- Synthesis of substituted 1,2,3,4-tetrahydrobenzo[b][1,6]naphthyridines
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Synthesis of the substituted compounds 9-14 (2-Me or 2-Et; 6-H, 6-OMe or 6-OH; 9-NHR) is reported.
- Wolinska, Ewa,Paliakov, Ekaterina,Strekowski, Lucjan
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- Phenazine derivatives with anti-inflammatory activity from the deep-sea sediment-derived yeast-like fungus cystobasidium laryngis IV17-028
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Three new phenazine derivatives (1-3), along with known compounds (4-7) of saphenic acid derivatives, were isolated from a deep-sea sediment-derived yeast-like fungus Cystobasidium larynigs collected from the Indian Ocean. The structures of the new compou
- Lee, Hwa-Sun,Kang, Jong Soon,Choi, Byeoung-Kyu,Lee, Hyi-Seung,Lee, Yeon-Ju,Lee, Jihoon,Shin, Hee Jae
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- 2-((3,5-Dinitrobenzyl)thio)quinazolinones: Potent Antimycobacterial Agents Activated by Deazaflavin (F420)-Dependent Nitroreductase (Ddn)
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Swapping the substituents in positions 2 and 4 of the previously synthesized but yet undisclosed 5-cyano-4-(methylthio)-2-arylpyrimidin-6-ones 4, ring closure, and further optimization led to the identification of the potent antitubercular 2-thio-substituted quinazolinone 26. Structure-activity relationship (SAR) studies indicated a crucial role for both meta-nitro substituents for antitubercular activity, while the introduction of polar substituents on the quinazolinone core allowed reduction of bovine serum albumin (BSA) binding (63c, 63d). While most of the tested quinazolinones exhibited no cytotoxicity against MRC-5, the most potent compound 26 was found to be mutagenic via the Ames test. This analogue exhibited moderate inhibitory potency against Mycobacterium tuberculosis thymidylate kinase, the target of the 3-cyanopyridones that lies at the basis of the current analogues, indicating that the whole-cell antimycobacterial activity of the present S-substituted thioquinazolinones is likely due to modulation of alternative or additional targets. Diminished antimycobacterial activity was observed against mutants affected in cofactor F420 biosynthesis (fbiC), cofactor reduction (fgd), or deazaflavin-dependent nitroreductase activity (rv3547), indicating that reductive activation of the 3,5-dinitrobenzyl analogues is key to antimycobacterial activity.
- Jian, Yanlin,Forbes, He Eun,Hulpia, Fabian,Risseeuw, Martijn D. P.,Caljon, Guy,Munier-Lehmann, Hélène,Boshoff, Helena I. M.,Van Calenbergh, Serge
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p. 440 - 457
(2021/01/14)
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- NaNO2/I2 as an alternative reagent for the synthesis of 1,2,3-benzotriazin-4(3H)-ones from 2-aminobenzamides
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An efficient transformation of 2-aminobenzamides to 1,2,3-benzotriazin-4(3H)-ones in the presence of sodium nitrite (NaNO2) and Iodine (I2) is described. The reaction is proposed to proceed via formation of nitrosyl halide that induces nitrosylation of the amino group of 2-aminobenzamide leading to diazotization followed by intramolecular cyclization.
- Barak, Dinesh S.,Mukhopadhyay, Sushobhan,Dahatonde, Dipak J.,Batra, Sanjay
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supporting information
p. 248 - 251
(2019/01/04)
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- TBHP as Methyl Source under Metal-Free Aerobic Conditions To Synthesize Quinazolin-4(3H)-ones and Quinazolines by Oxidative Amination of C(sp3)–H Bond
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tert-Butyl hydroperoxide (TBHP) served as the methyl source under metal-free aerobic conditions in the oxidative amination of the C(sp3)–H bond to synthesize quinazolin-4(3H)-ones and quinazolines from 2-aminobenzamides and 2-carbonyl-substituted anilines, respectively.
