| 摘要 |
Substituted piperazine compounds of formula (I) and its pharmaceutically acceptable acid addition salts are disclosed, wherein: X is selected from the group consisting of formula (a) and formula (b): wherein m = 1 or 2 or 3; R1, R2, R3, R4 and R5 are each independently selected from the group consisting of hydrogen, halo, NO2, CF3, CN, OR23, SR23, N(R23)2, S(O)R22, SO2R22, SO2N(R23)2, NR23CO2R22, NR23CON(R23)2, COR23, CO2R23, CON(R23)2, NR23SO2R22, C1- 15alkyl, C2-15 alkenyl, C2-15 alkynyl, heterocyclyl, aryl, and heteroaryl, wherein the alkyl and aryl substituent are optionally substituted with 1 substituent selected from the group consisting of halo, NO2, CF3, CN, OR23, SR23, N (R23)2, S(O)R22, and SO2R22, wherein R2 and R3 may join together to form a fused ring system having from three to four carbon atoms, and wherein R4 and R5 may join together to form-CH=CH-CH=CH-; R6, R7 and R8 are each independently selected from the group consisting of hydrogen and C,-,, alkyl; R9 R10, R11, R12, R13, R14, R15 and R16 are each independently selected from the group consisting of hydrogen, CO2R23, CON(R23)2, C1-4 alkyl, and aryl wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, CF3, CN, OR23, N(R23)2, CO2R23, CON(R23)2 and aryl, wherein R9 and R10 may together form a carbonyl, or R11 and R12 may together form a carbonyl, or R13 and R14 may together form a carbonyl, or R15 and R16 may together form a carbonyl wherein R11 and R13 or R9 and R15 or R9 and R11 or R11 and R15 or R9 and R13 may join together to form a bridging ring system having from 1 to 4 carbon atoms and wherein R9 and R10 or R11 and R12 or R13 and R14 or R15 and R16 may join to form a bridging ring system having from 1 to 5 carbon atoms with the proviso that R9, R10, R11, R12, R13, R14, R15 and R16 are not all hydrogen when R24 is unsubstituted phenyl and when X is represented formula (b); R22 is selected from the group consisting of C1-15 alkyl, aryl, and heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, alkyl, monoalkylamino, dialkylamino, alkyl amide, aryl amide, heteroaryl amide, CN, O-C1-6 alkyl, CF3, and heteroaryl; R23 is selected from the group consisting of H, C1-15 alkyl, aryl, and heteroaryl, wherein the alkyl and aryl substituents are optionally substituted with 1 substituent selected from the group consisting of halo, alkyl, monoalkylamino, dialkylamino, alkyl, CN,-O-C1-6 alkyl, and CF3; and R24 is selected from the group consisting of alkyl, cycloalkyl, and fused phenylcycloalkyl wherein the point of attachment is on the cycloalkyl wherein the alkyl, cycloalkyl, and fused phenylcycloalkyl are optionally substituted with from 1 to three substituents selected from the group consisting of halo, CF3, CN, OR23, SR23, S(O)R22, SO2R22, SO2N(R23)2, NR23CO2R22, C1-2 alkyl, and aryl wherein the optional aryl substituent is optionally substituted with from 1 to 3 substituents selected from the group consisting of halo, phenyl, CF3, CN, OR23, and C1-6 alkyl and a phenyl ring as described in the specification. Substituted piperazine compounds of formula (I) are useful in therapy to protect skeletal muscles against damage resulting from trauma or to protect skeletal muscles subsequent to muscle or systemic diseases such as intermittent claudication, to treat shock conditions, to preserve donor tissue and organs used in transplants, in the treatment of cardiovascular diseases including atrial and ventricular arrhythmias, Prinzmetal's (variant) angina, stable angina, and exercise induced angina, congestive heart disease, and myocardial infarction.
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