cas 543712-81-8, 2,5-Dichloro-N-(5-methyl-1H-pyrazol-3-yl)-4-pyrimidinamine

Articles about 543712-81-8Total 14 be found

Design, synthesis, and biological evaluation of proteolysis targeting chimeras (PRoTACS) for the dual degradation of IGF-1R and SrC
A focused PROTAC library was developed to degrade both IGF-1R and Src proteins, which are associated with various cancers. PROTACs with IGF-1R and Src degradation potentials were synthesized by tethering different inhibitor warhead units and the E3 ligase (CRBN) recruiting-pomalidomide with various linkers. The designed PROTACs 12a–b inhibited the proliferation and migration of MCF7 and A549 cancer cells with low micromolar potency (1–5 μM) in various cellular assays.
Lee, Jeeyeon,Lee, Na Keum,Manda, Sudhakar,Oh, Dong-Chan
supporting information

(2020/04/29)

Substituted heteroaryl compounds and compositions and uses thereof
The invention provides a substituted ceteroary compound as well as a composition and a purpose thereof. The substituted ceteroary compound is a compound shown as a formula (I) or a stereoisomer, a tautomer, a nitrogen oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug of the pharmaceutically acceptable salt of the compound shown as the formula (I) and is used for regulating diseases or disorders mediated by one kind or various kinds of Janus kinase activities. The invention also provides a medicine composition containing the compound and a method of treating or alleviating the disease or disorder degree of a patient by inhibiting the Janus kinase activity.
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Paragraph 0762; 0763; 0764; 0765

(2018/01/04)

SUBSTITUTED HETEROARYL COMPOUNDS AND METHODS OF USE
The present invention provides new heteroaryl compounds, pharmaceutical acceptable salts and formulations thereof useful in preventing, treating or lessening the severity of JAK-mediated diseases. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of JAK-mediated diseases.
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Paragraph 323

(2015/07/07)

4-SUBSTITUTED-(3-SUBSTITUTED-1H-PYRAZOLE-5-AMINO)-PYRIMIDINE DERIVATIVES HAVING ACTIVITY OF INHIBITING PROTEIN KINASE AND USE THEREOF
Provided are derivatives substituted by urea associated with 4-substituted-(3-substituted-1H-pyrazole-5-amino)-pyrimidine-2-amino of formula (I), wherein these compounds may selectively regulate or inhibit an information transmission process controlled by
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Paragraph 0061-0063

(2014/07/23)

4-SUBSTITUTED-(3-SUBSTITUTED-1H-PYRAZOLE-5-AMINO)-PYRIMIDINE DERIVATIVES HAVING ACTIVITY OF INHIBITING PROTEIN KINASE AND USE THEREOF
Provided are derivatives substituted by urea associated with 4-substituted-(3-substituted-1H-pyrazole-5-amino)-pyrimidine-2-amino of formula (I), wherein these compounds may selectively regulate or inhibit an information transmission process controlled by
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Paragraph 0093; 0094; 0095

(2015/01/07)

Use of ω-transaminase enzyme chemistry in the synthesis of a JAK2 kinase inhibitor
ω-Transaminase enzyme chemistry provides an excellent methodology to build synthetically useful chiral amines from their corresponding ketones. An application of this methodology, providing a long-term commercial manufacturing route to a JAK2 kinase inhibitor, is reported herein.
Frodsham, Lianne,Golden, Michael,Hard, Susan,Kenworthy, Martin N.,Klauber, David J.,Leslie, Kevin,Macleod, Claire,Meadows, Rebecca E.,Mulholland, Keith R.,Reilly, Julie,Squire, Christopher,Tomasi, Simone,Watt, Denise,Wells, Andrew S.
p. 1123 - 1130
(2013/10/08)