- Mukhopadhyay, Sushobhan,Barak, Dinesh S.,Batra, Sanjay
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supporting information
p. 2784 - 2794
(2018/06/04)
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- Novel deoxyvasicinone derivatives as potent multitarget-directed ligands for the treatment of Alzheimer's disease: Design, synthesis, and biological evaluation
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A series of multitarget ligands was designed by introducing several structurally diverse aminoacetamide groups at position 6 of the deoxyvasicinone group, with the aim of obtaining novel multifunctional anti-Alzheimer's disease agents using deoxyvasicinone as the substrate. In vitro studies showed that almost all of the derivatives were potent inhibitors of human recombinant acetylcholinesterase (hAChE) and human serum butyrylcholinesterase (hBChE), with IC50 values in the low nanomolar range, and exhibited moderate to high inhibition of Aβ1?42 self-aggregation. In particular, compounds 12h, 12n, and 12q showed promising inhibitory activity for hAChE, with IC50 values of 5.31 ± 2.8, 4.09 ± 0.23, and 7.61 ± 0.53 nM, respectively. Compounds 12h and 12q also exhibited the greatest ability to inhibit hBChE, with IC50 values of 4.35 ± 0.32 and 2.35 ± 0.14 nM, respectively. Moreover, enzyme kinetics confirmed that compound 12q caused a mixed type of AChE inhibition, by binding to both the active sites (PAS and CAS) of AChE. Remarkably, compound 12q also demonstrated the highest potential inhibitory activity for Aβ1?42 self-aggregation (63.9 ± 4.9%, 10 μM), and it was also an excellent metal chelator.
- Ma, Fang,Du, Hongtao
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supporting information
p. 118 - 127
(2017/09/20)
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- Heavily Substituted Atropisomeric Diarylamines by Unactivated Smiles Rearrangement of N-Aryl Anthranilamides
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Diarylamines find use as metal ligands and as structural components of drug molecules, and are commonly made by metal-catalyzed C?N coupling. However, the limited tolerance to steric hindrance of these couplings restricts the synthetic availability of more substituted diarylamines. Here we report a remarkable variant of the Smiles rearrangement that employs readily accessible N-aryl anthranilamides as precursors to diarylamines. Conformational predisposition of the anthranilamide starting material brings the aryl rings into proximity and allows the rearrangement to take place despite the absence of electron-withdrawing substituents, and even with sterically encumbered doubly ortho-substituted substrates. Some of the diarylamine products are resolvable into atropisomeric enantiomers, and are the first simple diarylamines to display atropisomerism.
- Costil, Romain,Dale, Harvey J. A.,Fey, Natalie,Whitcombe, George,Matlock, Johnathan V.,Clayden, Jonathan
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p. 12533 - 12537
(2017/09/13)
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- INDOLE CARBOXAMIDE COMPOUNDS
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Disclosed are compounds of Formula (I): or a salt thereof, wherein: X is CR4 or N; R1, R2, R3, R4, and A are defined herein. Also disclosed are methods of using such compounds as inhibitors of Bruton's tyrosine kinase (Btk), and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.
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Paragraph 0562-0563
(2016/05/19)
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- Discovery and characterization of 2-(cyclopropanesulfonamido)-n-(2-ethoxyphenyl)benzamide, ML382: A potent and selective positive allosteric modulator of MrgX1
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Previous studies have shown that the activation of mouse MrgC11, a G-protein-coupled receptor, by its peptide ligand BAM8-22 can inhibit chronic pain. A large-scale screen has been carried out to isolate small-molecule allosteric agonists of MrgX1, the human homologue of MrgC11. The goal of this study is to improve the efficacy and potency of positive allosteric modulators (PAMs) with therapeutic implications in combating chronic pain. Herein we report an iterative parallel synthesis effort and a structure-activity relationship study of a series of arylsulfonamides which led to the discovery of the first PAM of MrgX1, ML382.
- Wen, Wandong,Wang, Yan,Li, Zhe,Tseng, Pang-Yen,McManus, Owen B.,Wu, Meng,Li, Min,Lindsley, Craig W.,Dong, Xinzhong,Hopkins, Corey R.
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supporting information
p. 57 - 61
(2015/03/18)
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- Intramolecular metal-free oxidative aryl-aryl coupling: An unusual hypervalent-iodine-mediated rearrangement of 2-substituted n-phenylbenzamides
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Hypervalent-iodine-mediated oxidative coupling of the two aryl groups in either 2-acylamino-N-phenyl-benzamides or 2-hydroxy-N-phenylbenzamides, with concomitant insertion of the ortho-substituted N or O atom into the tether, has been described for the first time. This unusual metal-free rearrangement reaction involves an oxidative C(sp2)?C(sp2) aryl-aryl bond formation, cleavage of a C(sp2)?C(O) bond, and a lactamization/lactonization. Furthermore, unsymmetrical diaryl compounds can be easily obtained by removing the tether within the cyclized product.
