01695nas a2200205   4500008004100000022001400041245010500055210006900160260000800229300001100237490000800248520097100256653002401227653001501251653002301266100002301289700002401312700002501336856012801361       2024                        eng d  a0040-403900aAlternative synthetic route for the pharmacophore of anticancer agent: triazolopyridazine derivative0 aAlternative synthetic route for the pharmacophore of anticancer   cAUG  a1551930 v1463 a<p>
	ATAD2 has received attention as one of the potential oncogene with tumor-promoting aspects in many malignancies. ATAD2 is a highly conserved bromodomain family protein that exerts its biological functions by mainly AAA ATPase and bromodomain. Several small molecule inhibitors have been described in the literature. AZ13824374 (1) recently reported by Holt and co-workers showed promising in vitro (bio-chemical, cellular) and antiproliferative activity in range of breast cancer models. In this work, we described scalable synthetic route for triazolopyridazine derivative (2), a key intermediate of AZ13824374 (1) without using CO in the process. Triazolopyridazine helps to attain the bioactive conformation for AZ13824374 (1) through its crucial interaction with Tyr 1021 of ATAD2. Additionally, triazolopyridazine is extensively used as an intermediate for anticancer agents. This encouraged us to develop cost-effective and scalable process for it.</p>
10aAlternative process10aAnticancer10aTriazolopyridazine1 aKarche, Ranjit, S.1 aBankar, Shubham, R.1 aJadhav, Vrushali, H.  uhttps://library.ncl.res.in/content/alternative-synthetic-route-pharmacophore-anticancer-agent-triazolopyridazine-derivative01916nas a2200217   4500008004100000022001400041245018700055210006900242260000900311300001100320490000700331520108900338653001401427653001601441653001701457653002101474100002301495700002401518700002501542856013101567       2026                        eng d  a2365-654900aLiquid-assisted grinding mechanochemical approach for direct amidation of pyridone-carboxylic acid to synthesize an intermediate used in anti-viral API's bictegravir and cabotegravir0 aLiquidassisted grinding mechanochemical approach for direct amid  cAPR   ae057510 v113 a<p>
	Mechanochemistry is viewed as an appealing alternative for the synthesis of various compounds, since it is regarded as an eco-friendly and economical method that can be performed under solvent-free reaction conditions. In this work, neat grinding and liquid-assisted grinding (LAG) methods for direct amidation of pyridone-carboxylic acid and 2,4,6-trifluorobenzylamine/2,4-difluorobenzylamine were studied using EDC.HCl as a coupling reagent to synthesize important intermediates used in the synthesis of anti-HIV drug molecules bictegravir, cabotegravir, and dolutegravir. The products were easy to separate as they easily precipitated out from water, and the purity of the products obtained was similar to 97% for the intermediates, thus avoiding the need for their purification. This process eliminated the use of organic solvents for the reaction as well as for the work-up and product purification. The reaction was scaled up on a 15-g scale, giving good yields of the intermediates. The process was found to be practical, scalable, and reproducible on a gram scale.</p>
10aamidation10abictegravir10acabotegravir10amechanochemistry1 aKarche, Ranjit, S.1 aBankar, Shubham, R.1 aJadhav, Vrushali, H.  uhttps://library.ncl.res.in/content/liquid-assisted-grinding-mechanochemical-approach-direct-amidation-pyridone-carboxylic-acid