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Theoretical study of metiamide, a histamine H 2 antagonist
Author(s) -
Martins João B. L.,
Taft Carlton A.,
Perez Marco A.,
Stamato Fulvia M. L. G.,
Longo Elson
Publication year - 1998
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/(sici)1097-461x(1998)69:1<117::aid-qua13>3.0.co;2-3
Subject(s) - chemistry , metiamide , intramolecular force , computational chemistry , natural bond orbital , tautomer , hydrogen bond , molecule , imidazole , ab initio , stereochemistry , density functional theory , organic chemistry , antagonist , histamine h2 receptor , biochemistry , receptor
The requirements for H 2 ‐antagonist activity so far identified for most of the known antagonists of histamine are the presence of a heterocyclic ring containing a basic center linked via a methylene chain to a substituted guanidine or thiourea polar side chain. Metiamide is a potent H 2 antagonist (pA2=6.06). We have used the ab initio Hartree–Fock (HF) method in order to study the conformational properties of the N 3 (SINGLE BOND)H tautomers of metiamide molecule and histamine monocation. Three basis set (the 3‐21G*, 6‐31G**, and 6‐31+G**) were used, the results compared, and the geometric parameters fully optimized. Our results indicate the preference of metiamide for a folded conformation with an intramolecular hydrogen bonding between the imidazole ring and one of the NH groups. The optimized geometrical parameters and charge distributions of both molecules, using the Mulliken, and natural bond order (NBO) analysis, are given and discussed. © 1998 John Wiley & Sons, Inc. Int J Quant Chem 69: 117–128, 1998