13052-92-1Relevant academic research and scientific papers
Design, synthesis and biological evaluation of novel EGFR/HER2 dual inhibitors bearing a oxazolo[4,5-g]quinazolin-2(1H)-one scaffold
Yin, Siyuan,Tang, Chunming,Wang, Bin,Zhang, Ying,Zhou, Liliang,Xue, Lingjing,Zhang, Can
, p. 26 - 36 (2016)
For the purpose of developing novel EGFR/HER2 tyrosine kinases inhibitors with high inhibition activity and low toxicity, two novel series of oxazolo[4,5-g]quinazolin-2(1H)-one derivatives as EGFR/HER2 dual inhibitors introducing two electrophiles 2-(2-bromoacetyl)ethyl and 2-(2-chloroacetoxy)ethyl group as side-chain at 1-position respectively and evaluated their EGFR and HER2 inhibition activity and toxicity comparing with Lapatinib. All these compounds were evaluated by EGFR and HER2 kinase inhibition and two anti-proliferation assays in vitro. Most of the designed compounds exhibited moderate to high inhibition activity against EGFR and HER2. Especially, compounds 11o, 11p, 12e and 12f presented high inhibition against EGFR and HER2. Furthermore, compounds 11p and 12f also had well exhibition to excellent anti-proliferation activity against human lung adenocarcinoma cell line (A549) and human breast cancer cell line (SK-Br3), and 12f also exhibited the lowest toxicity against human embryonic lung fibroblast cell line (HELF) cell. Finally, compound 12f presented remarkably higher inhibition efficacy towards tumour growth than Lapatinib in a mouse lewis lung cancer (LLC) xenograft model.
Design, synthesis and biological activities of novel oxazolo[4,5- g ]quinazolin-2(1H)-one derivatives as EGFR inhibitors
Yin, Siyuan,Zhou, Liliang,Lin, Jinsheng,Xue, Lingjing,Zhang, Can
, p. 462 - 475 (2015)
A series of oxazolo[4,5-g]quinazolin-2(1H)-one derivatives employing Erlotinib as lead compound were synthesized and evaluated for their EGFR inhibition activity. These compounds having variation at the 1 and 8-position, included ether and esters hydrophilic side-chain and aromatic head fragment, respectively. All these compounds were evaluated by EGFR inhibition and two anti-proliferation assays in vitro. Four compounds were found more potent than Erlotinib in EGFR-TK assay. Furthermore, compounds 18, 42 and 50 also had good to excellent anti-proliferation activity against human epidermoid cancer cell line (KB) and renal cell carcinoma cell line (A498). Finally, compound 50 presented remarkably higher inhibition efficacy towards tumor growth than Erlotinib in a mouse lewis lung cancer (LLC) xenograft model. Furthermore, compound 50 displayed the most distinguished effect on extending the survival period of the tumor-bearing mice.
Synthetic method for derivatives of nocarbenzoxazoles and pharmaceutical composition containing the derivatives of nocarbenzoxazoles
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Paragraph 0032; 0038, (2019/10/22)
An object of the present invention is to provide an anti-inflammation agent having excellent efficacy and minimized side effects by solving side effects of conventional anti-inflammation agents, and to provide a synthesis method thereof. By using a POCl_3-mediated ring dehydration reaction using commercially available inexpensive raw materials and selective and/or complete demethylation and a reduction reaction as main reactions, nocabenzoxazole derivatives are easily synthesized in a 15 to 49% yield and it is confirmed by testing anti-inflammatory activity of compounds.COPYRIGHT KIPO 2019
Synthetic method for nocarbenzoxazoles and their derivatives
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Paragraph 0033; 0039, (2019/12/15)
An object of the present invention is to provide an anti-inflammation agent having excellent efficacy and minimized side effects by solving side effects of existing anti-inflammation agents, and to provide a novel nocarbenzoxazole derivative and a synthesis method thereof. By using a POCl_3-mediated ring dehydration reaction using commercially available inexpensive raw materials and selective and/or complete demethylation and a reduction reaction as main reactions, nocarbenzoxazole derivatives are easily synthesized in a 15 to 49% of yield and it is confirmed by testing anti-inflammatory activity of compounds.COPYRIGHT KIPO 2020
Synthetic method for nocarbenzoxazole G and derivatives of nocarbenzoxaoles
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Paragraph 0036; 0042, (2019/12/25)
An object of the present invention is to provide an anti-inflammation agent having excellent efficacy and minimized side effects by solving side effects of existing anti-inflammation agents, and to provide a novel nocarbenzoxazole derivative and a synthesis method thereof. By using a POCl_3-mediated ring dehydration reaction using commercially available inexpensive raw materials and selective and/or complete demethylation and a reduction reaction as main reactions, nocarbenzoxazole G and nocarbenzoxazole derivatives are easily synthesized in a 15 to 49% of yield and it is confirmed by testing anti-inflammatory activity of compounds.COPYRIGHT KIPO 2020
