Piperazine derivatives useful as CCR5 antagonists
View Patent ↗The use of CCR5 antagonists of the formula or a pharmaceutically acceptable salt thereof, wherein R is optionally substituted phenyl, pyridyl, thiophenyl or naphthyl; R 1 is hydrogen or alkyl; R 2 is substituted phenyl, substituted heteroaryl, naphthyl, fluorenyl, diphenylmethyl or optionally substituted phenyl- or heteroaryl-alkyl; R 3 is hydrogen, alkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, or optionally substituted phenyl, phenylalkyl, naphthyl, naphthylalkyl, heteroaryl or heteroarylalkyl; R 4 , R 5 and R 7 are hydrogen or alkyl; R 6 is hydrogen, alkyl or alkenyl; for the treatment of HIV, solid organ transplant rejection, graft v. host disease, arthritis, rheumatoid arthritis, inflammatory bowel disease, atopic dermatitis, psoriasis, asthma, allergies or multiple sclerosis is disclosed, as well as novel compounds, pharmaceutical compositions comprising them, and the combination of CCR5 antagonists of the invention in combination with antiviral agents useful in the treatment of HIV or agents useful in the treatment of inflammatory diseases.
1. A compound in pure and isolated form, said compound being
or a pharmaceutically acceptable salt or ester thereof.
2. A pharmaceutical composition comprising an effective amount of a compound of claim 1 or a pharmaceutically acceptable salt or ester thereof in combination with a pharmaceutically acceptable carrier.
3. A method of treating Human Immunodeficiency Virus comprising administering to a human in need of such treatment a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt, or ester thereof.
4. The method of claim 3 further comprising administering one or more antiviral or other agents useful in the treatment of Human Immuno-deficiency Virus in combination with the compound of claim 1 or a pharmaceutically acceptable salt, solvate or ester thereof.
5. The method of claim 4 wherein the antiviral agent is selected from the group consisting of nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors.
6. The method of claim 5 wherein the antiviral agent is selected from the group consisting of zidovudine, lamivudine, zalcitabine, didanosine, stavudine, abacavir, adefovir dipivoxil, Iobucavir, BCH-10652, emitricitabine, beta-L-FD4, DAPD, Iodenosine, nevirapine, delaviridine, efavirenz, PNU-142721, AG-1549, MKC-442, (+)-calanolide A and B, saquinavir, indinavir, ritonavir, nelfinavir, lasinavir, DMP-450, BMS-2322623, ABT-378, amprenavir, hydroxyurea, ribavirin, IL-2, IL-12, pentafuside, Yissum No. 11607 and AG-1549.
7. A method treating solid organ transplant rejection, graft v. host disease, arthritis, rheumatoid arthritis, inflammatory bowel disease, atopic dermatitis, psoriasis, asthma, allergies or multiple sclerosis, comprising administering to a human in need of such treatment a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt, or ester thereof.
8. The method of claim 7 for the treatment of solid organ transplant rejection, graft v. host disease, arthritis, rheumatoid arthritis, inflammatory bowel disease, atopic dermatitis, psoriasis, asthma, allergies or multiple sclerosis, further comprising one or more other agents useful in the treatment of said diseases.