223786-22-9Relevant academic research and scientific papers
MACROCYCLIC COMPOUND SERVING AS WEE1 INHIBITOR AND APPLICATIONS THEREOF
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, (2020/11/30)
Disclosed in the present invention are a macrocyclic compound serving as a Weel inhibitor, and applications thereof in the preparation of drugs for treating Weel-related diseases. The present invention specifically relates to a compound represented by for
Discovery and SARs of 5-Chloro- N4-phenyl- N2-(pyridin-2-yl)pyrimidine-2,4-diamine Derivatives as Oral Available and Dual CDK 6 and 9 Inhibitors with Potent Antitumor Activity
Wang, Yang,Chen, Xing,Yan, Yaoyao,Zhu, Xiaochen,Liu, Mingming,Liu, Xinhua
, p. 3327 - 3347 (2020/04/08)
Cyclin-dependent kinases (CDKs) are promising therapeutic targets for cancer therapy. Herein, we describe our efforts toward the discovery of a series of 5-chloro-N4-phenyl-N2-(pyridin-2-yl)pyrimidine-2,4-diamine derivatives as dual CDK6 and 9 inhibitors. Intensive structural modifications lead to the identification of compound 66 as the most active dual CDK6/9 inhibitor with balancing potency against these two targets and good selectivity over CDK2. Further biological studies revealed that compound 66 was directly bound to CDK6/9, resulting in suppression of their downstream signaling pathway and inhibition of cell proliferation by blocking cell cycle progression and inducing cellular apoptosis. More importantly, compound 66 significantly inhibited tumor growth in a xenograft mouse model with no obvious toxicity, indicating the promising therapeutic potential of CDK6/9 dual inhibitors for cancer treatment. Therefore, the above results are of great importance in the development of dual CDK6/9 inhibitors for cancer therapy.
Structure-Bioactivity Relationships of Lapatinib Derived Analogs against Schistosoma mansoni
Bachovchin, Kelly A.,Bag, Seema,Buskes, Melissa J.,Caffrey, Conor R.,Campbell, Robert F.,Clements, Monica,El-Sakkary, Nelly,Ferrins, Lori,Jalani, Hitesh B.,Klug, Dana M.,Leonard, Allison,Pollastri, Michael P.,Sciotti, Richard J.,Singh, Baljinder
supporting information, p. 258 - 265 (2020/03/30)
We recently reported a series of compounds for a solubility-driven optimization campaign of antitrypanosomal compounds. Extending a parasite-hopping approach to the series, a subset of compounds from this library has been cross-screened for activity against the metazoan flatworm parasite, Schistosoma mansoni. This study reports the identification and preliminary development of several potently bioactive compounds against adult schistosomes, one or more of which represent promising leads for further assessment and optimization.
8,9-DIHYDROIMIDAZOLE[1,2-A]PYRIMIDO[5,4-E]PYRIMIDINE-5(6H)-KETONE COMPOUND
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Paragraph 0152, (2019/10/10)
Disclosed are 8,9-dihydroimidazo[1,2-a]pyrimido[5,4-e]pyrimidin-5(6H)-one compounds, specifically represented by the Formula I: or a pharmaceutically acceptable salt or prodrug thereof, wherein A and R1-R7 are defined herein. Compounds having Formula I are Wee1 kinase inhibitors. Therefore, compounds of the disclosure may be used to treat diseases caused by abnormal Wee1 activity.
Design and synthesis of 4-(Heterocyclic substituted amino)-1h-pyrazole-3-carboxamide derivatives and their potent activity against acute myeloid leukemia (AML)
Zhi, Yanle,Wang, Zhijie,Yao, Chao,Li, Baoquan,Heng, Hao,Cai, Jiongheng,Xiang, Li,Wang, Yue,Lu, Tao,Lu, Shuai
, (2019/11/21)
Fms-like receptor tyrosine kinase 3 (FLT3) has been emerging as an attractive target for the treatment of acute myeloid leukemia (AML). By modifying the structure of FN-1501, a potent FLT3 inhibitor, 24 novel 1H-pyrazole-3-carboxamide derivatives were designed and synthesized. Compound 8t showed strong activity against FLT3 (IC50: 0.089 nM) and CDK2/4 (IC50: 0.719/0.770 nM), which is more efficient than FN-1501(FLT3, IC50: 2.33 nM; CDK2/4, IC50: 1.02/0.39 nM). Compound 8t also showed excellent inhibitory activity against a variety of FLT3 mutants (IC50 50: 1.22 nM). In addition, compound 8t significantly inhibited the proliferation of most human cell lines of NCI60 (GI50 1 μM for most cell lines). Taken together, these results demonstrated the potential of 8t as a novel compound for further development into a kinase inhibitor applied in cancer therapeutics.
