Claims
- 1. A compound of the formula I in which substituents R2 and R3 are arranged in cis-configuration: wherein:R2 is phenyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of OH, halogen, nitro, cyano, SH, SR4, trihalo-C1-C6-alkyl, C1-C6-alkyl, C1-C6-alkoxy and phenyl; R3 is: (a) phenyl substituted with —X—(CH2)n—Y, wherein: X is a valency bond, O or S, n is an integer in the range of 1 to 12, Y is H, halogen, OH, OR4, NHCOR4, NHSO2R4, CONHR4, CONR24, COOH, COOR4, SO2R4, SOR4, SONHR4, SONR2, a C3-C7 heterocyclic ring, saturated or unsaturated, containing one or two heteroatoms independently selected from the group consisting of O, S and N, optionally being substituted with 1 to 3 substituents independently selected from the group consisting of H, OH, halogen, nitro, cyano, SH, SR4, trihalo-C1-C6-alkyl, C1-C6-alkyl and C1-C6-alkoxy; or (b) —(CH2)n—V, wherein n is as defined above and V is H, OH, OR4, NHR4, NR24, NHCOR4, NHSC2R4, CONHR4, CONR24, COOH, COOR4, SO2R4, SOR4, SONHR4, SONR24, a C3-C7 heterocyclic ring, saturated or unsaturated, containing one or two heteroatoms independently selected from the group consisting of O, S and N, optionally being substituted with 1 to 3 substituents independently selected from the group consisting of H, OH, halogen, nitro, cyano, SH, SR4, trihalo-C1-C6-alkyl, C1-C6-alkyl and C1-C6-alkoxy; or (c) phenyl fused to a C3-C7 heterocyclic ring, saturated or unsaturated, containing one or two heteroatoms independently selected from the group consisting of O, S and N, optionally being substituted with 1 to 3 substituents independently selected from the group consisting of H, OH, halogen, nitro, cyano, SH, SR4, trihalo-C1-C6-alkyl, C1-C6-alkyl and C1-C6-alkoxy; and R4 is C1-C6-alkyl; and optical and geometrical isomers, and pharmaceutically acceptable salts thereof.
- 2. A compound of the formula I in which substituents R2 and R3 are arranged in cis-configuration: wherein:R2 is phenyl optionally substituted with 1 to 3 substituents independently selected from the group consisting of OH, halogen, nitro, cyano, SH, SR4, trihalo-C1-C6-alkyl, C1-C6-alkyl and C1-C6-alkoxy; R3 is: (a) phenyl substituted with —X—(CH2)n—Y, wherein: X is a valency bond, O or S, n is an integer in the range of 1 to 12, Y is H, OH, OR4, NHCOR4, NHSO2R4, CONHR4, CONR24, COOH, COOR4, SO2R4, SOR4, SONHR4, SONR24, a C3-C7 heterocyclic ring, saturated or unsaturated, containing one or two heteroatoms independently selected from the group consisting of O, S and N, optionally being substituted with 1 to 3 substituents independently selected from the group consisting of H, OH, halogen, nitro, cyano, SH, SR4, trihalo-C1-C6-alkyl, C1-C6-alkyl and C1-C6-alkoxy; or (b) —(CH2)n—V, wherein n is as defined above and V is H, OH, OR4, NHR4, NR24, NHCOR4, NHSO2R4, CONHR4, CONR24, COOH, COOR4, SO2R4, SOR4, SONHR4, SONR24, a C3-C7 heterocyclic ring, saturated or unsaturated, containing one or two heteroatoms independently selected from the group consisting of O, S and N, optionally being substituted with 1 to 3 substituents independently selected from the group consisting of H, OH, halogen, nitro, cyano, SH, SR4, trihalo-C1-C6-alkyl, C1-C6-alkyl and C1-C6-alkoxy; or (c) phenyl fused to a C3-C7 heterocyclic ring, saturated or unsaturated, containing one or two heteroatoms independently selected from the group consisting of O, S and N, optionally being substituted with 1 to 3 substituents independently selected from the group consisting of H, OH, halogen, nitro, cyano, SH, SR4, trihalo-C1-C6-alkyl, C1-C6-alkyl and C1-C6-alkoxy; and R4 is C1-C6-alkyl; and optical and geometrical isomers, and pharmaceutically acceptable salts thereof.
