1192277-41-0

Upstream product

• 851518-35-9 (S)-tert-butyl 3-((R)-4-benzyl-2-oxooxazolidine-3-carbonyl)hex-5-enoate 
• 155399-10-3 (4R)-3-(4-pentenoyl)-4-(phenylmethyl)-1,3-oxazolidin-2-one 
• 39716-58-0 pent-4-enoyl chloride 
• 56613-80-0 D-2-phenylglycinol 
• 591-80-0 pent-4-enoic acid 
• 1192277-39-6 (R)-N-(2-hydroxy-1-phenylethyl)pent-4-enamide 

Downstream Products

• 1192277-43-2 tert-butyl 2-((3R,11S,E)-5,12-dioxo-3-phenyl-1-oxa-4-azacyclododec-8-en-11-yl)acetate 
• 1192277-46-5 2-((3R,11S,E)-5,12-dioxo-3-phenyl-1-oxa-4-azacyclododec-8-en-11-yl)acetic acid 
• 1192277-45-4 N-(4-chlorobenzyl)-2-((3R,11S,E)-5,12-dioxo-3-phenyl-1-oxa-4-azacyclododec-8-en-11-yl)acetamide 

Relevant academic research and scientific papers

Macrocyclic hedgehog pathway inhibitors: Optimization of cellular activity and mode of action studies

Macrocyclic Hedgehog (Hh) pathway inhibitors have been discovered with improved potency and maximal inhibition relative to the previously reported macrocycle robotnikinin. Analogues were prepared using a modular and efficient build-couple-pair (BCP) approach, with a ring-closing metathesis step to form the macrocyclic ring. Varying the position of the macrocycle nitrogen and oxygen atoms provided inhibitors with improved activity in cellular assays; the most potent analogue was 29 (BRD-6851), with an IC50 of 0.4 μM against C3H10T1/2 cells undergoing Hh-induced activation, as measured by Gli1 transcription and alkaline phosphatase induction. Studies with Patched knockout (Ptch-/-) cells and competition studies with the Smoothened (Smo) agonists SAG and purmorphamine demonstrate that in contrast to robotnikinin, select analogues are Smo antagonists.

SONIC HEDGEHOG MODULATORS

The present invention relates to 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 t