The LMC delta opioid recognition pharmacophore: Comparison of SNC80 and oxymorphindole

Bioorganic and Medicinal Chemistry Letters

Volumn 9, Issue 3, 1999, Pages 357-362

  Coop, Andrew ^a   Jacobson, Arthur E ^a  

^a NATIONAL INSTITUTES OF HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 [ALPHA (4 ALLYL 2,5 DIMETHYL 1 PIPERAZINYL) 3 METHOXYBENZYL] N,N DIETHYLBENZAMIDE; DELTA OPIATE RECEPTOR; OXYMORPHINDOLE;

ARTICLE; COMPARATIVE STUDY; DRUG SELECTIVITY; DRUG SYNTHESIS; MOLECULAR MODEL; MOLECULAR RECOGNITION; PHARMACOPHORE; RECEPTOR BINDING; STRUCTURE ANALYSIS;

ANALGESICS; BENZAMIDES; MODELS, MOLECULAR; MOLECULAR STRUCTURE; MORPHOLINES; PIPERAZINES; RECEPTORS, OPIOID, DELTA;

EID: 0033535142     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(98)00745-8     Document Type: Article

References (16)

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11. Modeling procedure. Software: Tripos' Sybyl version 6.4 on a Silicon Graphics O2 computer (IRK OS version 6.3). The protonated molecules were sketched, their chirality checked for accord with the known stereochemistry, and each was then energy minimized using, either individually or sequentially, the conjugate-gradient or Powell optimization programs with gradient termination set at 0.01 kcal/(mol*A) with the Tripos force field and Gasteiger-Huckel charges. Other force-field values were set at the Sybyl default, and a sufficient number of iterations were run to assure optimization for that conformation. To lessen the possibility of obtaining a conformer within a local minimum energy well, and to examine other theoretically possible, higher energy, conformations, simulated annealing was utilized, a Sybyl dynamics procedure. The Sybyl default values were used: initial temperature = 700 K, time to equilibrate at initial temperature = 1000 fs, target temperature for annealing = 200 K, time to spend for annealing = 1000 fs, annealing function = exponential. The resulting conformers were sorted by potential energy and energy minimized. Conformers within 5 kcal/mol were individually examined, overlapped, and those with disparate conformations were used to determine the pharmacophore. The three points chosen for this pharmacophore were the protonated tertiary nitrogen atom, the center of the aromatic ring situated βγ to that nitrogen, and the centroid of the moiety attached to the C7 atom (determined using the Sybyl software).
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