| abstract |
A cyclopropylindole compound, characterized in that it is of the formula (1) or a pharmaceutically acceptable salt or solvate thereof wherein A1 and A2 are each independently C1-4 alkylene or a bond; A3 is C1-4 alkylene or C1-4 alkylidene; A4 is C1-4 alkylene or a bond and is bonded to X, X1 or X2; X, X1, X2 and X3 are independently C or CH; J is C1-4 alkyl; p is 0 or 1; R1 and R2 are independently H, C1-3 alkyl, C3-6 cycloalkyl, phenyl, -O-phenyl, -N (H) C (O) O-C1-4 alkyl or C1-4-N alkyl (H) C (O) O-; such C3-6 cycloalkyl, phenyl or O-phenyl, is independently and optionally substituted with C1-4 alkyl, C1-3 alkoxy or halo; or are independently selected from the group of eterocíclicas parts consisting of thienyl, furanyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, pyridyl, pyrimidinyl, piperidinyl, piperazinyl, morpholino, adamantyl, indolyl, isoindolyl , indolinyl, quinolinyl, dihydroquinolinyl, tetrahydroquinolinyl, isoquinolinyl, dihydroisoquinolinyl and tetrahydroisoquinolinyl, wherein the heterocyclic portions are optionally substituted with halo, C1-4 alkyl, C1-4 alkoxy or cyano; or wherein A1-R1 and A2-R2 together with the nitrogen to which they are attached, form pyrrolyl, pyrrolinyl, pyrrolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, pyridyl, pyrimidinyl, piperidinyl, piperazinyl, morpholino, adamantyl indolyl, isoindolyl, indolinyl, quinolinyl, dihydroquinolinyl, tetrahydroquinolinyl, isoquinolinyl, dihydroisoquinolinyl or tetrahydroisoquinolinyl and optionally substituted with halo, C1-4 alkyl, C1-4 alkoxy, cyano or benzyl; R3 is H or C1-4 alkyl; m is 0 or 1; R4 and R5 are independently hydrogen, cyano, halo, nitro or C1-3 perfluoroalkyl; wherein R4 or R5 can be independently linked to X, X1, X2 or X3; n is 0 or 1; G is N, O or S; G1 is N or CH; Y is (D) H where D is C; and Z is (E) H where E is C; with the proviso that both R4 and R5 are attached to the same X, X1, X2 or X3; if G is O or S, then m is 0; if G is N, then m is 1; if R1 is -N (H) C (O) O-C1-4alkyl, C1-4alkyl-N (H) C (O) O-, or the heterocyclic portion wherein said heterocyclic portion contains a nitrogen atom and the nitrogen atom is attached to A1 then A1 is C1-4 alkylene; if R2 is -N (H) C (O) O-C1-4alkyl, C1-4alkyl-N (H) C (O) O-, or the heterocyclic portion wherein the heterocyclic portion contains a nitrogen atom and the nitrogen atom is attached to A2 then A2 is C2-4 alkylene; if R1 is N (H) C (O) O-C1-4 alkyl, C1-4 alkyl (N) C (O) O- or a heterocyclic portion selected from the group consisting of thienyl, furanyl, pyrrolyl , pyrrolinyl, pyrrolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, pyridyl, pyrimidinyl, piperidinyl, piperazinyl, morpholinyl, adamantyl, indolyl, isoindolyl, indolinyl, quinolinyl, dihydroquinolinyl, tetrahydroquinolinyl, isoquinolinyl, I dihydroisoquinolinyl and tetrahydroisoquinolinyl, where heterocyclic portions are optionally substituted with halo, C1-4 alkyl, C1-4 alkoxy or cyano, then R2 is H or C1-3 alkyl; if R2 is -N (H) C (O) O-C1-4alkyl, C1-4alkyl-N (H) C (O) O- or a heterocyclic portion selected from the group consisting of thienyl, furanyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, pyridyl, pyrimidinyl, piperidinyl, piperazinyl, morpholinyl, adamantyl, indolyl, isoindolyl, indolinyl, quinolinyl, dihydroquinolinyl, tetrahydroquinolinyl, isoquinolinyl, dihydroisoquinolinyl and tetrahydroisoquinolinyl, wherein the heterocyclic portions are optionally substituted with halo, C1-4 alkyl, C1-4 alkoxy or cyano, then R1 is H or C1-3 alkyl; if A4, R4 or R5 join X, then X is C; if A4, R4 or R5 join X1, then X1 is C; if A4, R4 or R5 are linked to X2, then X2 is C; if R4 or R5 are linked to X3, then X3 is C; if R4 is F and binds to X and if A3 is methylene, then -A1-R1 and A2-R2 together with the nitrogen to which they are attached are not N-methylpiperazinyl; and if R4 is F and binds to X and if A3 is methylene, then -A1-R1 and A2-R2 together with the nitrogen to which they are attached are not tetrahydroquinolinyl. The compounds of formula (1) are useful as selective serotonin reuptake inhibitors. A pharmaceutically acceptable formulation, comprising a compound of the formula (1). Use of said compounds to prepare said formulation useful for treating depression, anxiety disorders, premature ejaculation, urinary incontinence, chronic pain, obsessive-compulsive disorder, eating disorders, premenstrual dysphoric disorder, hot flashes, panic disorders, stress disorder posttraumatic or social phobia. Processes for the preparation of intermediary compounds useful for obtaining the compounds of the formula (1). |