| abstract |
An agent for enhancing the drug effects of an antitumor drug, which comprises a compound of the formula I: <CHEM> wherein Ar<1> is phenyl, pyridyl, furyl or 2,1,3-benzooxadiazol-4-yl, which may be substituted by one or two substituents selected from the group consisting of NO2, CF3, Br, Cl, F, R<6> (wherein R<6> is C1-C4 alkyl), OH, OR<6>, OCHF2, COOR<6>, NH2, NHR<6>, NR<6>R<7> (wherein R<7> has the same meaning as R<6>), CONH2, CONHR<6>, CONR<6>R<7>, COSR<6>, SR<6>, S(O)R<6>, S(O)2R<6>, SO3H, SO3R<6>, SO2NH2, SO2NHR<6>, SO2NR<6>R<7>, CN and phenyloxy; the nitrogen-containing hetero ring portion represents a 1,4-dihydropyridine ring or a pyridine ring; Z is a group of the formula II: <CHEM> wherein each of R<4> and R<5> which may be the same or different is OH, C1-C12 linear or branched primary or secondary alkyloxy, C3-C6 linear or branched unsaturated alkyloxy, C3-C6 cycloalkyloxy, C1-C6 alkoxy substituted by C3-C6 cycloalkyl, OAr<2> (wherein Ar<2> is phenyl which may be substituted by halogen, C1-C3 alkyl or C1-C3 alkoxy), OANR<6>R<7> (wherein A is C2-C6 alkylene which may be substituted by C1-C3 alkyl or Ar<2>), OAN(CH2Ar<2>)R<6>, OAOR<6>, OACN, NH2, NHR<6>, NR<6>R<7>, 1-piperidinyl or 1-pyrrolidinyl, or R<4> and R<5> together form OYO (wherein Y is C2-C4 linear saturated or unsaturated alkylene which may be substituted by R<6>, CO2R<6>, OR<6> or A), NHYO, R<6>NYO, NHYNH, R<6>NYNH or R<6>NYNR<7>, or Z is CO2R<8> (wherein R<8> has the same meaning as R<3> defined hereinafter); R<1> is present only when the nitrogen-containing hetero ring is a 1,4-dihydropyridine ring, and it is R<6>, ANR<6>R<7>, AN(CH2CH2)2O, AOR<6> or CH2phenyl; R<2> is R<6>, Ar<2>, Ar<2>CH=CH, Ar<2>CH(OH)CH2, CHO, CN, CH2OH, CH2OR<6>, CH2CH2N(CH2CH2)2NR<6>, NH2, NHR<6> or NR<6>R<7>; R<3> is hydrogen, C1-C12 linear or branched alkyl, C3-C6 linear or branched unsaturated alkyl, C3-C6 cycloalkyl, C1-C6 alkyl substituted by C3-C6 cycloalkyl, AOR<6>, AO(CH2)mAr<2> (wherein m is an integer of from 0 to 3), (CH2)mAr<2>, ANH2, ANHR<6>, ANR<6>R<7>, ANR<6>(CH2)mAr<2>, AN{(CH2)mAr<2>}{(CH2)nAr<3>} (wherein n has the same meaning as m, and Ar<3> has the same meaning as Ar<2>), 1-benzyl-4-piperidinyl, 1-benzyl-2-piperidinyl, 2-pyridinylmethyl, 3-pyridinylmethyl, AQ (wherein Q is pyrrolidine or piperidine which may be substituted by (CH2)mAr<2>), 4-R<6>- 1-piperazinyl, 4-Ar<2>-1-piperazinyl, 4-(Ar<2>)2CH-1-piperazinyl or 4-(Ar<2>)2CH-1-(1,4-diazacycloheptyl); or a pharmaceutically acceptable salt of the compound. |