Substituted aminophenyl compounds and acylaminophenyl compounds and pharmaceutical compositions containing them

Claim 2

A compound of Formula I: wherein R 1 is H, C 1 -C 5 linear or branched alkyl, loweralkenyl, -(CH 2 ) m COOR 6 , -(CH2)n-cycloloweralkyl, or -(CH 2 ) m NR 4 R 5 ; R 2 is H, loweralkyl, substituted or unsubstituted phenyl (wherein the substitutents may be 1 or 2 of halo, loweralkyl, loweralkoxy, carboxyl, carboxyloweralkyl, nitro, -CF 3 , or hydroxy), - (CH 2 ) m SCH 3 , -(CH 2 ) m SOCH 3 , -(CH 2 ) m SO 2 CH 3 , or -(CH 2 ) n COOR 6 ; R 3 is R 4 and R 5 are independently H, loweralkyl, or cycloloweralkyl; R 6 is H , loweralkyl, cycloloweralkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted phenylloweralkyl (wherein the substituents may be 1 or 2 of halo, loweralkyl, loweralkoxy, nitro, or CF3 ); R 7 and R 7a are independently a- or β-naphthyl, loweralkyl, substituted or unsubstituted phenyl (wherein the substituents may be 1 to 2 of halo, -NO 2 , -OH, -NR 4 R 5 , loweralkyl, or loweralkoxy), (with the proviso that q is not 1 in -(CH 2 ) n NH(CH 2 ) q R 7 and that q is not 0 in when R 7 is R 8 is H, loweralkyl, cycloloweralkyl, R 10 is H, -OH, or -CH 3 ; R 11 and R 12 are independently loweralkyl or ' cycloloweralkyl; R 13 is H, or R 14 is l oweralkyl or phenylloweralkyl; R 16 is H , loweralkyl, OR 11 , or R17 is A 1 A 2 A 3 -, A 1 A 3 -, or A 1 -; where A 1 is H, Boc, Cbz, or acetyl; A 2 is Tyr, Tyr-O-sulfate or phenyl; A3 is Met, nor-Leu, or nor-Val; m is 1-4; n is 0-4; q is 0-4; r is 1 or 2; X 1 is H, -NO 2 , CF 3 CN, OH, loweralkyl, halo, loweralkylthio, loweralkoxy, -(CH 2 ) n COOR 6 , or -NR 4 R 5 ; X 2 and X 3 are independently H, -OH,-NO 2 , halo, loweralkylthio, loweralkyl, or loweralkoxy; X 4 is S, O, or NR 8 ; X 5 is H, CF 3 , CN, COOR 6 , N0 2 , or halo; X 6 is 0 or HH; X 7 is O, or HH; X 8 is and salts and quaternary ammonium salts of the compounds of formula I.

Claim 3

A compound of claim 1 wherein in formula I R 1 is H, loweralkyl, or -(CH 2 ) m COOR 6 ; R 2 is substituted or unsubstituted phenyl (wherein the substitutents may be 1 or 2 of halo, loweralkyl, loweralkoxy, carboxyl, carboxyloweralkyl, nitro, -CF 3 , or hydroxy), or -(CH 2 ) n COOR 6 ; R 3 is -(CH 2 ) n R 7 ; R 6 is H , loweralkyl, cycloloweralkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted phenylloweralkyl (wherein the substituents may be 1 or 2 of halo, loweralkyl, loweralkoxy, nitro, or CF3); R 7 is a- or β-naphthyl, loweralkyl, substituted or unsubstituted phenyl (wherein the substituents may be 1 to 2 of halo, -NO 2 , -OH, -NR 4 R 5 , loweralkyl, or loweralkoxy), R 8 is H or loweralkyl; R 4 and R 5 are independently hydrogen, loweralkyl or cycloloweralkyl; R 10 is hydrogen; R 13 is R 16 is OR 11 , or R 11 is loweralkyl; R 17 is A 1 A 2 A 3 -, A 1 A 3 -, or A l -; where A 1 is H, Boc, Cbz, or acetyl; A 2 is Tyr, Tyr-O-sulfate or phenyl; A3 is Met, nor-Leu, or nor-Val; m is 1-4; n is 0-4; r is 1 or 2; X 1 is H, -NO 2 , CF 3 CN, or halo; X 2 and X 3 are independently H, -OH,-NO 2 , halo, loweralkyl, or loweralkoxy; X 4 is S, 0, or NR 8 ; X 5 is H, CF 3 , CN, COOR 6 , or halo; X 6 is 0 or HH; X 7 is O, or HH; X 8 is C=O; and salts and quaternary ammonium salts of the compounds of formula I.

Claim 4

A compound of claim 1 or 2 having the formula I wherein R 1 is H, methyl, ethyl, or -(CH 2 ) 1-2 COOR 6 ; R 2 is substituted or unsubstituted phenyl (wherein the substitutents may be 1 or 2 of halo, or carboxyl), or-(CH 2 ) 1-2 COOR 6 ; R 3 is -(CH 2 ) n R 7 ; R 6 is H or loweralkyl; R 7 is a- or β-naphthyl, loweralkyl, unsubstituted phenyl, R 8 is H, methyl, or ethyl; R 10 is H; R 13 is H, or R 16 is m is 1-4; n is 0-4; r is 1 or 2; X 1 is H, -NO 2 , CF 3 CN, or halo; X 2 and X 3 are independently H, -OH, -NO 2 , or halo; X 5 is H or halo; X 7 is 0 or HH; X 8 is C=0; and salts and quaternary ammonium salts of the compounds of formula I.