- 3. A compound according to claim 1 having the formula wherein R1, R2 and R3 are as defined above.
- 4. A compound according to claim 1 in which R2 is phenyl optionally substituted with 1 to 5 substituents independently selected from the group consisting of OH, halogen, nitro cyano, SH, SR4, trihalo-C1-C6-alkyl, C1-C6-alkyl and C1-C6-alkoxy.
- 5. A compound according to claim 1 in which R2 is phenyl optionally substituted with 1 to 3 substituents independently selected from the group consisting of OH, halogen, nitro, cyano, SH, SR4, trihalo-C1-C6-alkyl, C1-C6-alkyl and C1-C6-alkoxy.
- 6. A compound according to claim 1 in which R3 is phenyl substituted with —X—(CH2)n—Y, wherein:X is a valency bond, O or S, n is an integer in the range of 1 to 12, Y is H, OH, OR4, NHCOR4, NHSO2R4, CONHR4, CONR24, COOH, COOR4, SO2R4, SOR4, SONHR4, SONR24, a C3-C7 heterocyclic ring, saturated or unsaturated, containing one or two heteroatoms independently selected from the group consisting of O, S and N, optionally being substituted with 1 to 3 substituents independently selected from the group consisting of H, OH, halogen, nitro, cyano, SH, SR4, trihalo-C1-C6-alkyl, C1-C6-alkyl and C1-C6-alkoxy.
- 7. A compound according to claim 1 wherein R3 is —(CH2)n—V, wherein n is as defined above and V is H, OH, OR4, NHR4, NR24, NHCOR4, NHSO2R4, CONHR4, CONR24, COOH, COOR4, SO2R4, SOR4, SONHR4, SONR24, a C3-C7 heterocyclic ring, saturated or unsaturated, containing one or two heteroatoms independently selected from the group consisting of O, S and N, optionally being substituted with 1 to 3 substituents independently selected from the group consisting of H, OH, halogen, nitro, cyano, SH, SR4, trihalo-C1-C6-alkyl, C1-C6-alkyl and C1-C6-alkoxy.
- 8. A compound according to claim 1 wherein R3 is phenyl fused to a C3-C7 heterocyclic ring, saturated or unsaturated, containing one or two heteroatoms independently selected from the group consisting of O, S and N, optionally being substituted with 1 to 3 substituents independently selected from the group consisting of H, OH, halogen, nitro, cyano, SH, SR4, trihalo-C1-C6-alkyl, C1-C6-alkyl and C1-C6-alkoxy.
- 9. A compound according to claim 1 having the formula wherein R is H or C1-C6 alkyl.
- 10. A compound according to claim 1 having the formula wherein m is an integer from 0 to 10.
- 11. A compounds according to claim 1 having the formula wherein m is as defined above.
- 12. A compound according to claim 1 having the formula wherein m is as defined above.
- 13. A compound according to claim 1 having the formula wherein R4 is as defined above.
- 14. A compound according to claim 1 having the formula wherein R4 is as defined above.
- 15. A compound according to claim 1 having the formula wherein R6 represents one or more of the following substituents: methoxy, hydroxy, trifluormethyl, fluoro and chloro.
