Abbott Laboratories Corporation

Richard A Craig

Andrew O Stewart

Megumi Kawai

George S Sheppard

Clint D Brooks

Pramila A Bhatia

Jieyi Wang

Jack Henkin

Teodozyj Kolasa

Dee W Brooks

Jyoti R Patel

Xenia Beebe Searle

Linda M Lynch

Nwe Y BaMaung

David John Augeri

David A Betebenner

Stephen W Fesik

Steven K Davidsen

Anwer Basha

Yan Guo

Jimmie L Moore

Philip J Hajduk

Michael R Michaelides

James D Ratajczyk

David G Nettesheim

Teodozyji Kolasa

Nwe Ba-Maung

Jamie R Giesler-Stacey

Fan Yang

Compounds having the formulaare useful for treating conditions which arise from or are exacerbated by angiogenesis. Also disclosed are pharmaceutical compositions comprising the compounds, methods of treatment using the compounds, methods of inhibiting angiogenesis, and methods of treating cancer.

3-Amino-2-hydroxyalkanoic acids and their prodrugs

Compounds having the formulaare methionine aminopeptidase type 2 (MetAP2) inhibitors and are useful for inhibiting angiogenesis. Also disclosed are MetAP2-inhibiting compositions and methods of inhibiting angiogenesis in a mammal.

Hydrazide and alkoxyamide angiogenesis inhibitors

Compounds having Formula Ior pharmaceutically acceptable salts or prodrugs thereof, are useful for treating pathological states which arise from or are exacerbated by angiogenesis. The invention also relates to pharmaceutical compositions comprising these compounds and to methods of inhibiting angiogenesis in a mammal.

Antiangiogenic drug to treat cancer, arthritis and retinopathy

3-Substituted indole carbohydrazides having the formula

3-substituted indole angiogenesis inhibitors

Inhibitors of matrix metalloproteinases

A class of substituted b-amino acids are potent inhibitor of methionine aminopeptidase type 2 (MetAP2) and are thus useful in inhibiting angiogenesis and disease conditions which depend upon angiogenesis for their development such as diabetic retinopathy, tumor growth, and conditions of inflammation. Pharmaceutical compounds containing the compounds and methods of inhibiting methionine aminopeptidase-2, and angiogenesis are also disclosed.

Substituted &bgr;-amino acid inhibitors of methionine aminopeptidase-2

Compounds having the formula ##STR1## or a pharmaceutically acceptable salt thereof wherein Y is selected from halogen, alkyl, and haloalkyl; n is 0, 1, 2, or 3; X is absent or is alkylene; A is absent or is selected from optionally substituted alkylene, optionally substituted cycloalkylene, optionally substituted cycloalkylene wherein one or two of the carbon atoms is replaced with one or two heteroatoms independently selected from O, S, and N, optionally substituted alkenylene, and ##STR2## or R.sup.2 and A together define a saturated 5- to 8-membered optionally substituted carbocyclic or heterocyclic ring to which the group Z is attached; Z is selected from (a) hydrogen, (b) COM wherein M is selected from the group consisting of --OR.sup.5, a pharmaceutically acceptable cation, --NR.sup.7 R.sup.8, and a pharmaceutically acceptable, metabolically cleavable group, (c) --OR.sup.3, (d) tetrazolyl, (e) --CH(OR.sup.3)--CH.sub.2 OR.sup.9, (f) --CH(OR.sup.3)--CH.sub.2 --CH.sub.2 OR.sup.9, (g) --CH(OR.sup.3)--CH(OR.sup.9)--CH.sub.2 OR.sup.10, and (h) .dbd.N--OR.sup.3 ; and R.sup.1, R.sup.2, R.sup.3, R.sup.9, and R.sup.10 are independently selected from (a) hydrogen, (b) alkyl, and (c) optionally substituted phenyl, are prostaglandin biosynthesis inhibitors and are useful in the treatment of inflammatory disease states. Also disclosed are prostaglandin inhibiting compositions, a method of inhibiting prostaglandin biosynthesis in a mammal.

