US2008095740A1PendingUtilityA1
Piperidine derivatives useful as ccr5 antagonists
Est. expiryDec 18, 2022(expired)· nominal 20-yr term from priority
A61P 37/08A61P 37/02A61P 31/12A61P 37/00A61P 31/18A61P 37/06A61P 43/00A61P 25/00A61P 29/00A61P 19/00A61P 11/06A61P 17/06A61P 19/04A61P 19/02A61P 1/00A61P 17/04A61P 17/00C07D 401/14A61K 31/506
57
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
The present invention provides a compound of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein the various moieties are as defined in the specification. The present invention also provides pharmaceutical compositions containing the compound of this invention, and methods of treatment using the compound of this invention. The invention also relates to the use of a combination of a compound of this invention and one or more antiviral or other agents useful in the treatment of Human Immunodeficiency Virus (HIV). The invention further relates to the use of a compound of this invention, alone or in combination with another agent, in 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.
Claims
exact text as granted — not AI-modified1 . A pharmaceutical composition comprising:
(a) a therapeutically effective amount of one or more compounds of structural formula I: or a pharmaceutically acceptable salt or solvate thereof; wherein: n is 0, 1, 2, 3 or 4; s is 0, 1, 2, 3 or 4 t is 1, 2, 3 or 4 with the provisos that i) when n is 0 and s is 2, then t is 1, 3 or 4; and ii) when n is 0 and t is 2, then s is 0, 1, 3 or 4; X is N; Z is N or CH; R 1 is H, alkyl, aralkyl, —S(O 2 )alkyl, —S(O 2 )aryl, —C(O)alkyl, —C(O)aryl, -alkyl-aryl-R 8 , -alkyl-heteroaryl-R 8 , —S(O 2 )cycloalkyl, —S(O 2 )-aryl-R 8 , —C(O)cycloalkyl, —C(O)-aryl-R 8 , —C(O)NR 20 R 21 or —S(O 2 )NR 20 R 21 ; R 2 , R 4 , R 5 , R 6 and R 7 can be the same or different each being independently H or alkyl; R 3 is H, alkyl, cycloalkyl, aralkyl, heteroaralkyl, aryl or heteroaryl; or R 2 and R 3 taken together are ═N(O-alkyl), ═N(OH), ═N—N(R 20 R 21 ) or ═CH(alkyl) provided that when one or both of X and Z is N, R 2 and R 3 together are not ═CH(alkyl); R 8 is aryl, heteroaryl, fluorenyl; and diphenylmethyl, heteroaryl-N-oxide, wherein each R 10 is the same or different and independently selected from —CH 3 or halogen, Y is N or N(→O) and each of said aryl, fluorenyl, diphenyl and heteroaryl is unsubstituted or optionally independently substituted with 1 to 4 substituents which substituents can be the same or different each being independently selected from the group consisting of R 11 , R 12 , R 13 , R 14 and R 15 ; R 9 is H, alkyl, —CF 3 , cycloalkyl, —OH, —OCH 3 , —NH 2 , —N(H)C(O)N(H)alkyl, —NHS(O 2 )R 20 or —N(H)C(O)alkyl; R 11 and R 12 can be the same or different and are each independently selected from the group consisting of alkyl, haloalkyl, halogen, —NR 18 R 19 , —OH, —CF 3 , —OCH 3 , —O-acyl and —OCF 3 ; R 13 is selected from the group consisting of H, R 11 , aryl, —NO 2 , —CN, —CH 2 F, —CHF 2 , —C(O)H, —CH═NOR 18 , pyridyl-N-oxide, pyrimidinyl, pyrazinyl, —N(R 19 )CONR 19 R 20 , —N(H)C(O)N(H)(haloalkyl), —N(H)C(O)N(H)(cycloalkylalkyl), —N(H)C(O)alkyl, —N(H)C(O)CF 3 , —N(H)S(O 2 )N(alkyl) 2 , —N(H)S(O 2 )alkyl, —N(S(O 2 )CF 3 ) 2 , —N(H)C(O)Oalkyl, cycloalkyl, —SR 21 , —S(O)R 21 , —S(O 2 )R 21 , —S(O 2 )N(H)(alkyl), —OS(O 2 )alkyl, —OS(O 2 )CF 3 , hydroxyalkyl, —C(O)NR 18 R 19 , —C(O)N(CH 2 CH 2 —O—CH 3 ) 2 , —OC(O)N(H)alkyl, —CO 2 R 18 , —Si(CH 3 ) 3 and —B(OC(CH 3 ) 2 ) 2 ; R 14 is selected from the group consisting of alkyl, haloalkyl, NH 2 and R 15 -phenyl; R 15 is 1 to 3 substituents selected from the group consisting of H, alkyl, haloalkyl, —CF 3 , —CO 2 R 19 , —CN, alkoxy and halogen; wherein said R 15 moieties can be the same or different each being independently selected when there are more than one R 15 present; R 16 and R 17 can be the same or different each being independently selected from the group consisting of hydrogen and alkyl, or R 16 and R 17 together are an alkylene group and with the carbon to which they are attached form a spiro ring of 3 to 6 carbon atoms; R 18 , R 19 and R 20 can each be the same or different and are each independently selected from the group consisting of H, alkyl, cycloalkyl, aryl and heteroaryl; and R 21 is selected from the group consisting of alkyl, haloalkyl, hydroxyalkyl, alkylene, cycloalkyl, aryl and aralkyl; wherein each of said alkyl, alkylene, aryl, arylalkyl, aralkyl, alkoxy, hydroxyalkyl, heteroaryl, heteroaralkyl, cycloalkylalkyl and cycloalkyl in the definitions above can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, where said moieties are independently selected from the group consisting of —OH, alkoxy, —CN, halogen, —NR 18 R 19 , —C(O)NR 18 R 19 , —N(R 18 )C(O)R 19 , —N(R 18 )S(O 2 )R 19 , —S(O 2 )NR 18 R 19 , —C(O)OR 18 , —OCF 3 , —CF 3 , —S(O 2 )R 18 and —C(O)R 18 ; and (b) one or more antiviral or other agents useful in the treatment of Human Immunodeficiency Virus.
2 . The pharmaceutical composition of claim 1 , wherein in structural formula I, R 1 and R 3 are as defined in the following table:
R 1
R 3
PMB
H
3 . The pharmaceutical composition of claim 1 , wherein the compound of structural Formula I is a compound represented by the structural formulae:
or a pharmaceutically acceptable salt or solvate thereof.
4 . The pharmaceutical composition of claim 1 , wherein said antiviral agent is selected from the group consisting of nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors.
5 . The pharmaceutical composition of claim 1 , wherein said antiviral agent is selected from the group consisting of zidovudine, lamivudine, zalcitabine, didanosine, stavudine, abacavir, adefovir dipivoxil, lobucavir. BCH-10652, emitricitabine, beta-L-FD4, DAPD, lodenosine, 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.
6 . A method of treating Human Immunodeficiency Virus comprising administering to a patient in need of such treatment a therapeutically effective amount of one or more compounds of structural formula I:
or a pharmaceutically acceptable salt or solvate thereof; wherein:
n is 0, 1, 2, 3 or 4;
s is 0, 1, 2, 3 or 4;
t is 1, 2, 3 or 4 with the provisos that
i) when n is 0 and s is 2, then t is 1, 3 or 4;
and
ii) when n is 0 and t is 2, then s is 0, 1, 3 or 4;
X is N;
Z is N or CH;
R 1 is H, alkyl, aralkyl, —S(O 2 )alkyl, —S(O 2 )aryl, —C(O)alkyl, —C(O)aryl, -alkyl-aryl-R 8 , -alkyl-heteroaryl-R 8 , —S(O 2 )cycloalkyl, —S(O 2 )-aryl-R 8 , —C(O)cycloalkyl, —C(O)-aryl-R 8 , —C(O)NR 20 R 21 or —S(O 2 )NR 20 R 21 ;
R 2 , R 4 , R 5 , R 6 and R 7 can be the same or different each being independently H or alkyl;
R 3 is H, alkyl, cycloalkyl, aralkyl, heteroaralkyl, aryl or heteroaryl;
or R 2 and R 3 taken together are ═N(O-alkyl), ═N(OH), ═N—N(R 20 R 21 ) or ═CH(alkyl) provided that when one or both of X and Z is N, R 2 and R 3 together are not ═CH(alkyl);
