C and 75% relative humidity. Methods for preparation of the dosage form are also provided.
A61K 31/4025 - Composés hétérocycliques ayant l'azote comme hétéro-atome d'un cycle, p. ex. guanéthidine ou rifamycines ayant des cycles à cinq chaînons avec un azote comme seul hétéro-atome d'un cycle, p. ex. sulpiride, succinimide, tolmétine, buflomédil non condensés et contenant d'autres hétérocycles, p. ex. cromakalim
11.
METHODS AND INTERMEDIATES FOR SYNTHESIS OF SELECTIVE DPP-IV INHIBITORS
Methods and intermediates for the synthesis of selective inhibitors of dipeptidyl peptidase IV (DPP-IV) are provided. Coupling of a carboxylate salt with a boro-proline derivative provides a protected form of a DPP-IV inhibitor, which may be deblocked to yield the medicinal compound. The carboxylate salt can be a crystalline form of a sodium salt or a dicyclohexylammonium salt. The inhibitor can be used in the treatment of diabetes.
The present invention provides novel macrocyclic compounds that mimic peptide substrates of the hepatitis C viral protease and inhibit the viral protease, more particularly as inhibitors of the NS3 serine protease from hepatitis C virus. Methods for synthesis of the compounds are also provided. The compounds find utility as antiviral agents directed at hepatitis C. The invention further provides methods of employing such inhibitors, alone or in combination with other therapeutic agents, to treat hepatitis C infection in a subject in need of such treatment.
C07K 7/50 - Peptides cycliques contenant au moins une liaison peptidique anormale
13.
N-CYCLOPROPYL-HYDROXYPROLINE-BASED TRIPEPTIDIC HEPATITIS C SERINE PROTEASE INHIBITORS CONTAINING AN ISOINDOLE, PYRROLOPYRIDINE, PYRROLOPYRIMIDINE OR PYRROLOPYRAZINE HETEROCYCLE IN THE SIDE CHAIN
The present invention provides novel compounds that mimic peptides with a C-terminal penultimate proline, such compounds being useful as protease inhibitors, particularly as inhibitors of serine proteases, and more particularly as inhibitors of the NS3 serine protease from hepatitis C virus. The compounds find utility as antiviral agents directed at hepatitis C.
C07D 403/12 - Composés hétérocycliques contenant plusieurs hétérocycles, comportant des atomes d'azote comme uniques hétéro-atomes du cycle, non prévus par le groupe contenant deux hétérocycles liés par une chaîne contenant des hétéro-atomes comme chaînons
A61K 31/437 - Composés hétérocycliques ayant l'azote comme hétéro-atome d'un cycle, p. ex. guanéthidine ou rifamycines ayant des cycles à six chaînons avec un azote comme seul hétéro-atome d'un cycle condensés en ortho ou en péri avec des systèmes hétérocycliques le système hétérocyclique contenant un cycle à cinq chaînons ayant l'azote comme hétéro-atome du cycle, p. ex. indolizine, bêta-carboline
A61K 31/519 - PyrimidinesPyrimidines hydrogénées, p. ex. triméthoprime condensées en ortho ou en péri avec des hétérocycles
A61K 31/4985 - Pyrazines ou pipérazines condensées en ortho ou en péri avec des systèmes hétérocycliques
Macrocyclic inhibitors of Hepatitis C protease of formula (I) are provided, the inhibitors including a boronic acid or ester group, a macrocyclic ring of about 13 to 25 atoms including at least two amide linkages, a proline-analogous group, and a connecting segment joining moieties on either side of the proline-analogous group. Methods of making the HCV protease-inhibitory compounds, methods of using the compounds, formulations of the compounds:, and pharmaceutical combinations including the compounds, are provided.
This invention relates to DPP-IV inhibitory citrate or tartrate salts of pyrrolidinylaminoacetyl pyrrolidine boronic acid compounds that are physically and chemically stable, substantially non-deliquescent solids under ambient conditions.
A61K 31/505 - PyrimidinesPyrimidines hydrogénées, p. ex. triméthoprime
A61K 31/44 - Pyridines non condenséesLeurs dérivés hydrogénés
C07D 207/00 - Composés hétérocycliques contenant des cycles à cinq chaînons, non condensés avec d'autres cycles, ne comportant qu'un atome d'azote comme unique hétéro-atome du cycle
16.
HEPATITIS C SERINE PROTEASE INHIBITORS AND USES THEREFOR
The invention provides compounds that inhibit a viral protease enzyme of the hepatitis C virus (HCV). The compounds are adapted for treatment of a HCV infection in a patient with the disease. The compounds include analogs of tripeptides and tetrapeptides that resemble the viral protease substrate. The invention also provides pharmaceutical compositions and combinations, methods of preparation of the compounds, and methods of treatment of patients afflicted with HCV using the compounds.
The present invention is directed to pyrrolidinylaminoacetyl pyrrolidine boronic acid compounds that display selective, potent dipeptidyl peptidase IV inhibitory activity. These compounds are useful for the treatment of disorders that can be regulated or normalized via inhibition of DPP-IV including those characterized by impaired glycemic control such as Diabetes Mellitus and related conditions. The compounds can be administered alone or with another medicament that displays pharmacological activity for treatment of these and other diseases.
C07D 403/12 - Composés hétérocycliques contenant plusieurs hétérocycles, comportant des atomes d'azote comme uniques hétéro-atomes du cycle, non prévus par le groupe contenant deux hétérocycles liés par une chaîne contenant des hétéro-atomes comme chaînons
A solid form of an L-tartrate salt hydrate of a pyrrolidine compound of formula (IA), a cyclic form thereto or a mixture thereof. The solid form comprises 8-14% water by weight and is non-hygroscopic when exposed to atmosphere at a relative humidity of 40 to 60% at 25.degree.C. The solid form is useful in the treatment of diabetes or a malcondition wherein inhibition of dipeptidyl peptidase-IV (DPP-IV) is indicated. (see formula IA)
brevets
