ROBERTA E GLYNN
Broker in Waltham, MA

2002002, Mar 7, 2002

Aug 12, 1997

08/909790

RICHARD JOHN BOOTH - YPSILANTI MI, US
KENNETH GORDON CARSON - NEEDHAM MA, US
DAVID THOMAS CONNOR - ANN ARBOR MI, US
ROBERTA ELLEN GLYNN - WALTHAM MA, US
BRUCE DAVID ROTH - PLYMOUTH MI, US
CHARLES F. SCHWENDER - GLEN GARDNER NJ, US
BHARAT KALIDAS TRIVEDI - FARMINGTON HILLS MI, US
PAUL CHARLES UNANGST - ANN ARBOR MI, US

A61K031/445, A61K031/415, C07D211/26, C07D211/32

514/317000, 514/331000, 514/399000, 546/229000, 546/235000

Aryl alkenamides derivatives of Formula I or a pharmaceutically acceptable salt thereof are novel MCP-1 antagonists and are thus useful in the treatment of inflammation, atherosclerosis, restenosis, and immune disorders such as arthritis and transplant rejection V=O, S, NH or a bond; Ar can be unsubstituted or substituted benzimidazole, phenyl, biphenyl, pyridyl, naphthyl, quinoline, isoquinoline or indole; n=2-6; m=1-3; X=O (oxygen), S (sulfur), CH, NH or H; Rand Rcan independently be hydrogen, lower alkyl of from 1-4 carbon atoms, —(CH)OR, —(CH)NRR, —(CH)′CONRR, —(CH)′COOR, —(CH)Ar′, where n′=0-6 r=0-4 Rand Rcan independently be hydrogen, lower alkyl of from 1-4 carbon atoms, —(CH)OR, or —(CH)—Ar′, which can be unsubstituted or substituted with up to 3 substitutents, where “Ar′” is phenyl, pyridyl, or indole; Rand Rmay also be taken together to form a cyclic ring of 3-8 atoms which may also contain oxygen or the group NRwhere Rcan be hydrogen, lower alkyl of from 1-4 carbon atoms, cycloalkyl of from 5-12 carbon atoms, or —(CH)-Phenyl, which can be unsubstituted or substituted with up to 3 substitutents; Rcan be hydrogen, lower alkyl or (CH)-Phenyl; m=1-3; Rand Rmay be also taken together to form a ring of 3-8 atoms which may also contain oxygen or the group NR, which ring may be substituted on one or more carbon atoms with the group NRR; the subtituents are defined as: halogen, nitro, CF, alkyl of from 1-12 carbon atoms; —(CH)OR—(CH)NRR—(CH)CONRR—(CH)C(O)ORor —(CH)SO—OR; R, R, Rand Rcan each independently be hydrogen, lower alkyl or aryl; and Rand Ror Rand Ror X or Rwhen taken together can form a 5-7 membered ring including cycloalkyl, cycloalkenyl, aryl, or heteroaryl containing nitrogen, oxygen or sulfur.