Sonic hedgehog modulators

US8530456B2 · kind B2 · utility

Assignees

• President and Fellows of Harvard College · US
• Massachusetts Institute of Technology · US
• The General Hospital Corporation · US

Inventors

• Lee F. Peng · Somerville, US
• Julia Lamenzo · Arlington, US
• Nicole Maloof · Brookline, US
• Kazuo Nakai · Itami, JP
• Benjamin Stanton · Menlo Park, US
• Sara Jean Buhrlage · Somerville, US
• Lawrence MacPherson · Marlborough, US
• Michel Weiwer · Cambridge, US
• Stuart L. Schreiber · Cambridge, US

Key dates

• Filing date: Apr 21, 2009
• Grant date: Sep 10, 2013
• Expiry date: Aug 16, 2029

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D413/12
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

The present invention relates to macrocyclic small molecule inhibitors of the Sonic Hedgehog signaling pathway, syntheses thereof, and intermediates thereto. Such small molecule modulators of the Sonic Hedgehog signaling pathway are useful in the treatment of proliferative diseases (e.g., basal cell carcinoma, Gorlin syndrome, medulloblastoma, or pancreatic cancer), pulmonary diseases (e.g., interstitial pnuemonitis or interstitial pulmonary fibrosis), and developmental disorders (e.g., phocomelia or cyclopia). Novel non-natural macrocycles are provided that inhibit Sonic Hedgehog induced-protein transcription.