96923-01-2Relevant articles and documents
Rational Design and Evaluation of 6-(Pyrimidin-2-ylamino)-3,4-dihydroquinoxalin-2(1 H)-ones as Polypharmacological Inhibitors of BET and Kinases
Lv, Kaikai,Chen, Weicong,Chen, Danqi,Mou, Jie,Zhang, Huijie,Fan, Tiantian,Li, Yanlian,Cao, Danyan,Wang, Xin,Chen, Lin,Shen, Jingkang,Pei, Dongsheng,Xiong, Bing
, p. 9787 - 9802 (2020/10/19)
Cancer exhibits diverse heterogeneity with a complicated molecular basis that usually harbors genetic and epigenetic abnormality, which poses a big challenge for single-target agents. In the current work, we proposed a hybrid strategy by incorporating pharmacophores that bind to the acetylated lysine binding pocket of BET proteins with a typical kinase hinge binder to generate novel polypharmacological inhibitors of BET and kinases. Through elaborating the core structure of 6-(pyrimidin-2-ylamino)-3,4-dihydroquinoxalin-2(1H)-one, we demonstrated that this rational design can produce high potent inhibitors of CDK9 and BET proteins. In this series, compound 40 was identified as the potential lead compound with balanced activities of BRD4 (IC50 = 12.7 nM) and CDK9 (IC50 = 22.4 nM), as well as good antiproliferative activities on a small cancer cell panel. Together, the current study provided a new method for the discovery of bromodomain and kinase dual inhibitors rather than only being discovered by serendipity.
1-CYANO-PYRROLIDINE DERIVATIVES AS INHIBITORS OF USP30.
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Page/Page column 53, (2018/02/03)
The present invention relates to novel compounds and methods for the manufacture of inhibitors of deubiquitylatingenzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C- terminal hydrolase 30 or Ubiquitin Specific Peptidase 30 (USP30). The invention further relates to the use of DUB inhibitors in the treatment of conditions involving mitochondrial dysfunction and cancer. Compounds of the invention include compounds having the formula (I) (I) or a pharmaceutically acceptable salt thereof, wherein R1, R 2, R 3, m, L and X are as defined herein.
Poly(: O -aminothiophenol)-stabilized Pd nanoparticles as efficient heterogenous catalysts for Suzuki cross-coupling reactions
Chen, Yuan,Wang, Minggui,Zhang, Long,Liu, Yan,Han, Jie
, p. 47104 - 47110 (2017/10/16)
Poly(o-aminothiophenol) (PATP)-stabilized Pd nanoparticles with Pd nanoparticles embedded in a polymer matrix have been obtained through a facile one-step route by mixing o-aminothiophenol monomer and Pd(NO3)2 in an acidic aqueous solution without additional template or surfactant. The redox reaction between o-aminothiophenol and Pd(NO3)2 leads to the simultaneous formation of a PATP polymer and Pd nanoparticles. The PATP-stabilized Pd nanoparticles have been characterized by TEM, FTIR, XRD, ICP-MS and XPS. Catalytic results showed that PATP-stabilized Pd nanoparticles were highly stable and active catalysts for Suzuki cross-coupling reactions, where high yields could be achieved with arylboronic acid and aryl halides bearing a variety of substituents.
3-Hydroxypyrimidine-2,4-diones as Selective Active Site Inhibitors of HIV Reverse Transcriptase-Associated RNase H: Design, Synthesis, and Biochemical Evaluations
Tang, Jing,Liu, Feng,Nagy, Eva,Miller, Lena,Kirby, Karen A.,Wilson, Daniel J.,Wu, Bulan,Sarafianos, Stefan G.,Parniak, Michael A.,Wang, Zhengqiang
, p. 2648 - 2659 (2016/04/10)
Human immunodeficiency virus (HIV) reverse transcriptase (RT) associated ribonuclease H (RNase H) remains an unvalidated antiviral target. A major challenge of specifically targeting HIV RNase H arises from the general lack of selectivity over RT polymerase (pol) and integrase (IN) strand transfer (ST) inhibitions. We report herein the synthesis and biochemical evaluations of three novel 3-hydroxypyrimidine-2,4-dione (HPD) subtypes carefully designed to achieve selective RNase H inhibition. Biochemical studies showed the two subtypes with an N-1 methyl group (9 and 10) inhibited RNase H in low micromolar range without siginificantly inhibiting RT polymerase, whereas the N-1 unsubstituted subtype 11 inhibited RNase H in submicromolar range and RT polymerase in low micromolar range. Subtype 11 also exhibited substantially reduced inhibition in the HIV-1 INST assay and no significant cytotoxicity in the cell viability assay, suggesting that it may be amenable to further structure-activity relationship (SAR) for identifying RNase H inhibitors with antiviral activity.
