63069-49-8Relevant articles and documents
COMBINATION THERAPY FOR TREATING MPS1
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Paragraph 0603; 0605-0607, (2021/08/14)
The application is directed to compounds of formula (I) and their salts and solvates, wherein B, R1, R2, R3, R3', R4, R4', and R5 are as set forth in the specification, as well as to methods for their preparation, pharmaceutical compositions comprising the same, and use thereof for the treatment and/or prevention of, e.g., MPS1, optionally in combination with α-L-iduronidase or an analog or variant thereof, e.g., laronidase.
Tunable Electrosynthesis of Anthranilic Acid Derivatives via a C-C Bond Cleavage of Isatins
Qian, Peng,Liu, Jiaojiao,Zhang, Yan,Wang, Zhiyong
, p. 16008 - 16015 (2021/07/31)
A facile and direct electrocatalytic C-C bond cleavage/functionalization reaction of isatins was developed. With isatins as the amino-attached C1 sources, a variety of aminobenzoates, and aminobenzamides were synthesized in moderate to good yields under mild conditions.
Oxidative ring-opening of isatins for the synthesis of 2-aminobenzamides and 2-aminobenzoates
Wang, Yu-Wei,Zheng, Lei,Jia, Feng-Cheng,Chen, Yun-Feng,Wu, An-Xin
, p. 1497 - 1503 (2019/02/13)
An efficient and practical isatin-based oxidative domino protocol has been developed for the facile synthesis of 2-aminobenzamides and 2-aminobenzoates. The robust nature of this reaction system is reflected by accessible starting materials, room temperature and high-yield gram-scale synthesis.
Design, synthesis and biological activities of 2,3-dihydroquinazolin-4(1H)-one derivatives as TRPM2 inhibitors
Zhang, Han,Liu, Huan,Luo, Xiao,Wang, Yuxi,Liu, Yuan,Jin, Hongwei,Liu, Zhenming,Yang, Wei,Yu, Peilin,Zhang, Liangren,Zhang, Lihe
, p. 235 - 252 (2018/05/09)
Transient receptor potential melastatin 2 (TRPM2), a Ca2+-permeable cationic channel, plays critical roles in insulin release, cytokine production, body temperature regulation and cell death as a reactive oxygen species (ROS) and temperature sensor. However, few TRPM2 inhibitors have been reported, especially TRP-subtype selective inhibitors, which hampers the investigation and validation of TRPM2 as a drug target. To discover novel TRPM2 inhibitors, 3D similarity-based virtual screening method was employed, by which 2,3-dihydroquinazolin-4(1H)-one derivative H1 was identified as a TRPM2 inhibitor. A series of novel 2,3-dihydroquinazolin-4(1H)-one derivatives were subsequently synthesized and characterized. Their inhibitory activities against the TRPM2 channel were evaluated by calcium imaging and electrophysiology approaches. Some of the compounds exhibited significant inhibitory activity, especially D9 which showed an IC50 of 3.7 μM against TRPM2 and did not affect the TRPM8 channel. The summarized structure-activity relationship (SAR) provides valuable insights for further development of specific TRPM2 targeted inhibitors.
POLY-ADP RIBOSE POLYMERASE (PARP) INHIBITORS
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Page/Page column 77, (2018/07/29)
The present invention is related to a pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a compound represented by the following structural formula: The present invention is also related a method of treating a subject with a disease which can be ameliorated by inhibition of poly(ADP-ribose)polymerase (PARP). The definitions of the variables are provided herein.
Synthesis, modelling, and anticonvulsant studies of new quinazolines showing three highly active compounds with low toxicity and high affinity to the GABA-A receptor
Zayed, Mohamed F.,Ihmaid, Saleh K.,Ahmed, Hany E.A.,El-Adl, Khaled,Asiri, Ahmed M.,Omar, Abdelsattar M.
