Back to Search
Start Over
Synthesis and biological activity of various derivatives of a novel class of potent, selective, and orally active prostaglandin D2 receptor antagonists. 1. Bicyclo[2.2.1]heptane derivatives
- Source :
- Journal of medicinal chemistry. 46(12)
- Publication Year :
- 2003
-
Abstract
- Novel prostaglandin D(2) (PGD(2)) receptor antagonists were synthesized as a potential new class of antiallergic agents having a bicyclo[2.2.1]heptane ring system with sulfonamide groups. Some of them exhibit extremely potent antagonism of the PGD(2) receptor in radioligand binding and cAMP formation assays with IC(50) values below 50 nM and much less antagonism of TXA(2) and PGI(2) receptors. These potent PGD(2) receptor antagonists, when given orally, dramatically suppress various allergic inflammatory responses such as increased vascular permeability in allergic rhinitis, conjunctivitis, and asthma models. The excellent pharmacological profiles of PGD(2) receptor antagonists, originally synthesized in our laboratories, are of potentially great clinical significance. This study also provides experimental evidence suggesting that PGD(2) plays an important role in the pathogenesis of allergic diseases.
- Subjects :
- Blood Platelets
Sulfonamides
Prostaglandin D2
Guinea Pigs
Receptors, Prostaglandin
Receptors, Thromboxane
Administration, Oral
Stereoisomerism
In Vitro Techniques
Receptors, Epoprostenol
Airway Obstruction
Capillary Permeability
Bridged Bicyclo Compounds
Radioligand Assay
Structure-Activity Relationship
Drug Discovery
Anti-Allergic Agents
Cyclic AMP
Molecular Medicine
Animals
Hexanes
Humans
Receptors, Immunologic
Conjunctiva
Subjects
Details
- ISSN :
- 00222623
- Volume :
- 46
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Journal of medicinal chemistry
- Accession number :
- edsair.doi.dedup.....610352be581d728477b310cd762979e0