Claim 5

A compound according to one of the claims 1 - 3, having the formula I wherein R 1 is H , methyl, ethyl, or -(CH 2 ) 1-2 COOH ; R 2 is phenyl, o-fluorophenyl, p-chlorophenyl, o-carboxyphenyl, 2,6-difluorophenyl, -CH 2 COOEt, or -CH 2 COO-t-Bu; R 3 is -(CH 2 ) n R 7 ; R 7 is a- or β-naphthyl, R 10 is H; R 13 is H , or R 16 is m is 1-4; n is 0-4; q is 0-4; r is 1; X 1 is H, 4-chloro, 4-fluoro, or 4-nitro; X 2 and X 3 are independently H , - OH , fluoro, or bromo; X 7 is 0; X 8 is C=O; and salts and quaternary ammonium salts of the compounds of formula I.

Claim 6

A compound according to one of the claims 1 - 4 having the formula I, which is 2- N -( N a- B oc-D-tryptophanyl)amino-5-chlorobenzophenone; 2-N-(N-a-Boc-L-tryptophanyl)amino-5-chlorobenzo phenone; 2-N-(N α -Boc-L-tryptophanyl)amino-2'-fluorobenzo phenone; 2- N -( N a -Boc-D-tryptophanyl)amino-2'-fluorobenzo phenone; 2- N -( N a- B oc-L-tryptophanyl)aminobenzophenone; 2-N-(N α -Boc-D-tryptophanyl)aminobenzophenone ; 2-N-(N α- Boc-DL-1-naphthylalanyl)aminobenzophenone ; 2-2 N -(N a- B oc-DL-2-naphthylalanyl)aminobenzophenone; 2-N-[[2(RS)-2-Bocamino-2-(3-thienyl)]acetyl]amino-2'-fluorobenzophenone; 2-N-[[2(RS)-2-(3-thienoylamino)-2-(3-thienyl)]acetyl]-amino-2'-fluorobenzophenone; 2-N-(N α -Boc-DL-β-(2-thienyl)alanyl)amino-2'-fluorobenzophenone; 2-N-(N α -3-Thienoyl-DL-β-(2-thienyl)alanyl)amino 2'-fluorobenzophenone; 2-N-[3-(3'indolyl)propanoyl]amino-5-chlorobenzophenone; 2- N -(N a- p-Chlorobenzoyl-L-tryptophanyl)aminobenzophenone; 2-N-(N α -acetyl-L-tryptophanyl)aminobenzophenone; 2- N -( N a- 3-thienoyl-L-tryptophanyl)aminobenzophenone; 2- N -( N a- B oc-glycyl-L-tryptophanyl)aminobenzophenone; 2- N -(N a- Boc-L-methionyl-glycyl-L-tryptophanyl)aminobenzophenone; 2- N -(N a- Benzyloxycarbonyl-L-tryosyl-L-methionyl- glycyl-L-tryptophanyl)aminobenzophenone; 2- N -( N a- 3-thienoyl-L-tryptophanyl)amino-5-chlorobenzophenone; 2-N-[2(S)-[2-(3'a-2',3'-dihydroindolyl)methyl-2-(3- thienoylamino)]acetyl]amino-5-chlorobenzophenone; 2-N-[2(S)-[2-(3'β-2',3'-dihydroindolyl)methyl-2-(3- thienoylamino)]acetyl]amino-5-chlorobenzophenone; 2-N-[2-(S)-[2-[3α'-1'-(Boc-L-leucyl)-2',3'-dihydro- indolyl]methyl-2-(3-thienoylamino)]acetyl]amino-5-chlorobenzophenone; 2-N-[2(S)-[2-[3'β-1'-(Boc-L-leucyl)-2',3'-dihydro- indolyl]methyl-2-(3-thienoylamino)]acetyl]amino-5-chlorobenzophenone; 2-N-[2(S)-[2-[3'α-1'-(Boc-D-leucyl)-2',3'-dihydro- indolyl]methyl-2-(3-thienoylamino)]acetyl]amino-5-chlorobenzophenone; 2-N-[2(S)-[2-[3'β-1'-(Boc-D-leucyl)-2',3'-dihydro- indolyl]methyl-2-(3-thienoylamino)]acetyl]amino-5-chlorobenzophenone; 2-N-[3-(3'-indolyl)propanoyl]amino-5-chlorobenzophenone; 1-( N a- B oc-L-tryptophanylamino)-2-(N-phenylamino) benzene.

Claim 7

A pharmaceutical composition useful for treating gastrointestinal disorders, central nervous system disorders, or regulating appetite in mammals, characterized in that it contains as-pharmaceutically effective component at least one compound of formula I according to claim 1 or a pharmaceutically acceptable salt of the compounds of formula I or a quaternary ammonium salt of the compounds of formula I.

Claim 8

A pharmaceutical composition according to claim 6 characterized in that it contains as pharmaceutically active ingredient at least one compound of formula I according to claim 2 or a pharmaceutically acceptable salt of said compounds of formula I or an ammonium salt of said compounds of formula I.

Claim 9

A pharmaceutical composition according to claim 6 or 7 characterized in that it contains as active ingredient at least one compound of formula I according to claim 3 or 4, or a pharmaceutically acceptable salt or quaternary ammonium salt of said compound of formula I.

Claim 10

Pharmaceutical composition according to one of the patent claims 6 - 8, characterized in that it contains as pharmaceutically active ingredient at least one compound of formula I according to claim 5 or a pharmaceutically acceptable salt or quaternary ammonium salt of said compound of formula I.

Claim 11

Pharmaceutical composition according to one of the patent claims 6 - 9, characterized in that it contains as further component a pharmaceutically acceptable carrier.