- 16. A compound according to claim 1 selected from the following:(−)-cis-4-(4-(Carboxymethoxy)phenyl)-7-hydroxy-3-phenylchromane, (−)-cis-7-Hydroxy-4-(4-methoxycarbonylmethoxy)phenyl)-3-phenylchromane, (−)-cis-4-(4-(Ethoxycarbonylmethoxy)phenyl)-7-hydroxy-3-phenylchromane, (−)-cis-4-(4-(Benzyloxycarbonylmethoxy)phenyl)-7-hydroxy-3-phenylchromane, (−)-cis-7-Hydroxy-3-phenyl-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (−)-cis-7-Hydroxy-3-phenyl-4-(4-(3-pyrrolidinopropoxy)phenyl)chromane, (−)-cis-7-Hydroxy-3-phenyl-4-(4-(4-pyrrolidinobutoxy)phenyl)chromane, (−)-cis-7-Hydroxy-3-phenyl-4-(4-(5-pyrrolidinopentoxy)phenyl)chromane, (−)-cis-7-Hydroxy-3-phenyl-4-(4-(6-pyrrolidinohexyloxy)phenyl)chromane, (−)-cis-7-Hydroxy-3-phenyl-4-(4-(7-pyrrolidinoheptyloxy)phenyl)chromane, (−)-cis-7-Hydroxy-3-phenyl-4-(4-(8-pyrrolidinooctyloxy)phenyl)chromane, (−)-cis-7-Hydroxy-3-phenyl-4-(4-(9-pyrrolidinononyloxy)phenyl)chromane, (−)-cis-7-Hydroxy-3-phenyl-4-(4-(10-pyrrolidinodecyloxy)phenyl)chromane, (−)-cis-7-Hydroxy-3-phenyl-4-(4-(11-pyrrolidinoundecyloxy)phenyl)chromane, (−)-cis-7-Hydroxy-3-phenyl-4-(4-(12-pyrrolidinododecyloxy)phenyl)chromane, (−)-cis-7-Hydroxy-3-phenyl-4-(4-(2-piperidinoethoxy)phenyl)chromane, (−)-cis-7-Hydroxy-3-phenyl-4-(4-(3-piperidinopropoxy)phenyl)chromane, (−)-cis-7-Hydroxy-3-phenyl-4-(4-(4-piperidinobutoxy)phenyl)chromane, (−)-cis-7-Hydroxy-4-(4-(2-perhydroazepinoethoxy)phenyl)-3-phenylchromane, (−)-cis-7-Hydroxy-4-(4-(3-perhydroazepinopropoxy)phenyl)-3-phenylchromane, (−)-cis-7-Hydroxy-4-(4-(4-perhydroazepinobutoxy)phenyl)-3-phenylchromane, (−)-cis-4-(2,3-Dihydro-1,4-benzoxazin-6-yl)-7-hydroxy-3-phenylchromane, (−)-cis-7-Hydroxy-4-(4-methyl-2,3-dihydro-1,4-benzoxazin-6-yl)-3-phenylchromane, (−)-cis-4-(4-Ethyl-2,3-dihydro-1,4-benzoxazin-6-yl)-7-hydroxy-3-phenylchromane, (−)-cis-7-Hydroxy-3-(4-hydroxyphenyl)-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (−)-cis-7-Hydroxy-3-(4-trifluoromethylphenyl)-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (−)-cis-7-Hydroxy-3-(4-fluorophenyl)-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (−)-cis-3-(4-Chlorophenyl)-7-hydroxy-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (−)-cis-3-(3,4-Dimethoxyphenyl)-7-hydroxy-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (−)-cis-7-Hydroxy-3-(pentafluorophenyl)-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (−)-cis-4-(4-(Carboxymethoxy)phenyl)-6-hydroxy-3-phenylchromane, (−)-cis-6-Hydroxy-4-(4-(methoxycarbonylmethoxy)phenyl)-3-phenylchromane, (−)-cis-4-(4-(Ethoxycarbonylmethoxy)phenyl)-6-hydroxy-3-phenylchromane, (−)-cis-4-(4-(Benzyloxycarbonylmethoxy)phenyl)-6-hydroxy-3-phenylchromane, (−)-cis-6-Hydroxy-3-phenyl-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (−)-cis-6-Hydroxy-3-phenyl-4-(4-(3-pyrrolidinopropoxy)phenyl)chromane, (−)-cis-6-Hydroxy-3-phenyl-4-(4-(4-pyrrolidinobutoxy)phenyl)chromane, (−)-cis-6-Hydroxy-3-phenyl-4-(4-(5-pyrrolidinopentoxy)phenyl)chromane, (−)-cis-6-Hydroxy-3-phenyl-4-(4-(6-pyrrolidinohexyloxy)phenyl)chromane, (−)-cis-6-Hydroxy-3-phenyl-4-(4-(7-pyrrolidinoheptyloxy)phenyl)chromane, (−)-cis-6-Hydroxy-3-phenyl-4-(4-(8-pyrrolidinooctyloxy)phenyl)chromane, (−)-cis-6-Hydroxy