34583-63-6Relevant academic research and scientific papers
SSAO INHIBITORS AND USE THEREOF
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Paragraph 00402, (2021/05/07)
Provided are a compound of formula (I') or (I), a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, which modulates the activity of SSAO, a pharmaceutical composition comprising a compound of formula (I') or (I), and a method of treating or preventing a disease in which SSAO plays a role.
The discovery of a potent and selective pyrazolo-[2,3-e]-[1,2,4]-triazine cannabinoid type 2 receptor agonist
Moir, Michael,Lane, Samuel,Montgomery, Andrew P.,Hibbs, David,Connor, Mark,Kassiou, Michael
, (2020/12/21)
The development of selective CB2 receptor agonists is a promising therapeutic approach for the treatment of inflammatory diseases, without CB1 receptor mediated psychoactive side effects. Preliminary structure-activity relationship studies on pyrazoylidene benzamide agonists revealed the -ylidene benzamide moiety was crucial for functional activity at the CB2 receptor. A small library of compounds with varying linkage moieties between the pyrazole and substituted phenyl group has culminated in the discovery of a potent and selective pyrazolo-[2,3-e]-[1,2,4]-triazine agonist 19 (CB2R EC50 = 19 nM, CB1R EC50 > 10 μM). Docking studies have revealed key structural features of the linkage group that are important for potent functional activity.
5-OXA-2-AZASPIRO[3.4]OCTANE DERIVATIVES AS M4 AGONISTS
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Page/Page column 136; 73, (2021/04/17)
Provided herein are compounds according to Formula (I) or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R5, and R7 are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I) as well as the use of such compounds as M4 receptor agonists.
5-AMINO-8-(4-PYRIDYL)-[1,2,4]TRIAZOLO[4,3-C]PYRIMIDIN-3-ONE COMPOUNDS FOR USE AGAINST CANCER
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Page/Page column 65-66, (2021/10/02)
Described herein are triazalone compounds of Formula (I) and pharmaceutically acceptable salts thereof. Methods of making and using compounds of Formula (I) are also described. Compounds of Formula (I) and pharmaceutically acceptable salts thereof can be
C-2 auxiliaries for stereoselective glycosylation based on common additive functional groups
Boltje, Thomas J.,De Kleijne, Frank F. J.,Moons, Sam J.,White, Paul B.
, p. 1165 - 1184 (2020/02/22)
The stereoselective introduction of the glycosidic bond is one of the main challenges in chemical oligosaccharide synthesis. Stereoselective glycosylation can be achieved using neighbouring group participation of a C-2 auxiliary or using additives, for example. Both methods aim to generate a defined reactive intermediate that reacts in a stereoselective manner with alcohol nucleophiles. This inspired us to develop new C-2 auxiliaries based on commonly used additive functionalities such as ethers, phosphine oxides and tertiary amides. Good 1,2-trans-selectivity was observed for the phosphine oxide and amide-based auxiliaries expanding the toolbox with new auxiliaries for stereoselective glycosylation reactions.
Structure-activity relationship studies of (E)-3,4-dihydroxystyryl alkyl sulfones as novel neuroprotective agents based on improved antioxidant, anti-inflammatory activities and BBB permeability
Chen, Ying,Wu, Bolin,Hao, Yameng,Liu, Yunqi,Zhang, Zhili,Tian, Chao,Ning, Xianling,Guo, Ying,Liu, Junyi,Wang, Xiaowei
, p. 420 - 433 (2019/03/29)
(E)-3,4-dihydroxystyryl alkyl sulfones, as new analogues of neurodegenerative agents, were designed and synthesized. The biological results demonstrated that most of the target compounds preserved antioxidant and anti-inflammatory potency in scavenging reactive free radicals, protecting neuronal cells against neurotoxins such as H2O2, 6-hydroxydopamine and inhibiting lipopolysaccharide (LPS)-induced over-production of NO. Among these compounds, 6.22 with cyclopentyl propyl exhibited prominent antioxidant activity at low concentration (2.5 μM) in H2O2 model (cell viability = 94.5%). In addition, 6.22 (IC50 = 1.6 μM) displayed better anti-inflammatory activity than that of lead compound 1 (IC50 = 13.4 μM). In view of the outstanding performance of 6.22, the apoptotic rates of H2O2-damaged PC12 cells were detected by Annexin V-FITC/PI assay. 6.22 showed higher potency in inhibition of apoptosis than 1 at low concentration (2.5 μM), consisting with the antioxidant and anti-inflammatory models. Furthermore, with the predicted CNS (+) blood-brain barrier (BBB) permeability (Pe = 6.84 × 10?6 cm s?1), low cytotoxicity and favorable physiochemical properties based on calculation, compound 6.22 can be further developed as a potential multifunctional neuroprotective agent.
