Drug effect-enhancing agent for antitumor drug

Abstract

Abstract An agent for enhancing the drug effects of an antitumor drug, which comprises a compound of the formula I: wherein Ar¹ 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, R⁶ (wherein R⁶ is C₁-C₄ alkyl), OH, OR⁶, OCHF₂, COOR⁶, NH₂, NHR⁶, NR⁶R⁷ (wherein R⁷ has the same meaning as R⁶), CONH₂, CONHR⁶, CONR⁶R⁷, COSR⁶, SR⁶, S(O)R⁶, S(O)₂R⁶, SO₃H, SO₃R⁶, SO₂NH₂, SO₂NHR⁶, SO₂NR⁶R⁷, 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: wherein each of R⁴ and R⁵ 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, OAr² (wherein Ar² is phenyl which may be substituted by halogen, C₁-C₃ alkyl or C₁-C₃ alkoxy), OANR⁶R⁷ (wherein A is C₂-C₆ alkylene which may be substituted by C₁-C₃ alkyl or Ar²), OAN(CH₂Ar²)R⁶, OAOR⁶, OACN, NH₂, NHR⁶, NR⁶R⁷, 1-piperidinyl or 1-­pyrrolidinyl, or R⁴ and R⁵ together form OYO (wherein Y is C₂-C₄ linear saturated or unsaturated alkylene which may be substituted by R⁶, CO₂R⁶, OR⁶ or A), NHYO, R⁶NYO, NHYNH, R⁶NYNH or R⁶NYNR⁷, or Z is CO₂R⁸ (wherein R⁸ has the same meaning as R³ defined hereinafter); R¹ is present only when the nitrogen-containing hetero ring is a 1,4-dihydropyridine ring, and it is R⁶, ANR⁶R⁷, AN(CH₂CH₂)₂O, AOR⁶ or CH₂phenyl; R² is R⁶, Ar², Ar²CH=CH, Ar²CH(OH)CH₂, CHO, CN, CH₂OH, CH₂OR⁶, CH₂CH₂N(CH₂CH₂)₂NR⁶, NH₂, NHR⁶ or NR⁶R⁷; R³ 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, AOR⁶, AO(CH₂) m Ar² (wherein m is an integer of from 0 to 3), (CH₂) m Ar², ANH₂, ANHR⁶, ANR⁶R⁷, ANR⁶(CH₂) m Ar², AN{(CH₂) m Ar²}{(CH₂) n Ar³} (wherein n has the same meaning as m, and Ar³ has the same meaning as Ar²), 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) m Ar²), 4-R⁶-­ 1-piperazinyl, 4-Ar²-1-piperazinyl, 4-(Ar²)₂CH-1-­piperazinyl or 4-(Ar²)₂CH-1-(1,4-diazacycloheptyl); or a pharmaceutically acceptable salt of the compound.

Inventors

• 👤 Shin-Ichi Akiyama
• 👤 Ryozo Sakoda
• 👤 Kiyotomo Seto
• 👤 Norimasa Seibutsukagaku Kenkyusho Shudo

Bibliographic Details