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 process for preparing 2, 2 - dimethyl butyric acid (by machine translation)
-
Paragraph 0044; 0045; 0046; 0047; 0048; 0049; 0050-0074, (2019/04/26)
A 2, 2 - dimethyl butyric acid preparation process, relates to the field of chemical synthesis. The 2, 2 - dimethyl butyric acid and the preparing process comprises: will be ert-amyl halogen magnesium format after the addition reaction of the reagent with the carbon dioxide obtained by the hydrolysis, it adopts ert-amyl halogen magnesium format reagent with the carbon dioxide to carbonyl addition reaction, the preparation process is simple in operation, easily available raw materials, high yield, while at the same time the finished product made easy to purify, after the purification can be up to 99% and above, has better application prospect. (by machine translation)
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.