31930-18-4Relevant articles and documents
Discovery of 5-methyl-N-(2-arylquinazolin-7-yl)isoxazole-4-carboxamide analogues as highly selective FLT3 inhibitors
Hah, Jung-Mi,Im, Daseul,Jang, Miyoung,Kim, Jinwoong,Moon, Hyungwoo,Oh, Youri
, p. 1110 - 1115 (2020)
A series of 4-arylamido 5-methylisoxazole derivatives with quinazoline core was designed and synthesised based on conformational rigidification of a previous type II FMS inhibitor. Most of quinazoline analogues displayed activity against FLT3 and FLT3-ITD. Compound 7d, 5-methyl-N-(2-(3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)phenyl)quinazolin-7-yl)isoxazole-4-carboxamide, exhibited the most potent inhibitory activity against FLT3 (IC50= 106 nM) with excellent selectivity profiles over 36 other protein kinases including cKit and FMS kinase. Compound 7d was also active in FLT-ITD, with an IC50 value of 301 nM, and other FLT3 mutants showing potential as an AML therapeutics.
Design of a small-molecule entry inhibitor with activity against primary measles virus strains
Plemper, Richard K.,Doyle, Joshua,Sun, Aiming,Prussia, Andrew,Cheng, Li-Ting,Rota, Paul A.,Liotta, Dennis C.,Snyder, James P.,Compans, Richard W.
, p. 3755 - 3761 (2005)
The incidence of measles virus (MV) infection has been significantly reduced in many nations through extensive vaccination; however, the virus still causes significant morbidity and mortality in developing countries. Measles outbreaks also occur in some d
Visible-light induced copper(i)-catalyzed oxidative cyclization of: O -aminobenzamides with methanol and ethanol via HAT
Bhargava Reddy, Mandapati,Prasanth, Kesavan,Anandhan, Ramasamy
supporting information, p. 9601 - 9605 (2020/12/28)
The use of the in situ generated ligand-copper superoxo complex absorbing light energy to activate the alpha C(sp3)-H of MeOH and EtOH via the hydrogen atom transfer (HAT) process for the synthesis of quinazolinones by oxidative cyclization of alcohols with o-aminobenzamide has been investigated. The synthetic utility of this protocol offers an efficient synthesis of a quinazolinone intermediate for erlotinb (anti-cancer agent) and 30 examples were reported.
Synthesis and nematicidal activities of 1,2,3-benzotriazin-4-one containing 4,5-dihydrothiazole-2-thiol derivatives against Meloidogyne incognita
Chen, Xiulei,Zhou, Zhen,Li, Zhong,Xu, Xiaoyong
, p. 194 - 200 (2019/09/13)
A series of novel 1,2,3-benzotriazin-4-one derivatives containing 4,5-dihydrothiazole-2-thiol were synthesized and characterized by 1H NMR, 13C NMR, 19F NMR and HRMS. The bioassay results showed that compounds 3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)-7-methoxybenzo[d][1–3]triazin-4(3H)-one, 3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)-6-nitrobenzo[d][1–3]triazin-4(3H)-one, 7-chloro-3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)benzo[d][1–3]triazin-4(3H)-one exhibited good control efficacy against the cucumber root-knot nematode disease caused by Meloidogyne incognita at the concentration of 10.0 mg L?1 in vivo. Compound 7-chloro-3-(3-((4,5-dihydrothiazol-2-yl)thio)propyl)benzo[d][1–3]triazin-4(3H)-one showed excellent nematicidal activity with inhibition 68.3% at a concentration of 1.0 mg L?1. It suggested that the structure of 1,2,3-benzotriazin-4-one containing 4,5-dihydro-thiazole-2-thiol could be optimized further.
Fluorescent biaryl uracils with C5-dihydro- And quinazolinone heterocyclic appendages in PNA
Heidari, Ali,Ghorbani-Choghamarani, Arash,Hajjami, Maryam,Hudson, Robert H.E.
, (2020/04/29)
There has been much effort to exploit fluorescence techniques in the detection of nucleic acids. Canonical nucleic acids are essentially nonfluorescent; however, the modification of the nucleobase has proved to be a fruitful way to engender fluorescence. Much of the chemistry used to prepare modified nucleobases relies on expensive transition metal catalysts. In this work, we describe the synthesis of biaryl quinazolinone-uracil nucleobase analogs prepared by the condensation of anthranilamide derivatives and 5-formyluracil using inexpensive copper salts. A selection of modified nucleobases were prepared, and the effect of methoxy- or nitro- group substitution on the photophysical properties was examined. Both the dihydroquinazolinone and quinazolinone modified uracils have much larger molar absorptivity (~4-8×) than natural uracil and produce modest blue fluorescence. The quinazolinone-modified uracils display higher quantum yields than the corresponding dihydroquinazolinones and also show temperature and viscosity dependent emission consistent with molecular rotor behavior. Peptide nucleic acid (PNA) monomers possessing quinazolinone modified uracils were prepared and incorporated into oligomers. In the sequence context examined, the nitro-substituted, methoxy-substituted and unmodified quinazolinone inserts resulted in a stabilization (?Tm = +4.0/insert; +2.0/insert; +1.0/insert, respectively) relative to control PNA sequence upon hybridization to complementary DNA. All three derivatives responded to hybridization by the “turn-on” of fluorescence intensity by ca. 3-to-4 fold and may find use as probes for complementary DNA sequences.