- Shang, Siyun,Zhang-Negrerie, Daisy,Du, Yunfei,Zhao, Kang
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supporting information
p. 6216 - 6219
(2014/06/23)
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- Design, synthesis and biological evaluation of 5-amino-1H-pyrazole-4- carboxamide derivatives as potential antitumor agents
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Adenosine deaminase (ADA) inhibitors have been found to have antitumor activities. Here, thirteen potential adenosine deaminase inhibitors 5-amino-1H-pyrazole-4-carboxamide derivatives were designed, synthesized and screened for antitumor activities. Comp
- Yang, Baowei,Liu, Wukun,Mei, Yicheng,Huang, Dandan,Qian, Hai,Huang, Wenlong,Gust, Ronald
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p. 749 - 755
(2014/07/07)
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- SUBSTITUTED TETRAHYDROCARBAZOLE AND CARBAZOLE CARBOXAMIDE COMPOUNDS
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Disclosed are compounds of Formula (I) wherein: the two dotted lines represent either two single or two double bonds; Q is: R1 is F, Cl, —CN, or —CH3; R2 is Cl or —CH3; R3 is —C(CH3)2OH or —CH2CH2OH; Ra is H or —CH3; each Rb is independently F, Cl, —CH3, and/or —OCH3; and n is zero, 1, or 2. Also disclosed are methods of using such compounds as inhibitors of Bruton's tyrosine kinase (Btk), and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.
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Paragraph 0341; 0342
(2015/01/07)
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- 2-(Quinolin-4-ylthio)-1,3,4-oxadiazole derivatives: Design, synthesis, antibacterial and antifungal studies
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A series of novel hybrid 2-(7-chloroquinolin-4-ylthio)-5-(substituted)-1,3, 4-oxadiazole derivatives have been designed, synthesized which contains different pharmacophores like quinoline and 1,3,4-oxadiazole linked via sulfur atom. All the newly synthesized derivatives have been characterized by IR, 1H NMR, 13C NMR spectral and elemental analysis. Further, All the final synthesized scaffolds have been subjected to in vitro antimicrobial activity against several bacteria (E.coli, P.aeruginosa, S.aureus, S.pyogenus) and fungi (C.albicans, A.niger, A.clavatus) using broth dilution technique. Among the compounds tested, compounds 3f substituted with coumarin analogue and 3b with amine group at second position of phenyl to oxadiazole moiety are found to be most potent.
- Modh, Rahul P,Shah, Dhruvin,Chikhalia, Kishor H
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p. 1318 - 1324
(2014/01/06)
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- Copper-catalyzed domino intramolecular cyclization: A facile and efficient approach to polycyclic indole derivatives
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A mild and efficient Cu2O-catalyzed domino intramolecular C-N coupling/C-Y (Y = O, S, N) bond formation was successfully achieved. Thus oxazino[3,2-a]indole, thiazino[3,2-a]indole and indolo[2,1-b]quinazoline derivatives were facilely assembled
- Xia, Ziming,Wang, Kuo,Zheng, Jiening,Ma, Zheyong,Jiang, Zhanguo,Wang, Xiaoxia,Lv, Xin
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experimental part
p. 1602 - 1611
(2012/03/22)
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- Synthesis, antimicrobial evaluation, ot-QSAR and mt-QSAR studies of 2-amino benzoic acid derivatives
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A series of 2-amino benzoic acid derivatives (1-28) were synthesized and evaluated for their in vitro antimicrobial activity against the panel of Gram positive, Gram negative bacterial and fungal strains. The results of antimicrobial studies indicated that, in general, the synthesized compounds were found to be bacteriostatic and fungistatic in action. QSAR studies performed by the development of one target and multi target models indicated that multi-target model was effective in describing the antimicrobial activity as well demonstrated the effect of structural parameters viz. LUMO, 3χv and W on antimicrobial activity of 2-amino benzoic acid derivatives. Springer Science+Business Media, LLC 2010.
- Mahiwal, Kuldeep,Kumar, Pradeep,Narasimhan, Balasubramanian
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experimental part
p. 293 - 307
(2012/09/07)
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- Design, synthesis and biological activity evaluation of 2-mercapto-4(3H)-quinazolinone derivatives as novel inhibitors of protein tyrosine phosphatase 1B
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A series of novel 2-mercapto-4(3H)-quinazolinone derivatives have been synthesized and their inhibitory effects on PTP1B and TCPTP are evaluated for the first time. Most of these derivatives showed good inhibitory activity on PTP1B and reasonable selectivity for PTP1B over TCPTP, among them 32 was the most potent PTP1B inhibitor (IC50 = 1.50 μ ;g/mL), and 27 possessed the best selectivity of 3.0-fold.
