Wyeth

Elan Pharmaceuticals, Inc.

Other

Arqule, Inc.

Anthony Frank Kreft

Eugene D Thorsett

Michael A Pleiss

Andrei William Konradi

Christopher Michael Semko

Dimitrios Sarantakis

Susan Ashwell

Darren B Dressen

Francine S Grant

Gregory Scott Welmaker

Ying-Zi Xu

Derek Cecil Cole

Louis John Lombardo

Reinhardt Bernhard Baudy

George Diamantidis

Dennis Michael Kubrak

Joseph Raymond Stock

Lynn Resnick

David S Casebier

Kevin R Woller

William Jay Moore

Kristina Martha Kutterer

Charles William Mann

Dennis Martin Kubrak

Boyd Lynn Harrison

Scott Christian Mayer

Molly Hoke

Minsheng Zhang

Thomas Joseph Caggiano

Koi Morris

Rocco John Galante

Tingzhong Wang

Gary Paul Stack

Donna Mary Huryn

Joan E Sabalski

Joshua D Berkowitz

Christopher Joseph Soares

Kiev S Ly

Christine M Tarby

Michael S Dappen

Madelene M Antane

Frank Stappenbeck

Francine S Farouz

Diane Barbara Hauze

Robert Warren Sullivan

Zheng Wang

Alexander Michael Porte

Michael A Pliess

Dimitrios Sarntakis

Disclosed are compounds which bind VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

Heteroaryl, heterocyclic and aryl compounds which inhibit leukocyte adhesion mediated by VLA-4

Compounds of Formula (I), are provided where T is CHO, COR, or C(OH)RR; Rand Rare hydrogen, optionally substituted lower alkyl, CF, optionally substituted alkenyl, or optionally substituted alkynyl; Ris hydrogen or optionally substituted lower alkyl; Ris (CF)alkyl, (CF)(substitutedalkyl), (CF)alkylphenyl, (CF)alkyl(substitutedphenyl), or (F)cycloalkyl; n=1-3; Ris hydrogen, halogen, CF, diene fused to Y when Y=C, or substituted diene fused to Y when Y=C; W, Y and Z are C, CRor N where at least one of W, Y or Z are C; Ris hydrogen, halogen, or optionally substituted lower alkyl; X is O, S, SO, or NR; Ris hydrogen, optionally substituted lower alkyl, optionally substituted benzyl, or optionally substituted phenyl; and Ris lower alkyl, CF, or optionally substituted phenyl. Methods of preparing and using these compounds for inhibiting beta amyloid production and for treatment of Alzheimer's Disease and Down's syndrome are also described.

Fluoro- and trifluoroalkyl-containing heterocyclic sulfonamide inhibitors of beta amyloid production and derivatives thereof

Compounds of Formula (I), wherein R, R, R, R, R, R, T, W, X, Y and Z are as defined herein are provided, together with pharmaceutically acceptable salt, hydrates and/or prodrugs thereof. Methods of using these compounds for inhibiting beta amyloid production and for treatment of Alzheimer's disease and Down's syndrome are described.

Heterocyclic sulfonamide inhibitors of beta amyloid production

Disclosed are certain alpha amino acid compounds which bind VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

Alpha amino acid derivatives-inhibitors of leukocyte adhesion mediated by VLA-4

Compounds of Formula (I), wherein R, R, R, R, R, R, T, W, X, Y and Z are as defined herein are provided, together with pharmaceutically acceptable salt, hydrates and/or prodrugs thereof. Methods of using these compounds for determining &#x3b2;-amyloid levels in a subject are described.

Heterocyclic sulfonamide inhibitors of &#x3b2; amyloid production

Compounds useful for lowering beta amyloid levels are provided. The compounds have the structure of formula Ia: wherein, Ris lower alkyl, substituted lower alkyl, phenyl, substituted phenyl, benzyl, substituted benzyl, benzyloxy, substituted benzyloxy, or SOR; Ris phenyl, substituted phenyl, heterocycle, substituted heterocycle, alkyl, or substituted alkyl; Ris lower alkyl, substituted lower alkyl, CF, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, or cycloalkyl; Ris hydrogen, lower alkyl, or substituted lower alkyl; Ris phenyl, substituted phenyl, heterocycle, substituted heterocycle, thiophene, or substituted thiophene; Ris hydrogen, lower alkyl, substituted lower alkyl, CF, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, cycloalkyl, or substituted cycloalkyl; W, X and Y are independently CRor N; and Ris hydrogen, halogen, lower alkyl, or substituted lower alkyl.