Photoredox Reaction of 2-Mercaptothiazolinium Salts with Silyl Enol Ethers
Zemtsov, Artem A.,Ashirbaev, Salavat S.,Levin, Vitalij V.,Kokorekin, Vladimir A.,Korlyukov, Alexander A.,Dilman, Alexander D.
, (2019/11/29)
A method for the generation of free radicals from thiazolinium salts upon photocatalytic reduction is described. The thiazolinium salts are generated by treatment with methyl triflate of 2-mercaptothiazolines, which can be readily obtained from alkyl bromides and tosylates via a nucleophilic substitution reaction or by hydrothiolation of alkenes. Silyl enol ethers were used to trap the radicals, furnishing ketones after successive single-electron oxidation and elimination of the silyl cation.
MANUFACTURING METHOD OF 1,1-DISUBSTITUTED HYDRAZINE COMPOUND
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Paragraph 0053-0055; 0062-0064, (2020/01/23)
PROBLEM TO BE SOLVED: To provide a manufacturing method of a 1,1-disubstituted hydrazine compound useful as a manufacturing intermediate. SOLUTION: There is provided a manufacturing method of a 1,1-disubstituted hydrazine compound represented by the formula (3) by reacting a hydrazino compound represented by the formula (1) with a compound represented by the formula (2): R-A in the presence of a correlation transfer catalyst, and a base such as alkali metal hydroxide, alkali earth metal hydroxide, and alkali metal alkoxide in a mixed solvent of water and a water insoluble organic solvent. In the formula, Q represents O, S or the like; R represents a C1 to 12 organic group which may have a substituent; A represents Cl, Br, a tosyl group or the like; Ra1 to Ra4 each independently represent H, a halogen atom, a C1 to 6 alkyl group, or the like. SELECTED DRAWING: None COPYRIGHT: (C)2020,JPOandINPIT
Anti-Selective Catalytic Asymmetric Nitroaldol Reaction of α-Keto Esters: Intriguing Solvent Effect, Flow Reaction, and Synthesis of Active Pharmaceutical Ingredients
Karasawa, Tomoya,Oriez, Rapha?l,Kumagai, Naoya,Shibasaki, Masakatsu
, p. 12290 - 12295 (2018/09/27)
A rare-earth metal/alkali metal bimetallic catalyst proved particularly effective for enantioselectively coupling nitroalkanes and α-keto esters in an anti-selective manner to afford synthetically versatile, densely functionalized, and optically active α-nitro tertiary alcohols. A chiral diamide ligand captured two distinct metal cations, giving rise to a catalytically competent solid-phase heterobimetallic catalyst by simple mixing via self-assembly. The advantage of the solid-phase asymmetric catalyst was realized by successful application to the enantio- and diastereoselective reaction in a continuous-flow platform. The use of closely related solvents in terms of structures and polarity parameters, THF and its methylated congener 2-Me-THF, had an unexpectedly large solvent effect both on the reaction rate and the stereoselectivity. The nitroaldol products share a privileged unit for active pharmaceutical ingredients, as demonstrated by the streamlined enantioselective synthesis of the marketed antifungal agents efinaconazole and albaconazole.
Palladium-Catalyzed Atom-Transfer Radical Cyclization at Remote Unactivated C(sp3)?H Sites: Hydrogen-Atom Transfer of Hybrid Vinyl Palladium Radical Intermediates
Ratushnyy, Maxim,Parasram, Marvin,Wang, Yang,Gevorgyan, Vladimir
supporting information, p. 2712 - 2715 (2018/03/02)
A novel mild, visible-light-induced palladium-catalyzed hydrogen atom translocation/atom-transfer radical cyclization (HAT/ATRC) cascade has been developed. This protocol involves a 1,5-HAT process of previously unknown hybrid vinyl palladium radical intermediates, thus leading to iodomethyl carbo- and heterocyclic structures.