R 8 is aryl, heteroaryl, fluorenyl; and diphenylmethyl, heteroaryl-N-oxide,
wherein each R 10 is the same or different and independently selected from —CH 3 or halogen, Y is N or N(→O) and each of said aryl, fluorenyl, diphenyl and heteroaryl is unsubstituted or optionally independently substituted with 1 to 4 substituents which substituents can be the same or different each being independently selected from the group consisting of R 11 , R 12 , R 3 , R 14 and R 15 ;
R 9 is H, alkyl, —CF 3 , cycloalkyl, —OH, —OCH 3 , —NH 2 , —N(H)C(O)N(H)alkyl, —NHS(O 2 )R 20 or —N(H)C(O)alkyl;
R 11 and R 12 can be the same or different and are each independently selected from the group consisting of alkyl, haloalkyl, halogen, —NR 18 R 19 , —OH, —CF 3 , —OCH 3 , —O-acyl and —OCF 3 ;
R 13 is selected from the group consisting of H, R 11 , aryl, —NO 2 , —CN, —CH 2 F, —CHF 21 —C(O)H, CH═NOR 18 , pyridyl-N-oxide, pyrimidinyl, pyrazinyl, —N(R 19 )CONR 19 R 20 , —N(H)C(O)N(H)(haloalkyl), —N(H)C(O)N(H)(cycloalkylalkyl), —N(H)C(O)alkyl, —N(H)C(O)CF 3 , —N(H)S(O 2 )N(alkyl) 2 , —N(H)S(O 2 )alkyl, —N(S(O 2 )CF 3 ) 2 , —N(H)C(O)Oalkyl, cycloalkyl, —SR 21 —S(O)R 21 , —S(O 2 )R 21 , —S(O 2 )N(H)(alkyl), —OS(O 2 )alkyl, —OS(O 2 )CF 3 , hydroxyalkyl, —C(O)NR 18 R 19 , —C(O)N(CH 2 CH 2 —O—CH 3 ) 2 , —OC(O)N(H)alkyl, —CO 2 R 18 , —Si(CH 3 ) 3 and —B(OC(CH 3 ) 2 ) 2 ;
R 14 is selected from the group consisting of alkyl, haloalkyl, NH 2 and R 15 -phenyl;
R 15 is 1 to 3 substituents selected from the group consisting of H, alkyl, haloalkyl, —CF 3 , —CO 2 R 19 , —CN, alkoxy and halogen; wherein said R 15 moieties can be the same or different each being independently selected when there are more than one R 15 present;
R 16 and R 17 can be the same or different each being independently selected from the group consisting of hydrogen and alkyl, or R 16 and R 17 together are an alkylene group and with the carbon to which they are attached form a spiro ring of 3 to 6 carbon atoms;
R 18 , R 19 and R 20 can each be the same or different and are each independently selected from the group consisting of H, alkyl, cycloalkyl, aryl and heteroaryl; and
R 21 is selected from the group consisting of alkyl, haloalkyl, hydroxyalkyl, alkylene, cycloalkyl, aryl and aralkyl; wherein each of said alkyl, alkylene, aryl, arylalkyl, aralkyl, alkoxy, hydroxyalkyl, heteroaryl, heteroaralkyl, cycloalkylalkyl and cycloalkyl in the definitions above can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, where said moieties are independently selected from the group consisting of —OH, alkoxy, —CN, halogen, —NR 18 R 19 , —C(O)NR 18 R 19 , —N(R 18 )C(O)R 19 , —N(R 18 )S(O 2 )R 19 , —S(O 2 )NR 18 R 19 , —C(O)R 18 , —OCF 3 , —CF 3 , —S(O 2 )R 18 and —C(O)R 18 .
7 . The method of claim 6 , wherein in structural formula I, R 1 and R 3 are as defined in the following table:
R 1
R 3
PMB
H
8 . The method of claim 6 , wherein the compound of structural Formula I is a compound represented by the structural formulae:
or a pharmaceutically acceptable salt or solvate thereof.
9 . The method of claim 6 , further comprising administering one or more antiviral or other agents useful in the treatment of Human Immuno-deficiency Virus.
10 . The method of claim 9 , wherein said antiviral agent is selected from the group consisting of nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors.