Discovery of 5-chloro- N 2-[(1 S)-1-(5-fluoropyrimidin-2-yl) ethyl]- N 4-(5-methyl-1 H -pyrazol-3-yl)pyrimidine-2,4-diamine (AZD1480) as a novel inhibitor of the jak/stat pathway
The myeloproliferative neoplasms, polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis are a heterogeneous but related group of hematological malignancies characterized by clonal expansion of one or more myeloid lineages. The discovery of the Jak2 V617F gain of function mutation highlighted Jak2 as a potential therapeutic target in the MPNs. Herein, we disclose the discovery of a series of pyrazol-3-yl pyrimidin-4-amines and the identification of 9e (AZD1480) as a potent Jak2 inhibitor. 9e inhibits signaling and proliferation of Jak2 V617F cell lines in vitro, demonstrates in vivo efficacy in a TEL-Jak2 model, has excellent physical properties and preclinical pharmacokinetics, and is currently being evaluated in Phase I clinical trials.
Ioannidis, Stephanos,Lamb, Michelle L.,Wang, Tao,Almeida, Lynsie,Block, Michael H.,Davies, Audrey M.,Peng, Bo,Su, Mei,Zhang, Hai-Jun,Hoffmann, Ethan,Rivard, Caroline,Green, Isabelle,Howard, Tina,Pollard, Hannah,Read, Jon,Alimzhanov, Marat,Bebernitz, Geraldine,Bell, Kirsten,Ye, Minwei,Huszar, Dennis,Zinda, Michael
experimental part
p. 262 - 276
(2011/03/20)

CHEMICAL COMPOUNDS 916-1
The present invention relates to compounds of Formula (I) and to their salts, pharmaceutical compositions, methods of use, and methods for their preparation. These compounds provide a treatment for myeloproliferative disorders and cancer.
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Page/Page column 56-57

(2009/03/07)

COMPOUNDS AND COMPOSITIONS AS KINASE INHIBITORS
The invention provides novel pyrimidine derivatives and pharmaceutical compositions thereof, and methods for using such compounds. For example, the pyrimidine derivatives of the invention may be used to treat, ameliorate or prevent a condition which responds to inhibition of insulin-like growth factor (IGF-1R) or analplastic lymphoma kinase (ALK).
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Page/Page column 29-30

(2010/01/30)

Identification of 4-aminopyrazolylpyrimidines as potent inhibitors of Trk kinases
The design, synthesis and biological evaluation of a series of 4-aminopyrazolylpyrimidines as potent Trk kinase inhibitors is reported. High-throughput screening identified a promising hit in the 4- aminopyrazolylpyrimidine chemotype. Initial optimization of the series led to more potent Trk inhibitors. Further optimization using two strategies resulted in significant improvement of physical properties and led to the discovery of 10z (AZ-23), a potent, orally bioavailable Trk A/B inhibitor. The compound offers the potential to test the hypothesis that modulation of Trk activity will be of benefit in the treatment of cancer and other indications in vivo.
Wang, Tao,Lamb, Michelle L.,Scott, David A.,Wang, Haixia,Block, Michael H.,Lyne, Paul D.,Lee, John W.,Davies, Audrey M.,Zhang, Hai-Jun,Zhu, Yanyi,Gu, Fei,Han, Yongxin,Wang, Bin,Mohr, Peter J.,Kaus, Robert J.,Josey, John A.,Hoffmann, Ethan,Thress, Ken,MacIntyre, Terry,Wang, Haiyun,Omer, Charles A.,Yu, Dingwei
experimental part
p. 4672 - 4684
(2009/07/25)

4- (3-AMINOPYRAZOLE) PYRIMIDINE DERIVATIVES FOR USE AS TYROSINE KINASE INHIBITORS IN THE TREATMENT OF CANCER
This invention relates to novel compounds having the formula (I) and to their pharmaceutical compositions and to their methods of use. These novel compounds provide a treatment for cancer.
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Page/Page column 58

(2010/11/27)

PYRIMIDINES AS IGF-I INHIBITORS
A compound of formula (I) wherein the substituents are as defined in the text for use in inhibiting insulin-like growth factor 1 receptor activity in a warm blooded animal such as man.
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Page/Page column 70; 74

(2010/11/24)

CHEMICAL COMPOUNDS
This invention relates to novel compounds having the formula (I) and to their pharmaceutical compositions and to their methods of use. These novel compounds provide a treatment for cancer.
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Page/Page column 63

(2010/11/25)

PYRAZOLE DERIVATIVES AS INHIBITORS OF RECEPTOR TYROSYNE KINASES
Compounds of formula (I): and their use in the inhibition of Trk activity are described.
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Page/Page column 96

(2008/06/13)