A novel monoquaternary neuromuscular blocking agent

Bamford, D. G.; Biggs, David F.; Chaplen, P.; Davis, M.; Maconochie, J.

doi:10.1007/bf01918678

Cited by 9 publications

(3 citation statements)

References 5 publications

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“…It is evident that some protein active sites bind bilaterally symmetrical molecules, but do not possess apparent "bivalent complementary cavities. For instance, the neuromuscular blocking properties of bisquaternary pyrrolidine (1, 3) and piperidine derivatives (2, 4) represent competitive inhibitors of acetylcholine esterase (Scheme 1) [2,3]. The effectiveness of these agents is related to the disparity between compounds possessing one vs two quaternary nitrogens.…”

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confidence: 98%

Paradigms and paradoxes: Mechanisms for possible enhanced biological activity of bilaterally symmetrical chemicals

et al. 2006

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We propose a mechanism that bilateral symmetry yields an entropic advantage for enzyme recognition. We suggest that bilateral symmetry may be a guiding principle used by nature to produce some particularly effective receptor-ligand interactions. An essential result is that bilateral symmetry is common among enzyme inhibitors, which coupled with an enhanced bond energy that connects dimer molecules compared to a reduced bond energy profile for higher oligomers provides a clue to explain the abundance of bilaterally symmetrical molecules found in Nature. Keywords Molecular bilateral symmetry . Enzyme recognition . Receptor-ligand interactionsRecent interest has focused on natural product bilateral symmetry and the prediction of selectivity of dimeric molecules by density functional theory (DFT) and semiempirical calculations [1]. It has been shown that bilateral symmetry [defined as including C 2 (sigma mirror or rotation axis), C s , and C 2v point groups in molecules] is present in a number of natural product structures. Dimeric natural products were found to evolve more energy per connection than the corresponding trimers or tetramers. The assumption of maximization of interaction energy suggests the corollary

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confidence: 98%

Paradigms and paradoxes: Mechanisms for possible enhanced biological activity of bilaterally symmetrical chemicals

et al. 2006

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“…(C13H20IN3) C, , N. Nitro-l-tetralones. Nitration of tetralin (132 g)15 gave a mixture of 5-and 6-nitrotetralin (137 g), bp 160-170°(23 mm), which was fractionated (Vigreux column) to yield (1) NMR spectrum (CCU) similar to that of 4nitro-o-xylene], CrOs (80 g) was added to a stirred mixture of 5-nitrotetralin (plus 6-isomer impurity) (100 g) and AcOH (400 ml) at 70-80°(steam bath) during 45 min and the temperature held for a further 2 h. An excess of CrOs was decomposed with MeOH (10 ml) and the solvents were evaporated in vacuo. The residue in EtzO (300 ml) was washed successively with H2O, 5% NaHCOs-HzO, and H2O; then the Et20 was dried and evaporated, and unreacted nitrotetralin (58 g) was distilled at 100-105°( 0.15 mm) .…”

Section: Methodsmentioning

confidence: 99%

Monoquaternary neuromuscular blocking agents based on 1-tetralone and 1-indanone

Biggs¹,

Casy²,

Chu³

et al. 1976

J. Med. Chem.

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The preparation of three isomeric 1-tetralone hydrozones 4 and three isomeric 1-indanone hydrozones 5 possessing a single quaternary ammonium center is described. Several of the compounds possessed significant neuromuscular blocking activity, and two approached suxamethonium in potency. 1H NMR evidence obtained from a study of the N,N-dimethylhydrozones indicated that the hydrazones adopted an E configuration in solution.

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“…The review of Savarese and Kitz 30 (1973) also discussed two, structurally unusual compounds: The azo bis-arylimidazopyridinium derivative, AH 9165 (fazadinium) 31 and the monoquaternary phenylammonium keto-thiosemicarbazone derivative, M&B 15,944 A. 32 The first agents underwent rapid liver microsomal metabolism, while the explanation for the short duration of action of the second class remained uncertain. The same review discussed the possible importance of bulky terminal groups in the pharmacodynamics of muscle relaxants explored earlier by several investigators (see Introduction).…”

Section: H I S T O R Y O F T H E R E S E a R C H T O W A R D S H mentioning

confidence: 99%

Development of ultra short‐acting muscle relaxant agents: History, research strategies, and challenges

Gyermek

2005

Medicinal Research Reviews

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Author has reviewed the literature and his own work related to the chemistry, pharmacology, and clinical aspects of new muscle relaxants. Emphasis has been placed on the basic science concepts and technologies (e.g. structure-activity relationships, nicotinic receptor pharmacology, and investigation of side effects) behind the development of rapidly and short acting nondepolarizing muscle relaxants.

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A novel monoquaternary neuromuscular blocking agent

Cited by 9 publications

References 5 publications

Paradigms and paradoxes: Mechanisms for possible enhanced biological activity of bilaterally symmetrical chemicals

Paradigms and paradoxes: Mechanisms for possible enhanced biological activity of bilaterally symmetrical chemicals

Monoquaternary neuromuscular blocking agents based on 1-tetralone and 1-indanone

Development of ultra short‐acting muscle relaxant agents: History, research strategies, and challenges

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