11 . The method of claim 10 , wherein said antiviral agent is selected from the group consisting of zidovudine, lamivudine, zalcitabine, didanosine, stavudine, abacavir, adefovir dipivoxil, lobucavir, BCH-10652, emitricitabine, beta-L-FD4, DAPD, lodenosine, 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.
12 . A method of 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 patient in need of such treatment a therapeutically effective amount of one or more compounds of structural formula I:
or a pharmaceutically acceptable salt or solvate thereof; wherein:
n is 0, 1, 2, 3 or 4;
s is 0, 1, 2, 3 or 4;
t is 1, 2, 3 or 4 with the provisos that
i) when n is 0 and s is 2, then t is 1, 3 or 4;
and
ii) when n is 0 and t is 2, then s is 0, 1, 3 or 4;
X is N;
Z is N or CH;
R 1 is H, alkyl, aralkyl, —S(O 2 )alkyl, —S(O 2 )aryl, —C(O)alkyl, —C(O)aryl, -alkyl-aryl-R 8 , -alkyl-heteroaryl-R 8 , —S(O 2 )cycloalkyl, —S(O 2 )-aryl-R 8 , —C(O)cycloalkyl, —C(O)-aryl-R 8 , —C(O)NR 20 R 21 or —S(O 2 )NR 20 R 21 ;
R 2 , R 4 , R 5 , R 6 and R 7 can be the same or different each being independently H or alkyl;
R 3 is H, alkyl, cycloalkyl, aralkyl, heteroaralkyl, aryl or heteroaryl;
or R 2 and R 3 taken together are —N(O-alkyl), ═N(OH), ═N—N(R 20 R 21 ) or ═CH(alkyl) provided that when one or both of X and Z is N, R 2 and R 3 together are not ═CH(alkyl);
R 8 is aryl, heteroaryl, fluorenyl; and diphenylmethyl, heteroaryl-N-oxide,
wherein each R 10 is the same or different and independently selected from —CH 3 or halogen, Y is N or N(→O) and each of said aryl, fluorenyl, diphenyl and heteroaryl is unsubstituted or optionally independently substituted with 1 to 4 substituents which substituents can be the same or different each being independently selected from the group consisting of R 11 , R 12 , R 13 , R 14 and R 15 ;
R 9 is H, alkyl, —CF 3 , cycloalkyl, —OH, —OCH 3 , —NH 2 , —N(H)C(O)N(H)alkyl, —NHS(O 2 )R 20 or —N(H)C(O)alkyl;
R 11 and R 12 can be the same or different and are each independently selected from the group consisting of alkyl, haloalkyl, halogen, —NR 18 R 19 , —OH, —CF 3 , —OCH 3 , —O-acyl and —OCF 3 ;
R 13 is selected from the group consisting of H, R 11 , aryl, —NO 2 , —CN, —CH 2 F, —CHF 2 , —C(O)H, —CH═NOR 18 , pyridyl-N-oxide, pyrimidinyl, pyrazinyl, —N(R 19 )CONR 19 R 20 , —N(H)C(O)N(H)(haloalkyl), —N(H)C(O)N(H)(cycloalkylalkyl), —N(H)C(O)alkyl, —N(H)C(O)CF 3 , —N(H)S(O 2 )N(alkyl) 2 , —N(H)S(O 2 )alkyl, —N(S(O 2 )CF 3 ) 2 , —N(H)CO)Oalkyl, cycloalkyl, —SR 21 , —S(O)R 21 , —S(O 2 )R 21 , —S(O 2 )N(H)(alkyl), —OS(O 2 )alkyl, —OS(O 2 )CF 3 , hydroxyalkyl, —C(O)NR 18 R 19 , —C(O)N(CH 2 CH 2 —O—CH 3 ) 2 , —OC(O)N(H)alkyl, —CO 2 R 18 , —Si(CH 3 ) 3 and —B(OC(CH 3 ) 2 ) 2 ;
R 14 is selected from the group consisting of alkyl, haloalkyl, NH 2 and R 15 -phenyl;
R 15 is 1 to 3 substituents selected from the group consisting of H, alkyl, haloalkyl, —CF 3 , —CO 2 R 19 , —CN, alkoxy and halogen; wherein said R 15 moieties can be the same or different each being independently selected when there are more than one R 15 present;
R 16 and R 17 can be the same or different each being independently selected from the group consisting of hydrogen and alkyl, or R 16 and R 17 together are an alkylene group and with the carbon to which they are attached form a spiro ring of 3 to 6 carbon atoms;
R 18 , R 19 and R 20 can each be the same or different and are each independently selected from the group consisting of H, alkyl, cycloalkyl, aryl and heteroaryl; and
R 21 is selected from the group consisting of alkyl, haloalkyl, hydroxyalkyl, alkylene, cycloalkyl, aryl and aralkyl; wherein each of said alkyl, alkylene, aryl, arylalkyl, aralkyl, alkoxy, hydroxyalkyl, heteroaryl, heteroaralkyl, cycloalkylalkyl and cycloalkyl in the definitions above can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, where said moieties are independently selected from the group consisting of —OH, alkoxy, —CN, halogen, —NR 18 R 19 , —C(O)NR 18 R 19 , —N(R 18 )C(O)R 19 , —N(R 18 )S(O 2 )R 19 , —S(O 2 )NR 18 R 19 , —C(O)OR 18 , OCF 3 , —CF 3 , —S(O 2 )R 18 and —C(O)R 18 .