-3-phenyl-4-(4-(9-pyrrolidinononyloxy)phenyl)chromane, (−)-cis-6-Hydroxy-3-phenyl-4-(4-(10-pyrrolidinodecyloxy)phenyl)chromane, (−)-cis-6-Hydroxy-3-phenyl-4-(4-(11-pyrrolidinoundecyloxy)phenyl)chromane, (−)-cis-6-Hydroxy-3-phenyl-4-(4-(12-pyrrolidinododecyloxy)phenyl)chromane, (−)-cis-6-Hydroxy-3-phenyl-4-(4-(2-piperidinoethoxy)phenyl)chromane, (−)-cis-6-Hydroxy-3-phenyl-4-(4-(3-piperidinopropoxy)phenyl)chromane, (−)-cis-6-Hydroxy-3-phenyl-4-(4-(4-piperidinobutoxy)phenyl)chromane, (−)-cis-6-Hydroxy-4-(4-(2-perhydroazepinoethoxy)phenyl)-3-phenylchromane, (−)-cis-6-Hydroxy-4-(4-(3-perhydroazepinopropoxy)phenyl)-3-phenylchromane, (−)-cis-6-Hydroxy-4-(4-(4-perhydroazepinobutoxy)phenyl)-3-phenylchromane, (−)-cis-4-(2,3-Dihydro-1,4-benzoxazin-6-yl)-6-hydroxy-3-phenylchromane, (−)-cis-6-Hydroxy-4-(4-methyl-2,3-dihydro-1,4-benzoxazin-6-yl)-3-phenylchromane, (−)-cis-4-(4-Ethyl-2,3-dihydro-1,4-benzoxazin-6-yl)-6-hydroxy-3-phenylchromane, (−)-cis-6-Hydroxy-3-(4-hydroxyphenyl)-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (−)-cis-6-Hydroxy-3-(4-trifluoromethylphenyl)-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (−)-cis-6-Hydroxy-3-(4-fluorophenyl)-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (−)-cis-3-(4-Chlorophenyl)-6-hydroxy-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (−)-cis-3-(3,4-Dimethoxyphenyl)-6-hydroxy-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (−)-cis-6-Hydroxy-3-(pentafluorophenyl)-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (+)-cis-4-(4-(Carboxymethoxy)phenyl)-7-hydroxy-3-phenylchromane, (+)-cis-7-Hydroxy-4-(4-(methoxycarbonylmethoxy)phenyl)-3-phenylchromane, (+)-cis-4-(4-(Ethoxycarbonylmethoxy)phenyl)-7-hydroxy-3-phenylchromane, (+)-cis-4-(4-(Benzyloxycarbonylmethoxy)phenyl)-7-hydroxy-3-phenylchromane, (+)-cis-7-Hydroxy-3-phenyl-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (+)-cis-7-Hydroxy-3-phenyl-4-(4-(3-pyrrolidinopropoxy)phenyl)chromane, (+)-cis-7-Hydroxy-3-phenyl-4-(4-(4-pyrrolidinobutoxy)phenyl)chromane, (+)-cis-7-Hydroxy-3-phenyl-4-(4-(5-pyrrolidinopentoxy)phenyl)chromane, (+)-cis-7-Hydroxy-3-phenyl-4-(4-(6-pyrrolidinohexyloxy)phenyl)chromane, (+)-cis-7-Hydroxy-3-phenyl-4-(4-(7-pyrrolidinoheptyloxy)phenyl)chromane, (+)-cis-7-Hydroxy-3-phenyl-4-(4-(8-pyrrolidinooctyloxy)phenyl)chromane, (+)-cis-7-Hydroxy-3-phenyl-4-(4-(9-pyrrolidinononyloxy)phenyl)chromane, (+)-cis-7-Hydroxy-3-phenyl-4-(4-(10-pyrrolidinodecyloxy)phenyl)chromane, (+)-cis-7-Hydroxy-3-phenyl-4-(4-(11-pyrrolidinoundecyloxy)phenyl)chromane, (+)-cis-7-Hydroxy-3-phenyl-4-(4-(12-pyrrolidinododecyloxy)phenyl)chromane, (+)-cis-7-Hydroxy-3-phenyl-4-(4-(2-piperidinoethoxy)phenyl)chromane, (+)-cis-7-Hydroxy-3-phenyl-4-(4-(3-piperidinopropoxy)phenyl)chromane, (+)-cis-7-Hydroxy-3-phenyl-4-(4-(4-piperidinobutoxy)phenyl)chromane, (+)-cis-7-Hydroxy-4-(4-(2-perhydroazepinoethoxy)phenyl)-3-phenylchromane, (+)-cis-7-Hydroxy-4-(4-(3-perhydroazepinopropoxy)phenyl)-3-phenylchromane, (+)-cis-7-Hydroxy-4-(4-(4-perhydroazepinobutoxy)phenyl)-3-phenylchromane, (+)-cis-4-(2,3-Dihydro-1,4-benzoxazin-6-yl)-7-hydroxy-3-phenylchromane, (+)-cis-7-Hydroxy-4-(4-methyl-2,3-dihydro-1,4-benzoxazin-6-yl)-3-phenylchromane, (+)-cis-4-(4-