- From Methaqualone and Beyond: Structure - Activity Relationship of 6-, 7-, and 8-Substituted 2,3-Diphenyl-quinazolin-4(3H)-ones and in Silico Prediction of Putative Binding Modes of Quinazolin-4(3H)-ones as Positive Allosteric Modulators of GABAA
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Methaqualone (2-methyl-3-(o-tolyl)-quinazolin-4(3H)-one, MTQ) is a moderately potent positive allosteric modulator (PAM) of GABAA receptors (GABAARs). In a previous structure-activity relationship (SAR) study probing the importance of 2- and 3-substituent
- Wang, Peng-Fei,Jensen, Anders A.,Bunch, Lennart
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p. 4362 - 4375
(2020/11/30)
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- Pd-Catalyzed regioselective C-H halogenation of quinazolinones and benzoxazinones
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A Pd-catalyzed ortho-selective halogenation of benzoxazinone and quinazolinone scaffolds has been described employing N-halosuccinimide as both a halogen source and an oxidant reagent via C-H bond activation. This transformation shows high chemo- and regioselectivities and demonstrates a broad range of benzoxazinone and quinazolinone substrates with different functional groups and has been scaled up to the gram level.
- Dabiri, Minoo,Farajinia Lehi, Noushin,Kazemi Movahed, Siyavash,Khavasi, Hamid Reza
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supporting information
p. 6264 - 6268
(2017/08/02)
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- Design, Synthesis, and Pharmacological Characterization of N-(4-(2 (6,7-Dimethoxy-3,4-dihydroisoquinolin-2(1H)yl)ethyl)phenyl)quinazolin-4-amine Derivatives: Novel Inhibitors Reversing P-Glycoprotein-Mediated Multidrug Resistance
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P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) is a principal obstacle for successful cancer chemotherapy. A novel P-gp inhibitor with a quinazoline scaffold, 12k, was considered to be the most promising for in-depth study. 12k possessed high potency (EC50 = 57.9 ± 3.5 nM), low cytotoxicity, and long duration of activity in reversing doxorubicin (DOX) resistance in K562/A02 cells. 12k also boosted the potency of other MDR-related cytotoxic agents with different structures, increased accumulation of DOX, blocked P-gp-mediated Rh123 efflux, and suppressed P-gp ATPase activity in K562/A02 MDR cells. However, 12k did not have any effects on CYP3A4 activity or P-gp expression. In particular, 12k had a good half-life and oral bioavailability and displayed no influence on DOX metabolism to obviate the side effects closely related to increased plasma concentrations of cytotoxic agents in vivo.
- Qiu, Qianqian,Liu, Baomin,Cui, Jian,Li, Zheng,Deng, Xin,Qiang, Hao,Li, Jieming,Liao, Chen,Zhang, Bo,Shi, Wei,Pan, Miaobo,Huang, Wenlong,Qian, Hai
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supporting information
p. 3289 - 3302
(2017/05/05)
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- RETRACTED ARTICLE: Palladium-Catalyzed Decarboxylative Selective Acylation of 4H-Benzo[d][1,3]oxazin-4-one Derivatives with α-Oxo Carboxylic acids via Preferential Cyclic Imine-N-Directed Aryl C-H Activation
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The benzoxazine scaffolds are of much interest as they are found in a large array of natural products and pharmaceutical drugs with diverse activities. We have developed a palladium-catalyzed decarboxylative selective mono- and bis-acylation of 4H-benzo[d
- Majhi, Biju,Kundu, Debasish,Ghosh, Tubai,Ranu, Brindaban C.
