595-37-9Relevant articles and documents
Identification of 2,2-Dimethylbutanoic Acid (HST5040), a Clinical Development Candidate for the Treatment of Propionic Acidemia and Methylmalonic Acidemia
Armstrong, Allison J.,Henke, Brad R.,Collado, Maria Sol,Taylor, Justin M.,Pourtaheri, Taylor D.,Dillberger, John E.,Roper, Thomas D.,Wamhoff, Brian R.,Olson, Matthew W.,Figler, Robert A.,Hoang, Stephen A.,Reardon, John E.,Johns, Brian A.
, p. 5037 - 5048 (2021)
Propionic acidemia (PA) and methylmalonic acidemia (MMA) are rare autosomal recessive disorders of propionyl-CoA (P-CoA) catabolism, caused by a deficiency in the enzymes P-CoA carboxylase and methylmalonyl-CoA (M-CoA) mutase, respectively. PA and MMA are classified as intoxication-type inborn errors of metabolism because the intramitochondrial accumulation of P-CoA, M-CoA, and other metabolites results in secondary inhibition of multiple pathways of intermediary metabolism, leading to organ dysfunction and failure. Herein, we describe the structure-activity relationships of a series of short-chain carboxylic acids which reduce disease-related metabolites in PA and MMA primary hepatocyte disease models. These studies culminated in the identification of 2,2-dimethylbutanoic acid (10, HST5040) as a clinical candidate for the treatment of PA and MMA. Additionally, we describe the in vitro and in vivo absorption, distribution, metabolism, and excretion profile of HST5040, data from preclinical studies, and the synthesis of the sodium salt of HST5040 for clinical trials.
A 2, 2 - dimethyl butyric acid
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, (2019/04/13)
The invention relates to a pesticide synthesis technology field, discloses a 2, 2 - dimethyl butyric acid, use chloro- uncle pentane preparing Grignard reagent, then with the ester compound produced by the reaction of 2, 2 - dimethyl ester, followed by hydrolysis to obtain 2, 2 - dimethyl butyric acid. To avoid the traditional production of large amount of sulfuric acid used in the method of defect, reducing the risk of the working personnel, and the use of some conventional chemical reagent can prepare 2, 2 - dimethyl butyric acid, convenient to make the 2, 2 - dimethyl butyric acid.
Palladium-catalyzed 2-pyridylmethyl-directed β-C(sp3)–H activation and cyclization of aliphatic amides with gem-dibromoolefins: A rapid access to γ-lactams
Zhou, Danni,Wang, Chunxia,Li, Mingliang,Long, Zheng,Lan, Jingbo
supporting information, p. 191 - 193 (2017/11/17)
The direct Pd-catalyzed β-C(sp3)–H activation and cyclization of aliphatic amides bearing a removable 2-pyridylmethyl directing group with gem-dibromoolefins is described for the first time to construct a variety of γ-lactams. The resulting products with Z- and E-configurations can be easily separated and purified after the reaction, demonstrating the effectiveness and applicability of the method herein developed.