Iminoxyderivatives of fenamates as inhibitors of prostaglandin

Compounds having the formula: ##STR1## wherein W is the same at each occurrence and is selected from optionally substituted quinolyl, optionally substituted benzothiazolyl, optionally substituted benzoxazolyl, optionally substituted benzimidazolyl, optionally substituted quinoxalyl, optionally substituted pyridyl, optionally substituted pyrimidyl, and optionally substituted thiazolyl; R.sup.1 and R.sup.2 are independently selected from hydrogen, alkyl, halolalkyl, alkoxy, halogen; R.sup.3 is a valence bond or is selected from hydrogen and alkyl; X is a valence bond or is selected from alkylene, alkenylen, and alkynylene; and Z is selected from (a) COM, (b) CH.dbd.N--O--A--COM, (c) CH.sub.2 --O--N.dbd.A--COM wherein A is selected from alkylene and cycloalkylene, and M is selected from (a) a pharmaceutically acceptable metabolically cleavable group, (b) --OR.sup.6, (c) --NR.sup.7 R.sup.8, (d) --NR.sup.6 SO.sub.2 R.sup.9, (e) --NH-Tetrazolyl, and (f) glycinyl inhibit leukotriene biosynthesis and are useful in the treatment of allergic and inflammatory disease states. Also disclosed are leukotriene biosynthesis inhibiting compositions and a method of inhibiting leukotriene biosynthesis.

Symmetrical bis-heteroarylmethoxy-phenylalkyl carboxylates as inhibitors

Compounds having the formula: ##STR1## wherein W is the same at each occurrence and is selected from optionally substituted quinolyl, optionally substituted benzothiazolyl, optionally substituted benzoxazolyl, optionally substituted benzimidazolyl, optionally substituted quinoxalyl, optionally substituted pyridyl, optionally substituted pyrimidyl, and optionally substituted thiazolyl; R.sup.1 and R.sup.2 are independently selected from hydrogen, alkyl, halolalkyl, alkoxy, halogen; R.sup.3 is a valence bond or is selected from hydrogen and alkyl; X is a valence bond or is selected from alkylene, alkenylen, and alkynylene; and Z is selected from (a) COM, (b) CH.dbd.N--O--A--COM, (c) CH.sub.2 --O--N.dbd.A--COM wherein A is selected from alkylene and cycloalkylene, and M is selected from (a) a pharmaceutically acceptable metabolically cleavable group, (b) --OR.sup.6, (c) --NR.sup.7 R.sup.8, (d)--NR.sup.6 SO.sub.2 R.sup.9, (e)-NH-Tetrazolyl, and (f) glycinyl inhibit leukotriene biosynthesis and are useful in the treatment of allergic and inflammatory disease states. Also disclosed are leukotriene biosynthesis inhibiting compositions and a method of inhibiting leukotriene biosynthesis.

Symmetrical bis-heteroaryl-methoxy-phenylalkyl carboxylates as

The present invention provides a class of substituted indole and indene iminoxy derivatives of the formula ##STR1## which inhibit leukotriene biosynthesis and are useful in the treatment of allergic and inflammatory disease states.

Iminoxy derivatives of indole and indene compounds as inhibitors of

Substituted arylalkynyl-and heteroarylalkynl-N-hydroxyurea inhibitors of

Compounds of the structure ##STR1## wherein Z is selected from optionally substituted thienyl, thiazolyl, oxazolyl and furyl are potent inhibitors of lipoxygenase enzymes and thus inhibit the biosynthesis of leukotrienes. These compounds are useful in the treatment or amelioration of allergic and inflammatory disease states.

Substituted aryl- and heteroarylalkenyl-N-hydroxyurea inhibitors of

Compounds useful in inhibiting the biosynthesis of leukotrienes have the structure ##STR1## where M is hydrogen, a pharmaceutically acceptable cation, or a metabolically cleavable group, R.sup.4 is alkyl, cycloalkyl or --NR.sup.5 R.sup.6, where R.sup.5 and R.sup.6 are hydrogen, alkyl, cycloalkyl or alkanoyl, where A is a valence bond or is a straight or branched divalent alkylene group of from one to twelve carbon atoms, R.sup.2 and R.sup.3 are independently selected from hydrogen, straight or branched alkyl of from one to twelve carbon atoms, halogen, or trifluoroalkyl, and R.sup.1 is selected from phenoxy, phenylthio, 2-, 3-, or 4-pyridyloxy, 1 or 2-naphthyloxy, or 2,4,5, or 8-quinolyloxy, all optionally substituted with alkyl, haloalkyl, alkoxy, hydroxy or halogen.

Growing community of inventors

Racine, WI, United States of America

Richard A Craig