Takayoshi Ishizaki

Resolution of a CBI precursor and incorporation into the synthesis of (+)-cbi, (+)-CBI-CDPI1, (+)-CBI-CDPI2: enhanced functional analogs of (+)-CC-1065. A critical appraisal of a proposed relationship between electrophile reactivity, DNA binding properties, and cytotoxic potency.

Abstract Details of the resolution of an immediate CBI precursor, (+)− and (−)- 8 , and its subsequent incorporation into (+)− and (−)-CBI-CDPI n, optically-active enhanced functional analogs of (+)-CC-1065, are described. In marked contrast to a previously detailed direct relationship between electrophile reactivity and cytotoxic potency, an inverse relationship between the properties is detailed.

Synthesis and preliminary evaluation of (+)-CBI-indole2: an enhanced functional analog of (+)-CC-1065

Abstract The synthesis and comparative preliminary evaluation of (+)-CBI-indole 2 ( 3 ) are detailed in efforts that further demonstrate a direct relationship between the chemical stability of the agents and their biological potency/DNA alkylation intensity.

A potent, simple derivative of an analog of the CC-1065 alkylation subunit

Abstract A simple semicarbazide derivative of CBI, an analog of the authentic CPI alkylation subunit of CC-1065, exhibits enhanced in vitro cytotoxic potency and DNA alkylation properties ( ca. 100x) derived from noncovalent electrostatic DNA binding.

Synthesis and antirheumatic activity of novel tetrahydro-6-quinolineacetic acid derivatives

Abstract A study of the structural optimization of tetrahydroquinoline-6-acetic acid and the development of a novel DMARD with prompt action are detailed. ( S )-(+)-8-Chloro-1,2,3,4-tetrahydro-2-trifluoromethyl-6-quinolineacetic acid (IRA-378) exhibits the effect against both acute and chronic inflammations. It also has suppressive effects of bone destruction in adjuvant arthritis and Ca release from bones in vitro .