13 . The method of claim 12 , wherein in structural formula I, R 1 and R 3 are as defined in the following table:
R 1
R 3
PMB
H
14 . The method of claim 12 , wherein the compound of structural Formula I is a compound represented by the structural formulae:
or a pharmaceutically acceptable salt or solvate thereof.
15 . The method of claim 12 , further comprising administering with said one or more compounds, one or more pharmaceutically acceptable carriers.
16 . The method of claim 15 , further comprising administering one or more additional agents useful in the treatment of said diseases.
17 . A kit comprising in separate containers in a single package pharmaceutical compositions for use in combination to treat Human Immunodeficiency Virus which comprises:
(a) in one container a pharmaceutical composition comprising one or more compounds_of structural formula I: or a pharmaceutically acceptable salt or solvate thereof; wherein: n is 0, 1, 2, 3 or 4; s is 0, 1, 2, 3 or 4; t is 1, 2, 3 or 4 with the provisos that i) when n is 0 and s is 2, then t is 1, 3 or 4; and ii) when n is 0 and t is 2, then s is 0, 1, 3 or 4; X is N; Z is N or CH; R 1 is H, alkyl, aralkyl, —S(O 2 )alkyl, —S(O 2 )aryl, —C(O)alkyl, —C(O)aryl, -alkyl-aryl-R 8 , -alkyl-heteroaryl-R 8 , —S(O 2 )cycloalkyl, —S(O 2 )-aryl-R 8 , —C(O)cycloalkyl, —C(O)-aryl-R 8 , —C(O)NR 20 R 21 or —S(O 2 )NR 20 R 24 ; R 2 , R 4 , R 5 , R 6 and R 7 can be the same or different each being independently H or alkyl; R 3 is H, alkyl, cycloalkyl, aralkyl, heteroaralkyl, aryl or heteroaryl; or R 2 and R 3 taken together are ═N(O-alkyl), —N(OH), ═N—N(R 20 R 21 ) or ═CH(alkyl) provided that when one or both of X and Z is N, R 2 and R 3 together are not ═CH(alkyl); R 8 is aryl, heteroaryl, fluorenyl; and diphenylmethyl, heteroaryl-N-oxide, wherein each R 10 is the same or different and independently selected from —CH 3 or halogen, Y is N or N(→O) and each of said aryl, fluorenyl, diphenyl and heteroaryl is unsubstituted or optionally independently substituted with 1 to 4 substituents which substituents can be the same or different each being independently selected from the group consisting of R 11 , R 12 , R 13 , R 14 and R 15 ; R 9 is H, alkyl, —CF 3 , cycloalkyl, —OH, —OCH 3 , —NH 2 , —N(H)C(O)N(H)alkyl, —NHS(O 2 )R 20 or —N(H)C(O)alkyl; R 11 and R 12 can be the same or different and are each independently selected from the group consisting of alkyl, haloalkyl, halogen, —NR 18 R 19 , —OH, —CF 3 , —OCH 3 , —O-acyl and —OCF 3 ; R 13 is selected from the