Synthesis and nematicidal evaluation of 1,2,3-benzotriazin-4-one derivatives containing piperazine as linker against Meloidogyne incognita
Chen, Xiulei,Jia, Haowu,Li, Zhong,Xu, Xiaoyong
, p. 1207 - 1213 (2019/03/29)
To explore new skeleton with nematicidal activity, a series of novel 1,2,3-benzotriazin-4-one derivatives containing piperazine as linker were synthesized and varied fragments were also introduced to increase structure diversity of the new skeleton. Their inhibitory activities in vivo were evaluated against Meloidogyne incognita. The newly prepared compounds A6, A8, A21, A28 and A38 exhibited more than 50% inhibition at the concentration of 20 mg/L. Especially compound A6 displayed 71.4% inhibition against Meloidogyne incognita at the concentration of 20 mg/L. The nematicidal activities varied significantly depending on the types and positions of the substituents, which provided guidance for further structure modification.
Synthesis and Nematicidal Activities of 1,2,3-Benzotriazin-4-one Derivatives against Meloidogyne incognita
Wang, Gaolei,Chen, Xiulei,Deng, Yayun,Li, Zhong,Xu, Xiaoyong
, p. 6883 - 6889 (2015/08/18)
A series of novel 1,2,3-benzotriazin-4-one derivatives were synthesized by the reaction of 3-bromoalkyl-1,2,3-benzotriazin-4-ones with potassium salt of 2-cyanoimino-4-oxothiazolidine in the presence of potassium iodide. Nematicidal assays in vivo showed that some of them exhibited good control efficacy against the cucumber root-knot nematode disease caused by Meloidogyne incognita, up to 100% at the concentration of 10.0 mg L-1, which indicated that 1,2,3-benzotriazin-4-one derivatives might be potential for novel promising nematicides. The nematicidal activity was influenced by the combination of substituent type, substituted position, and linker length in the molecule. The inhibition rate data at the concentrations of 5.0 and 1.0 mg L-1 for the compounds with high inhibitory activities were also provided. When tested in vitro, none of them showed direct inhibition against M. incognita. The investigation of a significant difference between in vivo and in vitro data is in progress.
Copper-catalyzed direct amination of ortho-functionalized haloarenes with sodium azide as the amino source
Zhao, Haibo,Fu, Hua,Qiao, Renzhong
experimental part, p. 3311 - 3316 (2010/08/05)
A simple copper-catalyzed direct amination of ortho-functionalized haloarenes (2-halobenzoic acid, 2-halobenzamide, and N-(2-bromophenyl)acetamide derivatives) has been developed with use of NaN3 as the amino source in ethanol, and the corresponding ortho-functionalized aromatic amines were synthesized in good to excellent yields. The protocol undergoes one-pot Ullmann-type coupling of ortho-functionalized haloarenes with NaN3 to lead to ortho-functionalized azidoarenes, followed by reduction with ethanol.
Effect of the electronic structure of the radical anions of 4-substituted 1,2-and 1,3-dinitrobenzenes on the regioselectivity of reduction of the nitro groups
Orlov,Begunov,Demidova,Rusakov
, p. 76 - 81 (2007/10/03)
Theoretical and experimental regularities of the regioselectivity of the reduction of one of the two nitro groups in unsymmetrical dinitrobenzenes were studied. It was found that the regioselectivity of the formation of isomeric nitroanilines depends on the structure of the substrate and the nature of the reducing agent. The reduction regioselectivity model was verified, according to which radical anion protonation is the major reaction direction. Pleiades Publishing, Inc. 2006.
Nonpeptide inhibitors of measles virus entry
Sun, Aiming,Prussia, Andrew,Zhan, Weiqiang,Murray, Ernest E.,Doyle, Joshua,Cheng, Li-Ting,Yoon, Jeong-Joong,Radchenko, Eugene V.,Palyulin, Vladimir A.,Compans, Richard W.,Liotta, Dennis C.,Plemper, Richard K.,Snyder, James P.
, p. 5080 - 5092 (2007/10/03)
Measles virus (MV) is one of the most infectious pathogens known. Despite the existence of a vaccine, over 500 000 deaths/year result from MV or associated complications. Anti-measles compounds could conceivably reverse these statistics. Previously, we described a homology model of the MV fusion protein trimer and a putative binding site near the head-neck region. The resulting model permitted the identification of two nonpeptidic entry inhibitors. Here, we present the design, synthesis, and bioevaluation of several series of fusion inhibitors and describe their structure-activity relationships (SAR). Five simply substituted anilides show low-μM blockade of the MV, one of which (AS-48) exhibits IC50 = 0.6-3.0 μM across a panel of wild-type MV strains found in the field. Molecular field topology analysis (MFTA), a 2D QSAR approach based on local molecular properties (atomic charges, hydrogen-bonding capacity and local lipophilicity), applied to the anilide series suggests structural modifications to improve potency.
