642 results about "Dipeptidyl peptidase" patented technology

The invention discloses certain N-(substituted glycyl)-4-cyanothiazolidines, pharmaceutical compositions containing said compounds as an active ingredient thereof, and the use of said compounds in inhibiting dipeptidyl peptidase-IV.

The invention discloses certain N-(substituted glycyl)-thiazolidines, pharmaceutical compositions containing said compounds as an active ingredient thereof, and the use of said compounds in inhibiting dipeptidyl peptidase-IV.

Compounds, pharmaceuticals, kits and methods are provided for use with DPP-IV and other S9 proteases that comprise a compound comprising: wherein M is N or CR4; Q1 and Q2 are each independently selected from the group consisting of CO, SO, SO2, and C═NR9; and each L, X, R1, R2, and R3 are as defined herein.

Pharmaceutical compositions comprising 2-[6-(3-Amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-4-fluoro-benzonitrile and pharmaceutically acceptable salts thereof are provided as well as kits and articles of manufacture comprising the pharmaceutical compositions as well as methods of using the pharmaceutical compositions.

The invention relates to new therapeutically active and selective inhibitors of the enzyme dipeptidyl peptidase-IV (“DPP-IV”), pharmaceutical compositions comprising the compounds and the use of such compounds for treating diseases that are associated with proteins that are subject to processing by DPP-IV, such as Type 2 diabetes, metabolic syndrome (syndrome X or insulin resistance syndrome), hyperglycemia, impaired glucose tolerance, glucosuria, metabolic acidosis, arthritis, cataracts, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, diabetic cardiomyopathy, Type 1 diabetes, obesity, conditions exacerbated by obesity, hypertension, hyperlipidemia, atherosclerosis, osteoporosis, osteopenia, frailty, bone loss, bone fracture, acute coronary syndrome, infertility due to polycystic ovary syndrome, short bowel syndrome, anxiety, depression, insomnia, chronic fatigue, epilepsy, eating disorders, chronic pain, alcohol addiction, diseases associated with intestinal motility, ulcers, irritable bowel syndrome, inflammatory bowel syndrome and to prevent disease progression in Type 2 diabetes. The invention also relates to a method of identifying an insulin secretagogue agent for diabetes.

The invention relates to new therapeutically active and selective inhibitors of the enzyme dipeptidyl peptidase-IV, pharmaceutical compositions comprising the compounds and the use of such compounds for treating diseases that are associated with proteins that are subject to processing by DPP-IV, such as Type 2 diabetes mellitus, hyperglycemia, impaired glucose tolerance, metabolic syndrome (Syndrome X or insulin resistance syndrome), glucosuria, metabolic acidosis, cataracts, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, diabetic cardiomyopathy, Type 1 diabetes, obesity, conditions exacerbated by obesity, hypertension, hyperlipidemia, atherosclerosis, osteoporosis, osteopenia, frailty, bone loss, bone fracture, acute coronary syndrome, infertility due to polycystic ovary syndrome, short bowel syndrome, anxiety, depression, insomnia, chronic fatigue, epilepsy, eating disorders, chronic pain, alcohol addiction, diseases associated with intestinal motility, ulcers, irritable bowel syndrome, inflammatory bowel syndrome and to prevent disease progression in Type 2 diabetes. The invention also relates to a method of identifying an insulin secretagogue agent for diabetes.

The invention comprises the use of activity-reducing effectors of dipeptidyl peptidase (DP IV) and DP IV-analogous enzyme activity in the blood of a mammal to lower the blood sugar level and the blood pressure in mammalian organisms.

The present invention relates to novel fluorescent dyes, novel fluorogenic and fluorescent reporter molecules and new enzyme assay processes that can be used to detect the activity of caspases and other enzymes involved in apoptosis in whole cells, cell lines and tissue samples derived from any living organism or organ. The reporter molecules and assay processes can be used in drug screening procedures to identify compounds which act as inhibitors or inducers of the caspase cascade in whole cells or tissues. The reagents and assays described herein are also useful for determining the chemosensitivity of human cancer cells to treatment with chemotherapeutic drugs. The present invention also relates to novel fluorogenic and fluorescent reporter molecules and new enzyme assay processes that can be used to detect the activity of type 2 methionine aminopeptidase, dipeptidyl peptidase IV, calpain, aminopeptidase, HIV protease, adenovirus protease, HSV-1 protease, HCMV protease and HCV protease.

