Stereochemical analogs of a muscarinic, ganglionic stimulant. 2. Cis and trans olefinic, epoxide, and cyclopropane analogs related to 4-[N-(3-chlorophenyl)carbamoyloxy]-2-butynyltrimethylammonium chloride (McN-A-343).
Preparation of analogs of 4-[N-(3-chlorophenyl) carbamoyloxy]-2-butynyltrimethylammonium chloride [1 (McN-A-343)], cis- and trans-4-[N-(4-chlorophenyl)carbamoyloxy]-2-butenyltrimethylammonium iodides (5 and 6), and the corresponding epoxides and cyclopropanes is reported. Pharmacological testing for ganglion-stimulating activity demonstrated that the trans olefin 6 and trans epoxide 8 have properties similar to 1, while the trans cyclopropane analog 10 was inactive. All cis compounds were inactive. The muscarinic ganglion-stimulating properties of the active compounds are interpreted in terms of similar fit at the receptor level by the alkyltrimethylammonium ion and the ether oxygen 5.7 A distant, as well as an electron-rich center midway between groups in the form of a double bond or unshared electron pairs. Comparison of smooth muscle and ganglion-stimulating properties of the compounds showed that trans epoxide 8 was the most selective for muscarinic ganglionic sites.
D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D000475:Alkenes / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D003521:Cyclopropanes / Q000138:chemical synthesis / Q000494:pharmacology; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D005731:Ganglionic Stimulants / Q000138:chemical synthesis*; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010277:Parasympathomimetics / Q000138:chemical synthesis*; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis*; D011817:Rabbits; D011950:Receptors, Cholinergic / Q000187:drug effects
D000475:Alkenes; D003521:Cyclopropanes; D004852:Epoxy Compounds; D005731:Ganglionic Stimulants; D010277:Parasympathomimetics; D000644:Quaternary Ammonium Compounds; D011950:Receptors, Cholinergic; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride