US 7,320,960 B2 | ||
Carbamyloxy compounds which inhibit leukocyte adhesion mediated by VLA-4 | ||
Eugene D. Thorsett, Moss Beach, Calif. (US); Christopher M. Semko, Fremont, Calif. (US); Dimitrios Sarantakis, Newtown, Pa. (US); Michael A. Pleiss, Sunnyvale, Calif. (US); Anthony Kreft, Langhorne, Pa. (US); Andrei W. Konradi, San Francisco, Calif. (US); Francine S. Grant, San Francisco, Calif. (US); Darren B. Dressen, San Mateo, Calif. (US); Susan Ashwell, Plainsboro, N.J. (US); Reinhardt Bernhard Baudy, Doylestown, Pa. (US); and Louis John Lombardo, Belle Mead, N.J. (US) | ||
Assigned to Elan Pharmaceuticals, Inc., S. San Francisco, Calif. (US); and Wyeth, Madison, N.J. (US) | ||
Filed on Dec. 11, 2002, as Appl. No. 10/316,205. | ||
Application 10/316205 is a division of application No. 09/987900, filed on Nov. 16, 2001, granted, now 6,525,026. | ||
Application 09/987900 is a division of application No. 09/126958, filed on Jul. 31, 1998, granted, now 6,489,300. | ||
Claims priority of provisional application 60/054453, filed on Aug. 01, 1997. | ||
Claims priority of provisional application 60/112020, filed on Jul. 31, 1997. | ||
Prior Publication US 2004/0014677 A1, Jan. 22, 2004 | ||
This patent is subject to a terminal disclaimer. | ||
Int. Cl. C07K 5/06 (2006.01) |
U.S. Cl. 514—19 [548/100; 514/183; 562/445] | 20 Claims |
1. A method for treating an inflammatory condition in a mammalian patient, said inflammatory condition selected from the group
consisting of asthma, atherosclerosis, diabetes, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, tissue
transplantation, tumor metastasis, meningitis, encephalitis, nephritis, atopic dermatitis, and psoriasis, which method comprises
administering to a said patient a therapeutically effective amount of a pharmaceutical composition comprising a pharmaceutically
acceptable carrier and a compound of formula I:
![]() R1 is selected from the group consisting of alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl,
heterocyclic, substituted heterocyclic heteroaryl and substituted heteroaryl;
R2 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl,
heterocyclic, substituted heterocyclic, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, and
R1 and R2 together with the nitrogen atom bound to R2 and the SO2 group bound to R1 can form a heterocyclic or substituted heterocyclic group;
R3 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted
aryl, heteroaryl, substituted heteroaryl, heterocyclic, and substituted heterocyclic and, when R2 does not form a heterocyclic with R1, R2 and R3 together with the nitrogen atom bound to R2 and the carbon atom bound to R3 can form a heterocyclic or substituted heterocyclic group;
R5 is —(CH2)x—Ar—R5′ where R5′ is selected from the group consisting of —O-Z-NR8R8′ and —O-Z-R12 wherein R8 and R8′ are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl,
heterocyclic, substituted heterocyclic, and where R8 and R8′ are joined to form a heterocycle or a substituted heterocycle, R12 is selected from the group consisting of heterocycle and substituted heterocycle, and Z is selected from the group consisting
of —C(O)— and —SO2—,
Ar is aryl, heteroaryl, substituted aryl or substituted heteroaryl,
x is an integer of from 1 to 4;
Q is —C(X)NR7— wherein R7 is selected from the group consisting of hydrogen and alkyl; and X is selected from the group consisting of oxygen and sulfur;
and pharmaceutically acceptable salts thereof
with the proviso that the compound is not selected from the group consisting of:
N-(toluene-4-sulfonyl)-L-prolyl-L-4-(4-methylpiperazin-1-ylcarbonyloxy)phenylalanine,
N-(toluene-4-sulfonyl)-L-prolyl-L-4(N,N-dimethylcarbamyloxy)phenylalanine,
N-(1-methylpyrazole-4-sulfonyl)-L-prolyl-L-4-(N,N-dimethylcarbamyloxy)phenylalanine,
N-(toluene-4-sulfonyl-)-L-(1,1-dioxo-5,5-dimethyl)thiaprolyl-L-4(N,N-dimethylcarbamyloxy)phenylalanine,
N-(toluene-4-sulfonyl-)-N-methyl-L-alaninyl-L-4-(N,N-dimethylcarbamyloxy)phenylalanine,
N-(toluene-4-sulfonyl-)-L-[(1,1-dioxo)thiamorpholin-3-carbonyl]-L-4-(N,N-dimethylcarbamyloxy)phenylalanine,
N-(N-p-toluenesulfonyl)prolyl-4-(piperazinoyloxy)phenylalanine,
N-(N-p-toluenesulfonyl)sarcosyl-4-(N,N-dimethylcarbamyloxy)phenylalanine, and
N-(toluene-4-sulfonyl)-L-(5,5-dimethyl)thiaprolyl-L-4-[3-(N,N-dimethyl)propoxyl]-phenylalanine.
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