5339-05-9Relevant academic research and scientific papers
WEE1 inhibitors as well as preparation and application thereof
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, (2020/10/14)
The invention relates to WEE1 inhibitors as well as preparation and application thereof. The present invention relates to compounds of formula (I), or pharmaceutically acceptable salts, solvates, polymorphs or isomers thereof, and their use in the preparation of medicaments for the treatment of diseases associated with WEE1 activity.
Development of Potent Pyrazolopyrimidinone-Based WEE1 Inhibitors with Limited Single-Agent Cytotoxicity for Cancer Therapy
Matheson, Christopher J.,Casalvieri, Kimberly A.,Backos, Donald S.,Reigan, Philip
supporting information, p. 1681 - 1694 (2018/08/01)
WEE1 kinase regulates the G2/M cell-cycle checkpoint, a critical mechanism for DNA repair in cancer cells that can confer resistance to DNA-damaging agents. We previously reported a series of pyrazolopyrimidinones based on AZD1775, a known WEE1 inhibitor, as an initial investigation into the structural requirements for WEE1 inhibition. Our lead inhibitor demonstrated WEE1 inhibition in the same nanomolar range as AZD1775, and potentiated the effects of cisplatin in medulloblastoma cells, but had reduced single-agent cytotoxicity. These results prompted the development of a more comprehensive series of WEE1 inhibitors. Herein we report a series of pyrazolopyrimidinones and identify a more potent WEE1 inhibitor than AZD1775 and additional compounds that demonstrate that WEE1 inhibition can be achieved with reduced single-agent cytotoxicity. These studies support that WEE1 inhibition can be uncoupled from the potent cytotoxic effects observed with AZD1775, and this may have important ramifications in the clinical setting where WEE1 inhibitors are used as chemosensitizers for DNA-targeted chemotherapy.
8-ETHYL-6-(ARYL)PYRIDO [2,3-D]PYRIMIDIN-7(8H) -ONES FOR THE TREATMENT OF NERVOUS SYSTEM DISORDERS AND CANCER
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Paragraph 00595, (2013/04/10)
Provided herein are PAK inhibitors and methods of utilizing PAK inhibitors for the treatment of CNS disorders such as neuropsychiatric disorders or neurofibromatosis. Also described herein are methods of utilizing PAK inhibitors for the treatment of cancer.
Synthesis and biological evaluation of new 4β-anilino-4′-O- demethyl-4-desoxypodophyllotoxin derivatives as potential antitumor agents
Wang, Li,Yang, Fenyan,Yang, Xiaochun,Guan, Xianghong,Hu, Chunqi,Liu, Tao,He, Qiaojun,Yang, Bo,Hu, Yongzhou
, p. 285 - 296 (2011/03/17)
A series of new 4β-anilino-4′-O-demethyl-4-desoxypodophyllotoxin derivatives were prepared and evaluated for their cytotoxicities against four human cancer cell lines including KB, KB/VCR, A549 and 95D. Most compounds showed better growth-inhibition activities against tested cell lines than that of etoposide (VP-16). Preliminary structure-activity relationships (SARs) were concluded and it indicated that the side chains substituted at 4β position of podophyllotoxin significantly influenced the cytotoxic activity, especially for the drug resistance profile. In vivo studies of compound 26c on highly metastatic human lung cancer xenograft in nude mice showed that it can significantly inhibit tumor growth with administrating by oral route.
IMIDAZOPYRIDINES AS A NOVEL SCAFFOLD FOR MULTI-TARGETED KINASE INHIBITION
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Page/Page column 234, (2011/05/11)
Compounds that inhibit protein kinases, compositions containing the compounds and methods of treating diseases using the compounds are disclosed. Formula (I).
PYRIMIDINE INHIBITORS OF KINASE ACTIVITY
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Page/Page column 112, (2010/12/26)
The present invention relates to compounds of formula (I) or pharmaceutical acceptable salts or solvates thereof, wherein G1, R2, R3, R4, R5, n, p, q, Ar1, and Ar2 are defined in the description. The present invention relates also to methods of making said compounds, and compositions comprising said compounds which are useful for inhibiting kinases such as IGF-IR.
QUINOLONE CARBOXYLIC ACID DERIVATIVES FOR TREATMENT OF HYPERPROLIFERATIVE CONDITIONS
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Page/Page column 64-65, (2010/02/14)
Quinolone carboxylic acid derivatives of formula (I) wherein Ar is an optionally substituted phenyl, pyridyl, or pyrimidinyl group and the substituent groups R1, R4, R10, R11, R19, and R20 are as defined in the specification, pharmaceutical compositions containing them, and methods of using them in treatment of hyperproliferative diseases such as cancer are disclosed and claimed.
Aryl aniline derivatives as beta2 adrenergic receptor agonists
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Page/Page column 18, (2008/06/13)
The invention provides novel β2 adrenergic receptor agonist compounds. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat diseases associated with β2 adrenergic
INDOLE DERIVATIVES, PROCESS FOR PRODUCING THE SAME AND MEDICINAL USES OF THE SAME
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, (2008/06/13)
A novel compound which is a δ-opioid antagonist having high selectivity and activity, that exhibits immunosuppressive action, antiallergic action, anti-inflammatory action and brain cell-protecting action is disclosed. The compound according to the present invention is an indole derivative represented by the formula (I): STR1 and pharmaceutically acceptable acid addition salts thereof. The present invention also provides an immunosuppressive agent, antiallergic agent, anti-inflammatory agent and brain cell-protecting agent comprising the derivative or the salt as an effective ingredient.
