N-substituted alpha aminoacid amides as calcium channel modulators

摘要

A pharmaceutical compound having the formula <CHEM> in which R<1> is alkyl, -SO2R<14> where R<14> is alkyl, optionally substituted aryl or optionally substituted heteroaryl, R<2> is hydrogen, alkyl optionally substituted with one or more hydroxy or C1-4 alkoxy groups, optionally substituted aryl, optionally substituted heteroaryl, -OR<15>, -P(O)(OR<15>)(OR<16>) or -NR<15>R<16> where R<15> and R<16> are each hydrogen or alkyl, or -SO2R<17> where R<17> is hydrogen, alkyl, optionally substituted aryl or optionally substituted heteroaryl, R<3> is hydrogen, -CN, -CO2R<18>, -CONR<18>R<19>,-CH<18> IDENTICAL CHR<19>, -C IDENTICAL CR<18>, -OCH2CO.R<18>, -SO2R<18>, -CH2OR<18>, -CH2OCO.R<18>, -CH2NHCOR<18>, -CH2N(COR<18>)2, -CHO, -OR<18>, -CH2NR<18>R<19>, -CH2OR<18>, -CH=NR<18> or -CH=N-OR<18>, where R<18> and R<19> are each hydrogen or alkyl, X is a bond or -SO2-, R<4>, R<5>, R<6>, R<8>, R<9> and R<10> are each hydrogen or alkyl, n is 1 to 4, A is -CH2- or -YCO- where Y is a bond, -O-, optionally substituted phenylene, -CH=CH-, or -NR<20>- where R<20> is hydrogen or alkyl, R<7> is the C- alpha substituent of an amino acid or an ester thereof, or R<6> and R<7> together form a C3-5 alkylene chain optionally substituted by C1-4 alkyl or hydroxyl, or a group of the formula -CH2-Z-CH2- where Z is -CO-, -S-, -SO- or -SO2-, or R<7> and R<8> together form a C3 to C5 alkylene chain optionally substituted by C1-4 alkyl or hydroxyl, B is -CON(R<21>)-, -CON(R<21>)N(R<22>)- or <CHEM> where -x=y- is -C(R<22>)=N-, -N=C(R<22>)- or -N=N-, where R<21> is hydrogen, alkyl or -NR<23>R<24> where R<23> and R<24> are each hydrogen or alkyl, and where R<22> is hydrogen or alkyl, or R<8> and R<21> together form a C2-4 alkylene chain, m is 0 to 2, R<11> is hydrogen or alkyl, R<12> is hydrogen, alkyl, optionally substituted aryl, optionally substituted heteroaryl, -CN, -OH, -CO2R<25>, -CONR<25>R<26>, where R<25> and R<26> are each hydrogen or alkyl, and R<13> is alkyl, optionally substituted aryl or optionally substituted heteroaryl, or R<12> and R<13> together form a C3-8 cycloalkyl group or C3-8 cycloalkyl fused to optionally substituted phenyl; or a salt or ester thereof.