US2003220315A1PendingUtilityA1
Alkenyldiarylmethane non-nucleoside HIV-1 reverse transcriptase inhibitors
Priority: Jan 16, 1998Filed: May 27, 2003Published: Nov 27, 2003
Est. expiryJan 16, 2018(expired)· nominal 20-yr term from priority
A61P 31/12C07D 263/32C07C 317/46C07C 323/16A61P 31/18C07C 323/62C07C 69/94A61P 43/00C07C 65/28
47
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Claims
Abstract
Alkenyldiarylmethane (ADAM) compounds have been found effective as anti-HIV agents. Novel ADAM compounds, their pharmaceutical formulations and a method of using same to treat viral infections are described.
Claims
exact text as granted — not AI-modified1 . A compound of the formula:
wherein X is selected from the group consisting of
wherein R 1 and R 6 are H or halo;
R 2 and R 5 are independently OR 11 ;
R 3 and R 4 are CO 2 R 12 or Z; or
R 2 and R 3 taken together with the carbon atoms (C 2 , C 3 ) to which they are attached and R 4 and R 5 taken together with the carbon atoms (C 4 , C 5 ) to Which they are attached form a 5- or 6-membered ring of the formula
wherein Q is O, S, or Se;
R 1 is C 1 -C 4 alkyl,
B is —OR 1 or ═O, and
r is 1 or 0;
provided that when B is ═O, r is 1, and bond a is a single bond, and when B is —OR 1 , r is 0 and bond a is a double bond;
R 8 is selected from the group consisting of (CH 2 ) m OR 13 , (CH 2 ) m N 3 , (CH 2 ) m COOR 14 , (CH 2 ) m Z, and (CH 2 ) m NH 2 ;
R 9 and R 10 are independently selected from the group consisting of H (C 1 -C 5 ) alkyl, (CH 2 ) n OR 13 , (CH 2 ) n N 3 , (CH 2 ) n COOR 14 , (CH 2 ) m Z and (CH 2 ) n NH 2 ;
R 11 , R 12 , R 13 and R 14 are independently selected from the group consisting of H and (C 1 -C 5 ) alkyl; m is 1-4; n is 0-4; and Z is selected from the following substituent groups:
with the proviso that when X is
R 8 is not (CH 2 ) 2 OH.
2 . The compound of claim 1 wherein X is
R 1 and R 6 are independently Br or Cl;
R 2 and R 5 are each OCH 3 ; and
R 3 and R 4 are each CO 2 CH 3 .
3 . The compound of claim 2 wherein R 8 is (CH 2 ) m N 3 or (CH 2 ) m COOR 14 .
4 . The compound of claim wherein R 8 is (CH 2 ) m Z.
5 . The compound of claim 1 wherein R 2 and R 3 taken together with the carbon atoms to which they are attached, and R 4 and R 5 taken together with the carbon atoms to which they are attached each form a 5- or 6-membered ring.
6 . A compound of the formula:
wherein X is selected from the group consisting of
wherein R 2 and R 5 are independently OR 11 ;
R 3 and R 4 are independently CO 2 R 12 or Z; or
R 2 and R 3 taken together with the carbon atoms (C 2 , C 3 ) to which they are attached and R 4 and R 5 taken together with the carbon atoms (C 4 , C 5 ) to which they are attached form a 5- or 6-membered ring of the formula
wherein Q is O, S, or Se;
R 1 is C 1 -C 4 alkyl, B is —OR 1 or ═O, and r is 1 or 0;
provided that when B is ═O, r is 1, and bond a is a single bond, and when B is —OR 1 , r is 0 and bond a is a double bond;
R 7 and R 8 are independently selected from the group consisting of H, (C 1 -C 4 ) alky, (CH 2 ) m OR 13 , (CH 2 ) m N 3 , (CH 2 ) m COOR 14 , (CH 2 ) m Z, and (CH 2 ) m NH 2 ;
R 9 and R 10 are independently selected from the group consisting of H, (C 1 -C 5 ) alkyl, (CH 2 ) n OR 13 , (CH 2 ) n N 3 , (CH 2 ) n COOR 14 , (CH 2 ) m Z and (CH 2 ) n NH 2 ;
R 11 , R 12 , R 13 and R 14 are independently selected from the group consisting of H and (C 1 -C 5 ) alkyl; m is 1-3; n is 0-4; and Z is selected from the following substituent groups:
7 . The compound of claim 6 wherein X is
R 2 and R 5 are each OCH 3 ; and
R 3 and R 4 are each CO 2 CH 3 .