, (2017/03/09)
Some novel fluorinated quinazolines (5a-j) were designed and synthesized to be evaluated for their anticonvulsant activity and their neurotoxicity. Structures of all newly synthesized compounds were confirmed by their infrared (IR), mass spectrometry (MS) spectra, 1H nuclear magnetic resonance (NMR), 13C-NMR, and elemental analysis (CHN). The anticonvulsant activity was evaluated by a subcutaneous pentylenetetrazole (scPTZ) test and maximal electroshock (MES)-induced seizure test, while neurotoxicity was evaluated by a rotorod test. The molecular docking was performed for all newly-synthesized compounds to assess their binding affinities to the GABA-A receptor in order to rationalize their anticonvulsant activities in a qualitative way. The data obtained from the molecular modeling was correlated with that obtained from the biological screening. These data showed considerable anticonvulsant activity for all newly-synthesized compounds. Compounds 5b, 5c, and 5d showed the highest binding affinities toward the GABA-A receptor, along with the highest anticonvulsant activities in experimental mice. These compounds also showed low neurotoxicity and low toxicity in the median lethal dose test compared to the reference drugs. A GABA enzymatic assay was performed for these highly active compounds to confirm the obtained results and explain the possible mechanism for anticonvulsant action. The most active compounds might be used as leads for future modification and optimization.
On the Synthesis and Reactivity of 2,3-Dihydropyrrolo[1,2- a ]quinazolin-5(1 H)-ones
Sutherell, Charlotte L.,Ley, Steven V.
supporting information, p. 135 - 144 (2016/12/24)
An improved, scalable synthetic route to the quinazolinone natural product 2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-one is reported. The applicability of this method to analogue synthesis and the synthesis of related natural products is explored. Finally, reactivity of the scaffold to a variety of electrophilic reagents, generating products stereoselectively, is reported.
TETRAHYDROISOQUINOLIN-2-YL-(QUINAZOLIN-4-YL) METHANONE COMPOUNDS AS CANCER CELL GROWTH INHIBITORS
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, (2014/09/29)
Tetrahydroisoquinolin-2-yl-(quinazolin-4-yl)methanone derivatives represented by formula (I), pharmacologically acceptable salts thereof, and compositions containing such compounds are described. Methods for treating hyperproliferative disorders by administering the compounds are also described. 1,2,3,4-tetrahydroisoquinoline derivatives for making tetrahydroisoquinolin-2-yl-(quinazolin-4-yl)methanone compounds are also described.
The synthesized novel fluorinated compound (LJJ-10) induces death receptor- and mitochondria-dependent apoptotic cell death in the human osteogenic sarcoma U-2 OS cells
Hour, Mann-Jen,Yang, Jai-Sing,Chen, Tai-Lin,Chen, Kuan-Tin,Kuo, Sheng-Chu,Chung, Jing-Gung,Lu, Chi-Cheng,Chen, Chia-Yi,Chuang, Yi-Hsuan
, p. 2709 - 2721 (2011/06/27)
We designed the 6-fluoro-2-(3-fluorophenyl)-4-substituted anilinoquinazoline derivatives as less toxic anti-cancer candidates. Our result demonstrated that LJJ-10 has greater cytotoxicity than that of the other compounds in human osteogenic sarcoma U-2 OS cells. LJJ-10-induced apoptosis was associated with enhancing ROS generation, DNA damage, and an increase of the protein levels of Fas, FasL, FADD, caspase-8, cytochrome c, Apaf-1, AIF, Endo G, caspase-9 and caspase-3 in U-2 OS cells. LJJ-10-triggered growth inhibition was significantly attenuated by N-acetylcysteine, cyclosporine A, anti-FasL monoclonal antibody, and caspase-8, -9 and -3 specific inhibitors in U-2 OS cells. We suggest that LJJ-10-induced apoptotic cell death in U-2 OS cells through death receptor- and mitochondria-dependent apoptotic signaling pathways.
ANTHRANILAMIDE INHIBITORS OF AURORA KINASE
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Page/Page column 28, (2008/12/07)
The present invention relates to a compound represented by the following formula: or a pharmaceutically acceptable salt thereof; where R1, R2, R3, R4, r and s are as previously defined. Compounds of the present invention are useful in the treatment of diseases associated with Aurora kinase activity such as cancer.
