912368-71-9

Upstream product

• 912368-70-8 tert-butyl (3S)-3-[(7-cyano-2-bromothieno[3,2-c]pyridin-4-yl)amino]piperidine-1-carboxylate 
• 98-80-6 phenylboronic acid 
• 690635-43-9 2-bromo-4-chlorothieno[3,2-c]pyridine-7-carbonitrile 
• 55040-43-2 2-bromo-4-oxo-4,5-dihydrothieno[3,2-c]pyridine-7-carbonitrile 
• 55040-34-1 4-oxo-4,5-dihydrothieno[3,2-c]pyridine-7-carbonitrile 
• 912368-69-5 (2Z)-3-cyano-3-(2-thienyl)acryloyl azide 
• 912368-68-4 (2Z)-3-cyano-3-(2-thienyl)acryloyl chloride 
• 912368-67-3 (2Z)-3-cyano-3-(2-thienyl)acrylic acid potassium salt 
• 20893-30-5 2-cyanomethylthiophene 

Downstream Products

• 912369-36-9 4-{[(3S)-1-(tert-butoxycarbonyl)piperidin-3-yl]amino}-2-phenylthieno[3,2-c]pyridine-7-carboxylic acid 

Relevant academic research and scientific papers

Adventures in Scaffold Morphing: Discovery of Fused Ring Heterocyclic Checkpoint Kinase 1 (CHK1) Inhibitors

Checkpoint kinase 1 (CHK1) inhibitors are potential cancer therapeutics that can be utilized for enhancing the efficacy of DNA damaging agents. Multiple small molecule CHK1 inhibitors from different chemical scaffolds have been developed and evaluated in clinical trials in combination with chemotherapeutics and radiation treatment. Scaffold morphing of thiophene carboxamide ureas (TCUs), such as AZD7762 (1) and a related series of triazoloquinolines (TZQs), led to the identification of fused-ring bicyclic CHK1 inhibitors, 7-carboxamide thienopyridines (7-CTPs), and 7-carboxamide indoles. X-ray crystal structures reveal a key intramolecular noncovalent sulfur-oxygen interaction in aligning the hinge-binding carboxamide group to the thienopyridine core in a coplanar fashion. An intramolecular hydrogen bond to an indole NH was also effective in locking the carboxamide in the preferred bound conformation to CHK1. Optimization on the 7-CTP series resulted in the identification of lead compound 44, which displayed respectable drug-like properties and good in vitro and in vivo potency.

Design, synthesis and SAR of thienopyridines as potent CHK1 inhibitors

A novel series of CHK1 inhibitors based on thienopyridine template has been designed and synthesized. These inhibitors maintain critical hydrogen bonding with the hinge and conserved water in the ATP binding site. Several compounds show single digit nanomolar CHK1 activities. Compound 70 shows excellent enzymatic activity of 1 nM.

SUBSTITUTED HETEROCYCLES AND THEIR USE AS CHK1, PDK1 AND PAK INHIBITORS

This invention relates to novel compounds of Formula (I) and to their pharmaceutical compositions and to their methods of use. These novel compounds possess CHK1 kinase inhibitory activity, PDK1 inhibitory activity and Pak kinase inhibitory activity and are accordingly useful in the treatment and/or prophylaxis of cancer.