Phenylindoles for the treatment of HIV

Abstract

The invention as disclosed herein is a method and composition for the treatment of HIV in humans and other host animals, that includes the administration of an effective HIV treatment amount of a phenylindole as described herein or a pharmaceutically acceptable salt or prodrug thereof, optionally in a pharmaceutically acceptable carrier. The compounds of this invention either possess antiviral (i.e., anti-HIV) activity, or are metabolized to a compound that exhibits such activity.

1 . A compound of the formula (I):  
     
       
         
         
             
             
         
       
     
     or its pharmaceutically acceptable salt thereof, wherein 
 (a) R 1  is hydrogen; acyl; —C(═O)H; —C(═W)H; —C(═O)R 2 ; —C(═W)R 2 ; —C(═O)OH; —C(═W)OH; —C(═O)OR 2 ; —C(═W)OR 2 ; —C(═O)SH; —C(═W)SH; —C(═O)SR 2 ; —C(═W)SR 2 ; —C(═O)NH 2 ; —C(═W)NH 2 ; —C(═O)NHR 2 ; —C(═W)NHR 2 ; —C(═O)NR 2 R 3 ; —C(═W)NR 2 R 3 ; —C(═W)NH—(CH 2 ) p -(amino acid) or —(CH 2 ) p -(amino acid);  
 (b) R 4′ , R 5′ , R 6′ , R 7′ , R 2″ , R 3″ , R 4″ , R 5″  and R 6″  are each independently H; halo (F, Cl, Br or I); —NO 2 ; —CN; —OH; —OR 2 ; —SH; —SR 2 ; —NH 2 ; —NHR 2 ; —NR 2 R 3 ; —NHSO 2 —C 1-3 alkyl; —NR 2 SO 2 —C 1-3 alkyl; —NHCO—C 1-3 alkyl; —NR 2 CO—C 1-3 alkyl; optionally substituted or unsubstituted branched or unbranched alkyl, alkenyl or alkynyl (such as an optionally substituted or unsubstituted branched or unbranched C 1-6 alkyl, C 2-6 alkenyl or C 2-6 alkynyl, and in particular CH 3 , CF 3 , vinyl bromide, —CR 2 R 2 —S(O) n —R 3 , —CR 2 R 2 NH 2 , —CR 2 R 2 NHR 2 , —CR 2 R 2 NR 2 R 3  and —CR 2 R 2 —C(═O)R 2 ); alkacyl; optionally substituted or unsubstituted acyl; —C(═O)H; —C(═W)H; —C(═O)R 2 ; —C(═W)R 2 ; —C(═O)OH; —C(═W)OH; —C(═O)OR 2 ; —C(═W)OR 2 ; —C(═O)—SH; —C(═W)SH; —C(═O)SR 2 ; —C(═W)SR 2 ; —C(═O)NH 2 ; —C(═W)NH 2 ; —C(═O)NHR 2 ; —C(═W)NHR 2 ; —C(═O)NR 2 R 3 ; —C(═W)—NR 2 R 3 , —C(═W)NH(CH 2 ) p -(amino acid), a residue of an amino acid or —(CH 2 ) p (amino acid); wherein if R 5′  is hydrogen, F, Cl, Br, —NO 2 , —CN, —OR 2 , —NR 2 R 2 , —NHSO 2 —C 1-3 alkyl or —NHCO—C 1-3 alkyl, then at least one of R 4′ , R 6′  and R 7′  is not hydrogen or alternatively, wherein at least two of R 4′ , R 5′ , R 6′ , R 7′  are not hydrogen.  
 (c) Z is optionally substituted or unsubstituted acyl, —C(═O)NH 2 ; —C(═W)—NH 2 ; —C(═O)NHR 2 ; —C(═W)NHR 2 ; —C(═O)NR 2 R 3 ; —C(═W)NR 2 R 3 ; —C(═W)NH(CH 2 ) p -(amino acid); a residue of an amino acid, —(CH 2 ) p -(amino acid); —C(═O)R 3 ; —C(═O)H; —C(═W)H; —C(═O)R 2 ; —C(═W)R 2 ; —C(═O)OR 3 ; —C(═O)OH; —C(═W)OH; —C(═O)OR 2 ; —C(═W)—OR 2 ; —C(═O)—SH; —C(═W)SH; —C(═O)SR 2 ; —C(═W)SR 2 ; optionally substituted or unsubstituted branched or unbranched alkyl, alkenyl or alkynyl (such as an optionally substituted or unsubstituted branched or unbranched C 1-6 alkyl, C 2-6 alkenyl or C 2-6 alkynyl, and in particular CH 3 , CF 3 , vinyl bromide, —CR 2 R 2 —S(O) n —R 3 , —CR 2 R 2 NH 2 , —CR 2 R 2 NHR 2 , —CR 2 R 2 NR 2 R 3  and —CR 2 R 2 —C(═O)R 2 ); —CN, or halo (F, Cl, Br or I);  
