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 A343)

Article abstract of DOI:10.1021/jm00223a026

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 these 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.