On April 20, 2017, Nicolaou, Kyriacos C.; Rhoades, Derek; Wang, Yanping; Totokotsopoulos, Sotirios published a patent.Category: pyrazoles-derivatives The title of the patent was Methods of synthesis, methods of treatment with, and drug conjugates of epothilone analogs. And the patent contained the following:
In one aspect, the present disclosure provides epothilone analogs I [wherein: X1 is absent, O or NRa; Ra is H, C≤8-alkyl, C≤8-cycloalkyl,(C≤6-alkyldiyl)-(C≤8-cycloalkyl), or a substituted version of either of these groups; provided that when X1 is absent, that the atoms to which it is attached are a part of a double bond;]. [X2, X3 and X4 are each independently O or NRb; wherein, Rb is H or C≤8-alkyl, C≤8-cycloalkyl, (C≤6-alkanediyl)-(C≤8-cycloalkyl), C≤b-aralkyl, or a substituted version of either of these groups;]. [Y1 and Y2 are each independently NH2, OH, or C≤8-alkoxy, C≤8-aralkoxy, C≤8-acyloxy, (C≤8-alkyl)amino, di(C≤8-alkyl)amino, C≤8-amido, or a substituted version of any of these groups, or ORc, wherein Rc is a hydroxy protecting group;]. [R1, R3, R4, R5, R6 and R7 are each independently H or C≤12-alkyl, C≤12-cycloalkyl, C≤12-alkenyl, C≤12-alkynyl, C≤12-aryl, or a substituted version of any of these groups; and,]. [R2 is C≤12-heteroaryl, C≤8-heteroarenediyl-Rd, or a substituted version of either of these groups; wherein Rd is C≤12-alkyl, C≤12-aryl, C≤12-aralkyl, C≤12-heteroaryl, C≤12-heteroaralkyl, or a substituted version of either of these groups;]. [Provided that R2 is not 2-methylthiazolyl, 2-(hydroxymethyl)thiazolyl, N-2-methyl-3- (methylthio)pyrazolyl or 2-(methylthio)thiazolyl;], or a pharmaceutically acceptable salt thereof. In another aspect, the present disclosure also provides methods of preparing the compounds disclosed herein. In another aspect, the present disclosure also provides pharmaceutical compositions and methods of use of the compounds disclosed herein. Addnl., drug conjugates with cell targeting moieties of the compounds are also provided. Thus, epothilone B pyrazole analog II was prepared and tested for pharmacol. activity [EC50 = 19 μM for induction of tubulin assembly; GI50 = 14 nM vs. MCF-7 cell line; GI50 = 38 nM vs. OVCAR-8 cell line]. The experimental process involved the reaction of 5-Bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole(cas: 1187582-58-6).Category: pyrazoles-derivatives
The Article related to epothilone analogs preparation antitumor, antibody epothilone analog conjugate preparation cancer cell targeting, Biomolecules and Their Synthetic Analogs: Other Bacterial and Fungal Metabolites and other aspects.Category: pyrazoles-derivatives
Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics