Piperidine and piperazine Derivatives, method for their preparation, Pharmaceutical compositions containing them and their use in the preparation of medicaments for the treatment of diseases mediated by the chemokine receptor CCR2.

摘要

A preparation method 1. Drug composition and use in C-C chemotherapy: a compound of formula (1) q-l-w-c (= x) - z-p, characterized by that Q is ammonia water in formula (R1) (R2), wherein R1 and R2 can be independently selected from H (provided that R1 and R2 are not limited) They are all H.C1-6 tar, c3-7 cyclopropyl sulfonyl, c2-6 alquenilo, c2-6 tar, cyclopropyl tar, up to 14 ring and chain atoms, up to 7 ring atoms of isocyclopropylene, up to 14 ring and chain atoms of isocyclopropylene, up to 14 ring atoms of isocyclopropylene, Heteromorphic ring heteromorphic ring ring ring ring ring ring ring ring ring ring ring ring ring ring ring ring ring ring ring ring ring ring ring ring ring ring up to 20 atoms, heteromorphic ring ring ring ring ring ring ring ring ring ring Aril oxi tar up to 14 rings and chain atomsAril cycloquilo with up to 14 ring atoms, aril arilalquilo with up to 20 ring and chain atoms, each chain or ring is there,Independent of each other,optionally substituted with up to 3 substituents each independently selected from halogen, hydroxy, C1-6 alkyl, C1-4 alkoxy optionally substituted with C1-4 alkoxy, cyano, C1-4 alkylsulfonyl, trifluoromethyl, carboxy, C1-4 alkoxycarbonyl, C1- 2-alkyloxycarbonylphenyl, phenyl, NH2, NO2, = O, C1-4 alkylcarbonyl, C3-7 cycloalkyl-heteroaryl of up to 10 ring atoms and one N atom of one heteroaromatic ring may be substituted with one oxide group, or R1 and R2 taken together with the N atom of Q represent a 4-7 membered saturated ring comprising another optional hetero atom selected from O,N or s substitutes, up to three substitutes, each of which is independently selected from the above substitutes; L is an adhesive containing C1-6 tar, C1-6 tar-c4-10 cycloquilo or c4-10 cycloquil-c1-6 tar, in each case, the mixture and / or cycloquilo may also include 1, 2 or 3 heterosexual or heterosexual C1-6 tar selected independently from n, s and / or a group = O; or selected together with the N atoms of Q and R2, There, the non bicycle group is up to 10 ring atoms,In addition to the N atom of amineptine, the isocyclic ethane and / or tar group may optionally include another or two heteroatoms selected independently from the N, s and / or group, in which each chain or ring is independent,Hydroxyl group, halogenated group or C1-4 tar group are selected to replace it, provided that (I) when l is a C5-7 cyclopropyl-c1-6 tar group, q is not a saturated aperiodic ring, which is composed of two N heteroatoms and is replaced or not replaced by a protective group, Y (II) if l represents the above-mentioned C1-6 tar abiotic cycloid, and the abiotic cycloid does not include additional heteroatoms, R1 does not represent a saturated heterocycle with only one n heteroatom, and the ring is not replaced or has a protective group of N heteroatoms;W is a crystal ring of 6 to 7 members composed of Y1 and Y2 ring atoms. Y1 and Y2 are connected with l group and C group (= x),Y1 and Y2 are independently selected between N and C respectively. If Y1 and Y2 are both N or C at the same time, then w is optional in any ring atom, replaced by 1, 2 or 3 R1 groups independently selected or by C2 bridge between two C atoms in the ring; if Y1 is C, Y2 is n and Y1, then Y1 is n and Y1. The alternative is hydrogen Xi or halide, X is O, N, n-cn or s; Z is NR3, where R3 is h or C1-4 tar, or Y2 is n, then Z can also be o; P is an arilo or a non periodic c5-10 group with up to 20 ring atoms in a single or double ring, and can be replaced by 1,2 or 3 alternatives independently selected in halide, c1-4oquilo, c2-4 alquenilo, c2-4 asphalt, Cano, trifluometilo, trifluorometoxi, c1-4oxy, C1-4 asphalt, trifluometio, carboxi C1-4 asphalt and NO2; or P alternative to phenyl, Phenyl or aralquiloxi, not more than 10 C atoms each, may optionally be replaced by one or two of any of the other alternatives listed above; or an acceptable salt or solution for pharmaceutical use. Item 18: the process of preparing a compound or an acceptable salt or solution for pharmaceutical use in accordance with Article 1,This process includes: (1) making a formula compound (2) (x) c-z-p react with a formula compound (3) q-l-w or (II) making a formula compound (4) q-l-w-c (x) - z-p react with a formula compound (5) Q, wherein Q, P, z-c (x),W and l (n) are defined in formula (1),In addition to Q, it is defined as formula (4), which includes a free amino acid group reacting with Q as an art of substituting Q, and then, optionally, including one or more steps (I),(I) or (I II) in any order: (I) eliminate all protected groups; (II) change compound (1) of formula to compound (1) of formula;(III) salt formation.