38580-83-5Relevant academic research and scientific papers
Visible Light-Catalyzed Benzylic C-H Bond Chlorination by a Combination of Organic Dye (Acr+-Mes) and N-Chlorosuccinimide
Xiang, Ming,Zhou, Chao,Yang, Xiu-Long,Chen, Bin,Tung, Chen-Ho,Wu, Li-Zhu
, p. 9080 - 9087 (2020/08/14)
By combining "N-chlorosuccinimide (NCS)"as the safe chlorine source with "Acr+-Mes"as the photocatalyst, we successfully achieved benzylic C-H bond chlorination under visible light irradiation. Furthermore, benzylic chlorides could be converted to benzylic ethers smoothly in a one-pot manner by adding sodium methoxide. This mild and scalable chlorination method worked effectively for diverse toluene derivatives, especially for electron-deficient substrates. Careful mechanistic studies supported that NCS provided a hydrogen abstractor "N-centered succinimidyl radical,"which was responsible for the cleavage of the benzylic C-H bond, relying on the reducing ability of Acr?-Mes.
Method for preparing N,N-dimethyl-1-alkyl diphenylmethylamine
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Paragraph 0052-0055, (2019/01/21)
The invention discloses a method for preparing N,N-dimethyl-1-alkyl diphenylmethylamine and relates to the field of fine chemical engineering. The method disclosed by the invention comprises the following steps: taking waste alkyl biphenyl recovered in the conventional process as a raw material, carrying out a free radical reaction between the raw material and a halogenating reagent in the presence of a catalyst so as to obtain halogenated alkyl biphenyl; reacting the halogenated alkyl biphenyl and organic alkali to obtain a quaternary ammonium salt; and finally, performing low temperature inversion under liquid ammonia conditions, thereby obtaining N,N-dimethyl-1-(2-methyl-[1,1'-biphenyl]-3-yl) methylamine. Usage of a high-risk reagent lithium aluminum hydride and a strong carcinogen iodomethane can be avoided in the preparation process of the N,N-dimethyl-1-(2-methyl-[1,1'-biphenyl]-3-yl) methylamine, harm to the human body is eliminated, production of three wastes is reduced, the environmental pollution is avoided, and the method is safe and environmental-friendly.
Computer-Assisted Discovery and Structural Optimization of a Novel Retinoid X Receptor Agonist Chemotype
Heitel, Pascal,Gellrich, Leonie,Kalinowsky, Lena,Heering, Jan,Kaiser, Astrid,Ohrndorf, Julia,Proschak, Ewgenij,Merk, Daniel
supporting information, p. 203 - 208 (2019/01/25)
As universal heterodimer partners of many nuclear receptors, the retinoid X receptors (RXRs) constitute key transcription factors. They regulate cell proliferation, differentiation, inflammation, and metabolic homeostasis and have recently been proposed as potential drug targets for neurodegenerative and inflammatory diseases. Owing to the hydrophobic nature of RXR ligand binding sites, available synthetic RXR ligands are lipophilic, and their structural diversity is limited. Here, we disclose the computer-assisted discovery of a novel RXR agonist chemotype and its systematic optimization toward potent RXR modulators. We have developed a nanomolar RXR agonist with high selectivity among nuclear receptors and superior physicochemical properties compared to classical rexinoids that appears suitable for in vivo applications and as lead for future RXR-targeting medicinal chemistry.
Process for synthesizing 2-biphenyl methanol
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Paragraph 0018; 0028; 0029, (2018/10/19)
The invention relates to the technical field of the synthesis of a liquid crystal material intermediate material, in particular to a novel process for synthesizing 2-biphenyl methanol. 2-methyl diphenyl is chlorinated into 2-chloromethyl biphenyl, and then 2-chloromethyl biphenyl is hydrolyzed to 2-biphenyl methanol. In the synthesis process, a mono chlorinated intermediate and a dichlorinated intermediate are directly hydrolyzed into 2-biphenyl methanol and 2-biphenyl formaldehyde without separation, the mixture reduces 2-biphenyl formaldehyde to 2-biphenyl methanol through potassium borohydride, and then the 2-biphenyl methanol finished product is obtained through refining. The process for synthesizing has the advantages of easy availability of raw materials, low cost, simple and convenient operation, friendly environment, good product quality and high yield.
Pd-catalyzed, highly selective C(sp2)-Br bond coupling reactions of o-(or m-, or p-) chloromethyl bromobenzene with arylboronic acids
Pei, Ming-ming,Liu, Ping,Liu, Yan,Lv, Xin-ming,Ma, Xiao-wei,Dai, Bin
, (2018/02/27)
Highly selective C(sp2)–C(sp2) cross-coupling of dihalogenated hydrocarbons comprising C(sp2)–Br and C(sp3)–Cl bonds with arylboronic acids is reported. This highly selective coupling reaction of the C(sp2)–Br bond is successfully achieved using Pd(OAc)2 and PCy3·HBF4 as the palladium source and ligand, respectively. A series of chloromethyl-1,1′-biphenyl compounds are obtained in moderate-to-excellent yields. Moreover, this protocol can be extended to the one-pot dual arylation of 1-bromo-4-(chloromethyl)benzene with two arylboronic acids, leading to diverse unsymmetrical 4-benzyl-1,1′-biphenyl derivatives.
