TH80182A - Acepin derivatives have been replaced as a serotonin receptor modulator. - Google Patents

Abstract

DC60 (26/09/48) The present invention relates generally to a series of compounds, to pharmaceutical mixtures containing compounds, and to the use of compounds and mixtures as therapeutic agents. In particular, the compounds of the present invention are hexahydrothienoacepinoindole and octahydrothioacepinoyldole. These compounds are serotonin receptor (5-HT) ligands and are useful for the treatment of diseases, disorders, and conditions in which modulation of serotonin receptor (5-HT) activity is desired (e.g., addiction, anxiety, depression, and morbid obesity). The present invention relates generally to a series of compounds, to pharmaceutical mixtures containing compounds, and to the use of compounds and mixtures as therapeutic agents. In particular, the compounds of the present invention are hexahydrothienoacepinoindole and octahydrothioacepinoyldole. These compounds are serotonin receptor (5-HT) ligands and are useful for the treatment of diseases, disorders, and conditions in which modulation of serotonin receptor (5-HT) activity is desired (e.g., addiction, anxiety, depression, and morbid obesity). Thienoacepindoles and octahydrothioacepindoles are serotonin receptor (5-HT) ligands and are useful in the treatment of diseases, disorders, and conditions in which modulation of serotonin receptor (5-HT) activity is desired (e.g., addiction, anxiety, depression, and obesity).

Claims (5)

1. Compounds of the formula (chemical formula) (I) where X is S, O or NR5; R1 and R2 are independently selected from groups containing H, halogen, C1-8 alkyl, C1-8 alkyl aryl, C1-8 alkyl heteroaryl, C1-8 alkenyl, perhalo alkyl, CN, OR5, SR5, N(R5)2, CON(R5)2, NR5COR5, NR5CO2R5, SO2N(R5)2, NR5SO2R5, aryl and heteroaryl, where such aryl and heteroaryl can be alternatively replaced by up to three selected representatives from the alkyl, halogen and alkoxy or R1 and R2 together forming a 5- or 6-membered ring; R3 is selected from groups consisting of H, C1-8 alkyl, C1-8 alkyl eryl, C1-8 alkyl heteroeryl, OR5, -CH2-O-C1-8 alkyl, -CH2OH, -COO-C1-8 alkyl, -CON(R5)2, and eryl; R3a is H or R3 and R3a together forming -CH2CH2- or R2 and R3 forming a 5- or 6-member ring; R4 is selected from groups consisting of H, C1-8 alkyl, C1-8 alkyl eryl, C1-8 alkyl heteroeryl, OR5, -CH2-O-C1-8 alkyl, -CH2OH, -COO-C1-8 alkyl, -CON(R5)2, and eryl; R4a is H, or R3 and R3a together form -CH2CH2-; and R5 is selected from a group consisting of H, C1-8 alkyl, C1-8 alkyl aryl, C1-8 alkyl heteroaryl, aryl, heteroaryl, and perhaloalkyl, or, together with the atom it attaches to, R5 forms a heteroaryl ring. 2. The compound as described in claim 1, where: X is S; R1 is chosen from a group containing a halogen, C1-8 alkyl, OR5, SO2N(R5)2 and a perhaloalkyl; R2 is chosen from a group containing a hydrogen, halogen, C1-8 alkyl and OR5, or coupled with R3 to form a 5-membered ring; R3 is hydrogen or C1-8 alkyl; R3 is hydrogen; R4 is hydrogen or C1-8 alkyl; R4 is hydrogen; and R5 is hydrogen or C1-8 alkyl, or, coupled with the atom to which it is attached, to form a heteroaryl ring. 3. The compounds described in claim 1 are selected from groups containing 5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-bromo-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-chloro-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2,3-dibromo-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2,3-dichloro-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-bromo-3-chloro-5,6,7,8-tetrahydro-4H-thieno [2,3-d]acepin; (R,S)-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-chloro-4-methoxy-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-chloro-4-methyl-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2.3-dichloro-4-methyl-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-(4-trifluoromethoxy-phenyl)-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-(3-trifluoromethyl-phenyl)-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-(2-trifluoromethyl-phenyl)-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-(4-trifluorophenyl)-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-(2,5-difluorophenyl)-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-(3-chloro-4-fluorophenyl)-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-(2,5-dichlorophenyl)-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-(5-fluoro-2-methoxyphenyl)-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-(3,4,5-trimethoxyphenyl)-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-(4-ethoxyphenyl)-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-(4-ethyl-phenyl)-5,6,7,8-tetrahydro-4H-thieno [2,3-d]acepin; 2-(3-methoxyphenyl)-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-phenyl-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-(3-fluoro-biphenyl-4-il)-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-(2-fluoro-biphenyl-4-il)-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-naphthalene-1-il-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-naphthalene-2-yl-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-(2,6-difluorophenyl)-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 3-(2,6-difluorophenyl)-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-(2-chloro-6-fluorobenzyl)-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 3-bromo-2-(2-chloro-6-fluorobenzyl)-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-amino-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin-3-carboxylic acid ethyl ester; 2-amino-5,6,7,8-tetrahydro-4H-thieno[2,3-c]acepin-3-carboxylic acid ethyl ester; 5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin-3-carboxylic acid ethyl ester; and 5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin-3-carboxylic acid ethyl ester 5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2,3-dichloro-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-bromo-3-chloro-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-bromo-3-methyl-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-bromo-3-methoxy-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-bromo-4-methyl-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-bromo-8-methyl-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-(pyrrolidin-1-sulfonyl)-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin-2-sulfonic acid dimethyl amide; 3-methyl)-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin-2-sulfonic acid dimethyl amide; 2-bromo-4,4a,5,6,7,8-hexahydro-3H-1-thiah-6-azaclopenta[cd]azuline; 2-methyl-4,4a,5,6,7,8-hexahydro-3H-1-thiah-6-azaclopenta[cd]azuline; trifluoromethyl-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 3-bromo-2-trifluoromethyl-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; and 2-tert-butyl-3-methoxy-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 4. The compounds described in claim 1 are selected from groups containing 5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2,3-dichloro-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-bromo-3-chloro-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-bromo-3-methyl-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-bromo-3-methoxy-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-bromo-4-methyl-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-bromo-8-methyl-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 2-(pyrrolidin-1-sulfonyl)-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin-2-sulfonic acid dimethyl amide; 3-methyl-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin-2-sulfonic acid dimethyl amide; 2-bromo-4,4a,5,6,7,8-hexahydro-3H-1-thia-6-azaclopenta[cd]azuline; 2-methyl-4,4a,5,6,7,8-hexahydro-3H-1-thia-6-azaclopenta[cd]azuline; trifluoromethyl-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; 3-bromo-2-trifluoromethyl-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin; and 2-tert-butyl-3-methoxy-5,6,7,8-tetrahydro-4H-thieno[2,3-d]acepin 4. A pharmaceutical mixture containing at least one compound of claim I and a pharmaceutically acceptable carrier. 5. The use of the compounds of claim 1 in the manufacture of pharmaceuticals for the treatment of diseases, disorders, and/or conditions in patients requiring such treatment, where modulation of 5-HT2C receptor function is desired.