Ethyl-2,3-dihydro-1,4-benzoxazin-6-yl)-7-hydroxy-3-phenylchromane, (+)-cis-7-Hydroxy-3-(4-hydroxyphenyl)-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (+)-cis-7-Hydroxy-3-(4-trifluoromethylphenyl)-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (+)-cis-7-Hydroxy-3-(4-fluorophenyl)-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (+)-cis-3-(4-Chlorophenyl)-7-hydroxy-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (+)-cis-3-(3,4-Dimethoxyphenyl)-7-hydroxy-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (+)-cis-7-Hydroxy-3-(pentafluorophenyl)-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (+)-cis-4-(4-(Carboxymethoxy)phenyl)-6-hydroxy-3-phenylchromane, (+)-cis-6-Hydroxy-4-(4-(methoxycarbonylmethoxy)phenyl)-3-phenylchromane, (+)-cis-4-(4-(Ethoxycarbonylmethoxy)phenyl)-6-hydroxy-3-phenylchromane, (+)-cis-4-(4-(Benzyloxycarbonylmethoxy)phenyl)-6-hydroxy-3-phenylchromane, (+)-cis-6-Hydroxy-3-phenyl-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (+)-cis-6-Hydroxy-3-phenyl-4-(4-(3-pyrrolidinopropoxy)phenyl)chromane, (+)-cis-6-Hydroxy-3-phenyl-4-(4-(4-pyrrolidinobutoxy)phenyl)chromane, (+)-cis-6-Hydroxy-3-phenyl-4-(4-(5-pyrrolidinopentoxy)phenyl)chromane, (+)-cis-6-Hydroxy-3-phenyl-4-(4-(6-pyrrolidinohexyloxy)phenyl)chromane, (+)-cis-6-Hydroxy-3-phenyl-4-(4-(7-pyrrolidinoheptyloxy)phenyl)chromane, (+)-cis-6-Hydroxy-3-phenyl-4-(4-(8-pyrrolidinooctyloxy)phenyl)chromane, (+)-cis-6-Hydroxy-3-phenyl-4-(4-(9-pyrrolidinononyloxy)phenyl)chromane, (+)-cis-6-Hydroxy-3-phenyl-4-(4-(10-pyrrolidinodecyloxy)phenyl)chromane, (+)-cis-6-Hydroxy-3-phenyl-4-(4-(11-pyrrolidinoundecyloxy)phenyl)chromane, (+)-cis-6-Hydroxy-3-phenyl-4-(4-(12-pyrrolidinododecyloxy)phenyl)chromane, (+)-cis-6-Hydroxy-3-phenyl-4-(4-(2-piperidinoethoxy)phenyl)chromane, (+)-cis-6-Hydroxy-3-phenyl-4-(4-(3-piperidinopropoxy)phenyl)chromane, (+)-cis-6-Hydroxy-3-phenyl-4-(4-(4-piperidiobutoxy)phenyl)chromane, (+)-cis-6-Hydroxy-4-(4-(2-perhydroazepinoethoxy)phenyl)-3-phenylchromane, (+)-cis-6-Hydroxy-4-(4-(3-perhydroazepinopropoxy)phenyl)-3-phenylchromane, (+)-cis-6-Hydroxy-4-(4-(4-perhydroazepinabutoxy)phenyl)-3-phenylchromane, (+)-cis-4-(2,3-Dihydro-1,4-benzoxazin-6-yl)-6-hydroxy-3-phenylchromane, (+)-cis-6-Hydroxy-4-(4-methyl-2,3-dihydro-1,4-benzoxazin-6-yl)-3-phenylchromane, (+)-cis-4-(4-Ethyl-2,3-dihydro-1,4-benzoxazin-6-yl)-6-hydroxy-3-phenylchromane, (+)-cis-6(Hydroxy-23-(4hydroxyheyl 4-(2-pyrrolidinoethoxyphenyl)chromane, (+)-cis-6-Hydroxy-3-(4-triluromethylphenyl)-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (+)-cis-6-Hydroxy-3-(4-fluoroyphenyl)-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (+)-cis-3-(4-Chlorophenyl)-6-hydyroxy-4-(4-(2-pyrrolidinnethoxy)phenyl)chromane, (+)-cis-3-(3,4-Dimethoxyphenyl)-6-hydroxy-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (+)-cis-6-Hydroxy-3-(pentafluorophenyl)-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (+)-cis-7-Hydroxy-3-phenyl-4-{4-{2-(pyrrolidin-1-yl)ethoxy}phenyl}chromane, (−)-cis-7-Hydroxy-3-phenyl-4-{4-[2-(pyrrolidin-1-yl)ethoxy]phenyl}chromane, (+)-cis-7-Hydroxy-4(4-(2-pyrrolidinoethoxy)phenyl)-3-(4-(trifluoromethyl)phenyl)-chromane (+)-cis-7-Hydroxy-3-(4-methylphenyl)-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (+)-cis-7-Hydroxy-3-(3-hydroxyphenyl)-4-(4-(2pyrrolidinoethy)phenyl)chromane, (−)-cis-7-Hydroxy-4-(4-(2-pyrrolidinoethoxy)phenyl)-3-(4-(trifluoromethyl)phenyl)-chromane, (−)-cis-7-Hydroxy-3-(4-methylphenyl)-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, and (−)-cis-7-Hydroxy-3-(3-hydroxyphenyl)-4-(4-(2-pyrrolidinoethoxy)phenyl)chromnane, or any mixture thereof.
