1824388-23-9Relevant articles and documents
Preparation method of PIM447 key intermediate
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, (2019/11/28)
The invention relates to a preparation method of a PIM447 key intermediate, namely a compound tert-butyl ((1S, 3R, 5S)-3-(3-aminopyridin-4-yl)-5-methyl cyclohexyl) carbamate. The method comprises thefollowing steps that a, a compound I and p-methoxybenzylamine are subjected to a reductive amination reaction to obtain a compound II; b, a mixture of the compound II and di-tert-butyl dicarbonate ester are subjected to an acylation reaction and purified to obtain a compound III; c, a mixture of the compound III is subjected to a reduction reaction under the action of a reducing agent, and purified to obtain a mixture of a compound IV a and a compound IV b; d, the mixture of the compound IV a and the compound IV b is subjected to Boc removal under an acidic condition to obtain a compound V; e,a mixture of the compound V is subjected to a catalytic hydrogenolysis reaction under the action of a catalyst to obtain a compound VI; f, a mixture of the compound VI and di-tert-butyl dicarbonate ester are subjected to an acylation reaction to obtain a compound VII; g, a mixture of the compound VII is subjected to chiral resolution for preparation of a chromatographic column to obtain a compound VII a. The synthetic route is shown in the description.
HETEROCYCLIC COMPOUNDS USEFUL AS PIM KINASE INHIBITORS
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, (2017/08/01)
The present application is concerned with heterocyclic compounds that inhibit the activity of Pim kinases and are useful in the treatment of diseases related to the activity of Pim kinases including, e.g., cancers and other diseases.
PYRIDINEAMINE COMPOUNDS USEFUL AS PIM KINASE INHIBITORS
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, (2016/12/22)
The present disclosure describes pyridineamine compounds, as well as their compositions and methods of use. The compounds inhibit the activity of the Pim kinases, and are useful in the treatment of diseases related to the activity of Pim kinases including, e.g., cancer, immune disorders and other diseases. Formula (I).
BICYCLIC HETEROAROMATIC CARBOXAMIDE COMPOUNDS USEFUL AS PIM KINASE INHIBITORS
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, (2016/02/26)
The present disclosure describes bicyclic heteroaromatic carboxamide derivatives of formula (I), as well as their compositions and methods of use. The compounds inhibit the activity of the Pim kinases, and are useful in the treatment of diseases related to the activity of Pim kinases including, e.g., cancer and other diseases.
Identification of N-(4-((1R,3S,5S)-3-amino-5-methylcyclohexyl)pyridin-3-yl)-6-(2,6-difluorophenyl)-5-fluoropicolinamide (PIM447), a potent and selective proviral insertion site of Moloney murine leukemia (PIM) 1, 2, and 3 kinase inhibitor in clinical trials for hematological malignancies
Burger, Matthew T.,Nishiguchi, Gisele,Han, Wooseok,Lan, Jiong,Simmons, Robert,Atallah, Gordana,Ding, Yu,Tamez, Victoriano,Zhang, Yanchen,Mathur, Michelle,Muller, Kristine,Bellamacina, Cornelia,Lindvall, Mika K.,Zang, Richard,Huh, Kay,Feucht, Paul,Zavorotinskaya, Tatiana,Dai, Yumin,Basham, Steve,Chan, Julie,Ginn, Elaine,Aycinena, Alex,Holash, Jocelyn,Castillo, Joseph,Langowski, John L.,Wang, Yingyun,Chen, Min Y.,Lambert, Amy,Fritsch, Christine,Kauffmann, Audry,Pfister, Estelle,Vanasse, K. Gary,Garcia, Pablo D.
, p. 8373 - 8386 (2015/11/25)
Pan proviral insertion site of Moloney murine leukemia (PIM) 1, 2, and 3 kinase inhibitors have recently begun to be tested in humans to assess whether pan PIM kinase inhibition may provide benefit to cancer patients. Herein, the synthesis, in vitro activity, in vivo activity in an acute myeloid leukemia xenograft model, and preclinical profile of the potent and selective pan PIM kinase inhibitor compound 8 (PIM447) are described. Starting from the reported aminopiperidyl pan PIM kinase inhibitor compound 3, a strategy to improve the microsomal stability was pursued resulting in the identification of potent aminocyclohexyl pan PIM inhibitors with high metabolic stability. From this aminocyclohexyl series, compound 8 entered the clinic in 2012 in multiple myeloma patients and is currently in several phase 1 trials of cancer patients with hematological malignancies.
FURO- AND THIENO-PYRIDINE CARBOXAMIDE COMPOUNDS USEFUL AS PIM KINASE INHIBITORS
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, (2015/03/04)
The present disclosure describes furo- and thieno-pyridine carboxamide compounds, as well as their compositions and methods of use. The compounds inhibit the activity of the Pim kinases, and are useful in the treatment of diseases related to the activity of Pim kinases including, e.g., cancer and other diseases.
ARYL-SUBSTITUTED FUSED BICYCLIC PYRIDAZINE COMPOUNDS
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, (2014/07/08)
The present invention provides a compound of formula (I) as described herein, and pharmaceutically acceptable salts, enantiomers, rotamers, tautomers, or racemates thereof. Also provided are methods of treating a disease or condition mediated by PIM kinase using the compounds of Formula (I), and pharmaceutical compositions comprising such compounds.
NOVEL AMINOTHIAZOLE CARBOXAMIDES AS KINASE INHIBITORS
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, (2014/03/25)
The present invention provides a compound of formula (I), as described herein, and pharmaceutically acceptable salts, enantiomers, rotamers, tautomers, or racemates thereof. Also provided are methods of treating a disease or condition mediated by PIM kina
NOVEL KINASE INHIBITORS
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, (2012/09/11)
The present invention provides compounds of Formula I: and related compounds as further described herein, and pharmaceutical compositions comprising these compounds. The invention further provides methods to use these compounds and compositions for treating disorders associated with undesired levels of Pim kinase activity, including cancers and autoimmune disorders.
Pim kinase inhibitors and methods of their use
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Page/Page column 36, (2010/09/05)
The present invention relates to new compounds of Formulas I and II, their tautomers, stereoisomers and polymorphs, and pharmaceutically acceptable salts, esters, metabolites or prodrugs thereof, compositions of the new compounds together with pharmaceutically acceptable carriers, and uses of the new compounds, either alone or in combination with at least one additional therapeutic agent, in the inhibition of Pim kinase activity and/or the prophylaxis or treatment of cancer.
