| 摘要 |
A process is disclosed for the preparation of disubstituted acetylene derivatives having retinoic acid like biological activity,wherein 6-ethynyl-chroman, 6-ethynyl-thio chroman and 6-ethynyl-1,2,3,4-tetrahydroquinoline derivatives of the formula shown below are reacted in the presence of catalysts with halogenated phenyl or heteroaryl derivatives of the formula shown below to provide the disubstituted acetylenes. In the formulae the symbols have the following meanings. R1, R2, R3, R4 and R5 are hydrogen or lower alkyl groups (of 1-6 carbons) where R1, R2, R3, R4 and R5 may be identical or different from one another with the proviso that at least one of the R4 and R5 groups is not hydrogen; X is S, O or NR' where R' is hydrogen or lower alkyl, Z represents hydrogen, or a metal ion or a metal ion bound to an anion, said metal ion capable of forming a salt with the ethynyl moiety of the formula X' - A - (CH2)n - B where X' is a leaving group, A is phenyl, or heteroaryl such as pyridinyl, thienyl, furyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiazolyl or oxazolyl, n is an integer between 0 to 5, and B is H, -COOH or a pharmaceutically acceptable salt, ester or amide thereof, said ester or amide having alkyl groups of 1 to 10 carbons or cyclic alkyl groups of 5 to 10 carbons, further B is CH2OH, CH2OR6, CH2OCOR6,. or B is CHO, CH (OR7)2, CHOR8O, or -COR9, CR9(OR7)2, or CR9OR6O where R6 is lower alkyl, R7 is lower alkyl, R8 is a divalent alkyl radical of 2 to 5 carbons and R9 is an alkyl, cycloalkyl or alkenyl group containing 1 to 5 carbons.
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