940-31-8Relevant academic research and scientific papers
INHIBITORS TO TARGET HIV-1 NEF-CD80/CD86 INTERACTIONS FOR THERAPEUTIC INTERVENTION
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Paragraph 000169; 000186; 000187; 000188, (2020/03/05)
The compounds of Formula I, II, and III along with their stereoisomers, pharmaceutically acceptable salts, polymorphs, solvates and hydrates thereof are described in the present disclosure. The said compounds restore immune activation in case of infections or a disease associated with an HIV infection in a subject in need thereof.
Access to Optically Enriched α-Aryloxycarboxylic Esters via Carbene-Catalyzed Dynamic Kinetic Resolution and Transesterification
Liu, Bin,Song, Runjiang,Xu, Jun,Majhi, Pankaj Kumar,Yang, Xing,Yang, Song,Jin, Zhichao,Chi, Yonggui Robin
supporting information, p. 3335 - 3338 (2020/04/30)
Optically active α-aryloxycarboxylic acids and their derivatives are important functional molecules. Disclosed here is a carbene-catalyzed dynamic kinetic resolution and transesterification reaction for access to this class of molecules with up to 99% yields and 99:1 er values. Addition of a chiral carbene catalyst to the ester substrate leads to two diastereomeric azolium ester intermediates that can quickly epimerize to each other and thus allows for effective dynamic kinetic resolution to be realized. The optically enriched ester products from our reaction can be quickly transformed to chiral herbicides and other bioactive molecules.
PRMT5 INHIBITORS AND USES THEREOF
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Paragraph 0267-0268, (2019/04/05)
Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.
Synthesis process of 2-phenoxypropionyl chloride
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Paragraph 0030; 0031, (2018/05/16)
The invention discloses a synthesis process of 2-phenoxypropionyl chloride. The synthesis process comprises the following steps: (1) under conditions of water and alkali, by taking phenol and 2-chloropropionic acid as raw materials, carrying out reaction, adding acid at the end of the reaction to adjust the pH till the solution is in a faintly acid state, and carrying out suction filtering to obtain 2-phenoxypropionic acid; (2) dissolving the 2-phenoxypropionic acid in an organic solvent, adding an acyl chlorinating agent for reaction, removing the organic solvent at the end of the reaction, and collecting a fraction with temperature of 80 DEG C, so as to obtain the 2-phenoxypropionyl chloride, wherein a mole ratio of the phenol to the 2-chloropropionic acid is 1 to 1.2-1.5; a mole ratio of the phenol and the alkali is 1 to 1.2-5.0; a mole ratio of solid powder a and the acyl chlorinating agent is 1 to 1.2-2.0. The method disclosed by the invention is easy to operate; selected reactionconditions are mild (0 to 80 DEG C); selected reagents are readily available; the amount of waste gas, wastewater and solid wastes is small; the synthesis process is environmentally friendly and lowin harm to a human body.
PRMT5 INHIBITORS CONTAINING A DIHYDRO- OR TETRAHYDROISOQUINOLINE AND USES THEREOF
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Paragraph 00275, (2014/07/08)
Described herein are compounds of Formula (A), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5- mediated disorders are also described.
Optimization of benzoxazole-based inhibitors of Cryptosporidium parvum inosine 5′-monophosphate dehydrogenase
Gorla, Suresh Kumar,Kavitha, Mandapati,Zhang, Minjia,Chin, James En Wai,Liu, Xiaoping,Striepen, Boris,Makowska-Grzyska, Magdalena,Kim, Youngchang,Joachimiak, Andrzej,Hedstrom, Lizbeth,Cuny, Gregory D.
, p. 4028 - 4043 (2013/06/27)
Cryptosporidium parvum is an enteric protozoan parasite that has emerged as a major cause of diarrhea, malnutrition, and gastroenteritis and poses a potential bioterrorism threat. C. parvum synthesizes guanine nucleotides from host adenosine in a streamlined pathway that relies on inosine 5′-monophosphate dehydrogenase (IMPDH). We have previously identified several parasite-selective C. parvum IMPDH (CpIMPDH) inhibitors by high-throughput screening. In this paper, we report the structure-activity relationship (SAR) for a series of benzoxazole derivatives with many compounds demonstrating CpIMPDH IC50 values in the nanomolar range and >500-fold selectivity over human IMPDH (hIMPDH). Unlike previously reported CpIMPDH inhibitors, these compounds are competitive inhibitors versus NAD +. The SAR study reveals that pyridine and other small heteroaromatic substituents are required at the 2-position of the benzoxazole for potent inhibitory activity. In addition, several other SAR conclusions are highlighted with regard to the benzoxazole and the amide portion of the inhibitor, including preferred stereochemistry. An X-ray crystal structure of a representative E·IMP·inhibitor complex is also presented. Overall, the secondary amine derivative 15a demonstrated excellent CpIMPDH inhibitory activity (IC 50 = 0.5 ± 0.1 nM) and moderate stability (t1/2 = 44 min) in mouse liver microsomes. Compound 73, the racemic version of 15a, also displayed superb antiparasitic activity in a Toxoplasma gondii strain that relies on CpIMPDH (EC50 = 20 ± 20 nM), and selectivity versus a wild-type T. gondii strain (200-fold). No toxicity was observed (LD 50 > 50 μM) against a panel of four mammalian cells lines.