Facile Synthesis and In Vitro Nitric Oxide Production Inhibitory Activity of Benzoxazoles
Park, Hyeong Jin,Kim, Jin-Kyung,Jun, Jong-Gab
, p. 743 - 749 (2018/05/07)
A Facile synthesis of natural benzoxazoles, nocarbenzoxazoles F (1), G (5) and their derivatives (2–4 and 6–8) was achieved from the commercially available inexpensive precursors with overall yields ranging from 15 to 49%. Our strategy to access this fami
A facile hybrid 'flow and batch' access to substituted 3,4-dihydro-2: H -benzo [b] [1,4]oxazinones
Lin, Andrew J. S.,Russell, Cecilia C.,Baker, Jennifer R.,Frailey, Shelby L.,Sakoff, Jennette A.,McCluskey, Adam
, p. 8732 - 8742 (2016/10/03)
We describe a simple flow chemistry approach to libraries of ethyl 3-oxo-2-(substituted-phenylamino)-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carboxylates (12a-l) and N-ethyl-3-oxo-2-(substituted-phenylamino)-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carboxamides (13a-l) in 38-87% yields. This scaffold is poorly described in the chemical literature. Screening against a panel of 11 cancer and one normal cell line showed that the amide linked library 13a-l was devoid of toxicity. Whereas the ester linked analogues 12b, 12c, 12g, 12j and 12l were highly cytotoxic with growth inhibition (GI50) values from 0.34 to >50 μM across all cell lines, with the 2-OH-Ph substituted 12l analogue presenting with sub-micromolar potency against the A2780 (ovarian; 0.34 ± 0.04 μM), BEC-2 (glioblastoma; 0.35 ± 0.06 μM), MIA (pancreas; 0.91 ± 0.054 μM) and SMA (murine glioblastoma; 0.77 ± 0.029 μM) carcinoma cell lines. Interestingly, the U87 glioblastoma cell line showed inherent resistance to growth inhibition by all analogues (GI50 32 to >50 μM) while the A2780 cells were highly sensitive (GI50 3.8-0.34 μM), suggesting that the analogues developed herein may be valuable lead compounds for the development of ovarian carcinoma specific cytotoxic agents. The differences in amide versus ester cytotoxicity was consitent with esterase cleaveage to release the cytotoxic warhead.
NOVEL CC-1065 ANALOGS AND THEIR CONJUGATES
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Page/Page column 155, (2010/06/17)
This invention relates to novel analogs of the DNA-alkylating agent CC-1065 and to their conjugates. Furthermore this invention concerns intermediates for the preparation of said agents and conjugates. The conjugates are designed to release their (multiple) payload after one or more activation steps and/or at a rate and time span controlled by the conjugate in order to selectively deliver and/or controllably release one or more of said DNA alkylating agents. The agents, conjugates, and intermediates can be used to treat an illness that is characterized by undesired (cell) proliferation. As an example, the agents and the conjugates of this invention may be used to treat a tumor.
BIPHENYL-4-YL-SULFONIC ACID ARYLAMIDES AND THEIR USE AS THERAPEUTIC AGENTS
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Page/Page column 66, (2008/12/07)
The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain aryl sulfonamides and related compounds (collectively referred to herein as "BPSAAA compounds"), as described herein, and including, for example, biphenyl-4-sulfonic acid (hydroxyalkyl-phenyl)-amides and related compounds. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, in treatment and/or prevention, for example, of inflammation and/or joint destruction and/or bone loss; of disorders mediated by excessive and/or inappropriate and/or prolonged activation of the immune system; of, inflammatory and autoimmune disorders, for example, rheumatoid arthritis, psoriasis, psoriatic arthritis, chronic obstructive pulmonary disease (COPD), atherosclerosis, inflammatory bowel disease, ankylosing spondylitis, and the like; of disorders associated with bone loss, such as bone loss associated with excessive osteoclast activation in rheumatoid arthritis, osteoporosis, cancer associated bone disease, Paget's disease and the like.
Regulatory molecules for the 5-HT3 receptor ion channel gating system
Yoshida, Satoshi,Watanabe, Takashi,Sato, Yasuo
, p. 3515 - 3523 (2008/02/07)
Substituted benzoxazole derivatives which possess a nitrogen-containing heterocycle at C2 are selective partial agonists of the 5-HT3 receptor. Alteration of substituents on the benzoxazole nucleus affords both agonist-like and antagonist-like compounds, and uniquely modifies the function of the 5-HT3 receptor ion channel gating system. SAR and corroborative computational docking study for these partial agonists successfully explained structure and function of the 5-HT3 receptor.
