Synthesis and octopaminergic-agonist activity of 3-(substituted phenyl)imidazolidine-2-thiones and related compounds

Akinori Hirashima, Kenji Shinkai, Eiichi Kuwano, Eiji Taniguchi, Morifusa Eto

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Abstract

3-(Substituted phenyl)imidazolidine-2-thiones (SPITs) and related compounds were synthesized by cyclizing monoethanolamine hydrogen sulfate with arylisothiocyanates in the presence of sodium hydroxide. The activity for stimulating adenylate cyclase prepared from thoracic nerve cords of the American cockroach, Periplaneta americana L., was examined with these compounds. A SPIT with a 2,6-diethylphenyl group (48) was the only full agonist, the other SPIT derivatives being partial agonists. Greater enzyme activation appeared to result from short-chain alkyl rather than halogen substitution at the 2,6-positions of the aromatic ring of SPITs. Increasing the chain length from methyl to ethyl in 2,6-disubstituted SPIT caused an increase in the enzyme activation. Meanwhile, further increase of the chain length from ethyl to isopropyl in 2,6-disubstituted SPIT caused a decrease in the enzyme activation. Superimposition of energy-minimized octopamine and 48 revealed structural and conformational similarities that account for the higher Vmax value of 48. There was a marked decrease in the enzyme activation after alkylating at C4or C5of the imidazolidine ring of the potent SPITs. Thus, a certain degree of bulkiness and hydrophobicity at the 2- and 6-positions on the phenyl ring of a SPIT and the N-terminal was favorable for activating adenylate cyclase.

Original languageEnglish
Pages (from-to)1179-1184
Number of pages6
JournalBioscience, Biotechnology and Biochemistry
Volume62
Issue number6
DOIs
Publication statusPublished - Jan 1 1998

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All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Analytical Chemistry
  • Biochemistry
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Organic Chemistry

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