- Li, Hui,Wang, Jin-Ping,Yang, Fan,Liu, Ting,Qiu, Wen-Wei,Li, Jing-Ya,Li, Jia,Tang, Jie
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experimental part
p. 1897 - 1911
(2012/09/07)
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- SUBSTITUTED DIPYRIDO-PYRIMIDO-DIAZEPINE AND BENZO-PYRIDO-PYRIMIDO COMPOUNDS
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The present invention relates to substituted dipyrido-pyrimido-diazepine compounds, substituted benzo-pyrido-pyrimido-diazepine compounds and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions contai
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Page/Page column 79-80
(2010/10/19)
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- 4-[1-(Substituted aryl/alkyl carbonyl)-benzoimidazol-2-yl]-benzenesulfonic acids: Synthesis, antimicrobial activity, QSAR studies, and antiviral evaluation
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A series of 4-[1-(substituted aryl/alkyl carbonyl)-benzoimidazol-2-yl]- benzene sulphonic acids (1-20) was synthesized and evaluated, in vitro, for their antimicrobial activity and the results indicated that compounds 4-[1-(4-Nitrobenzoyl)-1H-benzoimidazol-2-yl]-benzenesulfonic acid (9) and 4-(1-octadec-9-enoyl-1H-benzoimidazol-2-yl)-benzenesulfonic acid (18) were found to be the most active ones. QSAR investigations indicated that the multi-target QSAR model was effective in describing the antimicrobial activity over the one-target QSAR models. Further the mt-QSAR model indicated the importance of the topological parameter, Balaban index (J) followed by the electronic parameter, LUMO and topological parameter, valence second order molecular connectivity index (2χv) in describing the antimicrobial activity of synthesized compounds (1-20).
- Yadav, Snehlata,Kumar, Pradeep,De Clercq, Erik,Balzarini, Jan,Pannecouque, Christophe,Dewan, Sharwan Kumar,Narasimhan, Balasubramanian
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scheme or table
p. 5985 - 5997
(2011/01/13)
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- Facile synthesis of 1,2,3,4-tetrahydrobenzo [b] [1,6] naphth yridines
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Synthesis of analogs of known immunosuppressive quinolines is reported.
- Wolinska, Ewa,Paliakov, Ekaterina,Strekowski, Lucjan
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scheme or table
p. 63 - 65
(2010/03/03)
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- Nitrogen bridgehead compounds. Part 85 [1]. Synthesis and reactivity of 3,4-dihydro-1H,6H-[1,4]oxazino[3,4-b]quinazolin-6-ones
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3,4-Dihydro-1H,6H-[1,4]oxazino[3,4-b]quinazolin-6-one 3 and its 1-methyl and 1-hydroxy derivatives 8 and 13 were prepared by different routes. The active methylene group of compound 3 was reacted with electrohilic reagents (bromine, phenyldiazonium chlori
- Hermecz,Szilagyi,Orfi,Kokosi,Szasz
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p. 1413 - 1420
(2007/10/02)
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- Synthesis and in Vitro Aldolase Reductase Inhibitory Activity of Compounds Containing an N-Acylglycine Moiety
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A number of N-benzoylglycines (6), N-acetyl-N-phenylglycines (7), N-benzoyl-N-phenylglycines (8), and tricyclic N-acetic acids (9-12) were synthesized as analogues of the N-acylglycine-containing aldolase reductase inhibitors alrestatin and 2-oxoquinoline-1-acetic acid.Derivatives of 6, which represent ring-simplified analogues of alrestatin, are very weak inhibitors of aldolase reductase obtained from rat lens, producing 50percent inhibition only at concentrations exceeding 100 μM.Compounds of series 7 were designed as ring-opened analogues of the 2-oxoquinolines.While this derivatives are more potent than compounds of series 6 (IC 50s of 6-80 μM), they are less active than the corresponding 2-oxoquinolines.Analogues of series 8 were designed as hybrid structures of both alrestatin and the 2-oxoquinoline-1-acetic acids.These compounds are substantially more potent than compounds of series 6 and 7 and display inhibitory activities comparable to or greater than alrestatin or the 2-oxoquinolines (IC 50s of 0.1-10 μM).Of the rigid analogues of 8, the most potent derivative is benzoxindol (12) with an IC 50 of 0.67 μM, suggesting that fusion of the two aromatic rings of 8 in a coplanar conformation may optimize affinity for aldose reductase in this series.
- DeRuiter, Jack,Swearingen, Blake E.,Wandrekar, Vinay,Mayfield, Charles A.
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p. 1033 - 1038
(2007/10/02)
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