- 17. A compound according to claim 1 selected from the following:(±)-cis-7-Hydroxy-3-phenyl-4-{4-{2-(pyrrolidin-1-yl)ethoxy}phenyl}chromane, (±)-cis-7-Hydroxy-3-(4-fluorophenyl)-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (±)-cis-7-Hydroxy-3-(4-fluorophenyl)-4-(4-(2-piperidinoethoxy)phenyl)-chromane, (±)-cis-7-Hydroxy-3-(4-fluorophenyl)-4-(4-(3-piperidinopropoxy)phenyl)chromane, (±)-cis-7-Hydroxy-3-phenyl-4-(4-(2-piperidinoethoxy)phenyl)chromane, (±)-cis-7-Hydroxy-3-phenyl-4-(4-(2-piperidinoethoxy)phenyl)chromane, (±)-cis-7-Hydroxy-3-(4-hydroxyphenyi)-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (±)-cis-7-Hydroxy-3-(4-phenyl-phenyl)-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (±)-cis-7-Hydroxy-3-(4-methylphenyl)-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (±)-cis-7-Hydroxy-3-(4-methylphenyl)-4-(4-(2-piperidinoethoxy)phenyl)chromane, (±)-cis-7-Hydroxy-4-(4-(2-piperidinoethoxy)phenyl)-3-(4-(trifluoromethyl)phenyl)-chromane, (±)-cis-7-Hydroxy-4-(4-(2-pyrrolidinoethoxy)phenyl)-3-(4-(trifluoromethyl)phenyl)-chromane, (±)-cis-7-Hydroxy-3-(3-methylphenyl)-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (±)-cis-3-(3-Fluorophenyl)-7-hydroxy-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (±)-cis-7-Hydroxy-3-(3-hydroxyphenyl)-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (±)-cis-7-Hydroxy-3-(3-hydroxyphenyl)-4-(4-(2-piperidinoethoxy)phenyl)chromane, (±)-cis-7-Hydroxy-3-(3-hydroxyphenyl)-4-(4-(3-piperidinopropoxy)phenyl)chromane, (±)-cis-7-Hydroxy-4-(4-(2-pyrrolidinoethoxy)phenyl)-3-(3-(trifluoromethyl)phenyl)-chromane, (±)-cis-7-Hydroxy-4-(4-(2-piperidinoethoxy)phenyl)-3-(3-(trifluoromethyl)phenyl)-chromane, (±)-cis-3-(2-Fluorophenyl)-7-hydroxy-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (±)-cis-7-Hydroxy-3-(2,3,4,5,6-pentafluorophenyl)-4-(4-(2-pyrrolidinoethoxy)phenyl)-chromane, (±)-cis-7-Hydroxy-3-(2,3,4,5,6-pentafluorophenyl)-4-(4-(2-piperidinoethoxy)phenyl)-chromane, (±)-cis-6-Hydroxy-3-phenyl-4-(4-(2-pyrrolidinoethoxy)phenyl)-chromane, (±)-cis-6-Hydroxy-3-(3-hydroxyphenyl)-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane, (±)-cis-4-(4-Hexylphenyl)-7-hydroxy-3-phenylchromane, (+,−) cis[4-(7-Hydroxy-3-phenyl-chroman-4-yl)-phenoxy]-acetic acid, (+,−) cis 4-[4-(7-Hydroxy-3-phenyl-chroman-4-yl)-phenoxy]-butyric acid, (+,−) cis 7-hydroxy-4-[4-(6-morpholinohexyloxy)-phenyl]-3-phenyl-chroman, (+,−) cis 7-Hydroxy 4-[4-(morpholinoethyloxy)-phenyl]-3-phenyl-chroman, (+,−) cis 7-Hydroxy 4-[4-(N-methylpiperazinoethyloxy)-phenyl]-3-phenyl-chroman, (+,−) cis 7-Hydroxy 4-[4-(morpholinobutyloxy)-phenyl]-3-phenyl-chroman, (+,−) cis 7-Hydroxy-4[4-(morpholinodecyloxy)-phenyl]-3-phenylchroman, and (+,−) cis 7-Hydroxy 4-[4-(morpholinobutyloxy)-phenyl]-3-phenyl-chroman.
