- 6-(2-amino-1H-benzo[d]imidazole-6-yl)quinazoline-4(3H)-one compound
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The invention discloses a 6-(2-amino-1H-benzo[d]imidazole-6-yl)quinazoline-4(3H)-one compound,a preparation method and applications thereof, wherein the structural general formula (I) of the compoundis defined in the specification, R1 is hydrogen atom, morpholinomethyl, piperazinomethyl or substituted piperazinomethyl, R2 is hydrogen atom, butyl, morpholine substituted alkyl, benzyl, substitutedbenzyl, tryptamine, substituted tryptamine or N,N-dimethylamino, R3 is-C(O)R4 or-SO2R5, R4 and R5 are alkyl (C3-C6 alkyl), cycloalkyl (3-6-membered ring), alkoxy or alkyl substituted amino, and n is 1, 2, 3 or 4. The compound of the invention has inhibition activity on breast cancer, prostate cancer and human neuroblastoma.
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Paragraph 0041; 0045-0046; 0055; 0059-0060; 0069; 0073-0074
(2020/01/25)
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- Design, synthesis, biological evaluation of 6-(2-amino-1H-benzo[d]imidazole-6-yl)quinazolin-4(3H)-one derivatives as novel anticancer agents with Aurora kinase inhibition
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Aurora A kinase, a member of the Aurora kinase family, is frequently overexpressed in various human cancers. In addition, Overexpression of Aurora A kinase is associated with drug resistance and poor prognosis in many cancers including breast cancer. Therefore, Aurora A kinase has been considered as an attractive anticancer target for the treatment of human cancers. Herein, A series of 6-(2-amino-1H-benzo[d]imidazole-6-yl)quinazolin-4(3H)-one derivatives were designed, synthesized, and evaluated as Aurora A kinase inhibitors. The cell-based cytotoxicity assays showed that compound 16h was the most potent cytotoxic agent against all tested cancer cells and had a lower IC50 value than ENMD-2076 against MDA-MB-231 cells. Meanwhile, Aurora A kinase assay and Western blot analysis showed that 16h inhibited Aurora A kinase with an IC50 value of 21.94 nM and suppressed the phosphorylation of Histone H3 on Ser10 and Aurora A kinase on Thr288, which were consistent with the activation of Aurora A kinase. Accordingly, 16h caused aberrant mitotic phenotypes and obvious G2/M phase arrest in MDA-MB-231 cells and induced caspase-dependent apoptosis in MDA-MB-231 cells. These results demonstrated that 16h is a potential candidate for the development of anticancer agents targeting Aurora A kinase.
- Fan, Chengcheng,Fan, Yanhua,Wang, Daoping,Xu, Yongnan,Yang, Huarong,Yang, Xiaosheng,Yang, Ying,Zhong, Ting
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- Room-temperature borylation and one-pot two-step borylation/Suzuki-Miyaura cross-coupling reaction of aryl chlorides
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A highly efficient room-temperature borylation strategy of aryl chlorides is described. Utilizing Buchwald's second-generation preformed catalyst, boronate esters were obtained for a wide range of substrates in high yield. The method was also applied to Suzuki-Miyaura cross-coupling reaction in a one-pot two-step sequential manner, providing a facile and convenient access to the direct synthesis of biaryl compounds from aryl chlorides.
- Ji, Hong,Wu, Li-Yang,Cai, Jiang-Hong,Li, Guo-Rong,Gan, Na-Na,Wang, Zhao-Hua
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p. 13643 - 13648
(2018/04/24)
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- ORGANIC ELECTROLUMINESCENT COMPOUND AND ORGANIC ELECTROLUMINESCENT DEVICE COMPRISING THE SAME
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The present disclosure relates to an organic electroluminescent compound and an organic electroluminescent device comprising the same. By using the organic electroluminescent compound of the present disclosure, an organic electroluminescent device having low driving voltage, high luminous efficiency, and/or excellent lifespan characteristic can be produced.
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Paragraph 191; 197; 198
(2017/12/15)
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- BENZIMIDAZOLONE AND BENZOTHIAZOLONE COMPOUNDS AND THEIR USE AS AMPA RECEPTOR MODULATORS
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Provided herein are compounds of Formula (I), and pharmaceutically acceptable salts, N-oxides, or solvates thereof, Also provided herein are pharmaceutical compositions comprising compounds of Formula (I) and methods of using compounds of Formula (I).
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Page/Page column 95; 96
(2016/11/17)
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- METALLO-BETA-LACTAMASE INHIBITORS
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The present invention relates to compounds of formula (I) that are metallo-β-lactamase inhibitors, the synthesis of such compounds, and the use of such compounds for use with β-lactam antibiotics for overcoming resistance.