8 . The compound of claim 7 wherein R 8 is (CH 2 ) m OR 13 , (CH 2 ) m N 3 , (CH 2 ) m Z, or (CH 2 ) m COOR 14 .
9 . The compound of claim 6 wherein R 2 and R 3 taken together with the carbon atoms to which they are attached, and R 4 and R 5 taken together with the carbon atoms to which they are attached each form a 5- or 6-membered ring.
10 . A composition comprising a reverse transcriptase inhibitory effective amount of a compound of the formula:
wherein X is selected from the group consisting of
wherein R 1 and R 6 are H or halo;
R 2 and R 5 are independently OR 11 ;
R 3 and R 4 are CO 2 R 12 or Z; or
R 2 and R 3 taken together with the carbon atoms (C 2 , C 3 ) to which they are attached and R 4 and R 5 taken together with the carbon atoms (C 4 , C 5 ) to which they are attached form a 5- or 6-membered ring of the formula
wherein Q is O, S, or Se;
R 1 is C 1 -C 4 alkyl, B is —OR 1 or ═O, and r is 1 or 0;
provided that when B is ═O, r is 1, and bond a is a single bond, and when B is —OR 1 , r is 0 and bond a is a double bond;
R 8 is selected from the group consisting of (CH 2 ) m OR 13 , (CH 2 ) m N 3 , (CH 2 ) m COOR 14 , (CH 2 ) m Z, and (CH 2 ) m NH 2 ;
R 9 and R 10 are independently selected from the group consisting of H, (C 1 -C 5 ) alkyl, (CH 2 ) n OR 13 , (CH 2 ) n N 3 , (CH 2 ) n COOR 14 , (CH 2 ) m Z and (CH 2 ) n NH 2 ;
R 11 , R 12 , R 13 and R 14 are independently selected from the group consisting of H and (C 1 -C 5 ) alkyl; m is 1-4; n is 0-4; and Z is selected from the following substituent groups:
with the proviso that when X is
R 8 is not (CH 2 ) 2 OH, and
a pharmaceutically acceptable carrier.
11 . The composition of claim 10 wherein X is
R 1 and R 6 are Br or Cl, R 2 and R 5 are each OCH 3 , R 3 and R 4 are each CO 2 CH 3 and R 8 is (CH 2 ) n OH, (CH 2 ) n COOCH 3 , (CH 2 ) m Z or (CH 2 ) n N 3 .
12 . A method of treating a warm-blooded vertebrate suffering from a disease of viral origin, said method comprising the step-of administering to said vertebrate a therapeutically effective amount of an antiviral composition comprising a compound of the formula:
wherein X is selected from the group consisting of
wherein R 1 and R 6 are H or halo;
R 2 and R 5 are independently OR 11 ;
R 3 and R 4 are CO 2 R 12 or Z; or
R 2 and R 3 taken together with the carbon atoms (C 2 , C 3 ) to which they are attached and R 4 and R 5 taken together with the carbon atoms (C 4 , C 5 ) to which they are attached form a 5- or 6-membered ring of the formula
wherein Q is O, S, or Se;
R 1 is C 1 -C 4 alkyl, B is —OR 1 or ═O, and r is 1 or 0;
provided that when B is ═O, r is 1, and bond a is a single bond, and when B is —OR 1 , r is 0 and bond a is a double bond;
R 8 is selected from the group consisting of (CH 2 ) m OR 13 , (CH 2 ) m N 3 , (CH 2 ) m COOR 14 , (CH 2 ) m Z, and (CH 2 ) m NH 2 ;
R 9 and R 10 are independently selected from the group consisting of H, (C 1 -C 5 ) alkyl, (CH 2 ) n OR 13 , (CH 2 ) n N 3 , (CH 2 ) n COOR 14 , (CH 2 ) m Z and (CH 2 ) n NH 2 ;
R 11 , R 12 , R 13 and R 14 are independently selected from the group consisting of H and (C 1 -C 5 ) alkyl m is 1-4; n is 0-4; and Z is selected from the following substituent groups:
and a pharmaceutically acceptable carrier.
13 . The method of claim 12 wherein X is
R 1 and R 2 are Br and Cl;
R 2 and R 5 are each OCH 3 ; and
R 3 and R 4 are each CO 2 CH 3 .
14 . The method of claim 12 wherein R 8 is (CH 2 ) m OR 13 , (CH 2 ) m N 3 , (CH 2 ) m Z, or (CH 2 ) m COOR 14 .
15 . A compound of the formula
wherein X is Cl or Br; and R 3 and R 4 are COOR 1 or Z.Join the waitlist — get patent alerts
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