POTENTIAL PHOTOAFFINITY LABELS FOR TUBULIN - SYNTHESIS AND EVALUATIONOF DIAZOCYCLOHEXADIENONE AND AZIDE ANALOGS OF COLCHICINE, COMBRETASTATIN, AND 3,4,5-TRIMETHOXYBIPHENYL

Analogs of tubulin assembly inhibitors such as colchicine, combretasta tin, and 3,4,5-trimethoxybiphenyl which incorporate a 6-diazo-2,4-cycl ohexadienone (o-quinone diazide) ring have been synthesized and charac terized. The compounds synthesized include 2',3',4'-trimethoxyphenyl)c yclohexa-2,4-dien-1-one and its 3-methyl and 3-ethyl analogs (1a-c), 3 -(2,3,4-trimethoxyphenyl)-2,4-cyclohexadien-1-one and its 4-methyl and 4-ethyl derivatives (2a-c), ethoxyphenyl)ethenyl]-6-diazocyclohexa-2, 4-dienone (3), oxyphenyl)ethenyl]-6-diazocyclohexa-2,4-dien-1-one (4), the corresponding dihydro derivatives (5, 6) and two isomeric diazocy clohexadienones derived from N-acetylcolchinol (7, 8). Compounds in wh ich the cyclohexadienone oxygen is approximately isostructural with ca rbonyl or hydroxy functions of the parent compounds exhibit good activ ity in the tubulin assembly inhibition assay. 2'-Alkyl-4'azido-3,4,5-t rimethoxy-1,1'-biphenyls also show good activity as tubulin assembly i nhibitors.