937271-55-1Relevant articles and documents
COLORED CHARGED SILSESQUIOXANES
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Paragraph 0249-0251, (2016/04/09)
The present invention provides salts of a cation and an anion, wherein the cation comprises (i) a silsesquioxane moiety of formula (ii) a chromophoric moiety D, which may which may be substituted with one or more substituents selected from the group consisting of C1-10-alkyl, phenyl, halogen, OC1-6-alkyl, OH, NH2 and NO2, and (iii) a moiety of formula wherein L4 is C1-20-alkylene, phenylene-C1-20-alkylene or C1-20-alkylene-phenylene-C1-20alkylene, R11, R12, R13 and R14 are independently from each other hydrogen or C1-4-alkyl, R15, R16, R17 and R18 are independently from each other C1-4-alkyl, R19 is C1-20-alkyl, which may be substituted with phenyl, O—C1-6-alkyl or NO2, and d is an integer from 1 to 25, and electrophoretic devices comprising the salts.
Acid mediated ring closing metathesis: A powerful synthetic tool enabling the synthesis of clinical stage kinase inhibitors
William, Anthony D.,Lee, Angeline C.-H.
, p. 142 - 145 (2015/04/27)
The powerful olefin metathesis reaction was employed for the construction of late-phase clinical agents SB1317 and SB1518. In both cases RCM seems to proceed only in the presence of an acid and to predominantly furnish trans isomers. In case of SB1518 it proceeded in the presence of acid HCl, while for SB1317, it mainly proceeds in the presence of TFA (trifluroacetic acid).
Discovery of kinase spectrum selective macrocycle (16E)-14-methyl-20-oxa-5, 7,14,26-tetraazatetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8(27) ,9,11,16,21,23-decaene (SB1317/TG02), a potent inhibitor of cyclin dependent kinases (CDKs), Janus kinase 2 (JAK2), and Fms-like tyrosine kinase-3 (FLT3) for the treatment of cancer
William, Anthony D.,Lee, Angeline C.-H.,Goh, Kee Chuan,Blanchard, Stéphanie,Poulsen, Anders,Teo, Ee Ling,Nagaraj, Harish,Lee, Chai Ping,Wang, Haishan,Williams, Meredith,Sun, Eric T.,Hu, Changyong,Jayaraman, Ramesh,Pasha, Mohammed Khalid,Ethirajulu, Kantharaj,Wood, Jeanette M.,Dymock, Brian W.
experimental part, p. 169 - 196 (2012/03/12)
Herein, we describe the design, synthesis, and SAR of a series of unique small molecule macrocycles that show spectrum selective kinase inhibition of CDKs, JAK2, and FLT3. The most promising leads were assessed in vitro for their inhibition of cancer cell proliferation, solubility, CYP450 inhibition, and microsomal stability. This screening cascade revealed 26h as a preferred compound with target IC50 of 13, 73, and 56 nM for CDK2, JAK2 and FLT3, respectively. Pharmacokinetic (PK) studies of 26h in preclinical species showed good oral exposures. Oral efficacy was observed in colon (HCT-116) and lymphoma (Ramos) xenograft studies, in line with the observed PK/PD correlation. 26h (SB1317/TG02) was progressed into development in 2010 and is currently undergoing phase 1 clinical trials in advanced leukemias and multiple myeloma.
