Polycyclic N-Hetero Compounds. XXV. Synthesis of Novel D-homo-11,13,15-triazasteroidal Skeleton and Investigation of Its Antidepressive Activity
1986; Elsevier BV; Volume: 24; Issue: 4 Linguagem: Inglês
10.3987/r-1986-04-1119
ISSN1881-0942
AutoresTakashi Hirota, Keiko Kawanishi, Kenji Sasaki,
Tópico(s)Synthesis and Biological Evaluation
ResumoA synthesis of D-homo-ll,l3,15-triezesteroidal skeleton, corresponding to benzo[glpyrimido[l.2-~]quinazo1ine as a novel ring system is described.Antidepressive activity of these compounds was screened by inhibitory action of reserpine-induced hypothermia.Compounds VIIc and XVI exhibited antireserpine action.We have recently reported the synthesis of b e n z [ ~l i m i d a z o [ l . 2 -~l q u i n a z o l i n e ring system, corresponding to 11,13,15-triazasteroidal skeleton2, and investi-~ getion of its antidepressive sctivity3.In the paper, we have carried out the modification of 1,2,4,5-tetrahydrobenz[hl i m i d a z o [ l , 2 9 l q u i n a z o l i (1)' as a lead compound, because it exhibited entidepressive activity3 as strong as imipramine (11) which was widely used as a tricyclic antidepressant.In the course of this work, synthesis of D-homo-ll,l3,15-triazesteroidal enslogur, possessing b e n z o [ h ] p y r i m i d o [ l , 2 -~I q u i n a z o l i n e ring system, was designed.Furthermore, since there are no reports in literatures about this ring system, additional interest prompted us to synthesize its derivatives and to investigate their biological activities.VIIa-c VIa,b VIc: not isolated VIIC pyridine Scheme 1 4-Chloro-5,6-dihydrobenzo[~]quinazoline (111)'~ was used as a starting material.As shown in Scheme 1, the reaction o f 111 with 3-hydronypropylamine derivatives (IVa-c) afforded the corresponding 4 ( 3 -h ~d r o x y p r o p y l a m i n o ) -5 , 6 -d i h y d r o b e n z o - [hlquinazolines (Va-c).Cyclization of V with thionyl chloride or phosphoryl chloride gave 2 , 3 , 5 , 6 -t e t r a h y d r o -l H -b e n ~0 ~~l p y r i .i d o [ l , 2 -~] ~u i n ~z 0 1 i n i u m chloride (V1a.b).CompoundVIc could not be isolated because it was difficult to purify, however, the purification was successful in the next step.Treatment
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