Endothelin A receptor antagonist

Astles PC, Brown TJ, Handscombe CM, Harper MF, Harris NV, Lewis RA, Lockey PM, McCarthy C, McLay IM, Porter B, Roach AG, Smith C, Walsh RJA. Selective endothelin A receptor antagonists. 1. Discovery and structure-activity of 2,4-disubstituted benzoic acid derivatives. Eur J Med Ghent 1997 32 409-23. 

Murugesan N, Gu Z, Fadnis L, et al. Dual angiotensin II and endothelin A receptor antagonists synthesis of 2 -substituted N-3-isoxazolyl biphenylsulfonamides with improved potency and pharmacokinetics. J Med Chem 2005 48 171-179. 

Endothelin-A receptor antagonist BQ-610 blocks cigarette smoke-induced mitogenesis in rat airways and vessels. 

Kling A, Muller S, Raschack M, Unger L, Walker N, Wemet W. Discovery and optimization of a novel class of orally active non-peptidic endothelin-A receptor antagonists./. Med. Chem., 1996, 39, 2123-2128. 

Rivaroxaban (BAY 59-7939) <2005JME5900> is an oral anticoagulant currently under development. It acts by inhibiting the active form of coagulation factor Xa. Sitaxentan <2004JME1969, 2005MI985> is an orally active sulfonamide class endothelin-A receptor antagonist. 

Bosentan is an endothehn-A and endothehn-B receptor antagonist. It is effective in pulmonary arterial hjrpertension (1,2) and has been marketed for this indication. The studies showed an improvement in exercise capacity and dyspnea and an increased time to clinical worsening. Efficacy in pulmonary hjrpertension has also been reported in an open study with a selective endothelin-A receptor antagonist (3). 

Barst RJ, Rich S, Widlitz A, Horn EM, McLaughlin V, McFarhn J. Clinical efficacy of sitaxsentan, an endothelin-A receptor antagonist, in patients with pulmonary arterial hypertension open-label pilot study. Chest 2002 121(6) 1860-8. 

A.T. Gonon, A.V. Gourine, R.J.M. Middelveld, K. Alving and J. Pemow, Limitation of infarct size and attenuation of myeloperoxidase activity by an endothelin A receptor antagonist following ischemia and reperfusion, Bas. Res. Cardiol. 96, 454-462 (2001). 

Several experimental systems to check the inhibition potency of bile add transport have been characterized. Using sandwich-cultured human hepatocytes, bosentan, cyclosporin A, CI-1034 (endothelin-A receptor antagonist), glyburide, erythromycin estolate, and troleandomycin could inhibit the taurocholate efflux to the bile pocket [234]. Moreover, Mita et al. [235] construded NTCP/BSEP double-transfeded cells and some cholestasis-induced compounds inhibited both the NTCP-mediated uptake and the BSEP-mediated efflux of taurocholate. Then, they have found fluorescent bile acids whose transcellular transport was dearly observed, which may be used for the rapid identification of inhibitors of NTCP and BSEP in drug screening process [235]. 

Barst RJ, Langleben D, Badesch D, et al STRIDE-2 Study Group. Treatment of pulmonary arterial hypertension with the selective endothelin-A receptor antagonist sitaxsentan. J Am Coll Cardiol 2006 47(10) 2049-56. 

Synthesis and solution conformation of c(D-Trp-D-Cys(S03-Na ")-Pro-D-Val-Leu), a potent endothelin-A receptor antagonist. Int. 

Riechers, H., Albrecht, H.-P, Aberg, W., Baumann, E., Bernard, H., Bohm, H.-J., Klinge, D., Kling, A., Muller, S., Raschack, M., Unger, L., Walker, N., Wernet, W. Discovery and optimization of a novel class of orally active nonpeptidic Endothelin-A receptor antagonists. J. Med. Chem. 1996, 39, 2123-2128. 

McDuffie, J. E., Yu, X., Sobocinski, G., Song, Y, Chupka, J., and Albassam, M. (2006). Acute coronary artery injury in dogs following administration of Cl-1034, an endothelin A receptor antagonist. Cardiovasc Toxicol 6, 25-38. 

Design, synthesis and structure activity relationship of 1,3,6-trisubstituted-2-carboxy-quinol-4-ones as selective endothelin-A receptor antagonists... 

In an in vitro assay for antithrombin activity, a methylene chloride extract fraction of M. cerifera showed greater than 80% activity. Myricitrin has shown choleretic, bactericidal, and paramecicidal activities myricadiol has shown mineralocorticoid activity. Myriceric acid A is a selective endothelin A receptor antagonist. ... 

Scheme 4.86 Application of the conjugate addition of aryiiithium compound 398 to the chiral acceptor 397 in a synthesis of endothelin A receptor antagonist 400.

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