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Paragraph 1199
(2016/12/01)
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- METALLO-BETA-LACTAMASE INHIBITORS
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The present invention relates to compounds of formula I that are metallo-β-lactamase inhibitors, the synthesis of such compounds, and the use of such compounds for use with β-lactam antibiotics for overcoming resistance.
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Page/Page column 65
(2017/04/04)
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- N-aryl-2-aminobenzimidazoles: Novel, efficacious, antimalarial lead compounds
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From the phenotypic screening of the AstraZeneca corporate compound collection, N-aryl-2-aminobenzimidazoles have emerged as novel hits against the asexual blood stage of Plasmodium falciparum (Pf). Medicinal chemistry optimization of the potency against Pf and ADME properties resulted in the identification of 12 as a lead molecule. Compound 12 was efficacious in the P. berghei (Pb) model of malaria. This compound displayed an excellent pharmacokinetic profile with a long half-life (19 h) in rat blood. This profile led to an extended survival of animals for over 30 days following a dose of 50 mg/kg in the Pb malaria model. Compound 12 retains its potency against a panel of Pf isolates with known mechanisms of resistance. The fast killing observed in the in vitro parasite reduction ratio (PRR) assay coupled with the extended survival highlights the promise of this novel chemical class for the treatment of malaria.
- Ramachandran, Sreekanth,Hameed P., Shahul,Srivastava, Abhishek,Shanbhag, Gajanan,Morayya, Sapna,Rautela, Nikhil,Awasthy, Disha,Kavanagh, Stefan,Bharath, Sowmya,Reddy, Jitendar,Panduga, Vijender,Prabhakar,Saralaya, Ramanatha,Nanduri, Robert,Raichurkar, Anandkumar,Menasinakai, Sreenivasaiah,Achar, Vijayashree,Jiménez-Díaz, María Belén,Martínez, María Santos,Angulo-Barturen, I?igo,Ferrer, Santiago,Sanz, Laura María,Gamo, Francisco Javier,Duffy, Sandra,Avery, Vicky M.,Waterson, David,Lee, Marcus C. S.,Coburn-Flynn, Olivia,Fidock, David A.,Iyer, Pravin S.,Narayanan, Shridhar,Hosagrahara, Vinayak,Sambandamurthy, Vasan K.
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supporting information
p. 6642 - 6652
(2014/10/15)
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- ENZYME INHIBITORS
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The present subject matter relates generally to compounds having the formula (I): wherein each of X, Y, R1, R2, R3, R4, and n are as defined herein. Compounds of formula (I) may act as inhibitors of the thioredoxin reductase enzyme system. The subject matter also relates to use, formulation and preparation of the compounds. The compounds may be useful in the treatment of inflammatory and oxidative diseases and conditions. The compounds may also provide useful anti-proliferative and anti- apoptotic effects.
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Paragraph 00208
(2014/07/08)
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- Synthesis of nitric oxide probes with fluorescence lifetime sensitivity
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We present the rationale, synthesis and evaluation of the first activatable fluorescent probe that utilizes fluorescence lifetime change for detection of nitric oxide. The new probe DAP-LT1 features a near-infrared polymethine skeleton with a diaminobenzene functionality incorporated into the meso-position. The probe is partially quenched, and upon reaction with nitric oxide shows an increase in the fluorescence lifetime from 1.08 ns to 1.24 ns.
- Zhegalova, Natalia G.,Gonzales, Garrett,Berezin, Mikhail Y.
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p. 8228 - 8234
(2013/12/04)
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- HETEROCYCLIC COMPOUNDS FOR THE INHIBITION OF PASK
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Disclosed herein are new heterocyclic compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibiting PAS Kinase (PASK) activity in a human or animal subject are also provided for the treatment of diseases such as diabetes mellitus.
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Page/Page column 204
(2012/09/21)
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- NOVEL PYRIMIDINE COMPOUNDS AS MTOR AND P13K INHIBITORS
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The present invention relates to pyrimidine compounds of formula (I): which are useful in treating mTOR kinase- or PI3K kinase-related diseases.
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Page/Page column 120
(2011/07/30)
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- A new spirobifluorene-bridged bipolar system for a nitric oxide turn-on fluorescent probe
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Chemical equations presented. A new spirobifluorene-bridged bipolar molecule (EDADO) as a nitric oxide (NO) turn-on fluorescent probe was designed and synthesized. The fluorescence of EDADO is strongly quenched by photoinduced electron transfer (PET) from the electron-donating o-phenylenediamine-containing biphenyl branch to the orthogonally arranged electron-accepting 1,3,4-oxadiazole-containing conjugated oligoaryl system. Upon reacting with NO, EDADO is converted to EDADO-T, which exhibits strong fluorescence due to the suppression of PET.
