Pfizer Corporation

Bernard Hulin

Steven Wayne Goldstein

David A Clark

Dennis J Hoover

Judith L Treadway

William H Martin

James P Rizzi

Gerald F Holland

David W Piotrowski

Douglas Phillips

Robert L Dow

Reinhard Sarges

Kelly P Longo

Janice C Parker

The invention provides compounds of formula (I), or a pharmaceutically acceptable salt of said compound, or a solvate of said compound or salt, wherein R, R, R, HET, n, Q, X, Y, and Z are as described herein; compositions thereof; and uses thereof including treating Type 2 diabetes.

(2S,4S)-4-(piperazin-1-yl)pyrrolidine-2-methanone derivatives

The invention provides compounds of formula (I), prodrugs and stereoisomers thereof, and the pharmaceutically acceptable salts of the compounds, prodrugs, and stereoisomers, wherein R, R, R, HET, n, Q, X, Y, and Z are as described herein; compositions thereof; and uses thereof in treating diabetic complications including diabetic neuropathy, diabetic nephropathy, diabetic microangiopathy, and the like.

Therapeutic compounds

This invention relates to certain indole-2-carboxamides of formula (I) and the pharmaceutically acceptable salts and prodrugs thereof, wherein Ris carboxy, (C-C)alkoxycarbonyl, C(O)NRRor C(O)R, useful as inhibitors of glycogen phosphorylase, methods of treating glycogen phosphorylase dependent diseases or conditions with such compounds and pharmaceutical compositions comprising such compounds.

Substituted N-(indole-2-carbonyl) -amides and derivatives as glycogen phosphorylase inhibitors

The present invention relates to a method of making novel dipeptidyl peptidase-IV (&ldquo;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.

Synthesis of 3,3,4,4-tetrafluoropyrrolidine and novel dipeptidyl peptidase-IV inhibitor compounds

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.

Fluorinated cyclic amides as dipeptidyl peptidase IV inhibitors

This invention relates to certain indole-2-carboxamides of formula (I) and the pharmaceutically acceptable salts and prodrugs thereof, wherein R is carboxy, (C -C )alkoxycarbonyl, C(O)NR R or C(O)R , useful as inhibitors of glycogen phosphorylase, methods of treating glycogen phosphorylase dependent diseases or conditions with such compounds and pharmaceutical compositions comprising such compounds.

Substituted N-( indole-2-carbonyl-) amides and derivatives as glycogen phosphorylase inhibitors

Carboxylic acid derivatives as inhibitors of hyperproliferation diseases

Substituted n-(indole-2-carbonyl-) amides and derivatives as glycogen phosphorylase inhibitors

Substituted n-(indole-2-carbonyl)glycinamides and derivates as glycogen phosphorylase inhibitors

Substituted n-(indole-2-carbonyl)-glycinamides and derivatives as

This invention relates to certain 5-acyl-2-oxo-indole-3-carboxamides useful as inhibitors of glycogen phosphorylase, methods of treating glycogen phosphorylase dependent diseases or conditions with such compounds and pharmaceutical compositions comprising such compounds. This invention also relates to pharmaceutical compositions comprising those 5-acyl-2-oxo-indole-3-carboxamides in combination with antidiabetes agents and methods of treating glycogen phosphorylase dependent diseases or conditions with such compositions.

Glycogen phosphorylase inhibitors

Compounds of the formulae ##STR1## where R is cycloalkyl or aryl; R.sub.1 is alkyl, X is O or C.dbd.O; A is O or S; and B is N or CH are useful as hypoglycemic agents.

Oxazolidinedione hypoglycemic agents

Certain 3-(phenyl, chroman-2-yl, benzofuran-5-yl or benzoxazol-5-yl)-2-(hydroxy or mercapto)propionic acid derivatives and analogs are useful as hypoglycemic and hypocholesterolemic agents.

3-aryl-2-hydroxypropionic acid derivatives and analogs as hypoglycemic

Compounds of the formula ##STR1## where R is alkyl, cycloalkyl, phenyl or substituted phenyl are useful as hypoglycemic agents.

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Essex, CT, United States of America

Bernard Hulin