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p. 283 - 295
(2016/02/16)
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- Structural Exploration of Quinazolin-4(3H)-ones as Anticonvulsants: Rational Design, Synthesis, Pharmacological Evaluation, and Molecular Docking Studies
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Anticonvulsants effective against multiple seizures are of wide interest as antiepileptic drugs, especially if active against pharmaco-resistant seizures. Herein, we synthesized 16 different, rationally designed 2-((6,7-dimethoxy-4-oxo-2-phenylquinazolin-3(4H)-yl)amino)-N-(substituted phenyl)acetamides and screened for anticonvulsant activities through in vivo experiments. Compound 4d emerged as prototype with excellent anti-seizure action in mice against electroshock, chemically induced and pharmaco-resistant 6-Hz seizure models with no symptoms of neurotoxicity and hepatotoxicity (ED50 = 23.5 mg/kg, MES, mice, i.p.; ED50 = 32.6 mg/kg, scPTZ, mice, i.p.; ED50 = 45.2 mg/kg, 6-Hz, mice, i.p.; TD50 = 325.9 mg/kg, mice, i.p.). In addition, investigation of compound 4l in mice for its pharmacological profile proved it as safer anticonvulsant, devoid of the side effects such as motor dysfunction and hepatotoxicity of classical antiepileptic drugs (ED50 = 26.1 mg/kg, MES, mice, i.p.; ED50 = 79.4 mg/kg, scPTZ, mice, i.p.; TD50 = 361.2 mg/kg, mice, i.p.). We also predicted physiochemical and pharmacokinetic properties of structurally optimized quinazolin-4(3H)-ones by a computational protocol. A combination of in vivo anticonvulsant profile, ex vivo toxicity, and in silico studies suggested that the synthesized compounds may be useful as broad-spectrum anti-seizure drug candidates with favorable pharmacokinetic parameters.
- Ugale, Vinod G.,Bari, Sanjay B.
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p. 864 - 880
(2016/11/09)
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- Selective Oxidative Decarbonylative Cleavage of Unstrained C(sp3)-C(sp2) Bond: Synthesis of Substituted Benzoxazinones
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A transition metal (TM)-free practical synthesis of biologically relevant benzoxazinones has been established via a selective oxidative decarbonylative cleavage of an unstrained C(sp3)-C(sp2) bond employing iodine, sodium bicarbonate, and tbutyl hydroperoxide in DMSO at 95 °C. Control experiments and Density Functional Theory (DFT) calculations suggest that the reaction involves a [1,5]H shift and extrusion of CO gas as the key steps. The extrusion of CO has also been established using PMA-PdCl2.
- Verma, Ajay,Kumar, Sangit
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p. 4388 - 4391
(2016/10/11)
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- TBHP/CoCl2-mediated intramolecular oxidative cyclization of N-(2-formylphenyl)amides: An approach to the construction of 4H-3,1-benzoxazin-4-ones
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The intramolecular oxidative cyclization of N-(2-formylphenyl)amides has been realized through an oxidative C(sp2)-O(sp2) bond-forming reaction between an aldehyde carbon and amide oxygen. This new strategy, which uses tert-butyl hydroperoxide (TBHP) as an oxidant and CoCl2 as the catalyst, allows for the efficient Co-catalyzed synthesis of useful benzoxazin-4-one derivatives and features readily available starting materials and mild reaction conditions. The intramolecular cyclization of N-(2-formylphenyl)amides has been realized through an oxidative C(sp2)-O(sp2) bond-forming reaction between an aldehyde carbon and amide oxygen. This new strategy, which uses tert-butyl hydroperoxide (TBHP) as the oxidant and CoCl2 as the catalyst, allows for the efficient Co-catalyzed synthesis of useful benzoxazin-4-one derivatives.
- Yu, Junchao,Zhang-Negrerie, Daisy,Du, Yunfei
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p. 562 - 568
(2016/02/18)
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- Design and synthesis of VEGFR-2 tyrosine kinase inhibitors as potential anticancer agents by virtual based screening
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Vascular endothelial growth factor receptor-2 (VEGFR-2) plays a crucial role in cancer angiogenesis. A library of 6,7-dimethoxy quinazoline was prepared using a ligand based drug design approach and passed through different filters of virtual screening su
- Patel, Harun M.,Bari, Pankaj,Karpoormath, Rajshekhar,Noolvi, Malleshappa,Thapliyal, Neeta,Surana, Sanjay,Jain, Pritam
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p. 56724 - 56771
(2015/07/15)
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- Sulfate Radical Anion (SO4?-) Mediated C(sp3)-H Nitrogenation/Oxygenation in N-Aryl Benzylic Amines Expanded the Scope for the Synthesis of Benzamidine/Oxazine Heterocycles
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A transition-metal-free, K2S2O8-mediated intramolecular oxidative nitrogenation/oxygenation of C(sp3)-H in N-aryl benzylic amines followed by oxidation at the benzylic center has been developed for the synthesis of benzamidine/benzoxazine heterocycles, providing an expedient access to quinazolin-4(3H)-ones, N-aryl-2-arylbenzimidazoles, and 4H-3,1-benzoxazin-4-ones. A considerable amount of work dealing with the mechanistic study to understand the crucial intramolecular cyclization step largely favors an iminium ion as the key intermediate.