Improving metabolic stability with deuterium: The discovery of GPU-028, a potent free fatty acid receptor 4 agonists
Li, Zheng,Xu, Xue,Li, Gang,Fu, Xiaoting,Liu, Yanzhi,Feng, Yufeng,Wang, Mingyan,Ouyang, Yunting,Han, Jing
, p. 6647 - 6652 (2017/11/20)
The free fatty acid receptor 4 (FFA4) has emerged as a promising anti-diabetic target due to its function in improvement of insulin secretion and insulin resistance. The FFA4 agonist TUG-891 revealed great potential as a widely used pharmacological tool, but it has been suffered from high plasma clearance probably because the phenylpropanoic acid is vulnerable to β-oxidation. To identify metabolically stable analog without influence on physiological mechanism of TUG-891, we tried to incorporate deuterium at the α-position of phenylpropionic acid to afford compound 4 (GPU-028). As expected, GPU-028 revealed a longer half-life (T1/2 = 1.66 h), lower clearance (CL = 0.97 L/h/kg) and higher maximum plasma concentration (Cmax = 2035.23 μg/L), resulting in a 4-fold higher exposure than TUG-891. Although GPU-028 exhibited a similar agonistic activity in comparison to TUG-891, the hypoglycemic effect of GPU-028 was better than that of TUG-891 after treatment over four weeks in diet-induced obese mice. These positive results indicated that GPU-028 might be a better pharmacological tool than TUG-891 to explore physiological function of FFA4, especially on the in vivo study.
Simplifying nickel(0) catalysis: An air-stable nickel precatalyst for the internally selective benzylation of terminal alkenes
Standley, Eric A.,Jamison, Timothy F.
supporting information, p. 1585 - 1592 (2013/03/14)
The synthesis and characterization of the air-stable nickel(II) complex trans-(PCy2Ph)2Ni(o-tolyl)Cl is described in conjunction with an investigation of its use for the Mizoroki-Heck-type, room temperature, internally selective coupling of substituted benzyl chlorides with terminal alkenes. This reaction, which employs a terminal alkene as an alkenylmetal equivalent, provides rapid, convergent access to substituted allylbenzene derivatives in high yield and with regioselectivity greater than 95:5 in nearly all cases. The reaction is operationally simple, can be carried out on the benchtop with no purification or degassing of solvents or reagents, and requires no exclusion of air or water during setup. Synthesis of the precatalyst is accomplished through a straightforward procedure that employs inexpensive, commercially available reagents, requires no purification steps, and proceeds in high yield.
S-farnesyl-thiopropionic acid triazoles as potent inhibitors of isoprenylcysteine carboxyl methyltransferase
Bergman, Joel A.,Hahne, Kalub,Song, Jiao,Hrycyna, Christine A.,Gibbs, Richard A.
supporting information; experimental part, p. 15 - 19 (2012/03/27)
We report the design and synthesis of novel FTPA-triazole compounds as potent inhibitors of isoprenylcysteine carboxyl methyltransferase (Icmt), through a focus on thioether and isoprenoid mimetics. These mimetics were coupled utilizing a copper-assisted cycloaddition to assemble the potential inhibitors. Using the resulting triazole from the coupling as an isoprenyl mimetic resulted in the biphenyl-substituted FTPA triazole 10n. This lipid-modified analogue is a potent inhibitor of Icmt (IC50 = 0.8 ± 0.1 μM; calculated Ki = 0.4 μM).
β-aryl nitrile construction via palladium-catalyzed decarboxylative benzylation of α-cyano aliphatic carboxylate salts
Shang, Rui,Huang, Zheng,Xiao, Xiao,Lu, Xi,Fu, Yao,Liu, Lei
supporting information, p. 2465 - 2472,8 (2020/08/31)
The palladium-catalyzed decarboxylative benzylation of α-cyano aliphatic carboxylate salts with benzyl electrophiles was discovered. This reaction exhibits good functional group compatibility and proceeds under relatively mild conditions. A diverse range of quaternary, tertiary and secondary β-aryl nitriles can be conveniently prepared by this method. Copyright
MODULATORS OF C3A RECEPTOR AND METHODS OF USE THEREOF
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Page/Page column 82, (2008/12/07)
Provided are compounds that are modulators of C3a receptor activity, compositions containing the compounds and methods of use of the compounds and compositions. In certain embodiments, the compounds are pyridones. In certain embodiments, provided are methods for treatment or amelioration of diseases associated with modulation of C3a receptor activity.
