- Synthesis and biological evaluation of 3-(1,3,4-oxadiazol-2-yl)-1,8-naphthyridin-4(1H)-ones as cisplatin sensitizers
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A series of novel 3-(1,3,4-oxadiazol-2-yl)-1,8-naphthyridin-4(1H)-one derivatives were synthesized and their anti-cancer as well as cisplatin sensitization activities were evaluated. Among them, compounds 6e and 6h exhibited significant cisplatin sensitization activity against HCT116. Hoechst staining and annexin V-FITC/PI dual-labeling studies demonstrated that the combination of 6e/6h and cisplatin can induce tumour cell apoptosis. Western blot showed that the expression of ATR downstream protein, CHK1, decreased in 6e + cisplatin and 6h + cisplatin groups compared with that in the test compound and cisplatin group. Furthermore, docking of 6e/6h into the ATR structure active site revealed that the N1 and N8 atoms in the naphthyridine ring and the hybrid atom in the oxadiazole ring are involved in hydrogen bonding with Val170, Glu168 and Tyr155. Additionally, the naphthyridine ring is also involved in π-π stacking with Trp169. Accordingly, compounds 6e and 6h can be expected to be potential cisplatin sensitizers that can participate in HCT116 cancer therapy.
- Hou, Xueyan,Luo, Hao,Zhang, Mengqi,Yan, Guoyi,Pu, Chunlan,Lan, Suke,Li, Rui
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- OXOPYRIDO[1,2-A]PYRIMIDINE COMPOUNDS FOR THE TREATMENT AND PROPHYLAXIS OF BACTERIAL INFECTION
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The present invention relates to novel compounds of formula (I), wherein R1 to R7 are as described herein, and their pharmaceutically acceptable salt, enantiomer or diastereomer thereof, and compositions including the compounds and methods of using the compounds.
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Page/Page column 26
(2020/07/14)
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- 3 and 6 substituted 1, 8 naphthyridin - 4 - one derivatives and its preparation and use
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The invention specifically relates to 3-and-6-substituted 1,8-naphthyridine-4-one derivatives and a preparation method and application thereof, belonging to the field of the chemical pharmaceutical industry. The structure of the 3-and-6-substituted 1,8-na
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Paragraph 0120; 0121; 0122; 0123
(2017/08/02)
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- Pyrido[1,2-a]pyrimidone analogs as PI3K inhibitors
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The present invention discloses a class of pyrido[1,2-a]pyrimidone analogs as PI3K inhibitors, and particularly relates to a compound represented by a formula (I) or a pharmaceutically acceptable salt thereof. The formula (I) is defined in the specification.
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Paragraph 0253; 0258; 0259; 0260
(2016/10/08)
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- PYRIDO[1,2-a]PYRIMIDONE DERIVATIVES AS A mTOR/PI3K SUPPRESSOR
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The invention discloses pyrido[1,2-a]pyrimidone derivatives as a mTOR/PI3K suppressor; and in particular, this invention relates to a compound having the formula (I) structure or its pharmaceutically acceptable salts.
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Paragraph 0128; 0129
(2016/10/08)
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- A simple and efficient synthesis of novel naphthyridine-1-H-pyrazole-4- carboxylic acid esters/carbaldehydes using Vilsmeier-Haack reagent
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The reaction of hydrazide 4 with β-keto esters 5 gave hydrazones 6. Cyclization of 6 with Vilsmeier-Haack reagent (DMF-POCl3 ) for 20 min at room temperature gave 1-(4-oxo-1,4-dihydro-[ 1 ,8]naphthyridine-3-carbonyl)- 1 H -pyrazole-4-carboxylic acid ethyl esters 7. The treatment of 4 with substituted acetophenones 8 yielded the corresponding hydrazones 9 of substituted aceto phenones. The treatment of 9 with Vilsmeier-Haack reagent (DMF-POCl3) for 30 min at room temperature gave product 10, the reaction of which with (diacetoxyiodo)benzene in ethanol at room temperature for 12 h in the presence of molecular iodine furnished 7.
- Chaitanya, Muggu V.S.R.K.,Dubey, Pramod K.
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- A rapid and convenient synthesis of naphthyridinoyl pyrazolidinones under microwave irradiation condition
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Microwave-assisted synthesis of naphthyridinoylpyrazolidinones (7a-7j) has been achieved rapidly via the reaction of naphthyridine hydrazide (4) with different β-keto esters and ethoxymethylenemalonic ester (EMME) (5a-5e). Initially, the reaction of naphthyridine hydrazide (4) with various β-keto esters under microwave irradiation for 5 mins at 130oC results in the formation of condensed products 6a-6j. This condensation was followed by cyclization, also, in diphenyl ether under microwave irradiation for 10 mins at 230-250oC, yielding the corresponding cyclized products 7a-7j. Alternatively, both reactants 4 and each of the β -keto esters/EMME (5a-5e) were treated in diphenyl ether under microwave irradiation for 15 mins at 230-250oC giving the target molecules 7a-7j as one-pot reaction in good yields.
