Pfizer Corporation

Other

John Anthony Ragan

Bruce A Lefker

Philip Albert Carpino

Paul Andrew Dasilva-Jardine

Paul A Dasilva-Jardine

Jotham Wadsworth Coe

George Joseph Quallich

Stanton F McHardy

Randall James Gallaschun

Todd William Butler

Derek Lawrence Tickner

Anton Franz Joseph Fliri

Brian C Vanderplas

Brian Patrick Jones

Douglas John Meldrum Allen

David Jon Am Ende

Shane Allen Eisenbeis

Pamela Jane Clifford

Teresa Woodall Makowski

Alyson Kay Conrad

Gregory Randall Young

This present invention relates to a new and improved reductive amination process for the preparation of 3-azabicyclo[3.1.0]hexane derivatives and pharmaceutical compositions comprising such derivatives. The invention particularly relates to using such derivatives to treat certain disorders and conditions, including, for example, irritable bowel syndrome, drug addiction or dependency, alcohol addiction or dependency, depression, and eating disorders.

Preparation of 3-azabicyclo [3.1.0] hexane derivatives

Tetrahydroquinazoline-2,4-diones and therapeutic uses thereof

Growth-hormone secretagogues

This invention is directed to compounds of the formula

Method of treatment using certain growth-hormone secret agogues

A method for preparing pyrrole-carboxyamides which selectively bind to GABAa receptors; which comprises reacting 1,3-cycloakane-diones with bromoethylacetate followed by reaction of the resulting product with an acid halide followed by reaction with an aromatic amine and finally with an amonium source at an elevated temperature.

Method of synthesis of pyrrole amides

Process and intermediates for the preparation of

##STR1## This invention is directed to compounds of formula (I) and the pharmaceutically-acceptable salts thereof, where the substituents are as defined in the Specification, which are growth hormone secretagogues and which increase the level of endogenous growth hormone. The compounds of this invention are useful for the treatment and prevention of osteoporosis, congestive heart failure, frailty associated with aging, obesity; accelerating bone fracture repair, attenuating protein catabolic response after a major operation, reducing cachexia and protein loss due to chronic illness, accelerating wound healing, or accelerating the recovery of burn patients or patients having undergone major surgery; improving muscle strength, mobility, maintenance of skin thickness, metabolic homeostasis or renal homeostasis. The compounds of the present invention are also useful in treating osteoporosis when used in combination with: a bisphosphonate compound such as alendronate; estrogen, premarin, and optionally progesterone; an estrogen agonist or antagonist; or calcitonin, and pharmaceutical compositions useful therefor. Further, the present invention is directed to pharmaceutical compositions useful for increasing the endogenous production or release of growth hormone in a human or other animal which comprises an effective amount of a compound of the present invention and a growth hormone secretagogue selected from GHRP-6, Hexarelin, GHRP-1, growth hormone releasing factor (GRF), IGR-1, IGF-2 or B-HT920. The invention is also directed to intermediates useful in the preparation of compounds of formula (I).

Heterocyclic compounds

This invention is directed to compounds of the formula ##STR1## and the pharmaceutically-acceptable salts thereof, where the substituents are as defined in the Specification, which are growth hormone secretogogues and which increase the level of endogenous growth hormone. The compounds of this invention are useful for the treatment and prevention of osteoporosis, congestive heart failure, frailty associated with aging, obesity; accelerating bone fracture repair, attenuating protein catabolic response after a major operation, reducing cachexia and protein loss due to chronic illness, accelerating would healing, or accelerating the recovery of burn patients or patients having undergone major surgery; improving muscle strength, mobility, maintanence of skin thickness, metabolic homeostasis or renal homeostasis. The compounds of the present invention are also useful in treating osteoporosis when used in combination with: a bisphosphonate compound such as alendronate; estrogen, premarin, and optionally progesterone; an estrogen agonist or antagonist; or calcitonin, and pharmaceutical compositions useful therefor. Further, the present invention is directed to pharmaceutical compositions useful for increasing the endogenous production or release of growth hormone in a human or other animal which comprises an effective amount of a compound of the present invention and a growth hormone secretagogue selected from GHRP-6, Hexarelin, GHRP-1, growth hormone releasing factor (GRF), IGF-1, IGF-2, or B-HT920. The invention is also directed to intermediates useful in the preparation of compounds of formula I.

Growth hormone secretagogues

This invention is directed to compounds of the formula ##STR1## and the pharmaceutically-acceptable salts thereof, where the substituents are as defined in the Specification, which are growth hormone secretogogues and which increase the level of endogenous growth hormone. The compounds of this invention are useful for the treatment and prevention of osteoporosis, congestive heart failure, frailty associated with aging, obesity; accelerating bone fracture repair, attenuating protein catabolic response after a major operation, reducing cachexia and protein loss due to chronic illness, accelerating wound healing, or accelerating the recovery of burn patients or patients having undergone major surgery; improving muscle strength, mobility, maintanence of skin thickness, metabolic homeostasis or renal homeostasis. The compounds of the present invention are also useful in treating osteoporosis when used in combination with: a bisphosphonate compound such as alendronate; estrogen, premarin, and optionally progesterone; an estrogen agonist or antagonist; or calcitonin, and pharmaceutical compositions useful therefor. Further, the present invention is directed to pharmaceutical compositions useful for increasing the endogenous production or release of growth hormone in a human or other animal which comprises an effective amount of a compound of the present invention and a growth hormone secretagogue selected from GHRP-6, Hexarelin, GHRP-1, growth hormone releasing factor (GRF), IGF-1, IGF-2 or B-HT920. The invention is also directed to intermediates useful in the preparation of compounds of formula I.

Dipeptides which promote release of growth hormone

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Gales Ferry, CT, United States of America

John Anthony Ragan