281. Synthetic neuromuscular blocking agents. Part IV. Compounds related to both laudexium and suxamethonium

Abstract

Compounds possessing certain structural features of both laudexium and suxamethonium have been synthesised in an attempt to obtain a short-acting true curarising agent. The action of several of these compounds is antagonised by neostigmine ; whilst, however, some are short-acting as expected, others are long-acting. The alkylation of tetrahydropapaverine has been investigated.THE muscle relaxant suxamethonium (I) is very short-acting because of its ready enzymic hydrolysis to the comparatively inactive choline hydrogen succinate ; consequently it has proved to be of considerable value in anzsthesia, although the lack of a satisfactory antagonist is a disadvantage. Moreover, since the initial observation by Churchill-Davidson 2 of the post-operative muscle pains and stiffness which occasionally follow its use, growing concern for these factors has been expressed by several groups of worker^.^ Laudexium (11) is antagonised by neostigmine, but has a duration of action greater than + Me, N . [CHJ ,.O-CO .[CHd ,.CO-OfCHq ,*NMe 2c1-Y = OM e (17) Y*[CHJ 2.NH.CO*[CHJn-C0.NH-[CH~,.Y 2X-that of suxamethonium; however, so far as is known, it does not cause muscle pains or stiffness. It therefore appeared possible that by incorporating certain of the chemical features of both laudexium and suxamethonium into one molecule, some of the products

Convergent Synthesis of Glycodendropeptides by Click Chemistry Approaches

“…Trispropargyl alcohol 15 12 was prepared from commercially available pentaerythritol in good yield. Using its free hydroxy group, a short spacer was introduced by reaction with acid 16 ,13 obtained in one step from succinic anhydride and 2‐bromoethanol 14. Coupling of compounds 15 and 16 was mediated by dicyclohexylcarbodiimide (DCC) and dimethylaminopyridinium p ‐toluenesulfonate (DPTS) at room temperature, affording compound 17 in moderate yield (40 %) though the efficiency of this coupling could be substantially improved (to ~ 80 %) by heating at 40 °C.…”

“…2‐Bromoethyl 3‐(Prop‐2‐ynyloxy)‐2,2‐bis[(prop‐2‐ynyloxy)methyl]propyl Succinate (17): Alcohol 15 12 (50 mg, 0.2 mmol), 4‐(2‐bromoethoxy)‐4‐oxobutanoic acid 16 13 (105 mg, 0.47 mmol) and DPTS (29 mg, 0.1 mmol) were dissolved in CH 2 Cl 2 (7 mL). After flushing with Ar, DCC (103 mg, 0.5 mmol) in CH 2 Cl 2 (3 mL) was added.…”

Neuromuscular blocking agents: alkyl and heterocyclic analogues of simple linear trisonium compounds

“…The melting-point of the methiodide was indefinite. Gladych & Taylor (1962) have also observed that the quaternary salts of other tetrahydropapaverine derivatives melt over a wide range. Found : N, 3.0; I, 28.8.…”

Simple and selective one-pot replacement of the N-methyl group of tertiary amines by quaternization and demethylation with sodium sulfide or potassium thioacetate: an application to the synthesis of pergolide

“…H, 7.9; N, 3.8%); mp 86-88 ЊC (from EtOH) (lit., 16 89 ЊC); GLC (250 ЊC) t R 4.05 min; δ H (500 MHz; CDCl 3 ) 1.11 (3 H, t, J 7.1, NCH 2 CH 3 ), 2.48 (1 H, ddd, J 3.9, 4.4, 13.1, 4-Ha), 2.68 (2 H, q, J 7.1, NCH 2 CH 3 ), 2.72 (1 H, dd, J 7.8 and 13.5, 9-Ha), 2.79-2.89 (2 H, overlapping, 3-Ha and 4-Hb), 3.07 (1 H, dd, J 5.5 and 13.3, 9-Hb), 3.17 (16), 176 (6), 151 (9).…”