182137-63-9

Upstream product

• 501-53-1 benzyl chloroformate 
• 331258-42-5 methyl N-benzoyl-7-azabicyclo[2.2.1]heptane-1-carboxylate 
• 1330783-88-4 N-(3-oxo-2-oxabicyclo[2.2.2]oct-4-yl)benzamide 
• 331258-40-3 methyl 1-benzimido-4-oxocyclohexane-1-carboxylate 
• 182137-41-3 7-(tert-butyloxycarbonyl)-1-carboxy-7-azabicyclo[2.2.1]-heptane tert-butyl ester 
• 182137-60-6 7-[(benzyloxy)carbonyl]-7-azabicyclo[2.2.1]heptane-1-carboxylic acid 

Downstream Products

• 1330783-91-9 benzyl 1-{6-[1-(tert-butoxycarbonyl)-3-methyl-1H-pyrazol-4-yl]-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl}-7-azabicyclo[2.2.1]heptane-7-carboxylate 
• 1330783-90-8 benzyl 1-(6-bromo-4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl)-7-azabicyclo[2.2.1]heptane-7-carboxylate 

Relevant academic research and scientific papers

Discovery of a Novel, Highly Potent, and Selective Thieno[3,2- d]pyrimidinone-Based Cdc7 Inhibitor with a Quinuclidine Moiety (TAK-931) as an Orally Active Investigational Antitumor Agent

In our pursuit of developing a novel, potent, and selective cell division cycle 7 (Cdc7) inhibitor, we optimized the previously reported thieno[3,2-d]pyrimidinone analogue I showing time-dependent Cdc7 kinase inhibition and slow dissociation kinetics. These medicinal chemistry efforts led to the identification of compound 3d, which exhibited potent cellular activity, excellent kinase selectivity, and antitumor efficacy in a COLO205 xenograft mouse model. However, the issue of formaldehyde adduct formation emerged during a detailed study of 3d, which was deemed an obstacle to further development. A structure-based approach to circumvent the adduct formation culminated in the discovery of compound 11b (TAK-931) possessing a quinuclidine moiety as a preclinical candidate. In this paper, the design, synthesis, and biological evaluation of this series of compounds will be presented.

HETEROCYCLIC COMPOUND

Provided is a compound useful for the prophylaxis or treatment of cancer. The present invention relates to a compound represented by formula (I): wherein each symbol in the formula is as defined in the specification, or a salt thereof or a prodrug thereof, which is useful for the prophylaxis or treatment of cancer.

Chirospecific synthesis of conformationally constrained 7-azabicycloheptane amino acids by transannular alkylation

A new method is reported for the chirospecific preparation of optically pure 1-carboxy-7-azabicycloheptane amino acids for the generation of peptidomimetics as conformational probes. The method allows for the multigram preparation of these amino acid analogues through use of a thiolactam sulfide contraction and a transannular alkylation sequence as the key C-C bond-forming steps, starting from L-glutamic acid. The route provides access to two common intermediates, 7-(benzyloxycarbonyl)-1-carboxy-7-azabicyclo[2.2.1]-3-heptane and (1S,4R)-7-(benzyloxycarbonyl)-1-carboxy-7-azabicyclo[2.2.1]-3-heptanon e tert-butyl ester, for elaboration to symmetrical and chiral amino acid homologues, respectively. Decarboxylation of the C-1 carboxy unit of the latter intermediate also demonstrated the applicability of the method for a short, chirospecific preparation of a (+)-epibatidine intermediate, (1S,4R)-7-(tert-butyloxycarbonyl)-1-carboxy-7-azabicyclo[2.2.1]3-hepta none.