The invention relates to new therapeutically active and selective inhibitors of the enzyme dipeptidyl peptidase-IV, pharmaceutical compositions comprising the compounds and the use of such compounds for treating diseases that are associated with proteins that are subject to processing by DPP-IV, such as Type 2 diabetes mellitus, hyperglycemia, impaired glucose tolerance, metabolic syndrome (Syndrome X or insulin resistance syndrome), glucosuria, metabolic acidosis, cataracts, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, diabetic cardiomyopathy, Type 1 diabetes, obesity, conditions exacerbated by obesity, hypertension, hyperlipidemia, atherosclerosis, osteoporosis, osteopenia, frailty, bone loss, bone fracture, acute coronary syndrome, infertility due to polycystic ovary syndrome, short bowel syndrome, anxiety, depression, insomnia, chronic fatigue, epilepsy, eating disorders, chronic pain, alcohol addiction, diseases associated with intestinal motility, ulcers, irritable bowel syndrome, inflammatory bowel syndrome and to prevent disease progression in Type 2 diabetes. The invention also relates to a method of identifying an insulin secretagogue agent for diabetes.

The present invention relates to new compounds that act as specific inhibitors of the cysteine protease dipeptidyl peptidase I (DP I). Those compounds are represented by the general formula and the pharmaceutical salts thereof, in which R is an acyl-residue including urethane and peptide, or a branched or unbranched C1-C9 alkyl chain, a branched or unbranched C2-C9 alkenyl chain, a branched or unbranched C2-C9 alkynyl chain, a C3-C9 cycloalkyl, C4-C9 carbocyclic, C5-C14 aryl, C3-C9 heteroaryl, C3-C9 heterocyclic, all of the above residues may be optionally substituted, or is H, AS is an amino acid or a peptide mimetic thereof. The amino acid is peptide bound with R and R' is a branched or unbranched C1-C9 alkyl chain, a branched or unbranched C2-C9 alkenyl chain, a branched or unbranched C2-C9 alkynyl chain, a C3-C9 cycloalkyl, C4-C9 cycloalkenyl, C2-C9 heterocycloalkyl, C3-C9 heterocycloalkenyl, C5-C14 aryl, C3-C9 heteroaryl, C3-C9 heterocyclic, whereas the heterocycloalkyl, heterocycloalkenyl, heteroaryl, heterocyclic residue can have up to 6 hetero ring atoms, an amino acid or a peptide mimetic thereof, all of the above residues my be optionally substituted, or is H.

The present invention provides pharmaceutical agents comprising a dipeptidyl peptidase IV (DPPIV) inhibitor and a biguanide agent in combination, which enhance the effects of active circulating glucagon-like peptide-1 (GLP-1) and / or active circulating glucagon-like peptide-2 (GLP-2).

The sustained-release preparation of the present invention, which contains a dipeptidyl peptidase IV inhibitor and a hydrophilic polymer, can appropriately inhibit the DPP-IV activity, and is superior in convenience or compliance.

This invention relates to novel compounds, compositions containing the compounds, that inhibit dipeptidyl peptidase (especially DPP-IV) and neprilysin (NEP, neutral endopeptidase) as well as dipeptidyl peptidase (especially DPP-IV) and angiotensin converting enzyme (ACE) and / or dipeptidyl Peptidase (especially DPP-IV) and vasopeptidases (especially ACE and NEP). These compounds and pharmaceutical compositions thereof are useful for the treatment as well as the prevention of type 2 diabetes mellitus.

Pharmaceuticals, kits and methods are provided for use with DPP-IV and other S9 proteases that comprise a compound with the formula: where the labeled substituents are as described herein.

The present invention relates to a method of making novel dipeptidyl peptidase-IV ("DPP-IV') inhibitor compounds useful for treating, inter alia, diseases that are associated with proteins that are subject to processing by DPP-IV, such as Type 2 diabetes mellitus, metabolic syndrome (Syndrome X or insulin resistance syndrome), hyperglycemia, impaired glucose tolerance, glucosuria, metabolic acidosis, cataracts, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, diabetic cardiomyopathy, Type 1 diabetes, obesity, hypertension, hyperlipidemia, atherosclerosis, osteoporosis, osteopenia, frailty, bone loss, bone fracture, acute coronary syndrome, infertility due to polycystic ovary syndrome, short bowel syndrome and to prevent disease progression in Type 2 diabetes. The invention also relates to a method of making 3,3,4,4-tetrafluoropyrrolidine, a starting material utilized in the afore-mentioned method for preparing DPP-IV compounds.