- Lin, Li-Yen,Lin, Xiauo-Yun,Lin, Francis,Wong, Ken-Tsung
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supporting information; experimental part
p. 2216 - 2219
(2011/06/26)
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- PYRIMIDINE INHIBITORS OF KINASE ACTIVITY
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Described herein are compounds of formula (I) or pharmaceutical acceptable salts or solvates thereof, wherein G1, L1, R2, R3, n, p, Ar1, and Ar2 are defined in the description. Methods of making said compounds, and compositions comprising said compounds which are useful for inhibiting kinases such as IGF-IR are also disclosed.
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Page/Page column 58
(2010/12/26)
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- BENZIMIDAZOLE DERIVATIVES USEFUL AS TRP M8 RECEPTOR MODULATORS
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The present invention is directed to benzimidazole derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by TRP M8 (transient receptor potential M8 channel). More particularly, the compounds of the present invention are useful in the treatment of inflammatory pain, inflammatory hyperalgesia, inflammatory hypersensitivity condition, neuropathic pain, neuropathic cold allodynia, inflammatory somatic hyperalgesia, inflammatory visceral hyperalgesia, cardiovascular disease aggravated by cold, anxiety and depression.
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Page/Page column 70-71
(2010/12/17)
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- Development of multitargeted inhibitors of both the insulin-like growth factor receptor (IGF-IR) and members of the epidermal growth factor family of receptor tyrosine kinases
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Emerging clinical and pre-clinical data indicate that both insulin-like growth factor receptor (IGF-IR) and members of the epidermal growth factor (EGF) family of receptor tyrosine kinases (RTKs) exhibit significant cross-talk in human cancers. Therefore, a small molecule that successfully inhibits the signaling of both classes of oncogenic kinases might provide an attractive agent for chemotherapeutic use. Herein, we disclose the structure activity relationships that led to the synthesis and biological characterization of 14, a novel small molecule inhibitor of both IGF-IR and members of the epidermal growth factor family of RTKs.
- Hubbard, Robert D.,Bamaung, Nwe Y.,Fidanze, Steve D.,Erickson, Scott A.,Palazzo, Fabio,Wilsbacher, Julie L.,Zhang, Qian,Tucker, Lora A.,Hu, Xiaoming,Kovar, Peter,Osterling, Donald J.,Johnson, Eric F.,Bouska, Jennifer,Wang, Jieyi,Davidsen, Steven K.,Bell, Randy L.,Sheppard, George S.
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scheme or table
p. 1718 - 1721
(2009/11/30)
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- SMALL MOLECULE INHIBITORS OF PROTEIN ARGININE METHYLTRANSFERASES (PRMTS)
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The present invention relates to compounds that are useful as inhibitors of protein arginine methyltransferase that have a formula selected from Formula (I), Formula (II) and Formula (III), as well as racemic mixtures, diastereomers, enantiomers and tautomers thereof and N-oxides, hydrates, solvates, pharmaceutically acceptable salts, prodrugs and complexes thereof as defined herein. Said compound are useful as inhibitors of PRMTs and/or CARM-I. The invention further relates to compositions comprising such compounds and methods for their use.
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Page/Page column 124-125
(2008/12/08)
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- Pyrimidinone compounds useful as kinase inhibitors
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This invention relates to newly identified compounds for inhibiting hYAK3 proteins and methods for treating diseases associated with the imbalance or inappropriate activity of hYAK3 proteins.
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Page/Page column 11-12
(2010/11/27)
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- Pyrazolo[3,4-d]pyrimidines as potent inhibitors of the insulin-like growth factor receptor (IGF-IR)
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A high throughput screen of Abbott's compound repository revealed that the pyrazolo[3,4-d]pyrimidine class of kinase inhibitors possessed moderate potency for IGF-IR, a promising target for cancer chemotherapy. The synthesis and subsequent optimization of this class of compounds led to the discovery of 14, a compound that possesses in vivo IGF-IR inhibitory activity.
- Hubbard, Robert D.,Bamaung, Nwe Y.,Palazzo, Fabio,Zhang, Qian,Kovar, Peter,Osterling, Donald J.,Hu, Xiaoming,Wilsbacher, Julie L.,Johnson, Eric F.,Bouska, Jennifer,Wang, Jieyi,Bell, Randy L.,Davidsen, Steven K.,Sheppard, George S.
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p. 5406 - 5409
(2008/03/13)
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- PROTEIN KINASE INHIBITORS
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Compounds that inhibit protein kinases, compositions containing the compounds and methods of treating diseases using the compounds are disclosed.
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Page/Page column 42
(2010/11/28)
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- HETEROCYCLIC INHIBITORS OF PROTEIN ARGININE METHYL TRANSFERASES
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A compound of formula I, or a stereoisomer, a tautomer, a pharmaceutically acceptable salt or solvate thereof, methods of using such compounds in the treatment of hyperproliferative, inflammatory, infectious, and immunoregulatory disorders and diseases; and to pharmaceutical compositions containing such compounds
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Page/Page column 20
(2010/11/24)
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