Pd/mannose promoted tandem cross coupling-nitro reduction: Expedient synthesis of aminobiphenyls and aminostilbenes
Rohilla, Sandeep,Pant, Pradeep,Jain, Nidhi
, p. 31311 - 31317 (2015/04/22)
The dual role of d-mannose as a ligand for Pd catalyzed cross-coupling, and as a hydrogen source for nitro reduction is demonstrated in a modular cross coupling-nitro reduction sequence. The synthetic utility and generality of this green protocol has been illustrated by the synthesis of 20 aminobiphenyl and 10 aminostilbene derivatives in high yields through a one-pot Suzuki coupling-nitro reduction and a Heck coupling-nitro reduction, respectively, starting from halonitroarenes as substrates.
THERAPEUTIC COMPOUNDS
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Page/Page column 68, (2010/11/27)
This invention relates to a novel class of substituted amino-ethoxy benzene derivatives of formula (I) which are inhibitors of serine proteases and to their use in treating aberrant serine protease activity in a mammal, contraception, anti-coagulant methods and methods for treating aberrant cell proliferation, tumours, cancer, angiogenesis, angiogenesis-based retinopathies, autoimmummune disease, inflammation, skin disease, arthritis, rheutmatoid arthritis, asthma, osteoarthritis and multiple sclerosis. (I), Wherein Rm, Rn, Rp, Rq, V, W, X, Y and R8 are as defined in the claims.
Simple amine/Pd(OAc)2-catalyzed Suzuki coupling reactions of aryl bromides under mild aerobic conditions
Tao, Bin,Boykin, David W.
, p. 4330 - 4335 (2007/10/03)
A new palladium catalyst (DAPCy) made from Pd(OAc)2 and commercially available, inexpensive dicyclohexylamine has been developed for the Suzuki coupling reaction of aryl bromides with boronic acids to give the coupling products in good to high yields. The air-stable catalyst was characterized and well-defined by X-ray crystallography. A catalytic system involving DAPCy in dioxane demonstrates a temperature-dependent reactivity toward aryl bromides with different electronic substituents, and selectively couples electron-deficient aryl bromides with boronic acids over electron-rich ones at room temperature. Another catalytic system employing DAPCy in EtOH provides a general and convenient method to prepare biaryls from aryl bromides and boronic acids with a broad range of functional groups at room temperature and under aerobic conditions.
SYNTHESES AND PROPERTIES OF ARENEDIAZONIUM AND ANILINIUM CATION LARIAT ETHER COMPLEXES: AN "OSTRICH MOLECULE" COMPLEX AND EVIDENCE FOR INTRAMOLECULAR SIDEARM - MACRORING INTERACTION
Beadle, James R.,Dishong, Dennis M.,Khanna, Raj K.,Gokel, George W.
, p. 3935 - 3944 (2007/10/02)
The preparation of several novel lariat ethers (macrocyclic crown polyethers having sidearms bearing pendant donor groups) is reported.These compounds are ethers derived from known 2-hydroxymethyl-15-crown-5 or -21-crown-7.The sidearms include 2-aminophenyl, 2,4-diaminophenyl, 2-nitrophenyl, 2-(3'-nitrobiphenyl), and 2-(3'-aminobiphenyl).In several cases, the amino groups were converted into ammonium salts which showed substantial stabilization by intramolecular hydrogen bonding.Likewise, an -NH2(1+)*BF3(1-) complex showed evidence of intramolecular hydrogen bonding.Diazotization of the aminobiphenyl residue produced an arenediazonium cation which underwent intramolecular crown complexation, as judged by infrared spectroscopic studies to form what we call an "ostrich molecule" complex.Addition of N,N-dimethylaniline to the intramolecular arenediazonium cation complex afforded an azo compound, but europium shift reagent studies showed clearly that the diazonium cation reacted outside the macroring.