- 18. A pharmaceutical composition comprising an effective amount of a compound according to claims 1 to 17 or a pharmaceutical acceptable salt thereof and a pharmaceutical carrier or diluent.
- 19. A pharmaceutical composition according to claim 18 in the form of an oral dosage unit or parenteral dosage unit.
- 20. A method for treating estrogen-dependent cancers, senile dementia-Alzheimer's type and prostatic carcinoma comprising administering to a mammal in need thereof an effective amount of a compound of claim 1.
- 21. A method of contraception comprising administering to a male or female mammal an effective amount of a compound according to claim 1.
- 22. A method for treating estrogen related diseases or syndromes caused by an estrogen-deficient state in a mammal, comprising administering to a subject in need thereof an effective amount of a compound according to claim 1.
- 23. A method for treating bone loss, osteoporosis, cardiovascular diseases, cognitive disorders, menopausal symptoms, incontinence, obesity, dysmenorrhea, dysfunctional uterine bleeding, acne, hirsutism, post-partum lactation, threatened or habitual abortion, for regulating glucose metabolism, and for aiding ovarian development, said method comprising administering to a mammal in need thereof an effective amount of a compound of claim 1.
- 24. The method according to claim 23, wherein the menopausal symptoms are flushing, urogenital atrophy, depression, mania, or schizophrenia.
- 25. A method for preventing estrogen related diseases or syndromes caused by an estrogen-deficient state in a mammal, comprising administering to a subject in need thereof an effective amount of a compound according to claim 1.
- 26. A method for preventing bone loss, osteoporosis, cardiovascular diseases, cognitive disorders, menopausal symptoms, incontinence, obesity, dysmenorrhea, dysfunctional uterine bleeding, acne, hirsutism, post-partum lactation, threatened or habitual abortion, for regulating glucose metabolism, and for aiding ovarian development, said method comprising administering to a mammal in need thereof an effective amount of a compound of claim 1.
- 27. The method according to claim 25, wherein the menopausal symptoms are flushing, urogenital atrophy, depression, mania, or schizophrenia.
Priority Claims (1)
Number |
Date |
Country |
Kind |
1197/96 |
Oct 1996 |
DK |
|
CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims priority under 35 U.S.C. 119 of Danish application Serial No. 1197/96 filed Oct. 28, 1996 and U.S. provisional application Serial No. 60/030,502 filed Nov. 12, 1996, the contents of which are fully incorporated herein by reference.
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WO 9420098 |
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WO 9621444 |
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WO |
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Entry |
Salman et al., J. Med. Chem., vol. 26, pp. 592-595 (1993). |
Irmscher et al., Liebigs Ann. Chem., vol. 744, pp. 164-177 (1971). |
Provisional Applications (1)
|
Number |
Date |
Country |
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60/030502 |
Nov 1996 |
US |