Acid Mediated Ring Closing Metathesis: A Powerful Synthetic Tool Enabling the Synthesis of Clinical Stage Kinase Inhibitors.
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).
S*BIO Pte Ltd, 250 North Bridge Road, #28-00 Raffles City Tower, Singapore 179101; Institute of Chemical and Engineering Sciences (ICES), Agency for Science, Technology, and Research (A*STAR), 11 Biopolis Way, Helios Block, #03-08, Singapore 138667, Singapore. wanthony11@gmail.com.
Anthony D
AD
William
S*BIO Pte Ltd, 250 North Bridge Road, #28-00 Raffles City Tower, Singapore 179101.
Angeline C-H
AC
Lee
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D002986:Clinical Trials as Topic; D003500:Cyclization; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D008223:Lymphoma / Q000188:drug therapy / Q000201:enzymology; D015394:Molecular Structure; D055728:Primary Myelofibrosis / Q000188:drug therapy / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism
C561234:11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene; C570909:14-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; D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D006576:Heterocyclic Compounds, 4 or More Rings; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; C507924:JAK2 protein, human; D053614:Janus Kinase 2