group consisting of H, R 11 , aryl, —NO 2 , —CN, —CH 2 F, —CHF 2 , —C(O)H, —CH═NOR 18 , pyridyl-N-oxide, pyrimidinyl, pyrazinyl, —N(R 19 )CONR 19 R 20 , —N(H)C(O)N(H)(haloalkyl), —N(H)C(O)N(H)(cycloalkylalkyl), —N(H)C(O)alkyl, —N(H)C(O)CF 3 , —N(H)S(O 2 )N(alkyl) 2 , —N(H)S(O 2 )alkyl, —N(S(O 2 )CF 3 ) 2 , —N(H)C(O)Oalkyl, cycloalkyl, —SR 21 , —S(O)R 21 , —S(O 2 )R 21 , —S(O 2 )N(H)(alkyl), —OS(O 2 )alkyl, —OS(O 2 )CF 3 , hydroxyalkyl, —C(O)NR 18 R 19 , —C(O)N(CH 2 CH 2 —O—CH 3 ) 2 , —OC(O)N(H)alkyl, —CO 2 R 18 , —Si(CH 3 ) 3 and —B(OC(CH 3 ) 2 ) 2 ; R 14 is selected from the group consisting of alkyl, haloalkyl, NH 2 and R 15 -phenyl; R 15 is 1 to 3 substituents selected from the group consisting of H, alkyl, haloalkyl, —CF 3 , —CO 2 R 19 , —CN, alkoxy and halogen; wherein said R 15 moieties can be the same or different each being independently selected when there are more than one R 15 present; R 16 and R 17 can be the same or different each being independently selected from the group consisting of hydrogen and alkyl, or R 16 and R 17 together are an alkylene group and with the carbon to which they are attached form a spiro ring of 3 to 6 carbon atoms; R 18 , R 19 and R 20 can each be the same or different and are each independently selected from the group consisting of H, alkyl, cycloalkyl, aryl and heteroaryl; and R 21 is selected from the group consisting of alkyl, haloalkyl, hydroxyalkyl, alkylene, cycloalkyl, aryl and aralkyl; wherein each of said alkyl, alkylene, aryl, arylalkyl, aralkyl, alkoxy, hydroxyalkyl, heteroaryl, heteroaralkyl, cycloalkylalkyl and cycloalkyl in the definitions above can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, where said moieties are independently selected from the group consisting of —OH, alkoxy, —CN, halogen, —NR 18 R 19 , —CO)NR 18 R 19 , —N(R 18 )C(O)R 19 , —N(R 18 )S(O 2 )R 19 , —S(O 2 )NR 18 R 19 , —C(O)OR 18 , —OCF 3 , —CF 3 , —S(O 2 )R 18 and —C(O)R 18 in one or more pharmaceutically acceptable carriers; and (b) in a separate container, one or more pharmaceutical compositions comprising one or more antiviral or other agents useful in the treatment of Human Immunodeficiency Virus in one or more pharmaceutically acceptable carriers.
18 . The kit of claim 17 , wherein in structural formula I, R 1 and R 3 are as defined in the following table:
R 1
R 3
PMB
H
19 . The kit of claim 17 , wherein the compound of structural Formula I is a compound represented by the structural formulae:
or a pharmaceutically acceptable salt or solvate thereof.
