| US 7,531,573 B2 | ||
| Use of triaryl methane compounds for inhibiting unwanted cellular proliferation associated with inflammatory disease | ||
| Carlo Brugnara, Newton Highlands, Mass. (US); Jose Halperin, Brookline, Mass. (US); Emile M. Bellot, Jr., Beverly, Mass. (US); Mark Froimowitz, Newton Centre, Mass. (US); Richard John Lombardy, Littleton, Mass. (US); John J. Clifford, Bedford, Mass. (US); Ying-Duo Gao, Edison, N.J. (US); Reem M. Haidar, Woburn, Mass. (US); Eugene W. Kelleher, Bedford, Mass. (US); Falguni M. Kher, Billerica, Mass. (US); Adel M. Moussa, Burlington, Mass. (US); Yesh P. Sachdeva, Concord, Mass. (US); Minghua Sun, Libertyville, Ill. (US); and Heather N. Taft, Littleton, Mass. (US) | ||
| Assigned to Children's Medical Center Corporation, Boston, Mass. (US) | ||
| Filed on Jun. 03, 2003, as Appl. No. 10/454,372. | ||
| Application 10/454372 is a continuation of application No. 09/942258, filed on Aug. 28, 2001, abandoned. | ||
| Application 09/942258 is a continuation of application No. 09/159335, filed on Sep. 23, 1998, granted, now 6,331,564. | ||
| Application 09/159335 is a continuation of application No. 08/822550, filed on Mar. 19, 1997, granted, now 6,028,103, filed on Feb. 22, 2000. | ||
| Application 08/822550 is a continuation in part of application No. 08/618952, filed on Mar. 20, 1996, abandoned. | ||
| Application 08/618952 is a continuation in part of application No. 08/618760, filed on Mar. 20, 1996, abandoned. | ||
| Application 08/618760 is a continuation in part of application No. 08/307874, filed on Sep. 16, 1994, abandoned. | ||
| Application 08/618760 is a continuation in part of application No. 10/454372. | ||
| Application 10/454372 is a continuation in part of application No. 08/618762, filed on Mar. 20, 1996, abandoned. | ||
| Application 08/618762 is a continuation in part of application No. 08/618759, filed on Mar. 20, 1996, abandoned. | ||
| Application 08/618759 is a continuation in part of application No. 08/307887, filed on Sep. 16, 1994, abandoned. | ||
| Prior Publication US 2004/0127464 A1, Jul. 01, 2004 | ||
| Int. Cl. A61K 31/275 (2006.01) | ||
| U.S. Cl. 514—519 [514/520; 514/521] | 11 Claims |
| 1. A method for inhibiting unwanted non-malignant lymphoproliferation associated with an inflammatory disease,
wherein the inflammatory disease is diarrhea; autoimmune disease; proliferative glomerulonephritis; lupus erythematosus; scleroderma;
temporal arteritis; thromboangiitis obliterans; mucocutaneous lymph node syndrome; asthma; host versus graft; or inflammatory
bowel disease; and wherein
said method comprising the step of contacting a cell the proliferation of which contributes to inflammation in situ with an
effective amount of a compound having the formula:
 or a pharmaceutically acceptable salt or hydrate thereof, wherein:
n is 0, 1, 2, 3 or 4;
X is absent, (C1-C3) alkyl, (C1-C3) alkenyl, or (C1-C3) alkynyl;
Y is C, N, P, Si or Ge;
R1 is absent, -halo, —R, —OR, —SR, —NR2, —ONR2, —NO2, —CN, —C(O)R, —C(S)R, —C(O)OR, —C(S)OR, —C(O)SR, —C(S)SR, —C(O)NR2, —C(S)NR2, —C(O)NR(OR), —C(S)NR(OR), —C(O)NR(SR), C(S)NR(SR), —CH(CN)2, —CH[C(O)R]2, —CH[C(S)R]2, —CH[C(O)OR]2, —CH[C(S)OR]2, —CH[C(O)SR]2, —CH[C(S)SR]2 or aryl;
Ar1 is aryl, substituted aryl, heteroaryl other than imidazole, nitroimidazole and triazole, heteroarylium other than imidazolium,
nitroimidazolium and triazolium, (C5-C8) cycloalkyl or (C5-C8) heterocycloalkyl;
Ar2 is aryl or substituted aryl;
Ar3 is aryl, substituted aryl, biaryl or heteroaryl other than imidazole, nitroimidazole and triazole;
each R is independently selected from the group consisting of —H, (C1-C6) alkyl, substituted (C1-C6) alkyl, (C1-C6) alkenyl, substituted (C1-C6) alkenyl (C1-C6) alkynyl, substituted (C1-C6) alkynyl, and (C1-C6) alkoxy;
the aryl substituents are each independently selected from the group consisting of -halo, trihalomethyl, —R, —R′, —OR′, —SR′,
NR′2, —NO2, —CN, —C(O)R′, —C(S)R′, —C(O)OR′, —C(S)OR′, —C(O)SR′ and —C(S)SR′;
the alkyl, alkenyl and alkynyl substituents are each independently selected from the group consisting of -halo, —R′, —OR′,
—SR′, NR′2, —NO2, —CN, —C(O)R′, —C(S)R′, —C(O)OR′, —C(S)OR′, —C(O)SR′, —C(S)SR′, aryl, γ-butyrolactonyl, pyrrolidinyl and succinic anhydridyl;
and
each R′ is independently selected from the group consisting of —H, (C1-C6) alkyl, (C1-C6) alkenyl and (C1-C6) alkynyl;
wherein said administration is selected from the group consisting of oral, parenteral, intravenous, subcutaneous, transdermal
and transmucosal for a living human.
|