On June 7, 2012, Crew, Andrew P.; Dong, Hanqing; Ferraro, Caterina; Sherman, Dan; Siu, Kam W. published a patent.Recommanded Product: 215610-30-3 The title of the patent was Macrocyclic phosphonates and phosphinates, fused with five- and six-membered nitrogen heterocycles as specific focal adhesion kinase inhibitors in cancer therapy. And the patent contained the following:
Macrocyclic phosphonates or phosphinates I, II [1, X = N, CH; A1 = C6H4, heteroarylene; A3 = heteroarylene, preferably, A3 = pyrazolediyl, triazolediyl, imidazolediyl; L2 = O, bond; L3 = C2-6 alkylene; L4 = C1-2 alkylene; Q1-Q4 = N, N-oxide, optionally substituted CH, Q1-Q4 may form a fused (hetero)cycle; R1-R3 = H, organyl, preferably, R1 = Cl, CN, NO2, CF3; R4 = OH, C1-4 alkyl, C3-6 cycloalkyl, C4-6 heterocyclyl, alkoxy], including resolved enantiomers thereof, and a pharmaceutically acceptable salts thereof, useful as selective focal adhesion kinase (FAK) inhibitors, beneficial in therapy of aggressive tumors, were prepared by intramol. esterification of acyclic phosphonate or phosphinate group with OH-containing linker A3 or by Suzuki coupling of pinacolboronate-containing linker A3 with halo-substituted (hetero)aryl ring. The prepared compounds 1 were tested for inhibition of phospho-FAK Y397 in the presence of human plasma, showing IC50 values, in general, less than 0.4 μM. In an example, the phosphonate II (1a, X = N, R1 = CF3, R2 = R3 = H, R4 = Et, R5 = OMe; L3 = (CH2)3, X1+X2 = CH2NMeCO) was prepared by esterification of 0.07 mmol of the acyclic phosphonate, sodium Et [4-[4-[[7-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-4-yl]amino]-5-(trifluoromethyl)-2-pyrimidinyl]amino]-3-methoxybenzylphosphonate in the presence of 0.3684 mmol of PYBOP and 0.4 mmol of DIPEA in 50 mL of 1,2-dichloroethane and 10 mL of DMF for 3 h at 20° with a 12% yield. In another example, the phosphonate 1a exhibited inhibitory activity towards phospho-FAK Y397 at a concentration <0.4 μM both in the plasma-free conditions and in the presence of human or murine plasma. The experimental process involved the reaction of 5-Methoxy-1H-pyrazole(cas: 215610-30-3).Recommanded Product: 215610-30-3
The Article related to phosphonate cyclic macrocyclic preparation focal adhesion kinase inhibition, antitumor agent macrocyclic phosphonate phosphinate focal adhesion kinase inhibition, Organometallic and Organometalloidal Compounds: Phosphorus Compounds and other aspects.Recommanded Product: 215610-30-3
Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics