Claims
- 1. A compound according to the formula (I′): or a pharmaceutically effective salt thereof, whereinX is selected from the group consisting of O, S, S(O) and S(O)2; R1 is selected from the groups consisting of (a) hydrogen, halo, R5—, C2-6 alkenyl, C2-6 alkynyl, hydroxy-R5—, R5—O—, R5—S—, R5—O—R5—, mercapto-R5—, R5—S—R5—, —NH2, R5—NH—, (R5)2—N— or a heterocyclic group optionally substituted by one or two substituents selected from C1-4 alkyl, phenyl, and pyridyl; (b) Ar—, Ar—R5—, Ar—C2-6 alkenyl, Ar—C2-6 alkynyl, Ar—O—, Ar—O—Ar—, Ar—O—Ar—O—, Ar—O—R5—, Ar—R5—O—, Ar—S—, Ar—R5—S—, Ar—NH—, (Ar)2—R5—, Ar—R5—NH—, Ar—R5—N(R5)— or (Ar)2—N—; (c) R5—C(O)—, —NO2, cyano, NH2—C(O)—, R5—NH—C(O)—, (R5)2—N—C(O)—, Ar—C(O)—, (Ar—R5)2—N—C(O)—, Ar—R5—C(O)—, Ar—NH—C(O)—, Ar—R5—NH—C(O)—, R5—S(O)2— or R5—S(O)—; and (d) R5—C(O)—NH—, Ar—C(O)—NH—, Ar—R5—C(O)—NH— or H2N—C(O)—NH—; wherein Ar is aryl or heteroaryl optionally substituted by one or two substituents selected from C1-4 alkyl, halo-substituted C1-4 alkyl, halo-substituted C1-4 alkoxy, C1-4 alkylthio, nitro, hydroxy, amino and halo; and —A1—B1—A2—, together with the carbon atoms to which A1 and A2 are attached, defines a ring having 4 to 8 carbon atoms, said ring being optionally substituted with acetyl-, carboxyl-, —C(O)—NH2, —C(O)—OR5, —C(O)—NHR5, hydroxy, R5—, C1-4 alkoxy-, R5—NH—, or (R5)2—NH—, wherein A1 and A2 are independently, a direct bond or C1-6 alkylene, and B1 is carbonyl; each occurence of R4 is selected independently from hydrogen, halo, R5—, hydroxy-R5—, R5—O—R5—, R5—C(O)—, R5—O—C(O)—, and R5—NH—C(O)—; m is 0,1,2,3 or 4; and R5, if present, is C1-6 alkyl optionally substituted by up to four halogen atoms.
- 2. The compound of claim 1 wherein X is S.
- 3. The compound of claim 1 wherein R1 is 4-pyridyl or 3-pyridyl.
- 4. The compound of claim 3 wherein R1 is 4-pyridyl.
- 5. The compound of claim 1 wherein R1 comprises a phenyl group.
- 6. The compound of claim 5 wherein said phenyl group is selected from the group consisting of 2-fluorophenyl-, 4-fluorophenyl-, and 4-trifuoromethyl-phenyl-.
- 7. The compound of claim 1 selected from the group consisting of1,3-di(4-pyridyl)-5,6-dihydro-4H-cyclopenta(c)thiophen-4-one; 1,3-di(4-pyridyl)-4,5,6,7-tetrahydrobenzo(c)thiophen-4-one; 3-(2-fluorophenyl)-1-(4-pyridyl)-5,6-dihydro-4H-cyclopenta(c)thiophen-4-one; 1-(4-pyridyl)-3-(3-pyridyl)-5,6-dihydro-4H-cyclopenta(c)thiophen-4-one; 1-(4-pyridyl)-3-(4-trifluoromethylphenyl)-5,6-dihydro-4H-cyclopenta(c)thiophen-4-one; 1-(4-fluorophenyl)-3-(4-pyridyl)-5,6-dihydro-4H-cyclopenta(c)thiophen-4-one; and.
- 8. A pharmaceutical composition for the treatment of a disorder or condition selected from AIDS, ARC, arthritis, asthma, bone resorption disease, cachexia, cardiovascular disease, cerebral malaria, Crohn's disease, diabetes, fever or myalgia due to infection, gout, graft versus host reaction, inflammation of organs, inflammatory bowel disease, keloid formation, psoriasis, pulmonary inflammatory disease, respiratory distress syndrome, reperfusion injury, rhinitis, scar tissue formation, sepsis, septic shock, silicosis, toxic shock syndrome, transplant rejection, ulcerative colitis, rheumatoid arthritis, osteo arthritis, artherosclerosis, cancer, obesity, allergy, skin diseased, topical inflammatory disease states, viral infection and thrombosis, by inhibiting TNFα biosynthesis or CAM expression in a mammal, comprising an amount of the compound of claim 1, or a pharmaceutically effective salt thereof, that is effective in treating such disorder or condition, and a pharmaceutically acceptable carrier.
- 9. A method of treating a disorder or condition selected from AIDS, ARC, arthritis, asthma, bone resorption disease, cachexia, cardiovascular disease, cerebral malaria, Crohn's disease, diabetes, fever or myalgia due to infection, gout, graft versus host reaction, inflammation of organs, inflammatory bowel disease, keloid formation, psoriasis, pulmonary inflammatory disease, respiratory distress syndrome, reperfusion injury, rhinitis, scar tissue formation, sepsis, septic shock, silicosis, toxic shock syndrome, transplant rejection, ulcerative colitis, rheumatoid arthritis, osteo arthritis, artherosclerosis, cancer, obesity, allergy, skin diseased, topical inflammatory disease states, viral infection and thrombosis, by inhibiting TNFα biosynthesis or CAM expression in a mammal, comprising administering to a mammal in need of such treatment an amount of a compound of claim 1, or a pharmaceutically effective salt thereof, that is effective in treating such a disorder or condition.
Parent Case Info
The present application is a continuation of U.S. Ser. No. 09/317,570, filed May 24, 1999, now AB which is a continuation of U.S. Ser. No. 09/003,108, filed Jan. 6, 1998 (now U.S. Pat. No. 6,048,880), which claims priority under 35 USC section 119, via the Paris Convention, to international application PCT/IB97/00002 filed Jan. 6, 1997. The complete text and claims of the as-filed 09/003,108 application are hereby incorporated by reference as if fully set forth herein.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
5037824 |
Takasugi |
Aug 1991 |
A |
Foreign Referenced Citations (1)
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H03232884 |
Oct 1991 |
JP |
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Continuations (3)
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Number |
Date |
Country |
Parent |
09/317570 |
May 1999 |
US |
Child |
09/918153 |
|
US |
Parent |
09/003108 |
Jan 1998 |
US |
Child |
09/317570 |
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US |
Parent |
PCT/IB97/00002 |
Jan 1997 |
US |
Child |
09/003108 |
|
US |