Bioorganic & medicinal chemistry, 1994-09, Vol.2 (9), p.971-985
1994
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Details
- Autor(en) / Beteiligte
- Titel
- Conformationally constrained o-tolylpiperazine camphorsulfonamide oxytocin antagonists. Structural modifications that provide high receptor affinity and suggest a bioactive conformation
- Ist Teil von
- Bioorganic & medicinal chemistry, 1994-09, Vol.2 (9), p.971-985
- Ort / Verlag
- England: Elsevier Ltd
- Erscheinungsjahr
- 1994
- Quelle
- Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)
- Beschreibungen/Notizen
- A series of new o-tolylpiperazine camphorsulfonamide OT antagonists is described. Analogs containing conformationally constrained 1-acylamino-2-propyl substituents at the camphor C2 endo position exhibit high affinity for OT and AVP-V 1a receptors or high affinity and selectivity for OT receptors, depending on functionalities present in the acyl group. Determination of the preferred conformation of potency-enhancing 1-acylamino-2-propyl substituents using molecular mechanics energy calculations and X-ray crystallography, along with topological similarities to a conformationally constrained cyclic hexapeptide OT antagonist, suggests a receptor-bound conformation for this series of non-peptide OT antagonists. A series of novel o-tolylpiperazine camphorsulfonamide oxytocin antagonists containing rotationally restricted 1-acylamino-2-propyl substituents at the C2- endo position on camphor is described.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0968-0896eISSN: 1464-3391DOI: 10.1016/S0968-0896(00)82046-5Titel-ID: cdi_proquest_miscellaneous_77801094
- Format
- –
- Schlagworte
- Amino Acid Sequence, Animals, Camphor - analogs & derivatives, Camphor - chemistry, Camphor - pharmacology, Female, Humans, Kidney - metabolism, Kinetics, Liver - metabolism, Male, Models, Molecular, Molecular Conformation, Molecular Sequence Data, Oxytocin - antagonists & inhibitors, Oxytocin - metabolism, Piperazines - chemical synthesis, Piperazines - chemistry, Piperazines - pharmacology, Rats, Receptors, Oxytocin - antagonists & inhibitors, Receptors, Oxytocin - metabolism, Receptors, Vasopressin - drug effects, Receptors, Vasopressin - metabolism, Structure-Activity Relationship, Sulfonamides - chemical synthesis, Sulfonamides - chemistry, Sulfonamides - pharmacology, Tritium, Uterine Contraction - drug effects, Uterus - metabolism