- Laha, Joydev K.,Tummalapalli, K. S. Satyanarayana,Nair, Akshay,Patel, Nidhi
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p. 11351 - 11359
(2015/12/01)
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- [bmIm]OH: An efficient basic catalyst for the synthesis of 4H-benzo[d][1,3-]oxazin-4-one derivatives in solvent-free conditions
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Reusable [bmIm]OH was found to be a highly efficient renewable homogenous catalyst for the rapid and convenient synthesis of benzoxazine-4-one derivatives from o-iodobenzoic-acid and benzonitrile at 75 °C in moderate to good yields. This methodology provides a facile and straightforward path to construct other related heterocycles in an eco-compatible fashion.
- Waseem, Malik Abdul,Shireen,Srivastava, Anjali,Srivastava, Arjita,Rahila,Siddiqui
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supporting information
p. 6072 - 6076
(2015/01/08)
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- Copper-mediated oxidative tandem reactions with molecular oxygen: Synthesis of 2-arylbenzoxazinone derivatives from indoles
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We developed an efficient method for the transformation of indoles by utilizing a copper catalyst and molecular oxygen as the oxidant. The transformation involves a tandem oxidative process of 2-arylindoles. Our reaction afforded a variety of N-benzoyl an
- Yamashita, Mitsuaki,Iida, Akira
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supporting information
p. 2991 - 2993
(2014/05/06)
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- Oxidation of 2-arylindoles for synthesis of 2-arylbenzoxazinones with oxone as the sole oxidant
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A novel and efficient method for the oxidation of 2-arylindoles to synthesize 2-arylbenzoxazinones utilizing oxone as the sole oxidant has been developed. The reaction tolerates a wide range of functional groups and allows quick and atom-economical assembly of a variety of valuable 2-arylbenzoxazinones in high yields.
- Lian, Xiao-Li,Lei, Hao,Quan, Xue-Jing,Ren, Zhi-Hui,Wang, Yao-Yu,Guan, Zheng-Hui
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p. 8196 - 8198
(2013/09/12)
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- Copper-catalyzed C-N bond formation/rearrangement sequence: Synthesis of 4H-3,1-benzoxazin-4-ones
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A facile and efficient copper-catalyzed method for the synthesis of 4H-3,1-benzoxazin-4-one derivatives has been developed. This procedure is based on a tandem intramolecular C-N coupling/rearrangement process. This method would provide a new and useful strategy for construction of N-heterocycles.
- Ge, Zhi-Yuan,Xu, Qiong-Ming,Fei, Xi'Ang-Dong,Tang, Ting,Zhu, Yong-Ming,Ji, Shun-Jun
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p. 4524 - 4529
(2013/06/05)
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- Gelation-induced enhanced fluorescence emission from organogels of salicylanilide-containing compounds exhibiting excited-state intramolecular proton transfer: Synthesis and self-assembly
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Self-assembly structure, stability, hydrogen-bonding interaction, and optical properties of a new class of low molecular weight organogelators (LMOGs) formed by salicylanilides 3 and 4 have been investigated by fieldemission scanning electron microscopy (
- Nayak, Manoj Kumar,Kim, Byung-Hwa,Kwon, Ji Eon,Park, Sanghyuk,Seo, Jangwon,Chung, Jong Won,Park, Soo Young
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experimental part
p. 7437 - 7447
(2010/09/11)
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- Bis mono- and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase
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This invention relates to bis mono- and/or bicyclic aryl and/or heteroaryl compounds exhibiting protein tyrosine kinase inhibition activity. More specifically, it relates to the method of inhibiting abnormal cell proliferation in a patient suffering from a disorder characterized by such proliferation comprising the administration thereto of an EGF and/or PDGF receptor inhibiting effective amount of said bis mono- and/or bicyclic aryl and/or heteroaryl compound and to the preparation of said compounds and their use in pharmaceutical compositions used in this method.
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