- Improved, gram-scale synthesis of sildenafil in water using arylacetic acid as the acyl source in the pyrazolo[4,3-d]pyrimidin-7-one ring formation
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An improved, gram-scale synthesis of the blockbuster drug sildenafil, used for the treatment of male erectile dysfunction, has been developed. Unlike the previous literature, the current method demonstrates the use of arylacetic acid as an acyl source, a cheap oxidant K2S2O8, and water as the reaction medium in the key step of pyrrazolo[4,3-d]pyrimidin-7-one ring formation. As well as being a green and benign approach, the current method reduces the cost by half compared to our previous strategy. In addition, the general relevance of the method has been demonstrated in the synthesis of a variety of quinazolinone and benzothiazole derivatives with excellent functional group tolerance.
- Laha, Joydev K.,Gulati, Upma,Saima,Gupta, Anjali,Indurthi, Harish Kumar
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p. 2643 - 2648
(2021/02/16)
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- Synthesis of Difluoromethyl-Substituted Quinazolines through Selective Difluoromethylation
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A highly selective difluoromethylation of quinazolines has been achieved by using commercially available ethyl bromodifluoroacetate as difluorocarbene precursor, providing the corresponding difluoromethyl substituted quinazoline derivatives with up to 83% yield.
- Peng, Jing,Hu, Ludan,Chen, Mu-Wang,Deng, Zhihong,Peng, Yiyuan
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p. 2286 - 2292
(2021/03/04)
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- Antioxidant and ros inhibitory activities of heterocyclic 2-aryl-4(3h)-quinazolinone derivatives
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Background: Antioxidants are small molecules that prevent or delay the process of oxidations caused by highly reactive free radicals. These molecules are known for their ability to protect various cellular architecture and other biomolecules from oxidative stress and free radicals. Thus, antioxidants play a key role in the prevention of oxidative damages caused by highly reactive free radicals. Methods: In the present study, a series of previously synthesized heterocyclic 2-aryl-4(3H)-quinazolinone derivatives 1-25 were screened for antioxidant activity by employing in vitro DPPH and superoxide anion radical scavenging activities. ROS inhibitory activities were also evaluated by serum-opsonized zymosan activated whole blood phagocytes and isolated neutrophils. Cytotoxicity studies were carried out by employing an MTT assay against the 3T3 cell line. Results: Most of the 2-aryl-4(3H)-quinazolinone derivatives showed potent antioxidant activities in superoxide anion radical scavenging assay with IC50 value ranging between 0.57 μM-48.93 μM, as compared to positive control quercetin dihydrate (IC50 = 94.1 ± 1.1 μM ). Compounds 5, 6, and 14 showed excellent activity in DPPH assay. Compounds 5-8, 12-15, 17, and 20 showed promising activities in the ROS inhibition assay. All compounds were found to be non-cytotoxic against the 3T3 cell line. Structure antioxidant activity has been established. Conclusion: It can be concluded that most of the heterocyclic 2-aryl-4(3H)-quinazolinone derivatives 1-25 are identified as promising antioxidant agents that are capable of fighting against free radicals and oxidative stress. Thus, they can serve as a lead towards treating oxidative stress and related pathologies.
- Choudhary, Muhammad Iqbal,Khan, Khalid Mohammed,Perveen, Shahida,Saad, Syed Muhammad
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p. 806 - 815
(2021/11/17)
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- Copper-Catalyzed Self-Condensation of Benzamide: Domino Reactions towards Quinazolinones
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We herein report a simple and highly efficient microwave-assisted, copper-catalyzed and ligand-free synthetic method for 2-substituted 4(3H)-quinazolinones as domino reaction. This reaction proceeds via self-condensation of substrate (2-bromo/iodo benzamide) in the presence of a strong base and copper catalyst. The substituted quinazolinones were obtained in one-pot reaction by intramolecular cyclization (condensation) via Ullmann–type intermediate. Both the intermediates and quinazolinones were obtained in good yield and can be further used as building blocks for developing the potential novel drug-like compounds.
- Sayyad, Nisar,Cele, Zamani,Aleti, Rajeshwar Reddy,Bera, Milan,Cherukupalli, Srinivasulu,Chandrasekaran, Balakumar,Kushwaha, Narva Deshwar,Karpoormath, Rajshekhar
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supporting information
p. 5382 - 5388
(2018/10/20)
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- In vitro antileishmanial activities of 2-aryl-4(3H)-quinazolinones
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A series of synthetic 2-aryl-4(3H)-quinazolinones (1-25) was evaluated for in vitro antileishmanial activities against promastigotes of Leishmania major. Compound 1, with nitro group installed at C-4′, was found to be the most active analog having the IC50 value of 35.8 ± 0.1 μM against the standard, pentamidine (IC50 = 5.09 ± 0.09 μM). Fourteen other derivatives i.e. 2, 5-8, 10-12, 14, 16, 19, 22, 24, ad 25, showed a moderate to weak antilieshmanial activity with IC50 values between 62.8-90.45 μM. The results indicate the potential of these compounds as leads for further studies towards the development of antileishmanial drugs.
- Perveen, Shama,Saad, Syed Muhammad,Perveen, Shahnaz,Hameed, Abdul,Alam, Muhammad Tanveer,Khan, Khalid Mohammed,Choudhary, M. Iqbal
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p. 352 - 357
(2016/08/20)
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- 2-Arylquinazolin-4(3H)-ones: A novel class of thymidine phosphorylase inhibitors
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Thymidine phosphorylase (TP) over expression plays an important role in several pathological conditions, such as rheumatoid arthritis, chronic inflammatory diseases, psoriasis, and tumor angiogenesis. In this regard, a series of twenty-five 2-arylquinazolin-4(3H)-one derivatives 1-25 were evaluated for thymidine phosphorylase inhibitory activity. Six compounds 5, 6, 20, 2, 23, and 3 were found to be active against thymidine phosphorylase enzyme with IC50 values in the range of 42.9-294.6 μM. 7-Deazaxanthine (IC50 = 41.0 ± 1.63 μM) was used as a standard inhibitor. Compound 5 showed a significant activity (IC50 = 42.9 ± 1.0 μM), comparable to the standard. The enzyme kinetic studies on the most active compounds 5, 6, and 20 were performed for the determination of their modes of inhibition, and dissociation constants Ki. All active compounds were found to be largely non-cytotoxic against the mouse fibroblast 3T3 cell line. This study identifies a novel class of thymidine phosphorylase inhibitors which may be further investigated as leads to develop therapeutic agents.
- Javaid, Sumaira,Saad, Syed Muhammad,Perveen, Shahnaz,Khan, Khalid Mohammed,Choudhary, M. Iqbal
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p. 142 - 151
(2015/11/18)
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- QUINAZOLINES AS B-GLUCURONIDASE NOVEL INHIBITORS
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Quinazoline derivatives 1-25, (2-[3,4-bis(methyloxy)phenyl]quinazolin-4-(3H)-one) and 2-[2-(ethyloxy)phenyl]quinazoline-4-(3H)-one) are reported as β-glucuronidase inhibitors useful in the treatment of β-glucuronidase hyperactivity disorders.
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Paragraph 0019; 0020; 0032
(2014/09/29)
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- Synthesis and β-glucuronidase inhibitory activity of 2-arylquinazolin-4(3H)-ones
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2-Arylquinazolin-4(3H)-ones 1-25 were synthesized by reacting anthranilamide with various benzaldehydes using CuCl2·2H 2O as a catalyst in ethanol under reflux. Synthetic 2-arylquinazolin-4(3H)-ones 1-25 were evaluated for their β-glucuronidase inhibitory potential. A trend of inhibition IC50 against the enzyme in the range of 0.6-198.2 μM, was observed and compared with the standard d-saccharic acid 1,4-lactone (IC50 = 45.75 ± 2.16 μM). Compounds 13, 19, 4, 12, 14, 22, 23, 25, 15, 8, 17, 11, 21, 1, 3, 18, 9, 2, and 24 with the IC50 values within the range of 0.6-44.0 μM, indicated that the compounds have superior activity than the standard. The compounds showed no cytotoxic effects against PC-3 cells. A structure-activity relationship is established.
- Khan, Khalid Mohammed,Saad, Syed Muhammad,Shaikh, Nimra Naveed,Hussain, Shafqat,Fakhri, Muhammad Imran,Perveen, Shahnaz,Taha, Muhammad,Choudhary, Muhammad Iqbal
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p. 3449 - 3454
(2014/06/23)
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- Synthesis and use of new fluorogenic precipitating substrates
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New fluorogenic esterase, glycosidase, aryl sulfatase, microsomal dealkylase, guanidinobenzoatase and alkaline phosphatase substrates have been prepared which precipitate at the site of enzyme activity, both in vitro and in vivo.
- Naleway, John J.,Fox, Christina M. J.,Robinhold, Daniel,Terpetschnig, Ewald,Olson, Nels A.,Haugland, Richard P.
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p. 8569 - 8572
(2007/10/02)
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