Tetrahidrocarbazol derivatives as LIGANDS FOR g-protein coupled receptors (GPCRs), Pharmaceutical compositions containing them and uses for the treatment of Neurological Disorders or neurodegenerative, Fertility, HIV infection, and as antineoplastic agents.

摘要

1. It is derived from tetrahydrofluorocarbons, and its characteristic is that it is a formula (1), wherein: (a) V, W are selected independently from the group consisting of = O, = s, = S + O -,H2 is bound in the form of a Gemini; R1, R1 * in its presence, forms separately = O, = s or = S + - O - or two independent hydrogen; R2, R3 are selected separately from a group consisting of (I) hydrogen, asphalt, c9-30 tar, cyclomethyldiol, cyclomethyldiol and isocyclohexane, Or or or or or or XXX6 (or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or or (o) A-H (a = 1, 2, 3, 4, 5),-O (-X11-O) b-X12 (b 3D 1 2 3 4 5)-OC (O) -X13, -OC (O) -O-X14, -OC (O) - NHX15, -O-C (O) -NX16X17, -OP (O) (OX18) (OX19),-OSi (X20) (X21) (X22)-OS (O2) -X23, -NHC (O) -NH2, -NHC (O) -X24, -NX25C (O) -X26, -NH-C (O) -O-X27, -NH-C (O ) -NH-X28, -NH-C (O) -NX29X30, -NX31-C (O) -O-X32, -NX33-C (O) -NH-X34, -NX35-C (O) -NX36X37, -NHS (O2) -X38, -NX39S (O2) -X40, -S-X41, -S (O) -X42, -S (O2) -X43, -S (O2) NH-X44, -S (O2 ) NX45X46, -S (O2) O-X47, -P (O) (OX48) (OX49),-Yes (X50) (X51) (X52)-C (NH) -NH2, -C (NX53) -NH2, -c (NH) -NHX54, -C (NH) -NX55X56, -C (NX57) -NHX58, -C (NX59) -NX60X61, -NH -C (O) -NH-O-X62, -NHC (O) -NX63-O-X64, -NX65-C (O) -NX66-O-X67, -N (-C (O) -NH-O -X68) 2, -N (-C (O) -NX69-O-X70) 2, -N (-C (O) -NH-O-X71) (- C (O) -NX72-O-X73) ,-C (S) -X74, -C (S) -O-X75, -C (S) -NH-X76, -C (S) -NX77X78, -C (O) -NH-O-X79, -C (O) -NX80-O-X81, -C (S) -NH-O-X82, -C (S) -NX83-O-X84, -C (O) NH-NH-X85, -C (O) -NH-NX86X87, -C (O) -NX88-NX89X90, -C (S) -NH-NH-X91, -C (S) -NH-NX92X93, -C (S) -NX94-NX95X96, -C ( O) -C (O) -O-X97, -C (O) -C (O) -NH2, -C (O) -C (O) -NHX98, -C (O) -C (O) -NX99X100 , -C (S) -C (O) -O-X101, -C (O) -C (S) -O-X102, -C (S) -C (S) -O-X103, -C (S ) -c (O) -NH2, -C (S) -C (O) -NHX104, -C (S) -C (O) -NX105X106, -C (S) -C (S) -NH2, -C (S) -C (S) -NHX107, -C (S) -C (S) -NX108X109, -C (O) -C (S) -NH2, -C (O) -C (S) -NHX110, -C (O) -C (S) -NX111X112; where X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12, X13, X14, X15, X16, X17, X18, X19, X20, X21, X22, X23, X24, X25 , X26, X27, X28, X29, X30, X32, X33, X34, X35,X36 X37 X38 X39 X40 X42 X43 X44 X45 X46 X47 X48 X49 X50 X51 X52 X53 X54 X55 X56 X57 X58 X59 X60 X61 X62 X63 X64 X65 X66 X67 X68 X69 X70 X71 X72 X73 X74 X75 X76 X77 X78 X79 X80 X81 X82 X83 X84 X85 X86 X46 and / or X55, X56 and / or X60, X61 and / or X77, X78 and / or X86, X87 and / or X89, X90 and / or X92, X93 and / or X95, X96 and / or X99, X100 and / or X105, X106 and / or X108, X109 and / or X111, X112 and / or respectively can also form together, heterocyclyl; wherein optionally said substituents from the group of substituents (i) may in turn