51301-86-1Relevant articles and documents
SUBSTITUTED AMINO TRIAZOLES USEFUL AS CHITINASE INHIBITORS
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Paragraph 0447, (2021/02/05)
Disclosed are amino triazole compounds of formula (I). These compounds are inhibitors of acidic mammalian chitinase and chitotriosidase. Also disclosed are methods of using the compounds to treat asthma reactions caused by allergens, as well as acute and chronic inflammatory diseases, autoimmune diseases, dental diseases, neurologic diseases, metabolic diseases, liver diseases, polycystic ovary syndrome, endometriosis, and cancer.
Discovery of OATD-01, a First-in-Class Chitinase Inhibitor as Potential New Therapeutics for Idiopathic Pulmonary Fibrosis
Koralewski, Robert,Dymek, Barbara,Mazur, Marzena,Sklepkiewicz, Piotr,Olejniczak, Sylwia,Czestkowski, Wojciech,Matyszewski, Krzysztof,Andryianau, Gleb,Niedziejko, Piotr,Kowalski, Michal,Gruza, Mariusz,Borek, Bart?omiej,Jedrzejczak, Karol,Bartoszewicz, Agnieszka,Pluta, El?bieta,Rymaszewska, Aleksandra,Kania, Magdalena,Rejczak, Tomasz,Piasecka, Sylwia,Mlacki, Michal,Mazurkiewicz, Marcin,Piotrowicz, Micha?,Salamon, Magdalena,Zagozdzon, Agnieszka,Napiorkowska-Gromadzka, Agnieszka,Bartlomiejczak, Aneta,Mozga, Witold,Dobrzański, Pawe?,Dzwonek, Karolina,Golab, Jakub,Nowotny, Marcin,Olczak, Jacek,Golebiowski, Adam
supporting information, p. 15527 - 15540 (2020/11/17)
Chitotriosidase (CHIT1) and acidic mammalian chitinase (AMCase) are the enzymatically active chitinases that have been implicated in the pathology of chronic lung diseases such as asthma and interstitial lung diseases (ILDs), including idiopathic pulmonary fibrosis (IPF) and sarcoidosis. The clinical and preclinical data suggest that pharmacological inhibition of CHIT1 might represent a novel therapeutic approach in IPF. Structural modification of an advanced lead molecule 3 led to the identification of compound 9 (OATD-01), a highly active CHIT1 inhibitor with both an excellent PK profile in multiple species and selectivity against a panel of other off-targets. OATD-01 given orally once daily in a range of doses between 30 and 100 mg/kg showed significant antifibrotic efficacy in an animal model of bleomycin-induced pulmonary fibrosis. OATD-01 is the first-in-class CHIT1 inhibitor, currently completed phase 1b of clinical trials, to be a potential treatment for IPF.
Synthesis of an amidosulfonate-tagged biphenyl phosphine and its application in the Suzuki-Miyaura reaction affording biphenyl-substituted amino acids in water
Schulz, Ji?í,Císa?ová, Ivana,?těpni?ka, Petr
, p. 65 - 72 (2015/03/04)
An amidosulfonate-tagged phosphinobiphenyl, viz triethylammonium 2-(dicyclohexylphosphino)-4′-{[(sulfonatomethyl)amino]carbonyl}biphenyl (3), was prepared in two steps from 2-(dicyclohexylphosphino)biphenyl-4′-carboxylic acid and fully characterized including the crystal structure determination. As a highly polar phosphine ligand, compound 3 was employed in the Pd-catalyzed Suzuki-Miyaura cross-coupling of N-Boc protected 4-bromo and 4-chlorophenylalanine with aromatic boronic acids to afford the corresponding biphenyls in aqueous N,N-dimethylformamide or pure water. The coupling was demonstrated to proceed very well and without the loss of the Boc protecting group when the bromo-substituted substrate is reacted in the presence of 1 mol.% of Pd/3 catalyst in water at 40 °C. Reactions with boronic acids bearing electron-withdrawing substituents and, mainly, those with the less reactive chlorophenylalanine substrate required slightly higher reaction temperature and more catalyst to achieve similar results.