20 . A process for making a pharmaceutical composition, comprising combining (a) at least one compound of structural formula I:
or a pharmaceutically acceptable salt or solvate thereof; wherein:
n is 0, 1, 2, 3 or 4;
s is 0, 1, 2, 3 or 4;
t is 1, 2, 3 or 4 with the provisos that
i) when n is 0 and s is 2, then t is 1, 3 or 4;
and
ii) when n is 0 and t is 2, then s is 0, 1, 3 or 4;
X is N;
Z is N or CH;
R 1 is H, alkyl, aralkyl, —S(O 2 )alkyl, —S(O 2 )aryl, —C(O)alkyl, —C(O)aryl, -alkyl-aryl-R 8 , -alkyl-heteroaryl-R 8 , —S(O 2 )cycloalkyl, —S(O 2 )-aryl-R 8 , —C(O)cycloalkyl, —C(O)-aryl-R 8 , —C(O)NR 20 R 21 or —S(O 2 )NR 20 R 21 ;
R 2 , R 4 , R 5 , R 6 and R 7 can be the same or different each being independently H or alkyl;
R 3 is H, alkyl, cycloalkyl, aralkyl, heteroaralkyl, aryl or heteroaryl;
or R 2 and R 3 taken together are ═N(O-alkyl), ═N(OH), ═N—N(R 20 R 21 ) or —CH(alkyl) provided that when one or both of X and Z is N, R 2 and R 3 together are not ═CH(alkyl);
R 8 is aryl, heteroaryl, fluorenyl; and diphenylmethyl, heteroaryl-N-oxide,
wherein each R 10 is the same or different and independently selected from —CH 3 or halogen, Y is N or N(→O) and each of said aryl, fluorenyl, diphenyl and heteroaryl is unsubstituted or optionally independently substituted with 1 to 4 substituents which substituents can be the same or different each being independently selected from the group consisting of R 11 , R 12 , R 13 , R 14 and R 15 ;
R 9 is H, alkyl, —CF 3 , cycloalkyl, —OH, —OCH 3 , —NH 2 , —N(H)C(O)N(H)alkyl, —NHS(O 2 )R 20 or —N(H)C(O)alkyl;
R 11 and R 12 can be the same or different and are each independently selected from the group consisting of alkyl, haloalkyl, halogen, —NR 18 R 19 , —OH, —CF 3 , —OCH 3 , —O-acyl and —OCF 3 ;
R 13 is selected from the group consisting of H, R 11 , aryl, —NO 2 , —CN, —CH 2 F, —CHF 2 , —C(O)H, —CH═NOR 18 , pyridyl-N-oxide, pyrimidinyl, pyrazinyl, —N(R 19 )CONR 19 R 20 , —N(H)C(O)N(H)(haloalkyl), —N(H)C(O)N(H)(cycloalkylalkyl), —N(H)C(O)alkyl, —N(H)C(O)CF 3 , —N(H)S(O 2 )N(alkyl) 2 , —N(H)S(O 2 )alkyl, —N(S(O 2 )CF 3 ) 2 , —N(H)C(O)Oalkyl, cycloalkyl, —SR 21 , —S(O)R 21 , —S(O 2 )R 21 , —S(O 2 )N(H)(alkyl), —OS(O 2 )alkyl, —OS(O 2 )CF 3 , hydroxyalkyl, —C(O)NR 18 R 19 , —C(O)N(CH 2 CH 2 —O—CH 3 ) 2 , —OC(O)N(H)alkyl, —CO 2 R 18 , —Si(CH 3 ) 3 and —B(OC(CH 3 ) 2 ) 2 ;
R 14 is selected from the group consisting of alkyl, haloalkyl, NH 2 and R 15 -phenyl;
R 15 is 1 to 3 substituents selected from the group consisting of H, alkyl, haloalkyl, —CF 3 , —CO 2 R 19 , —CN, alkoxy and halogen; wherein said R 15 moieties can be the same or different each being independently selected when there are more than one R 15 present;
R 16 and R 17 can be the same or different each being independently selected from the group consisting of hydrogen and alkyl, or R 16 and R 17 together are an alkylene group and with the carbon to which they are attached form a spiro ring of 3 to 6 carbon atoms;
R 18 , R 19 and R 20 can each be the same or different and are each independently selected from the group consisting of H, alkyl, cycloalkyl, aryl and heteroaryl; and
R 21 is selected from the group consisting at alkyl, haloalkyl, hydroxyalkyl, alkylene, cycloalkyl, aryl and aralkyl; wherein each of said alkyl, alkylene, aryl, arylalkyl, aralkyl, alkoxy, hydroxyalkyl, heteroaryl, heteroaralkyl, cycloalkylalkyl and cycloalkyl in the definitions above can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, where said moieties are independently selected from the group consisting of —OH, alkoxy, —CN, halogen, —NR 18 R 19 , —C(O)NR 18 R 19 , —N(R 18 )C(O)R 19 , —N(R 18 )S(O 2 )R 19 , —S(O 2 )NR 18 R 19 , —C(O)OR 18 , —OCF 3 —CF 3 , —S(O 2 )R 18 and —C(O)R 18 ; and
(b) at least one pharmaceutically acceptable carrier.Cited by (0)
No later patents cite this yet.
References (0)
No backward citations on record.