Miles Laboratories, Inc.

Bayer Corporation

Miles Inc.

Other

Bayer Pharmaceuticals Corporation

Harold C Kluender

William G Biddlecom

Warren D Woessner

Brian R Dixon

Donald J Wolanin

Michael C VanZandt

Scott McClelland Wilhelm

William Harrison Bullock

David R Brittelli

Henry Clifford Arndt

Guenter Hans Benz

Charles J Sih

Jill E Wood

Stephan Schneider

Kerry Jeanne Combs

Roger Astbury Smith

Ulrich Rosentreter

Heinrich Meier

Wai C Wong

Paul F Corey

Stephen J O'Connor

Soongyu Choi

Zhonghua Zhang

Jianmei Fan

Trevor S Abram

Peter Norman

Rico C Lavoie

William F Brubaker

Brent L Podlogar

Warren D Woesner

Robert N Schut

Stephen R Tudhope

Lisa Marie Zadjura

Susan M Bjorge

This invention relates to 1,5,6,7-tetrahydropyrrolo[3,2-c]pyridine derivatives which have been found to suppress appetite and induce weight loss. The invention also provides methods for synthesis of the compounds, pharmaceutical compositions comprising the compounds, and methods of using such compositions for inducing weight loss and treating obesity and obesity-related disorders.

Preparation and use of 1,5,6,7-tetrahydropyrrolo[3,2-c]pyridine derivatives for treatment of obesity

Inhibitors for matrix metalloproteases, pharmaceutical compositions containing them, and a process for using them to treat a variety of physiological conditions. The compounds of the invention have the generalized formula

Substituted 5-biarylpentanoic acids and derivatives as matrix

Inhibitors for matrix metalloproteases, pharmaceutical compositions containing them, and a process for using them to treat a variety of physiological conditions. The compounds of the invention have the generalized formula ##STR1## in which T is a pharmaceutically-acceptable substituent group; A is CH.sub.2, CH, or N; G is CH.sub.2 or CH; and R.sup.1 is any of a variety of disclosed substituent groups. The class of compounds of the invention includes ring-containing materials in which the units A and G are joined. The compounds of the invention are mixtures of diastereomers, or individual diastereomers making up these mixtures.

Substituted 4-biphenyl-4-hydroxybutyric acid derivatives as matrix

Inhibitors for matrix metalloproteases, pharmaceutical compositions containing them, and a process for using them to treat a variety of physiological conditions. The compounds of the invention have the generalized formula ##STR1## wherein each T is a substituent group; x is 0, 1, or 2; the group D represents ##STR2## the group R6 represents variety of possible substituent groups on the carbon chain between D and G, and the group G represents M, ##STR3## in which M represents --CO.sub.2 H, --CON(R.sup.11).sub.2, or --CO.sub.2 R.sup.12, and R.sup.13 represents any of the side chains of the 19 noncyclic naturally occurring amino acids.

Substituted 4-biarylbutyric acid derivatives as matrix metalloprotease

Inhibitors for matrix metalloproteases, pharmaceutical compositions containing them, and a process for using them to treat a variety of physiological conditions. The compounds of the invention have the generalized formula ##STR1## wherein each T is a substituent g roup; x is 0, 1, or 2; the group D represents ##STR2## the subscript 'e' is 2 or 3; the group R.sup.14 represents a variety of possible substituent groups of the cycloalkyl ring between D and G; the subscript 'k' is 0-2; and the group G represents M, ##STR3## in which M represents --CO.sub.2 H, --CON(R.sup.11).sub.2, or --CO.sub.2 R.sup.12 ; and R.sup.13 represents any of the side chains of the 19 noncyclic occurring amino acids.

Substituted cycloalkanecarboxylic acid derivatives as matrix

Inhibitors for matrix metalloproteases, pharmaceutical compositions containing them, and a process for using them to treat a variety of physiological conditions. The compounds of the invention have the generalized formula ##STR1## wherein each T is a substituent group; x is 0, 1, or 2; the group D represents ##STR2## the group R6 represents a variety of possible substituent groups on the carbon chain between D and G, and the group G represents M, ##STR3## in which M represents --CO.sub.2 H, --CON(R.sup.11).sub.2, or --CO.sub.2 R.sup.12; and R.sup.13 represents any of the side chains of the 19 noncyclic naturally occurring amino acids.

Thiophene-containing butonic acid derivatives as matrix metalloprotease

Inhibitors for matrix metalloproteases, pharmaceutical compositions containing them, and a process for using them to treat a variety of physiological conditions. The compounds of the invention have the generalized formula ##STR1## wherein each T is a substituent group; x is 0, 1, or 2; the group D represents ##STR2## the subscript 'e' is 2 or 3; the group R.sup.14 represents a variety of possible substituent groups on the cycloalkyl ring between D and G, and the group G represents M, ##STR3## in which M represents --CO.sub.2 H, --CON(R.sup.11).sub.2, or --CO.sub.2 R.sup.12 ; and R.sup.13 represents any of the side chains of the 19 noncyclic naturally occurring amino acids.

