Patent ID: 6730707
Filing Date: 2004-05-04
Classification: A61K,A61P

Abstract:
A method of reducing intraocular pressure in a subject in need thereof, said method comprising:administering to said subject an indole derivative in an amount effective to reduce intraocular pressure, wherein said indole derivative is a compound of Formula I: wherein:n=0, 1, 2, 3, 4, or 5; m=0 or 1; R1 and R2 are each independently H, substituted or unsubstituted linear-, branched- or cyclo-alkyl, -alkenyl, -alkynyl, -aryl, -aralkyl, -aralkenyl, -aralkynyl, R6(CO)â€”, F, OR5, or either R1 or R2 is R6R7N(CO)â€”; or R1 and R2 when taken together is oxo; or a substituted or unsubstituted carbocycle, or heterocycle of 4, 5, 6, or 7 members; R3 and R4 are each independently H, substituted or unsubstituted linear-, branched- or cyclo-alkyl, -alkenyl, -alkynyl, -aryl, -aralkyl, -aralkenyl, -aralkynyl, R6(CO)-, or R3 and R4 when taken together is oxo; or a substituted or unsubstituted carbocycle or a heterocycle of 4, 5, 6, or 7 members; or R2 and R4 when taken together represent a substituted or unsubstituted carbocycle or heterocycle of 4, 5, 6, or 7 members; A=, NO2, CN or R5â€”X1â€”; B=halogen, NO2, CN, H, or R5-X1-; when B is not equal to halogen, NO2, CN or H, then B taken together with R1 represent a substituted or unsubstituted carbocyclic or heterocyclic ring of 5, 6, or 7 members; when B is not equal to halogen, NO2, CN or H, and when B is in position 7 of the indole, then B optionally taken together with E represent a substituted or unsubstituted heterocyclic ring of 5, 6, or 7 members; X1=O, S, NR9, â€”CF2â€”, â€”CH2â€”, â€”CH2CH2-, -CH2CH2CH2-, or absent; R5=H, substituted or unsubstituted linear-, branched- or cyclo-alkyl, -alkenyl, -alkynyl, -aryl, -aralkyl, -aralkenyl, -aralkynyl, R6R7N(CO)â€”, R6(CO)â€”, R8O(CO)â€”, R8S(O)2â€”, R8S(O)â€”, R8OS(O)2â€”, R8S(O)â€”, R6R7NS(O)2â€”, R6R7NP(O)(OR9)â€”, R8P(O)(OR9)â€”, (R8O)P(O)(OR9)â€”, or CF3â€”; provided that when E=H, D1=R5â€”X1 and X1=O, or â€”CH2â€”, or â€”CH2CH2â€”, orâ€”CH2CH2CH2â€”, then R5 is not H, or aryl; R6 and R7 are independently H, substituted or unsubstituted linear-, branched- or cyclo-alkyl, -alkenyl, -alkynyl, -aryl, -aralkyl, -aralkenyl, -aralkynyl or heterocyclic ring; when taken together, NR6R7 represent a substituted or unsubstituted ring of 3, 4, 5, 6, or 7 members; R8=substituted or unsubstituted linear-, branched- or cyclo-alkyl, -alkenyl, -alkynyl, aryl, -aralkyl, -aralkenyl, -aralkynyl, heterocyclic ring or CF3â€”; R9=H, substituted or unsubstituted linear-, branched- or cyclo-alkyl, -alkenyl, -alkynyl, aryl, -aralkyl, -aralkenyl, -aralkynyl; when taken together, R6 and R9 represent a ring of 5, 6, or 7 members; when B is in position 4 of the indole, B and Z1 taken together represent a substituted or unsubstituted heterocyclic ring of 5, 6, or 7 members; when B is in position 4 of the indole B and R1 taken together) represent a substituted or unsubstituted carbocyclic or heterocyclic ring of 5, 6, or 7 members; E=H, substituted or unsubstituted linear-, branched- or cyclo-alkyl, -alkenyl, -alkynyl, aryl, -aralkyl, -aralkenyl, -aralkynyl, R8O(CO)â€”, R8S(O)2â€”, or OR6; or E=R6(CO)â€”, provided that when Z1=NR10R11, one of R10 or R11 is H; or E=R6(CO)â€”, provided that when Z1=OR5, R5 is not H, alkyl, aryl, or aralkyl; or E=R6R7N(CO)â€”, provided that when Z1=NR10R11, one of R10 or R11 is H; or E=R6R7N(CO)â€”, provided that when Z1=OR5, R5 is not H, alkyl, aryl, or aralkyl; D1=halogen, NO2, CN or R5â€”X1â€”; D1 and E when taken together represent a substituted or unsubstituted heterocyclic ring of 4, 5, 6, or 7 members; D1 and R1 when taken together represent a substituted or unsubstituted carbocyclic or heterocyclic ring of 5, 6, or 7 members; D1 and R3 when taken together represent a substituted or unsubstituted carbocyclic or heterocyclic ring of 5, 6, or 7 members; D1 and Z1 when taken together represent a substituted or unsubstituted heterocyclic ring of 5, 6, or 7 members; Z1=OR5 or NR10R11; Z1 and R1 when taken together represent a substituted or unsubstituted heterocycle of 4, 5, 6, or 7 members; R10=H, substituted or unsubstituted linear-, branched- or cyclo-alkyl, -alkenyl, -alkynyl, aryl, -aralkyl, -aralkenyl, -aralkynyl, heterocycle, R6R7N(CO)â€”, R6(CO)â€”, R8O(CO)â€”, R8S(O)2â€”, R8OS(O)2â€”, R6R7NS(O)2â€”, CF3â€”; and R11=NR6R7(CO)â€”, R6(CO)â€”, R8O(CO)â€”, R8S(O)2â€”, R8OS(O)2â€”, R6R7NS(O)2â€”; alternatively, D1 and R6 are absent and the carbonyl participates in a ring bridging the two positions; provided that when n=0, m=1, R5=CH3, X1=O, B=D1=E=R3=R4=H, then Z is not â€”NHAc.