INDOLINONE DERIVATIVES AND THEIR USE IN TREATING DISEASE-STATES SUCH AS CANCER
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Page/Page column 17, (2009/01/24)
The present invention encompasses compounds of general formula (1) wherein R1 to R4 are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and their use for preparing a pharmaceutical composition having the above-mentioned properties.
Structure-activity relationship of quinoline derivatives as potent and selective α2c-adrenoceptor antagonists
H?glund, Iisa P. J.,Silver, Satu,Engstr?m, Mia T.,Salo, Harri,Tauber, Andrei,Kyyr?nen, Hanna-Kaisa,Saarenketo, Pauli,Hoffrén, Anna-Marja,Kokko, Kurt,Pohjanoksa, Katariina,Sallinen, Jukka,Savola, Juha-Matti,Wurster, Siegfried,Kallatsa, Oili A.
, p. 6351 - 6363 (2007/10/03)
Starting from two acridine compounds identified in a high-throughput screening campaign (1 and 2, Table 1), a series of 4-aminoquinolines was synthesized and tested for their properties on the human α2- adrenoceptor subtypes (α2A, α2B, and α2C). A number of compounds with good antagonist potencies against the α2C-adrenoceptor and excellent subtype selectivities over the other two subtypes were discovered. For example, (R)-{4-[4-(3,4-dimethylpiperazin-1-yl)phenylamino]quinolin-3-yl}methanol 6j had an antagonist potency of 8.5 nM against, and a subtype selectivity of more than 200-fold for, the α2c-adrenoceptor. Investigation of the structure-activity relationship identified a number of structural features, the most critical of which was an absolute need for a substituent in the 3-position of the quinoline ring. The 3-position on the piperazine ring was also found to play an appreciable role, as substitutions in that position exerted a significant and stereospecific beneficial effect on the α2C- adrenoceptor affinity and potency. Replacing the piperazine ring proved difficult, with 1,4-diazepanes representing the only viable alternative.
TETRAHYDROISOQUINOLINES AS FACTOR XA INHIBITORS
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Page/Page column 41, (2008/06/13)
The present invention is directed to compounds represented by Formula I and pharmaceutically acceptable salts, solvates, hydrates, and prodrugs thereof which are inhibitors of Factor Xa. The present invention is also directed to and intermediates used in making such compounds, pharmaceutical compositions containing such compounds, methods to prevent or treat a number of conditions characterized by undesired thrombosis and methods of inhibiting the coagulation of a blood sample.
UREAS AS FACTOR XA INHIBITORS
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Page/Page column 96, (2010/11/08)
The present invention is directed to compounds represented by Formula (I) and pharmaceutically acceptable salts, solvates, hydrates, and prodrugs thereof which are inhibitors of Factor Xa. The present invention is also directed to and intermediates used in making such compounds, pharmaceutical compositions containing such compounds, methods to prevent or treat a number of conditions characterized by undesired thrombosis and methods of inhibiting the coagulation of a blood sample.
Composition for dyeing keratinous fibers containing a paraphenylenediamine substituted by a diazacycloheptane radical
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Page/Page column 9-10, (2008/06/13)
The subject of the invention is a composition for the oxidation dyeing of keratinous fibres, in particular human hair, comprising an oxidation base of the para-phenylenediamine type, substituted with a diazacycloheptane radical. The invention also relates to the method for dyeing fibres using this composition, and the novel compounds of the type mentioned above.