Heterocyclic sulfonamide inhibitors of beta amyloid production containing an azole

Compounds of Formula I,  wherein R-Rare defined herein are provided, together with pharmaceutically acceptable salts, hydrates, metabolites, and/or prodrugs thereof. Uses of these compounds for inhibiting beta amyloid production and for the prevention and treatment of Alzheimer's Disease and Down's syndrome are also described.

Substituted phenylsulfonamide inhibitors of beta amyloid production

A compound of Formula (I), or pharmaceutically acceptable salts and/or hydrates or prodrugs thereof, wherein Formula (I) has the structure: is provided, wherein R-Rare defined herein. These compounds are useful in medicaments for treating a disease selected from the group consisting of Alzheimer's Disease, amyloid angiopathy, cerebral amyloid angiopathy, systemic amyloidosis, hereditary cerebral hemorrhage with amyloidosis of the Dutch type, inclusion body myositis, mild cognitive impairment (MCI) and Down's syndrome, in a subject.

Trifluoromethyl-containing phenylsulfonamide beta amyloid inhibitors

Compounds of Formula (I), are provided where T is CHO, COR, or C(OH)RR; Rand Rare hydrogen, optionally substituted lower alkyl, CF, optionally substituted alkenyl, or optionally substituted alkynyl; Ris hydrogen or optionally substituted lower alkyl; Ris (CF)alkyl, (CF)(substituted alkyl), (CF)alkylphenyl, (CF)alkyl(substituted phenyl), or (F)cycloalkyl; n=1-3; Ris hydrogen, halogen, CF, diene fused to Y when Y&#x2550;C, or substituted diene fused to Y when Y&#x2550;C; W, Y and Z are C, CRor N where at least one of W, Y or Z are C; Ris hydrogen, halogen, or optionally substituted lower alkyl; X is O, S, SO, or NR; Ris hydrogen, optionally substituted lower alkyl, optionally substituted benzyl, or optionally substituted phenyl; and Ris lower alkyl, CF, or optionally substituted phenyl. Methods of preparing and using these compounds for inhibiting beta amyloid production and for treatment of Alzheimer's Disease and Down's syndrome are also described.

Compounds useful for lowering beta amyloid levels are provided. The compounds have the structure of formula Ia: 

Carbamyloxy compounds which inhibit leukocyte adhesion mediated by VLA-4

Compounds of Formula (I), are provided where T is CHO, CON, or C(OH)RR; Rand Rare hydrogen, optionally substituted lower alkyl, CF, optionally substituted alkenyl, or optionally substituted alkynyl; Ris hydrogen or optionally substituted lower alkyl; Ris (CF)alkyl, (CF)(substitutedalkyl), (CF)alkylphenyl, (CF)alkyl(substitutedphenyl), or (F)cycloalkyl; n=1-3; Ris hydrogen, halogen, CF, diene fused to Y when Y&#x2550;C, or substituted diene fused to Y when Y&#x2550;C; W, Y and Z are C, CRor N where at least one of W, Y or Z are C; Ris hydrogen, halogen, or optionally substituted lower alkyl; X is O, S, SO, or NR; Ris hydrogen, optionally substituted lower alkyl, optionally substituted benzyl, or optionally substituted phenyl; and Ris lower alkyl, CF, or optionally substituted phenyl. Methods of preparing and using these compounds for inhibiting beta amyloid production and for treatment of Alzheimer's Disease and Down's syndrome are also described.

Disclosed are a series of phenylalanine derivatives, to compositions containing them, to processes for their preparation, and to their use in medicine.

Phenylalanine derivatives as alpha 4 integrin inhibitors

Growing community of inventors

Langhorne, PA, United States of America

Anthony Frank Kreft