Inhibitors for matrix metalloproteases, pharmaceutical compositions containing them, and a process for using them to treat a variety of physiological conditions. The compounds of the invention have the generalized formula ##STR1## wherein R.sup.1 represents C.sub.6 -C.sub.12 alkyl; C.sub.5 -C.sub.12 alkoxy; C.sub.5 -C.sub.12 alkylthio; a polyether of formula R.sup.2 O(C.sub.2 H.sub.4 O).sub.a -- in which a is 1 or 2 and R.sup.2 is C.sub.1 -C.sub.5 alkyl, phenyl, or benzyl; and substituted alkynyl of formula R.sup.3 (CH.sub.2).sub.b --C.tbd.C--; in which b is 1-10 and R.sup.3 is H--, HO--, or R.sup.4 O-- in which R.sup.4 is C.sub.1 -C.sub.3 alkyl, phenyl, or benzyl. The alkyl, phenyl, and benzyl portions of R.sup.1 may bear at least one pharmaceutically-acceptable substituent. The subscript n is 2-4. R.sup.5 represents phenyl; imidoyl of 4-12 carbon atoms; (3H)-benzo-1,2,3-triazin-4-on-3-yl; N-saccharinyl; (2H)-phthalazin-1-on-2-yl; 2-benzoxazolin-2-on-3-yl; 5,5-dimethyloxazolidine-2,4-dion-3-yl; and thiazolidine-2,4-dion-3-yl; with the phenyl and benzo portions of R.sup.5 permissibly bearing at least one pharmaceutically-acceptable substituent. Pharmaceutically acceptable salts of these materials are also included.

Substituted 4-arylbutyric acid derivatives as matrix metalloprotease

Inhibitors for matrix metalloproteases, pharmaceutical compositions containing them, and a process for using them treat a variety of physiological conditions. The compounds of the invention have the generalized formula ##STR1## wherein each T is a substituent group; x is 0, 1, or 2; the group D represents ##STR2## the group R6 represents a variety of possible substituent groups on the carbon chain between D and G, and the group G represents M, ##STR3## in which M represents --CO.sub.2 H, --CON(R.sup.11).sub.2, or --CO.sub.2 R.sup.12 ; and R.sup.13 represents any of the side chains of the 19 noncyclic naturally occurring amino acids.

Inhibitors for matrix metalloproteases, pharmaueutical compositions containing them, and a process for using them to treat a variety of physiological conditions. The compounds of the invention have the generalized formula ##STR1## wherein each Tis a substituent group; x is 0, 1, or 2; the group D represents ##STR2## the group R6 reresents a variety of possible substituent groups on the carbon chain between D and G, and the group G represents M, ##STR3## in which M represents --CO.sub.2 H, --CON(R.sup.11).sub.2, or --CO.sub.2 R.sup.12, and R.sup.13 represents any of the side chains of the 19 noncyclic naturally occurring amino acids.

Inhibitors for matrix metalloproteases, pharmaceutical compositions containing them, and a process for using them to treat a variety of physiological conditions. The compounds of the invention have the generalized formula ##STR1## wherein each T is a substituted group; x is 0, 1, or 2; the group D represents ##STR2## the group R6 represents a variety of possible substituent groups on the carbon chain between D and G, and the group G represents M, ##STR3## in which M represents --CO.sub.2 H, --CON(R.sup.11).sub.2, or --CO.sub.2 R.sup.12 ; and R.sup.13 represents any of the side chains of the 19 noncyclic naturally occurring amino acids.

Inhibitors for matrix metalloproteases, pharmaceutical compositions containing them, and a process for using them to treat a variety of physiological conditions. The compounds of the invention have the generalized formula ##STR1## wherein each T is a substituent group; x is 0, 1, or 2; the group D represents ##STR2## the group R6 represents a variety of possible substituent groups on the carbon chain between D and G, and the group G represents M, ##STR3## in which M represents --CO.sub.2 H, --CON(R.sup.11).sub.2, or --CO.sub.2 R.sup.12 ; and R.sup.13 represents any of the side chains of the 19 noncyclic naturally occurring amino acids.

Thiophenebutanoic acid derivatives as matrix metalloprotease inhibitors

Inhibitors for matrix metalloproteases, pharmaceutical compositions containing them, and a process for using them to treat a variety of physiological conditions. The presently claimed compounds have the generalized formula ##STR1## in which each T represents a substituent group; x is 0, 1, or 2; D represents ##STR2## .delta. is 0 or 1; U' represents O, S, or N, with the proviso that when U' is N, then .delta.=0, and when U' is O or S, then .delta.=1; R.sup.14 is any of a variety of substituent groups; and G represents M, ##STR3## in which M represents --CO.sub.2 H, --CON(R.sup.11).sub.2, or --CO.sub.2 R.sup.12, R.sup.11 represents H or an alkyl group, R.sup.12 represents an alkyl group, and R.sup.13 represents any of the side chains of the 19 noncyclic naturally occurring amino acids; and pharmaceutically acceptable salts thereof.

Derivatives of substituted 4-biarylbutyric acid as matrix

Aryl alkenoic acid derivatives, and physiologically acceptable salts thereof, are provided which are potent leukotriene antagonists and may be used for the treatment of circulatory diseases and preferably for respiratory diseases such as asthma. The derivatives have a general formula I ##STR1## in which X is --S--,

Aryl alkenoic acid derivatives as leukotriene antagonists

A therapeutic method for inhibiting gastric secretion in an individual for whom such therapy is indicated is disclosed. The method comprises administering to such an individual an effective inhibitory amount of certain derivatives of 15-deoxy-16-hydroxy-prostaglandin E.sub.1 esters.

Growing community of inventors

Madison, WI, United States of America

Harold C Kluender