API SYNTHESIS INTERNATIONAL: Ataciguat

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Sunday, 13 December 2015

Ataciguat

Ataciguat

HMR-1766 Hoechst Marion Roussel De Gmbh

5-Chloro-2-[[(5-chloro-2-thienyl)sulfonyl]amino]-N-[4-(4-morpholinylsulfonyl)phenyl]benzamide C₂₁H₁₉Cl₂N₃O₆S₃ _{UNII-QP166M390Q;} _{576.49306 g/mol}

A guanylate cyclase activator potentially for the treatment of aortic valve stenosis.

CAS No. 254877-67-3

Originator sanofi-aventis
Developer Mayo Clinic; National Center for Advancing Translational Sciences; Sanofi; sanofi-aventis
Class Anthranilic acids; Benzamides; Cardiovascular therapies; Chlorobenzenes; Morpholines; Small molecules; Sulfonamides; Thiophenes
Mechanism of Action Guanylate cyclase stimulants

30 Jun 2015 Mayo Clinic plans a phase II trial for Aortic valve stenosis in USA (NCT02481258)
29 Jan 2014 Phase-I clinical trials in Aortic valve stenosis in USA (PO)
01 Jan 2010 Discontinued - Phase-II for Peripheral arterial occlusive disorders in Austria, Canada, France, Germany, Italy, Poland, Portugal, Russia, South Africa and USA (PO) prior to 2010

SYNTHESIS

The Intermediates shown above is used in next step shown below

Paper

Organic Letters (2013), 15(7), 1638-1641

http://pubs.acs.org/doi/abs/10.1021/ol400411v http://pubs.acs.org/doi/suppl/10.1021/ol400411v/suppl_file/ol400411v_si_001.pdf

The Ru(II)-catalyzed intermolecular o-C–H amidation of arenes in N-benzoylated sulfoximine with sulfonyl azides is demonstrated. The reaction proceeds with broad substrate scope and tolerates various functional groups. Base hydrolysis of the amidation product provides the anthranilic acid derivatives and methylphenyl sulfoximine (MPS) directing group. This method is successfully employed for the synthesis of HMR 1766.

PATENT

WO 2009043495 http://www.google.com/patents/WO2009043495A1?cl=en

Patent http://www.google.com/patents/WO2008124505A2?cl=en

HMR-1766 (ataciguat sodium, see patent publication WO2000002851)

PATENT http://www.google.com/patents/WO2000002851A1?cl=en

Patent	Submitted	Granted
TRA COMBINATION THERAPIES [US2007238674]	2007-10-11
sGC STIMULATORS OR sGC ACTIVATORS ALONE AND IN COMBINATION WITH PDE5 INHBITORS FOR THE TREATMENT OF CYSTIC FIBROSIS [US2013035340]	2011-02-03	2013-02-07
SOLUBLE GUANYLATE CYCLASE (SGC) MODULATORS FOR TREATMENT OF LIPID RELATED DISORDERS [US2013123354]	2013-01-08	2013-05-16
Novel combination [US2005059660]	2004-07-29	2005-03-17
SGC STIMULATORS OF SGC ACTIVATORS IN COMBINATION WITH PDE5 INHBITORS FOR THE TREATMENT OF ERECTILE DYSFUNCTION [US2014288079]	2014-03-18	2014-09-25

Patent	Submitted	Granted
novel use of activators and stimulators of soluble guanylate cyclase for the prevention or treatment of renal disorders [US2010016305]	2010-01-21
HETEROARYL-SUBSTITUTED PIPERIDINES [US8119663]	2009-12-10	2012-02-21
Use of soluble guanylate cyclase activators for the treatment of Raynaud's Phenomenon [US2009215769]	2009-08-27
Use of Activators of Soluble Guanylate Cyclase for Promoting Wound Healing [US2009221573]	2009-09-03
Use of Suluble Guanylate Cyclase Acitvators for Treating Acute and Chronic Lung Diseases [US2009286781]	2009-11-19
Use of Activators of Soluble Guanylate Cyclase for Treating Reperfusion Damage [US2009298822]	2009-12-03
HETEROCYCLIC DERIVATIVE AND USE THEREOF [US2011028493]	2011-02-03
SUBSTITUTED PIPERIDINES [US8202862]	2010-12-02	2012-06-19
METHODS AND COMPOSITIONS FOR TREATING CARDIAC DYSFUNCTIONS [US2009022729]	2009-01-22
sGC STIMULATORS [US2014323448]	2014-04-29	2014-10-30