Minor structural modifications convert the dual TP/CRTH2 antagonist ramatroban into a highly selective and potent CRTH2 antagonist

Journal of Medicinal Chemistry

Volumn 48, Issue 4, 2005, Pages 897-900

  Ulven, Trond ^a   Kostenis, Evi ^a  

^a 7TM Pharma A S   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

CHEMOATTRACTANT RECEPTOR HOMOLOGOUS MOLECULE EXPRESSED ON TH2 CELL; G PROTEIN COUPLED RECEPTOR; PROSTAGLANDIN D2 RECEPTOR BLOCKING AGENT; PROSTAGLANDIN RECEPTOR; PROSTAGLANDIN RECEPTOR BLOCKING AGENT; RAMATROBAN; RAMATROBAN DERIVATIVE; THROMBOXANE A2 RECEPTOR BLOCKING AGENT; UNCLASSIFIED DRUG;

ALLERGIC RHINITIS; ARTICLE; ASTHMA; BINDING COMPETITION; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; IC 50; RECEPTOR BLOCKING; STRUCTURE ACTIVITY RELATION;

ANTI-ALLERGIC AGENTS; ARRESTINS; BINDING, COMPETITIVE; CARBAZOLES; CYCLIC AMP; ENERGY TRANSFER; INOSITOL PHOSPHATES; LUMINESCENT MEASUREMENTS; MOLECULAR CONFORMATION; PROTEIN TRANSPORT; RADIOLIGAND ASSAY; RECEPTORS, IMMUNOLOGIC; RECEPTORS, PROSTAGLANDIN; RECEPTORS, THROMBOXANE A2, PROSTAGLANDIN H2; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONAMIDES;

EID: 13944263887     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm049036i     Document Type: Article

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40. One conceivable metabolic process that could result in a lowered half-life of 13 relative to ramatroban is N-demethylation at the sulfonamide. It is notable that the predicted metabolite from this process would be 12, which is an equally potent CRTH2 antagonist and which also shows appreciable selectivity over TP and DP (Table 1).