The present invention relates to a series of prodrugs of inhibitors of DP-IV with improved properties. The compounds can be used for the treatment of a number of human diseases, including impaired glucose tolerance and type II diabetes. The compounds of the invention are described by general formula (1); wherein R1 is H or CN; R2 is selected from CH2R5, CH2CH2R5 and C(R3)(R4)—X2—(CH2)aR5; R3 and R4 are each independently selected from H and Me; R5 is selected from CON(R6)(R7), N(R8)C(=0)R9, N(R8)C(═S)R9, N(R8)SO2R10 and N(R8)R10; R6 and R7 are each independently R11(CH2)b or together they are —(CH2)2-Z-(CH2)2— or CH2-o-C6H4-Z-CH2—; R8 is H or Me; R9 is selected from R11(CH2)b, R11(CH2)bO and N(R6)(R7); R10 is R11(CH2)b; R11 is selected from H, alkyl, optionally substituted aryl, optionally substituted aroyl, optionally substituted arylsulphonyl and optionally substituted heteroaryl; R12 is selected from H2NCH(R13)CO, H2NCH(R14)CONHCH(R15)CO, C(R16)═C(R17)COR18 and R19OCO; R13, R14 and R15 are selected from the side chains of the proteinaceous amino acids; R16 is selected from H, lower alkyl (C1-C6) and phenyl; R17 is selected from H and lower alkyl (C1-C6); R18 is selected from H, lower alkyl (C1-C6), OH, O-(lower alkyl (C1-C6)) and phenyl; R19 is selected from lower alkyl (C1-C6), optionally substituted phenyl and R20C(=0)OC(R21)(R22); R20, R21 and R22 are each independently selected from H and lower alkyl (C1-C6); Z is selected from a covalent bond, —(CH2)c—, —O—, —SOd— and —N(R10)—; X1 is S or CH2; X2 is O, S or CH2; a is 1, 2 or 3; b is 0-3; c is 1 or 2; and d is 0, 1 or 2.

Methods and compounds for production of cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV are provided.

Compounds, pharmaceuticals, kits and methods are provided for use with DPP-IV and other S9 proteases that comprise a member selected from the group consisting of: wherein E is CH or N, Q is selected from the group consisting of CO, CS, SO, SO2, or C═NR4, and L, X, Z, R2 and R3 are as defined herein.

The present invention comprises the use of activity-reducing effectors of dipeptidyl peptidase (DP IV) and DP IV-analogous enzyme activity in the blood of a mammal to lower elevated post-prandial and basal blood glucose levels in mammalian organisms. The invention further comprises the use of activity-reducing effectors of dipeptidyl peptidase (DP IV) and DP IV-analogous enzyme activity in the blood of a mammal to increase the half-life of incretins in vivo.

The present invention relates to novel compounds, their use for inhibiting serine proteases, such as dipeptidyl peptidases, such as dipeptidyl peptidase IV (DPP-IV) and to methods for their production and their therapeutic utility.

The present invention provides modified therapeutic polypeptides or peptides partially or completely protected from DPP activity. The modified polypeptides or peptides comprise at least one additional amino acid at the amino terminus. The modified therapeutic polypeptides or peptides are useful in the treatment of diseases such as diabetes.

An agent for treating diabetes with sulfonylurea secondary failure which comprises a dipeptidyl peptidase IV inhibitor. The agent of the present invention is an agent for treating diabetes with sulfonylurea secondary failure showing excellent insulin-secreting and hypoglycemic effects on even diabetic patients on whom a sulfonylurea compound or a fast-acting insulin secretagogue has no insulin-secreting effect and therefore no sufficient hypoglycemic effect.

Compounds, pharmaceutical compositions, kits and methods are provided for use with DPP-IV and other S9 proteases that comprise a compound of the formula: wherein R2 is amino (C1-6)alkyl, hetero(C3-12)cycloakyl, hetero(C4-12)bicycloaryl, heteroaryl, or cyano; and W, X, Y, Z, R1, R5 and R7 are as defined herein.

The present invention relates to novel methods and compositions for detection and isolation of cancer cells with metastatic potential. The invention further relates to assays for measuring the metastatic potential of such cancer cells and drug screening assays for the identification of agents having anti-metastatic potential. The present invention further provides methods and compositions for inhibiting the metastatic potential of cancer cells by modulating the activity of serine integral membrane proteases [(SIMP) consisting of seprase and dipedidyl peptidase IV (DPPIV)]expressed on the surface of metastasizing cancer cells.