224441-73-0Relevant articles and documents
Nitrogen Mustard Derivatives
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, (2014/10/16)
The disclosure includes compounds of Formula (1): wherein X1, X2, Q, Z, R1, and R2 are defined herein. Also disclosed is a method for treating a neoplastic disease or an immune disease with these compounds.
CDK INHIBITORS
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Page/Page column 51-52, (2010/07/09)
The present invention relates to CDK inhibitors and their use in the treatment of cell proliferative diseases such as cancer.
CDK INHIBITORS CONTAINING A ZINC BINDING MOIETY
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, (2009/04/25)
The present invention relates to CDK inhibitors and their use in the treatment of cell proliferative diseases such as cancer. The compounds of the invention may further act as HDAC inhibitors.
N-(Cycloalkylamino)acyl-2-aminothiazole Inhibitors of Cyclin-Dependent Kinase 2. N-[5-[[[5-(1,1-Dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl] -4-piperidinecarboxamide (BMS-387032), a Highly Efficacious and Selective Antitumor Agent
Misra, Raj N.,Xiao, Hai-Yun,Kim, Kyoung S.,Lu, Songfeng,Han, Wen-Ching,Barbosa, Stephanie A.,Hunt, John T.,Rawlins, David B.,Shan, Weifang,Ahmed, Syed Z.,Qian, Ligang,Chen, Bang-Chi,Zhao, Rulin,Bednarz, Mark S.,Kellar, Kristen A.,Mulheron, Janet G.,Batorsky, Roberta,Roongta, Urvashi,Kamath, Amrita,Marathe, Punit,Ranadive, Sunanda A.,Sack, John S.,Tokarski, John S.,Pavletich, Nikola P.,Lee, Francis Y. F.,Webster, Kevin R.,Kimball, S. David
, p. 1719 - 1728 (2007/10/03)
N-Acyl-2-aminothiazoles with nonaromatic acyl side chains containing a basic amine were found to be potent, selective inhibitors of CDK2/cycE which exhibit antitumor activity in mice. In particular, compound 21 {N-[5-[[[5-(1,1-dimethylethyl)-2- oxazolyl]m
Methods for preventing and treating alopecia induced by chemotherapy or radiotherapy
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, (2008/06/13)
The invention provides a method for preventing or treating alopecia induced by chemotherapy or radiotherapy by administering to a mammalian specie in need thereof a therapeutically effective amount of a compound of formula I or II or a pharmaceutically ac
N-[5-[[[5-alkyl-2-oxazolyl]methyl]thio]-2-thiazolyl]-carboxamide inhibitors of cyclin dependent kinases
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, (2008/06/13)
The present invention describes compounds of formula I: and enantiomers, diastereomers and pharmaceutically acceptable salts thereof. The formula I compounds are protein kinase inhibitors and are useful in the treatment of proliferative diseases, for exam
Methods for preventing and treating alopecia induced by chemotherapy or radiotherapy
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, (2008/06/13)
The invention provides a method for preventing or treating alopecia induced by chemotherapy or radiotherapy by administering to a mammalian specie in need thereof a therapeutically effective amount of a compound of formula I or II or a pharmaceutically ac
Discovery of aminothiazole inhibitors of cyclin-dependent kinase 2: Synthesis, x-ray crystallographic analysis, and biological activities
Kim, Kyoung Soon,Kimball, S. David,Misra, Raj N.,Rawlins, David B.,Hunt, John T.,Xiao, Hai-Yun,Lu, Songfeng,Qian, Ligang,Han, Wen-Ching,Shan, Weifang,Mitt, Toomas,Cai, Zhen-Wei,Poss, Michael A.,Zhu, Hong,Sack, John S.,Tokarski, John S.,Chang, Chieh Ying,Pavletich, Nikola,Kamath, Amrita,Humphreys, William G.,Marathe, Punit,Bursuker, Isia,Kellar, Kristen A.,Roongta, Urvashi,Batorsky, Roberta,Mulheron, Janet G.,Bol, David,Fairchild, Craig R.,Lee, Francis Y.,Webster, Kevin R.
, p. 3905 - 3927 (2007/10/03)
High throughput screening identified 2-acetamido-thiazolylthio acetic ester 1 as an inhibitor of cyclin-dependent kinase 2 (CDK2). Because this compound is inactive in cells and unstable in plasma, we have stabilized it to metabolic hydrolysis by replacing the ester moiety with a 5-ethyl-substituted oxazole as in compound 14. Combinatorial and parallel synthesis provided a rapid analysis of the structure-activity relationship (SAR) for these inhibitors of CDK2, and over 100 analogues with IC50 values in the 1-10 nM range were rapidly prepared. The X-ray crystallographic data of the inhibitors bound to the active site of CDK2 protein provided insight into the binding modes of these inhibitors, and the SAR of this series of analogues was rationalized. Many of these analogues displayed potent and broad spectrum antiproliferative activity across a panel of tumor cell lines in vitro. In addition, A2780 ovarian carcinoma cells undergo rapid apoptosis following exposure to CDK2 inhibitors of this class. Mechanism of action studies have confirmed that the phosphorylation of CDK2 substrates such as RB, histone H1, and DNA polymerase α (p70 subunit) is reduced in the presence of compound 14. Further optimization led to compounds such as water soluble 45, which possesses a favorable pharmacokinetic profile in mice and demonstrates significant antitumor activity in vivo in several murine and human models, including an engineered murine mammary tumor that overexpresses cyclin E, the coactivator of CDK2.
Process for preparing azacycloalkanoylaminothiazoles
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, (2008/06/13)
The present invention relates to new, efficient processes for the preparation of 5-(2-oxazolylalkylthio)-2-azacycloalkanoylaminothiazole compounds of formula I or a pharmaceutically acceptable salt thereof, wherein: R is alkyl, aryl or heteroaryl; R1, R2, R3, R4 and R5 are each independently hydrogen, alkyl, aryl or heteroaryl; R6 and R7 are each independently hydrogen, alkyl, aryl, heteroaryl, halogen, hydroxy or alkoxy; R8 is hydrogen, alkyl, aryl, heteroaryl, CONR9R10, COR11 or COOR12; R9, R10, R11 and R12 are each independently hydrogen, alkyl or aryl; m equals 0 to 5; and n equals 0 to 5, which are novel, potent inhibitors of cyclin dependent kinases (cdks). The present invention further concerns new key intermediate compounds, a quaternary ammonium salt of formula III′ and a 2-oxazolylalkyl derivative of formula IX.