be independently substituted with one another with at least one substituent, identical or different, selected from the group consisting of (ii) alkyl, C9-30 alkyl, cycloalkyl , cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, -F, -Cl, -Br, -I, -CN, -CF3, -N3, -NH2, -NHX201, -NX202X203, -NO2, -OH , = O, -OCF3, -SH,-OSO3H, -OP (O) (OH) 2, -CHO, -COOH, -C (O) NH2, -SO3H, P (O) (OH) 2, -C (O) -X204, -C (O ) O-X205, -C (O) NH-X206, -C (O) NX207X208, -O-X209, -O (-X210-O) cH (c = 1, 2, 3, 4, 5),-O (-X211-O) d-X212 (d 3D 1 2 3 4 5)-OC (O) -X213, -OC (O) -O-X214, -OC (O) -NHX215, -O-C (O) -NX216X217, -op (O) (OX218) (OX219),OSi (X220) (X221) (X222)-Nx23x232336x236x237-nhs (or - X2 (o) - X2 (or - X2 (or - X2 (or) - S (O2) - x243, - S (O2) nh-x244, s (O2) nx245x246, - S (O2) o-x247, - P (o) (ox248) (ox249),-Yes (x250) (x251) (x252)-C (NH) -NH2, -C (NX253) -NH2, -C (NH) -NRX254, -C (NH) -NX255X256, -C (NX257) -NHX258, -C (NX259) -NX260X261, -NH -C (O) -NH-O-X262, -NH-C (O) NX263-O-X264, -NX265-C (O) -NX266-O-X267, -N (-C (O) -NH- O-X268) 2, -N (-C (O) -NX269-O-X270) 2, -N (-C (O) -NH-O-X271) (- C (O) -NX272-O-X273 ),-C (S) -X274, -C (S) -C-X275, -C (S) -NH-X276, -C (S) -NX277X278, -C (O) -NH-O-X279, -C (O) -NX280-O-X281, -C (S) -NH-O-X282, -C (S) NX283-O-X284, -C (O) -NH-NH-X285, -C (O) -NH-NX286X287, -C (O) -NX288-NX289X290, -C (S) -NH-NH-X291, -C (S) -NH-NX292X293, -C (S) -NX294-NX295X296, -C ( O) -C (O) -O-X297, -C (O) -C (O) -NH2, -C (O) -C (O) -NHX298, -C (O) -C (O) -NX299X300 , -C (S) -C (O) -O-X301, C (O) -C (S) -O-X302, -C (S) -C (S) -O-X303, -C (S) -C (O) -NH2, -C (S) -C (O) -NHX304, -C (S) -C (O) -NX305X306, -C (S) -C (S) -NH2, -C ( S) -C (S) -NHX307, -C (S) -C (S) -NX308X309, -C (O) -C (S) -NH2, -c (O) -C (S) -NHX310, C (O) -C (S) -NX311X312 where X201, X202, X203, X204, X205, X206, X207, X208, X209, X210, X211, X212, X213, X214, X215, X216, X217, X218, X219, X220 , X221, X222, X223,X224 X225 X226 X227 X228 X229 X230 X231 X232 X233 X234 X235 X236 X237 X238 X239 X240 X241 X242 X243 X244 X245 X246 X247 X248 X249 X250 X251 X252 X253 X254 X255 X256 X257 X258 X259 X260 X261 X262 X263 X264 X265 X266 X267 X268 X269 X270 X271 X272 X273 heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl and where alternatively X207, X208 and / or X216, X217 and / or X229, X230 and / or X236, X237 and / or X245, X246 and / or X255, X256 and / or X260 , X261 and / or X277, X278 and / or X286, X287 and / or X289, X290 and / or X292, X293 and / or X295, X296 and / or X299, X300 and / or X305, X306 and / or X308, X309 and / or X311, X312 and / or respectively can also together form heterocyclyl; wherein optionally said substituents from the group of substituents (ii) may in turn be independently substituted with one another with at least one substituent, identical or different, selected from the group consisting of: (iii) alkyl, C9-30 alkyl, cycloalkyl, cycloalkylalkyl,Straight ring,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, E-H (E = 1, 2, 3, 4, 5),-O (-X411-O) f-X412 (f 3D 1 2 3 4 5)-OC (O) -X413, -OC (O) -O-X414, -OC (O) -NHX415, -O-C (O) -NX416X417, OP (O) (OX418) (O419),-OSi (X420) (X421) (X422)-OS (O2) -X423, -NRC (O) -NH2, -NHC (O) -X424, -NX425C (O) -X426, -NH-C (O) -O-X427, -NH-C (O ) -NH-X428, -NH-C (O) -NX429X430, -NX431-C (O) -O-X432, -NX433-C (O) -NH-X434, -NX435-C (O) -NX436X437, -NHS (O2) -X438, -NX439S (O2) -X440, -S-X441, -S (O) -X442, -S (O2) -X443, -S (O2) NH-X444, S (O2) NX445X446, -S (O2) O-X447, -P (O) (OX448) (OX449),-Yes (x450) (x451) (x452)-C (NH) -NH2, -C (NX453) -NH2, -C (NR) -NHX454, -C (NH) NX455X456, -C (NX457) -NHX458, -C (NX459) -NX460X461, -NH- C (O) -NH-O-X462, -NH-C (O) -NX463-O-X464, -NX465-C (O) -NX466-O-X467, -N (-C (O) -NH- O-X468) 2, -N (-C (O) -NX469-O-X470) 2, -N (-C (O) -NH-O-X471) (- C (O) -NX472-O-X473 ),-C (S) -X474, -C (S) -O-X475, -C (S) -NH-X476, -C (S) -NX477X478, -NH-O-X479, -C (Q) -NX480 -O-X481, -C (S) -NH-O-X482, -C (S) -NX483-O-X484, -C (O) -NH-NH-X485, -C (O) -NH-NX486X487 , -C (O) -NX488-NX489X490, -C (S) -NH-NH-X491, -C (S) -NH-NX492X493, -C (S) -NX494-NX495X496, -C (O) -C (O) -O-X497, -C (O) -C (O) -NH2, -C (O) -C (O) -NHX498, -C (O) -C (O) -NX499X500, C (O ) -O-X501, -C (O) -C (S) -O-X502, -C (S) -C (S) -O-X503, -C (S) -C (O) -NH2, - C (S) -C (O) -NHX504, -C (S) -C (O) -NX505X506, -C (S) -C (S) -NH2, -C (S) -C (S) -NHX507 , -C (S) -C (S) -NX508X509, -C (O) -C (S) -NH2, -C (O) -C (S) -NHX510, -C (O) -C (S) -NX511X512; where X401, X402, X403, X404, X405, X406, X407, X408, X409, X410, X411, X412, X413, X414, X415, X416, X417, X418, X419, X420, X421, X422, X423, X424,X425, X426, X427, X428, X429, X430, X431, X432, X433, X434, X435, X436, X437, X438, X439, X440, X441, X442, X443, X444, X445, X446, X447, X448, 44 X450 X451 X452 X453 X454 X455 X456 X457 X458 X459 X460 X461 X462 X463 X464 X465 X466 X467 X468 X469 X470 X471 X472 X473 X47 X475 X476 X477 X478 X479 X480 X481 X482 X483 X484 X485 X486 X487 X488 X489 X490 X491 X492 X493 X494 X495 X496 X497 X498 X4 X500, X501, X502, X503, X504, X505, X506, X507, X508, X509, X510, X511, X512 are independently selected from the group consisting of: alkyl, c9-30 alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,Unorthodox unorthodox unorthodox unorthodox unorthodox unorthodox unorthodox unorthodox unorthodox unorthodox unorthodox unorthodox unorthodox unorthodox unorthodox or x511, X512 and / or can also be isomerized together; n is an independent 0 or 1, but the first condition is that if R1, R1 * does not exist (n is 0),R2, R3 cannot be hydrogen at the same time; the second condition is that if R1, R1 * exists (n is 1) and forms = or, = s or = S + - or - or two independent hydrogen, R2, R3 cannot be hydrogen at the same time; the third condition is that if R1, R1 * does not exist (n is 0),One R2, R3 cannot be hydrogen and the other R2, R3 is - C (= NH) - NH2; the fourth condition is that if R1, R1 * is present.