Claims
- 1. A method for enhancing the antitumor effect of an antitumor drug, comprising administering to a patient in need thereof an effective amount of a compound of the formula I: ##STR307## wherein Ar.sup.1 is phenyl, pyridyl, furyl or 2,1,3-benzoxadiazol-4-yl, which may be substituted by one or more substitutents selected from the group consisting of NO.sub.2, CF.sub.3, Br, Cl, F, R.sup.6 (wherein R.sup.6 is C.sub.1 -C.sub.4 alkyl), OH, OR.sup.6, OCHF.sub.2, COOR.sup.6, NH.sub.2, NHR.sup.6, NR.sup.6 R.sup.7 (wherein R.sup.7 has the same meaning as R.sup.6), CONH.sub.2, CONHR.sup.6, CONR.sup.6 R.sup.7, COSR.sup.6, SR.sup.6, S(O)R.sup.6, S(O).sub.2 R.sup.6, S(O).sub.2 R.sup.6, SO.sub.3 H, SO.sub.3 R.sup.6, SO.sub.2 NH.sub.2, SO.sub.2 NHR.sup.6, SO.sub.2 NR.sup.6 R.sup.7, CN and phenyloxy;
- the nitrogen-containing hetero ring portion represents a 1,4-dihydropyridine ring;
- Z is a group of the formula II: ##STR308## wherein each of R.sup.4 and R.sup.5 which may be the same or different is OH, C.sub.1 -C.sub.12 linear or branched primary or secondary alkyloxy, C.sub.3 -C.sub.6 linear or branched unsaturated alkyloxy, C.sub.3 -C.sub.6 cycloalkyloxy, C.sub.1 -C.sub.6 alkoxy substituted by C.sub.3 -C.sub.6 cycloalkyl, OAr.sup.2 (wherein Ar.sup.2 is phenyl which may be substituted by halogen, C.sub.1 -C.sub.3 alkyl or C.sub.1 -C.sub.3 alkoxy), OANR.sup.6 R.sup.7 (wherein A is C.sub.2 -C.sub.6 alkylene, which may be substituted by C.sub.1 -C.sub.3 alkyl or Ar.sup.2), OAN(CH.sub.2 Ar.sup.2)R.sup.6, OAOR.sup.6, OACN, NH.sub.2, NHR.sup.6, NR.sup.6 R.sup.7, 1-piperidinyl or 1-pyrrolidinyl, or R.sup.4 and R.sub.5 together form OY (wherein Y is C.sub.2 -C.sub.4 linear saturated or unsaturated alkylene which may substituted by R.sup.6, CO.sub.2 R.sup.6, OR.sup.6, or A), NHYO, R.sup.6 NYO, NHYNH, R.sup.6 NYNH or R.sup.6 NYNR.sup.7 ;
- R.sup.1 is hydrogen, R.sup.6, ANR.sup.6 R.sup.7, AN(CH.sub.2 CH.sub.2).sub.2 O, AOR.sup.6 or CH.sub.2 phenyl;
- R.sup.2 is R.sup.6, Ar.sup.2, Ar.sup.2 CH.dbd.CH, Ar.sup.2 CH(OH)CH.sub.2, CHO, CN, CH.sub.2 OH, CH.sub.2 OR.sup.6, CH.sub.2 CH.sub.2 N(CH.sub.2 CH.sub.2).sub.2 NR.sup.6 NH.sub.2, or NHR.sup.6 ;
- R.sup.3 is hydrogen, C.sub.1 -C.sub.12 linear or branched alkyl, C.sub.3 -C.sub.6 linear or branched unsaturated alkyl, C.sub.3 -C.sub.6 cycloalkyl, C.sub.1 -C.sub.6 alkyl substituted by C.sub.3 -C.sub.6 cycloalkyl, AOR.sup.6, AO(CH.sub.2).sub.m Ar.sup.2 (wherein m is an integer of from 0 to 3), (CH.sub.2).sub.m Ar.sup.2, ANH.sub.2, ANHR.sup.6, ANR.sup.6 R.sup.7, ANR.sup.6 (CH.sub.2).sub.m Ar.sup.2, AN{(CH.sub.2).sub.m Ar.sup.2 }{(CH.sub.2).sub.n Ar.sup.3 } (wherein n has the same meaning as m, and Ar.sup.3 has the same meaning as Ar.sup.2), the 1-benzyl-4-piperidinyl, 1-benzyl-2-piperidinyl, 2-pyridinylmethyl, 3-pyridinylmethyl, AQ (wherein Q is pyrrolidine or piperidine which may be substituted by (CH.sub.2).sub.m Ar.sup.2), 4-R.sup.6 -1-piperazinyl, 4-Ar.sup.2 -1-piperazinyl, 4-(Ar.sup.2).sub.2 CH-1-piperazinyl or 4-(Ar.sup.2).sub.2 CH-1-(1,4-diazacyclopheptyl);
- or a pharmaceutically acceptable salt of the compound.
- 2. The method according to claim 1, wherein any one of the substitutents R.sup.1, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 in the compound of the formula I contains at least one basic nitrogen atom capable of forming a salt.
Priority Claims (2)
Number |
Date |
Country |
Kind |
63-193002 |
Aug 1988 |
JPX |
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1-168549 |
Jun 1989 |
JPX |
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Parent Case Info
This is a division, of application Ser. No. 07/865,489, filed on Apr. 9, 1992, pending which is a division of application Ser. No. 07/729,904, filed on Jul. 15, 1991, now U.S. Pat. No. 5,130,303, which as a continuation of application Ser. No. 07/386,254, filed on Jul. 28, 1989, now abandoned.
Non-Patent Literature Citations (1)
Entry |
Kamiwatari, Mikio, Chemical Abstract 113:34417h (1990); from Kagoshima Daigaku Igaku Zasshi 41(3), (1989), pp. 225-234. |
Divisions (2)
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Number |
Date |
Country |
Parent |
865489 |
Apr 1992 |
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Parent |
729904 |
Jul 1991 |
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Continuations (1)
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386254 |
Jul 1989 |
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