Conformationally constrained, fully synthetic macrocyclic compounds

US9512139B2 · kind B2 · utility

Assignee

• POLYPHOR AG · CH

Inventors

• Daniel Obrecht · Amriswil, CH
• Philipp Ermert · Allschwil, CH
• Said Oumouch · Mulhouse, FR
• Franck Lach · Châlons-en-Champagne, FR
• Anatol Luther · Binzen, DE
• Karsten Marx · Basel, CH
• Kerstin Möhle · Wettswil, CH

Key dates

• Filing date: Aug 3, 2010
• Grant date: Dec 6, 2016
• Expiry date: Dec 18, 2030

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D498/18
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Conformationally restricted, spatially defined 12-30 membered macrocyclic ring systems of formulae Ia and Ib are constituted by three distinct molecular parts: Template A, conformation Modulator B and Bridge C. These macrocycles Ia and Ib are readily manufactured by parallel synthesis or combinatorial chemistry in solution or on solid phase. They are designed to interact with a variety of specific biological target classes, examples being the agonistic or antagonistic activity on G-protein coupled receptors (GPCRs), ion channels and signal transduction pathways. In particular, these macrocycles act as antagonists of the motilin receptor, the FP receptor and the purinergic receptors P2Y1, as modulators of the serotonin receptor of subtype 5-HT2B, as blockers of the voltage-gated potassium channel Kv1.3 and as inhibitors of the β-catenin-dependent “canonical” Wnt pathway. Thus they are showing great potential as medicaments for a variety of diseases.