 (d) Y is O, S or S(O) n ;  
 (e) each W is independently O, S, —NH 2 , —NHR 2 , —NR 2 R 2 , —N—CN, —N—NH 2 , —N—NHR 2 , —N—NR 2 R 2 , —N—OH or —N—OR 2 ;  
 (f) each R 2  is independently hydrogen or an optionally substituted or unsubstituted branched or unbranched lower alkyl, alkenyl or alkynyl (such as an optionally substituted or unsubstituted branched or unbranched C 1-3 alkyl, C 2-4 alkenyl or C 2-4 alkynyl, and in particular CH 3 , CF 3 , vinyl bromide, —CR 2 R 2 —S(O) n —R 3 , —CR 2 R 2 NH 2 , —CR 2 R 2 NHR 2 , —CR 2 R 2 NR 2 R 3  and —CR 2 R 2 —C(═O)R 2 );  
 (g) each R 3  is independently hydrogen; optionally substituted or unsubstituted branched or unbranched alkyl, alkenyl or alkynyl (such as an optionally substituted or unsubstituted branched or unbranched C 1-6 alkyl, C 2-6 alkenyl or C 2-6 alkynyl, and in particular CH 3 , CF 3 , vinyl bromide, —CR 2 R 2 —S(O) n —R 3 , —CR 2 R 2 NH 2 , —CR 2 R 2 NHR 2 , —CR 2 R 2 NR 2 R 3  and —CR 2 R 2 —C(═O)R 2 ); optionally substituted or unsubstituted aryl (such as phenyl); optionally substituted or unsubstituted heterocycle; optionally substituted or unsubstituted alkylaryl, optionally substituted or unsubstituted alkylheterocycle, optionally substituted or unsubstituted aralkyl, optionally substituted or unsubstituted heterocycle-alkyl;  
 (h) each n is independently 0, 1 or 2;  
 (i) each p is independently 0, 1, 2, 3, 4 or 5; and  
 (j) wherein if one or more of the optionally substituted branched or unbranched alkyl, alkenyl, alkynyl, lower alkyl, lower alkenyl or lower alkynyl; acyl; aryl; heterocycle; alkaryl; alkheterocycle; arylalkyl or alkylheterocycle substitutents is substituted, then preferably it is substituted with one or more of halogen (F, Cl, Br or I), —OH, —OR 2 , —SH, —SR 2 , oxime, hydrazine, —C(═O)H, —C(═W)H, —C(═O)R 2 , —C(═W)R 2 , —C(═O)OH, —C(═W)OH, —C(═O)OR 2 , —C(═W)OR 2 , —C(═O)SH, —C(═W)SH, —C(═O)SR 2 , —C(═W)SR 2 , —C(═O)NH 2 , —C(═W)NH 2 , —C(═O)—NHR 2 , —C(═W)NHR 2 , —C(═O)NR 2 R 3 , —C(═W)—NR 2 R 3 , —NH 2 , —NHR 2 , —NR 2 R 3 , —NHSO 2 —C 1-3 alkyl, —NR 2 SO 2 —C 1-3 alkyl, —NHCO—C 1-3 alkyl, —NR 2 CO—C 1-3 alkyl, —S(O) n —R 3 , C 1-3  alkoxy, C 1-3 thioether, a residue of an amino acid such as —NH(CH 2 ) p -(amino acid) or —C(═W)NH(CH 2 ) p -(amino acid.  
 
   
   
       2 - 29 . (canceled)