2 - piridona Derivatives, method for their preparation, Pharmaceutical compositions containing them, a process for preparing the same and their use in the manufacture of medicaments for the treatment of diseases mediated by the activity of Neutrophil Elastase (HNE).

摘要

Its preparation process, which includes the composition, processing method and use in treatment. These compounds are factors that inhibit the elasticity of neutron ofilos and are used to develop drugs for the treatment of HNE mediated diseases. Item 1: a compound whose characteristic is the response formula (1), wherein R1 represents h or C1-6 tar; W represents s (o) m, where M represents 0, 1 or 2 integer; Z represents a simple link, ch2-o-n25;R14 represents an H or H atom or a group selected between C1-6 tar and a saturated or unsaturated ring system composed of 3 to 10 members, wherein each group can optionally be replaced by at least one heteroatom in the ring selected between N and s, and each group can optionally be replaced by at least one alternative selected from phenyl, C1-6, halocarbon, C1-4, acoxy C1-4, acoxy C1-4, CN, oh, NO2, c1-3 tar is replaced by one or more F atoms, and Alcoy c1-3 is replaced by one or more F atoms, nr122r13, C: cr30, conr31r32, CHO, alkane c2-4, alkane (o) pr33 and os2r34; R12 and R13 represent independent h, C1-6, ilo-6;O group 12 R13 is added together to represent periodic rings of 5 to 7 members, optionally including an additional heteroatom between O, s, and nr26; R30 represents h, c1-3 tar, if (CH3) 3 or phenyl; R33 and R34 represent independent h or c1-3 tar; such tar is replaced by one or more atoms. F. R6 stands for H or F; R3 stands for phenyl or 5 or 6-member heteroaromatic ring, which contains 1 to 3 heteroatoms independently selected from O, s and N; the ring can be selectively replaced by at least one selected halogenated, C1-6 tar, cyanogen, alcox C1-6, nitrate, methyl carbon substitute,Nr35r36, c1-3 tar, replaced by one or more f or alcoxi c1-3 atoms, replaced by one or more F atoms; R35 and R36 independently represent h or c1-3 tar; such tar can also be replaced by one or more F atoms optionally; R4 stands for optional h or C1-6 tar, replaced by at least one selected alternative between F, hydroxy and alcoxi C1-6; x stands for a simple connection, or Nr24 or C1-6 tar-y -,It contains a simple link, O atom, Nr24 or s (o) W, and can be optionally replaced by Oh, halogeno, CN, nr37r38, alcox c1-3, conr39r40, so2r41 and so2nr42r43; The combination of O R4 and X makes - nr4x form a periodic ring with 5 to 7 members, optionally including an additional heteroatom between O, s and nr44; optionally replacing the ring with C1-6 or nr4546 tar; optionally replacing the ring with Oh tar; O R5 represents a selected monocyclic system between monophenyl (I) diphenyl (II) phenyl;iii) a 5-6 membered heteroaromatic ring comprising at least one heteroatom in the ring selected from N, O and S; iv) a partially unsaturated saturated C3-6 hydrocarbyl ring, or v) a 4- or 7-membered saturated or partially unsaturated heterocyclic ring comprising at least one heteroatom in the ring selected from O, S (O) and NR20, where at least a C atom in the ring may optionally be replaced by a carbonyl group, or R5 represents a bicyclic ring system where the two rings are independently selected from the monocyclic ring systems defined in ii),Three,iv) and v) above, where the two rings are either fused together,linked together or separated from each other by a binder group selected from O, S (O) to C1-6 alkylene optionally comprising one or more internal or terminal heteroatoms selected from O, S and NR27 and which are optionally substituted by at least one substituent selected from hydroxy, oxo and C1-6 alkoxy, the monocyclic or bicyclic ring system that are optionally substituted by at least one substituent selected from O, CN, OH, C1-6 alkyl, C1-6 alkoxy, halogen, NR47R48, NO2, OSO2R49, CO2R50, C (= NH) NH2, C (O) NR51R52, C (S) NR53R54, SC (= NH) NH2, NR55C (= NH) NH2, S (O) vR21, SO2NR56R57,C1-3 alkoxy substituted with one or more F atoms and C1-3 alkyl substituted with SO2R5 or with no or more F atoms; said C1-6 alkyl being also optionally substituted with at least one substituent selected from cyano, hydroxyl, C1-6 alkoxy, C1-6 alkylthio and -C (O) NR22R23; or R5 can also represent H; R20 represents H, C1-6 alkyl, C1-6 alkylcarbonyl or C1-6 alkoxycarbonyl; R21 represents H, C1-6 alkyl or C3-8 cycloalkyl, said alkyl or cycloalkyl group being also optionally substituted with one or more substituents independently selected from OH, CN, C1-3 alkoxy and CONR59R60; R37 and R38 independently represent H, C1-6 alkyl,C2-6 formyl or alkanoyl; R47 and R48 independently represent H, C1-6 alkyl, formyl, C2-6 alkanoyl, S (O) qR61 or SO2NR62R63; said alkyl group being optionally also substituted by halogen, CN, C1-4 alkoxy or CONR64R65; R41 and R61 independently represent H C1-6 alkyl or C3-6 cycloalkyl; p is 0, 1 or 2; q is 0, 1 or 2; r is 0, 1 or 2; t is 0, 1 or 2; w is 0, 1 or 2; v is 0, 1 or 2; R22, R23, R24, R25, R26, R27, R31, R32, R39, R40, R42, R43, R44, R45, R46, R49, R50, R51, R52, R53, R54, R55, R56, R57, R58, R59, R60, R62, R63, R64 and R65 each independently represents H or C1-6 alkyl;Or an acceptable salt Item 8: a process for preparing a formula compound (1) or a second acceptable salt is defined in Article 1, which is characterized by (a) reacting a formula compound (2), wherein L1 represents a discrete group (such as hydrogen halide) and R1, R3, R6, R14, W and Z have the values defined in the formula (1),A compound containing formula (3), where x, R4, and R5 have values defined in formula (1),Or (b) when w represents s-and Z represents a simple o-ch2 link,reacting a compound of the formula (4) wherein Hal represents a halogen atom and X, R1, R3, R4, R5 and R6 have the values defined in the formula (1),R14-z-m containing r14-z-s-m nucleic acid, wherein R14 and Z have the values defined in formula (1), while M represents an organic boric acid container or organic substance, or (c) when w represents - s-and Z represents a simple o-ch2 link,A formula compound (4) is reacted, wherein "Hal" represents a halogenated atom, while x, 1, R3, 4, R5 and R6 have values (1) defined in the formula,1.1. Tiol r14-z-s-h, where R14 and Z have the values defined in the formula in the case of copper salt (1);O (d) when w represents s - and Z represents a simple o-ch2 link, a compound of formula (5) is reacted, wherein X, R1, R3, R4, R5 and R6 have the values defined in formula (1),Using r14-z-l2 electrolyte, L2 represents a group of discrete substances such as halides, R14 and Z, with the values defined in the formula (1),(e) When it stands for - SO2 and Z stands for - nr25,A formula compound (6) is reacted, wherein X, R1, R3, R4, R5 and R6 have values (1) defined in the formula,1. Amine containing r14-nhr25, wherein R14 and R25 have the values defined in formula (1),O (f) when w represents sulfur (- S (o -) or a group of (- S (o) 2 -) sulfur, the corresponding compound is oxidized, and W represents an uncle (- S -);Select next (a)(b)(c)(d)(e) Or (f) driving one or more of the following compounds: converting the obtained compound into another compound of the compound; forming an acceptable salt for the pharmaceutical use of the compound.