Cyclic dibenzoylhydrazines reproducing the conformation of ecdysone agonists, RH-5849.
We have investigated the biologically active conformation of the non-steroidal ecdysone agonist, 1-tert-butyl-1,2-dibenzoylhydrazine (RH-5849) by means of design, synthesis and conformational analysis of cyclic derivatives of RH-5849. Among the synthesized compounds, a 6-membered cyclic hydrazine bearing two benzoyl groups (5) exists in three conformational states in solution, and the major unsymmetrical conformer of 5 is similar to that of RH-5849 on the basis of 1H NMR and X-ray analyses. The 3,3-dimethyl derivative of 5 (10) exists as a single unsymmetrical conformer. Although there is conformational similarity of the cyclic derivatives with RH-5849, these compounds did not show any hormonal or insecticidal activity. The hydrogen bonding character of the amide N-H group of the dibenzoylhydrazine seems to play a critical role in the appearance of the biological activity.
Toya
Tetsuya
T
Research & Development Laboratories, Nippon Kayaku Co., Ltd., 225-1 Koshikiya, Ageo, 362-0064, Saitama, Japan.
Yamaguchi
Kentaro
K
Endo
Yasuyuki
Y
D000818:Animals; D018360:Crystallography, X-Ray; D004440:Ecdysone / Q000819:agonists* / Q000737:chemistry; D006834:Hydrazines / Q000737:chemistry* / Q000494:pharmacology; D007306:Insecticides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007814:Larva / Q000187:drug effects; D008968:Molecular Conformation; D018716:Molecular Mimicry; D019906:Nuclear Magnetic Resonance, Biomolecular; D018411:Spodoptera / Q000187:drug effects; D013237:Stereoisomerism
D006834:Hydrazines; D007306:Insecticides; C056565:1,2-dibenzoyl-tert-butylhydrazine; D004440:Ecdysone; C006712:benzoylhydrazine