Newer potential quinazolinones as hypotensive agents

Abstract

A series of 3-(substitutedarylidene)hydrazinoacetylamino-2-methyl-6-bromo-quinazolin-4(3<i>H</i>)-ones <b>4a-e</b> has been prepared by the condensation of 3-(hydrazinoacetylamino)-2-methyl-6- bromoquinazolin-4(3<i>H</i>)-one <b>3</b> with different aromatic aldehydes. Compounds <b>4a-e</b> on treatment with chloro-acetylchloride in the presence of triethylamine are converted into 3-[2'-(substitutedaryl)-3'-chloro-4'-oxo-1'-azetidinyl] aminochloroacetylamino-2-methyl-6-bromoquinazolin-4(3<i>H</i>)-ones <b>5a-e</b>, which undergo Mannich reaction to yield compounds <b>6a-c</b>. The structures of all the new compounds&nbsp; have been confirmed by elemental analysis and spectral studies (IR,¹H NMR and mass spectroscopy). Compounds <b>4a-4e</b>, <b>5a-5e</b> and <b>6a-6e</b> have been evaluated for hypotensive activity and were round to exhibit activity ranging from 10-90 mmHg. The most active compound of this series is 3-[2'-(<i>p-N-N</i>-dimethylaminobenzylidine))-3<span dir="RTL" style="font-size:12.0pt;font-family:" times="" new="" roman";="" mso-bidi-language:he"="" lang="HE">׳-chloro-4'-oxo-]'-azetidinyl-aminoacetylamino [-2-[(<i>p</i>-methoxyphenyl)aminoethyl ]-2-methyl-6-bromoquinazo-lin-4(3<i>H</i>)-one <b>6d</b> which has shown blood pressure lowering activity of 90 mmHg, which lasted for 120 min. at a dose of 2.5<i> </i>mg/kg i.v.

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