Derivatives of imidazo 1,2-c pyrimidine, Pharmaceutical compositions containing them, method for Preparation and Use thereof in the treatment of autoimmune and inflammatory diseases.

摘要

They can be used to treat autoimmune diseases, inflammation, rejection of organs, tissues and transplanted cells, as well as blood and malignant diseases and their common diseases. 1: A compound consisting of a common formula (1) and a stereoisomer, salt and solution acceptable to the same agent, characterized by: X1 as N or cr3a, X2 as N or cr3b; R3a and R3b as independent h, C1-6, CF3, F, Cl, CN or CYCLOPROPYLENE C3-6; R1 as hetar1, hetar2, hetar3, AR1, ar2, C (= O) nrab, cyclopropyl oxide 3, C6 or C6. N - (c1-3 tar) pyridine;hetAr1 is a 5-membered heteroaryl ring having 1-3 ring heteroatoms independently selected from N, O and S and optionally substituted by one or more substituents independently selected from C1-6 alkyl, fluoro-C1-6 alkyl, difluoro- C1-6alkyl, trifluoro-C1-6alkyl, (C1-4alkoxy) C1-6alkyl, trimethylsilyl (C1-4alkoxy) C1-6alkyl, C3-6cycloalkyl, a 4-6 membered oxacyclic ring, hetCica -C1-2alkyl, hetAra-C1-2alkyl and (C1-4alkyl sulfonyl) (C1-6alkyl);Hetica is a heteromorphic cycle composed of 6 members, in which there are 1-2 heteroatoms, which are independently selected from N and O and can be replaced by C1-6 tar; hetara is a heteromorphic cycle composed of 6 members, in which there are 1-2 nitrogen atoms; Hetar2 is a partially or completely saturated heterocyclic ring composed of nine members. There are three nitrogen atoms in the ring, which can be replaced by one or more independent substitutes of C1-6 tar;Hetar3 is a heteromorphic organism composed of 6 members. There are 1-2 nitrogen atoms in the ring. It can be replaced by one or more C1-6, hetcib and alcoxi C1-6 tar independently; Hetcib is a six member outer ring containing 1-2 nitrogen atoms, which can be replaced by one or more C1-6 tar substitutes; AR1 is phenyl, which can be replaced by hetcic, heticd, hetarb, trifluoro tar C1-6 and alcox C1-6 substitutes;Hetcic is a heteromorphic cycle composed of six members, in which there are 1-2 heteroatoms, which are independently selected from n, or alternatively replaced by one or more independent substitutes of C1-6 tar; Hetcic is an aperiodic ring composed of 8 members, including 1-2 rings composed of atoms independently selected from N and O; hetarb is a heteromorphic ring composed of 5 members, including 1-2 nitrogen atoms, which can be replaced by one or more substitutes selected from C1-6 tar;Ar2 is a benzo ring fused to a 5-6 membered azacyclic ring and is optionally substituted with one or more substituents independently selected from C1-6alkyl; Ra is H; Rb is C1-6 alkyl, C3-6 cycloalkyl or hetArc; hetArc is a 6-membered heteroaryl having 1-2 ring N atoms; R2 is hydrogen, halogen, C1-4 alkyl, CF3, CN, C3-4 cycloalkyl, azetidinyl, or oxethanil; R3 is hydrogen, C1-6 alkyl, CF3, F, Cl, CN or C3-6 cycloalkyl; R4 is H or C1-6 alkyl, and R5 is H, C1-6 alkyl, -CH2CN, C3-6 cycloalkyl (optionally substituted by one or more halogens),hetCice, Ara or hetArd, or R4 and R5 together with the carbon atom to which they are attached form a 4-6 membered azacyclic ring optionally substituted with a substituent selected from C1-6alkyl, fluoro-C1-6alkyl, difluoro- C1-6alkyl, trifluoro-C1-6alkyl, tetrafluoro-C1-6alkyl, pentafluoro-C1-6alkyl, C3-4alkynyl, cyano-C1-4alkyl, benzyl, -CH2 (C3-6cycloalkyl),-Ch2hetcif, - C (= O) or (C1-6 tar),-C (= O) (C1-6 asphalt)-C (= O) (CR'r '), CF3, hetare, cycloquilo C3-6, oxacyly-so2rc of 4-6 members, or R4 and R5 together with carbon atoms form 4-member oxacyl rings, O R4 and R5, together with the carbon atoms they added, form a 3-6 selective carbon-6 ring, which is replaced by C1-6 tar, or R4 and R5, together with the carbon atoms they added, form a 7-9 double ring helical carbon, Or R4 and R5, together with the carbon atoms they add, form a different double ring spiral cycle composed of 7-9 members, and there is an heteroatom in the selected ring of O and n,wherein the ring nitrogen atom when present is optionally substituted with a substituent selected from C1-6alkyl, fluoro-C1-6alkyl, difluoro-C1-6alkyl, trifluoro-C1-6alkyl, tetrafluoro-C1-alkyl. 6, pentafluoro-C1-6alkyl and -SO2Rc; hetCice is a 5-6 membered heterocycle having one ring N atom and substituted with one substituent selected from C (= O) -C 1-6 alkyl; Ara is phenyl optionally substituted with one to more substituents independently selected from halogen, CF3, C1-6 alkyl, and C1-6 alkoxy;hetArd is a 6-membered heteroaryl having 1-2 ring nitrogen atoms and optionally substituted with one or more substituents independently selected from halogen, C1-6 alkoxy, C1-6 alkyl and CF3; hetCicf is a 6-membered oxacyclic ring; R 'and R' 'are independently hydrogen or methyl, or R' and R '' together with the carbon atom to which they are attached form a cyclopropylidine ring; hetAre is a 6-membered heteroaryl ring having 1-2 ring nitrogen atoms; Rc is C1-6alkyl, fluoro-C1-3alkyl, difluoro-C1-3alkyl, trifluoro-C1-3alkyl, tetrafluoro-C1-3alkyl, pentafluoro-C1-3alkyl,C3-6 cyclopentanediol (alternative to C1-6 tar)O-phenyl (optionally replaced by one or more independent groups selected from C1-6, CF3, cf3o and halogenated tar);R6 is hydrogen or methyl; R7 is hydrogen or C1-6 asphalt.