Dual antagonists of platelet activating factor and histamine. 2. pyridine ring substitution of N-acetyl-4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)piperidines

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Abstract

A Series of pyridine ring substituted 1-acetyl-4-(8-chloro-5,6-dihydro-11H-benzo[5,6] cyclohepta[1,2-b]pyridin-11-ylidene)piperidines which are antagonists of both PAF and histamine were prepared by one of three different methods. Analogs with substituents at C-3 were found to be the best dual antagonists among their corresponding reioisomers. Analogs with an electron donating substituent at the C-3 position are generally better antagonists of both PAF and histamine than analogs with electron withdrawing groups.

The syntheses and biological activities of pyridine ring substituted analogs of Sch 37370, a dual antagonist of PAF and histamine, are described.

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    In contrast to the corresponding four- and five-membered ring products, the six- and seven-membered bis-conjugated allenes formed from tethered bis(propargylic) alcohol derivatives are not isolated, since they undergo electrocyclisation to give bicyclic cyclobutene compounds 50 (Scheme 103).217 Finally, and as already mentioned, related intramolecular alkyne–allene coupling reactions starting from allenynes (1,2-dien-6-ynes and 1,2-dien-7-ynes) have been described as well.202–204 Titanacyclopropanes generated from Ti(Oi-Pr)4 and a Grignard reagent react with alkynes with a suitable leaving group at the propargylic position to give allenyltitanium complexes O1 that are in equilibrium with the corresponding propargyl–titanium complexes O2 via a metallotropic shift (Scheme 104).238

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A preliminary account of this work was presented at the 204th National Meeting of American Chemical Society, Division of Organic Chemistry, Washington, D.C., August 1992; ORG 298. For the previous paper in this series see reference 8a.

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