Spiro oxindole compounds - that is, a Pharmaceutical Composition and its use for the treatment of diseases or conditions mediated by the sodium channels.

摘要

1. Formula (1) using spiro oxygenates: where j, K, m, Q, x, cyclic a, R1, R2A r2b, r2c, r2d and R3 have defined values, i.e. stereoisomer, coaxial dwarf or coaxial variant; or acceptable pharmaceutical salt, N-oxide salt, solvato salt or their biological products, Used to treat and / or prevent diseases or conditions, such as pain, that are transmitted through the sodium channel. Item 1: a compound whose characteristic is its response formula (1), in which J and K are independent of 0, 1, 2 or 3; m is 0, 1, 2 or 4; X is o or s; ring a is a fused heterocyclic ring or a fused heterocyclic ring;Q is - C (R1a) 2-- that is...-S (o) P - (P is 0, 1, 2),-CF2, -OC (O) -,-That's it.-C (O) N (R5) --N (R5) - o -N (R5) C (O) -Each R1a is h-or5, or two R1a, plus the related carbon, to form an oxo group; R1 is hydrogen, tar, amino, asphalt, halo tar, arilo, cyclopropyl, cyclopropene, isopropene, isopropene, r8-c (o) R5, r8-c (o) n (R4) R5, s (o) t-r5 (T1 or R2),-R9-s (o) p-r5 (P is 0, 1 or 2),-Lulululu, Aoji Union, Zhihuan Sansan, non Huanhuan Huanhuan 444, Huanhuan 444, Huanhuan 4, 5, 5, 5, 5, 5, arilo, Zhili, or R6, R7, In addition to the nitroglycerin attached to them, they form an isomerization or isomerization isomerization, in which each group of arillo, allokiro, cyclopentadiene, cyclopentadiene, isopropene, isopropene,heteroaryl and heteroaryl for R6 and R7 may optionally be substituted with one or more substituents selected from the group consisting of alkyl, cycloalkyl, aryl, aralkyl, halo, haloalkyl, -R8-CN, -R8-OR5, heterocyclyl and heteroaryl; or R1 is aralkyl optionally substituted with one or more substituents selected from the group consisting of -R8-OR5, -C (O) OR5, halo, haloalkyl, alkyl, nitro, cyano, aryl, aralkyl, heterocyclyl and heteroaryl; or R1 is -R9-N (R10) R11, -R9- N (R12) C (O) R11 or -R9-C (O) N (R12) R11 or -R9-N (R10) C (O) N (R10) R11 where: each R10 is hydrogen, alkyl, aryl, aralkyl or heteroaryl; Each R11 is hydrogen, alkyl, haloalkyl, cycloalkyl,cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroarylalkyl, -R9-OC (O) R5, -R9-C (O) OR5, -R9-C (O) N (R4) R5, -R9-C ( O) R5, -R9-N (R4) R5, -R9-OR5, or -R9-CN; R12 is hydrogen, alkyl, aryl, aralkyl or -C (O) R5; and wherein each aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl and heteroarylalkyl group for R10 and R11 may optionally be substituted with one or more substituents selected from the group consisting of alkyl, cycloalkyl, aryl, aralkyl, halo, haloalkyl, nitro, -R8-CN, -R8-OR5, -R8-C (O) R5, heterocyclyl and heteroaryl;or R1 is heterocyclylalkyl or heteroarylalkyl where the heterocyclylalkyl or heteroarylalkyl group is optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, -R8-OR5, -R8-C (O) OR5, aryl and aralkyl ; R2a, R2b, R2c and R2d are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, halo, haloalkyl, haloalkenyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, aralkenyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroarylalkyl, -R8-CN, -R8-NO2, -R8-OR5, -R8-N (R4) R5, -R8-N = C (R4) R5, -R8-S (O) pR4, -R8- OS (O) 2CF3, -R8-C (O) R4, -R8-C (S) R4,-R8-C (O) OR4, -R8-C (S) OR4, -R8-C (O) N (R4) R5, -R8-C (S) N (R4) R5, -R8-N (R5 ) C (O) R4, -R8-N (R5) C (S) R4, -R8-N (R5) C (O) OR4, -R8-N (R5) C (S) OR4, -R8-N (R5) C (O) N (R4) R5, -R8-N (R5) C (S) N (R4) R5, -R8-N (R5) S (O) tR4, -R8-N (R5) S (O) t (R4) R5, - R8-S (O) tN (R4) R5, -R8-N (R5) C (= NR5) N (R4) R5, and -R8-N (R5) C (= N-CN) N (R4) R5, where each p is independently 0, 1, or 2 and each t is independently 1 or 2; and wherein each of the cycloalkyl, cycloalkylalkyl, aryl, aralkyl, aralkenyl, heterocyclyl, heterocyclylalkyl, heteroaryl and heteroarylalkyl groups for R2a, R2b, R2c and R2d may optionally be substituted with one or more substituents selected from the group consisting of alkyl alkenylalkynyl, alkoxy, halo, haloalkyl, haloalkenyl, haloalkoxy, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, aralkenyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroarylalkyl, -R8-CN, -R8-N (O) 2, -R8 -5, R8-N (R4) R5, -S (O) pR4, -R8-C (O) R4, -R8-C (O) OR4, -R8-C (O) N (R4) R5, -N (R5 ) C (O) R4, and -N (R5) S (O) tR4, where each p is independently 0, 1, or 2 and each t is independently 1 or 2; or R2a and R2b, together with the ring carbon atoms to which they are directly attached, can form a fused ring selected from cycloalkyl, aryl, heterocyclyl and heteroaryl, and R2c and R2d are as defined; or R2b and R2c,Together with the ring carbon atoms directly connected together, they can form a combined ring selected from cyclopentadiene, arilo, isopropene and isopropene, as well as between R2A and r2d; or r2c and r2d, together with the ring carbon atoms directly connected together, A selected combined ring can be formed between cyclopentadiene, arilo, isoacrylonitrile and isopropene and R2A and r2b; each R3 can be selected separately from a group consisting of asphalt, almond, asphalt, halogen, halogen, halogen, halogen, cyclopentadiene, cyclopentadienyl, arilo, aralquilo and aralquenilo, cumene) R5, -And there is one or one or one independent process or one independent process to obtain one or one or one or one independent aralquilo, aralquenilo, heterosexual, heterosexual in one or one or one independent way,The heterogenous and heteromorphic acrylonitrile of R3 can be replaced by one or more substitutes, such as coagulation, halogen, asphalt, tar, propoxy, halogen, halogen, epoxy, cyclopentyl, cyclopentadienyl propenyl, arilo, aralquilo, aralquenilo, isopropene, isopropenylpropenyl, isopropenylpropenyl, isopropylpropenyl, isopropylallyl, isopropylallyl One kind of water resource composition; each kind of independent R2 composition; each kind of different R5, from which one kind of independent flow of water resource is selected; each kind; each kind; each kind; each kind of water anyone, anything,1. Pitch, halogen, halogen, acylhaloglyl propylene, propoxy, cyclopentadiene, cyclopentadienyl allyl, arilo, aralquilo, isopropyl, isopropyl propylene, isopropyl allyl and isopropyl allyl; or when R4 and R5 are combined with the same nitrobenzene atom respectively, R4 and R5 are combined with the attached nitrobenzene atom; They can form an isomerization or isomerization; and each R8 is in a direct link or a linear or branched asphalt chain, or in a linear or branched asphalt chain, or in a linear or branched asphalt chain; and each R9 is a linear or branched asphalt chain, Linear or branched star chains or linear or branched tar chains; as stereoisomers,2. Enantiomero, tautomero or a mixture of both; or acceptable salt for pharmaceutical, N-oxidation, dissolution or production;