Electron-transfer-induced reductive cleavage of chlorinated aryloxyalkanoic acids
Azzena, Ugo,Pittalis, Mario
experimental part, p. 3360 - 3362 (2011/06/11)
We investigated the degradation of chlorinated herbicides, with an aryloxyalkanoic acid skeleton, under reductive electron transfer reaction conditions. Although Li and Na metals proved useless, activated forms of these metals, either their soluble naphthalene radical anions or 1,2-diarylethane dianions, promoted the degradation of the starting materials to various extents. Indeed, lithium naphthalenide promoted both extensive dehalogenation and dealkylation of chlorinated aryloxyalkanoic acids, with formation of the corresponding phenols as the main reaction products. In contrast, the employment of 1,2-diphenyl-1,2-disodioethane as a reducing agent led, in most examples, to the chemoselective recovery of the corresponding dechlorinated acids.
Kinetic resolution of α-substituted alkanoic acids promoted by homobenzotetramisole
Yang, Xing,Birman, Vladimir B.
supporting information; experimental part, p. 11296 - 11304 (2011/10/19)
A new method for catalytic nonenzymatic kinetic resolution of α-substituted alkanoic acids has been developed, which relies on their activation with DCC followed by enantioselective alcoholysis of the intermediate symm-anhydrides in the presence of the amidine-based catalyst homobenzotetramisole (HBTM). Moderate to excellent selectivity factors (s=5-96) have been obtained in the case of several classes of substrates, namely, α-aryl-, α-aryloxy/alkoxy-, α-halo-, α-azido-, and α-phthalimido-alkanoic acids. Under similar conditions, α-(arylthio/alkylthio)-alkanoic acids undergo dynamic kinetic resolution providing corresponding esters in up to 92 % ee and up to 93 % yield. Copyright
A great improvement of the enantioselectivity of lipase-catalyzed hydrolysis and esterification using co-solvents as an additive
Nishigaki, Tomohiro,Yasufuku, Yoshitaka,Murakami, Sayuri,Ebara, Yasuhito,Ueji, Shin-Ichi
experimental part, p. 617 - 622 (2009/04/11)
Addition of co-solvents such as tetrahydrofuran resulted in a great improvement of the enantioselectivity of lipase-catalyzed hydrolysis of butyl 2-(4-substituted phenoxy)propanoates in an aqueous buffer solution. On the other hand, lipase lyophilized from an aqueous solution containing the co-solvents catalyzed highly enantioselective esterification of 2-(4-substituted phenoxy)propionic acids, 2-(4-isobutylphenyl)propionic acid (ibuprofen), and 2-(6-methoxy-2-naph-thyl)propionic acid (naproxen) in an organic solvent. An increase in the E value up to two orders of magnitude was observed for some substrates. The origin of the enantioselectivity enhancement caused by the co-solvent addition was mainly attributed to a significant deceleration in the initial reaction rate for the incorrectly binding enantiomer, as compared with that for the correctly binding enantiomer. From the results of FT-1R, CD, and ESR spectra, the co-solvent addition was also found to bring about a partial destruction of the tertiary structure of lipase.
Chlorination of 2-phenoxypropanoic acid with NCP in aqueous acetic acid: Using a novel ortho-para relationship and the para/meta ratio of substituent effects for mechanism elucidation
Segurado, Manuel A. P.,Reis, Joao Carlos R.,De Oliveira, Jaime D. Gomes,Kabilan, Senthamaraikannan,Shanthi, Manohar
, p. 5327 - 5336 (2008/02/07)
(Graph Presented) Rate constants were measured for the oxidative chlorodehydrogenation of (R,S)-2-phenoxypropanoic acid and nine ortho-, ten para- and five meta-substituted derivatives using (R,S)-1-chloro-3-methyl-2,6- diphenylpiperidin-4-one (NCP) as chlorinating agent. The kinetics was run in 50% (v/v) aqueous acetic acid acidified with perchloric acid under pseudo-first-order conditions with respect to NCP at temperature intervals of 5 K between 298 and 318 K, except at the highest temperature for the meta derivatives. The dependence of rate constants on temperature was analyzed in terms of the isokinetic relationship (IKR). For the 20 reactions studied at five different temperatures, tne isokinetic temperature was estimated to be 382 K, which suggests the preferential involvement of water molecules in the rate-determining step. The dependence of rate constants on meta and para substitution was analyzed using the tetralinear extension of the Hammett equation. The parameter λ for the para/meta ratio of polar substituent effects was estimated to be 0.926, and its electrostatic modeling suggests the formation of an activated complex bearing an electric charge near the oxygen atom belonging to the phenoxy group. A new approach is introduced for examining the effect of ortho substituents on reaction rates. Using IKR-determined values of activation enthalpies for a set of nine pairs of substrates with a given substituent, a linear correlation is found between activation enthalpies of ortho and para derivatives. The correlation is interpreted in terms of the selectivity of the reactant toward para- or ortho-monosubstituted substrates, the slope of which being related to the ortho effect. This slope is thought to be approximated by the ratio of polar substituent effects from ortho and para positions in benzene derivatives. Using the electrostatic theory of through-space interactions and a dipole length of 0.153 nm, this ratio was calculated at various positions of a charged reaction center along the benzene C1-C4 axis, being about 2.5 near the ring and decreasing steeply with increasing distance until reaching a minimum value of -0.565 at 1.3 nm beyond the aromatic ring. Activation enthalpies and entropies were estimated for substrates bearing the isoselective substituent in either ortho and para positions, being demonstrated that they are much different from the values for the parent substrate. The electrophilic attack on the phenolic oxygen atom by the protonated chlorinating agent is proposed as the rate-determining step, this step being followed by the fast rearrangement of the intermediate thus formed, leading to products containing chlorine in the aromatic ring.