- Chaitanya, Muggu V.S.R.K.,Dubey, Pramod K.
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scheme or table
p. 368 - 374
(2012/08/28)
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- Efficient synthesis of novel 3-[5-(1H-benzimidazol-2-ylmethanesulfonyl)-4- phenyl-4H-(1,2,4)triazol-3-Yl]-1H-(1,8)naphthyridin-4-one derivatives
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of 1,4-dihydro-4-oxo-1,8-naphthyridine-3-carbohydrazide (4) with substituted phenyl isothiocyanates (5) in ethanol under reflux for 30 min gave thiosemicarbazide derivatives 6, which on cyclization in 2N NaOH under refluxing conditions for 1 h resulted in 3-(5-mercapto- 4-phenyl-4H-1,2,4-triazol-3-yl)- 1,8-naphthyridin-4(1H)-one (7). Alternatively, 7 could also be prepared from following sequence of reactions, i.e., 4→8→7. In another sequence of reactions, condensation of 7 with chloroacetic acid in dimethylformamide (DMF) and K2CO3 as a mild base at 120 °C for 2 h resulted in 2-((5-(1,4-dihydro-4-oxo-1,8-naphthyridin-3-yl)-4-phenyl-4H-1,2,4-triazol-3-yl) sulfanyl)acetic acid (10). The latter, on reaction with substituted o-phenylenediamine (11) in 6N HCl for 4 h yielded 3-(5-((1H-benzo[d]imidazol-2- yl)methylthio)-4-phenyl-4H-1,2,4-triazol-3-yl)-1,8-naphthyridin-4(1H)-one (12). Alternatively, 12 could also be prepared by reacting 7 with 13 in DMF and K 2CO3 as a mild base at 120 °C for 2 h, followed by oxidation with H2O2 resulting in the corresponding sulfonyl derivatives 14. Copyright
- Venkateshwarlu,Chaitanya,Dubey
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scheme or table
p. 711 - 721
(2012/06/29)
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- A facile and convenient synthesis of naphthyridinoyl pyrazoles
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The reaction of naphthyridine hydrazide (4) with each of the different β-keto esters like ethyl 2-chloroacetoacetate (5), ethyl benzoylacetate (6) and ethyl 4-chloroacetoacetate (7) and with ethoxymethylenemalonic ester (8), independently, in ethanol, resulted in the formation of condensed products 2-chloro-3-[4-oxo-1,4-dihydro-[1,8] naphthyridine-3-carbonyl hydrazono]-butyric acid ethyl ester (9), 3-[(4-oxo-1,4-dihydro-[1,8] naphthyridine-3-carbonyl)- hydrazono]-3-phenyl propionic acid ethyl ester (10), 4-chloro-3-[(4-oxo-1,4- dihydro-[1,8] naphthyridine-3-carbonyl)-hydrazono]-butyric acid ethyl ester (11) and 2-[N-(6-bromo-4-oxo-1,4-diydro-[1,8] naphtyiridine-3-carbonyl- hydrazinomethylene)-malonic acid diethyl ester] (12) respectively. Each of these on heating with diphenyl ether yielded the corresponding cyclized products 3-(4-chloro-3-methyl-5-oxo-4,5-dihydro-pyrazole-1-carbonyl)-1H-[1,8] naphthyridin-4-ohe (13), 3-(5-oxo-3-phenyl-4,5-dihydro-pyrazole-1-carbonyl)-1H- [1,8] naphthyridine-4-one (14), 3-(3-chloromethyl-5-oxo-4,5-dihydropyrazole-1- carbonyl)-1 H-[1,8] naphthyridine-4-one (15) and 3-(4-chloro-3-methyl-5-oxo-4,5- dihydropyrazole-1-carbonyl)-1H-[1,8] naphthyridin-4-one (16). Alternatively, treatment of naphthyridine hydrazide (4) with each of the β-keto esters 5,6 & 7 and with EMME (8) directly in diphenylether at 2507deg; as one-pot reaction, gave the final products 13,14,15 & 16 in good yields.
- Chaitanya,Dubey
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p. 109 - 112
(2013/09/23)
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- Synthesis of novel napththyridines as potential antibacterial agents
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The reaction of 2-aminopyridine (1) with ethoxymethylenemalonic ester gave 4-ethoxy-3-oxo-2-(pyridine-2-yl aminomethylene)-butyric acid ethyl ester (2) which on cyclization in the presence of hot PPA gave 4-oxo-1,4-dihydro-[1,8] naphthyridine-3-carboxylic
- Chaitanya,Dubey
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p. 105 - 108
(2013/09/23)
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