Pirrolocarbazoles FUSED isomers and isoindolonas compounds useful as Kinase Inhibitors, Pharmaceutical compositions containing, and uses in the manufacture of medicinal products

摘要

The compounds have the formula (1) or a pharmaceutically acceptable Salt or a stereoisomer thereof, where the Ring D: Select between phenyl cyclohexene Double bond with a to B; The B ring and the Ring F, independently, and each one along with the carbon Atoms to which they are UnitedSelect between: (a) a ring carbocu00edclico 6 members in which 1 to 3 carbon Atoms can be replaced by hetero Atoms; and b) a ring carbocu00edclico 5 members in which both: 1) a carbon Atom can be replaced with an atom of Oxygen, nitrogen or Sulfur; 2) two Carbon Atoms can be replaced with a Sulfur Atom and NitrogenAn atom of oxygen and two nitrogen or nitrogen Atoms; or 3) three carbon Atoms can be replaced with three nitrogen ATOMS, an atom of oxygen and two nitrogen or Sulfur Atom and two nitrogen; G - W - X is selected from: a) - C (A1A2) n - (R1) - C (B1B2), B (CH) - C (A1a) = o) - N - (R1), and (c) - N (R1) - C (= o) CH (A1a); r1 is selected from h,: (a)Alkyl substituted or non substituted C1 - 6, aryl or arylalkyl substituted or replaced without replacing, without replacing, without replacing or heteroaryl substituted or replaced without replacing or heteroarilalquilo; b) - C (= o) R7, where R7 is selected from alkyl or aryl substituted or replaced without replacing, Without replacing a Group carbocu00edclico replaced or not replacedHeterocyclic substituted or non substituted and groups; (c) - 0R8 R8, which is selected from H and alkyl C1 - 6; (d) - C (= o) - nhr8, nr9r10, - (CH2) pnr9r10 por8,, - (CH2) - or (CH2) and or por8 - (CH2) pnr9r10, where p is 1 to 4; and either (1) R9 and R10 are each independently selected from h, Lquilo C1 - 6 without replacing,And alkyl substituted; or 2) R9 and R10 together form a group of Formula Link - (CH2) 2 - X1 - (CH2) 2, where X1 is selected from - or - S -, -, and - CH2 - A1A is like; r1; R2, R3, R4 and R5 are each independently selected From: (a) h, aryl, carbociclilo, heterociclilo, - CN, CF3, - NO2, - Oh, or7 -, BR -, I - or (CH2) pnr9r10, OC (= o) - R7, OC (= o) - (CH2) or nr9r10, por8, F -, CL -, ch2or8, nr9r10,- nr8s (= o) - nr8c 2K5, R7 (= o) -, or nr8c R7 (= S); (b) ch2or11 R11 -, where is the rest of an amino acid which has been removed in the hydroxyl Group of the carboxyl Group; nr8c) - C (= o) - nr9r10, nr8c (= S) nr9r10, co2r12 -, - C (= o) R12, - C (= o) nr9r10, - C (= o) nr9r10, - ch = = nr7 nor12, - ch, - (CH2) pnr9r10, - (CH2) pnhr11, or - ch = nnr12r12a; where R12 is selected from h, alkyl C1 - 6, - Oh, - 6 - alkoxy C1, OC (= OR) R7,- nr9r10, OC (= o) - nr9r10, OC (= S) - or (CH2) pnr10, - (CH2) or c6-10 por8, arylalkyl or replaced without replacing, heterociclilalquilo or replaced without replacing, and a Group carbocu00edclico replaced or not replaced; r12a is same as R12; (d) - S (O) - (CH2) yr12, yr7, PS (OR) - ch2s yr11 and (OR) where is 0, 1 or 2; e) alqui The C1 C2 alquenilo - 8 - 8 - 8, and alquinilo C2, where: 1) each alkyl group, alquenilo,Or alquinilo is no substitute; or 2) each alkyl group, or alquenilo alquinilo is substituted with 1 to 3 groups selected from aryl c6-10, heterociclilo, arilalcoxi, heterocicloalcoxi, hidroxilalcoxi alquiloxi -, alkoxy, hidroxialquiltio, Alquiltio alkoxy -, F, CL, BR, I, - CN, - NO2, - Oh, or 7, PC - (CH2) x2 (x2 = o) - (CH2) nr9r10, PC (= o) - (CH2) nr9r10, X2 nr9r10 POC (= o) - (CH2) pco2r7, x2PS - (CH2) x2 (x2), yr7, - (CH2) pnr8c (= o) - nr9r10, OC (= o) - R7, OC (= o) - nhr12, or tetrahidropiranilo nr9r10 nr8co2r7, -, -, - nr8c (= o) - nr9r10, nr8c (= S) nr9r10 - NHC (= NH) NH2, - nr8c (= o) - R7, nr8c (= S) R7, nr8s 2R7 - (= o) - S (o) co2r12 yr7, -, - C (= o) nr9r10, - C (= o) - C (= o nr9r10, - ch2or8 R12), nnr12r12a, - ch = CH - ch = = nor12, nr7, Nnhch (- ch = n = NH) NH2, - S 2nr12r12a (= o), P (= o) - (2 - or11 0R8),A monosaccharide and C5 7 where each hydroxyl Group of monosaccharide is independently without replacing or being replaced by H, alkyl alquilcarboniloxi C1 - C2 - 4, 5, or c1-4 alkoxy; x2 is o, S, or nr8; Q is selected from - NR6, - O -, - S -; R6 is selected from H, so2r7 co2r7 -, -, - C (= R7), or - C (= o) nr9r10, alkyl - 8 alquenilo C1, C2 8And alquinilo C2 - 8; and any one of: 1) each alkyl group, or alquinilo is alquenilo, without replacing or alkyl group; 2) each, alquenilo Alquinilo Regardless, or is replaced, as defined for R2, R3, R4 and R5 in (e) above; and select between: (a) alquileno c1-3 without replacing; (b) a alquileno c1-3 replaced with R134a, R12 and R13 is selected from C1, tioalquilo - 4Halogen, alkyl - 8 alquenilo C1, C2 and C2 alquinilo - 8 - 8 (i), where each alquenilo C1 C2 alkyl - 8 - 8 - 8 is C2, and alquinilo without replacing or rent; (ii) each alquenilo C2 C1 - 8 - 8 - 8 alquinilo C2, and, independently, is replaced, as defined for R2, R3, R4 and R5 in (e) above; and (c) Functional Group selected from - ch = CH - ch (OH) - ch (OH) -, - O -, - S - S - (= o) - O - (= o) - 2 - (2 - (r6),- C = C (R13) 2 -, - C (= o) -, - C (= nor12) -, - C (or12 R12) -, - C (= o) CH (r6), CH (r6) - C (= o) -, - C (= nor12) (R6) - ch, - chr8c (= nor12) -, - C (= o) n (R8) - N (R8) - C (= o) - - - zch2 ch2z -, -, and - ch2zch2, where z is selected from (R12) -, - C or - - co2r12 -, - S, -, - C (= nor12) -, and - N - (R12); A1 and A2 is selected from h, h, h, H - or12; - SR12,; h, N (R12) 2; and a group where A1 and A2 are selected between a rest together = OR = SY = nr12, and B1 and B2 are selected from h, h, h, h, - - or12; SR12; h, N (R12) 2; and a group where B1 and B2 together form a rest or selected from =, = and = S, nr12; under the condition that at least one of The Couples A1 and A2, B1 and B2, OR = shape.