On August 28, 2014, Bartberger, Michael D.; Beck, Hilary Plake; Degraffenreid, Michael R.; Fox, Brian M.; Gonzalez Lopez De Turiso, Felix; Julian, Lisa D.; Kayser, Frank; Medina, Julio C.; Olson, Steven H.; Rew, Yosup; Roveto, Philip M.; Sun, Daqing; Yan, Xuelei published a patent.Related Products of 70931-59-8 The title of the patent was Preparation of cis-morpholinone and other compounds as MDM2 inhibitors for the treatment of cancer. And the patent contained the following:
The title compounds [I; X = O or S(O)2; R1 = H, C1-6alkyl, (CReRe)nC6-8aryl, (CReRe)nC3-8cycloalkyl, (CReRe)n-3-8 membered heterocycloalkyl, S(O)2C3-8cycloalkyl, C(O)C3-8cycloalkyl, or CRfRa(CReRe)n-Q; Q = (CReRe)nC6-8aryl, (CReRe)n-3-8 membered heterocycloalkyl, (CReRe)n-5-8 membered heteroaryl, (CReRe)nC3-8cycloalkyl, cyano, (CReRe)nOH, CO2H, NReRe, etc.; R2 = H, C1-6alkyl, (CReRe)nC(O)ORe, (CReRe)nNReRe, (CReRe)nC(O)NReRe, (CReRe)nOH, (CReRe)nC(O)H, (CReRe)nC6-8aryl, (CReRe)n-3-8 membered heterocycloalkyl, (CReRe)n-5-8 membered heteroaryl, (CReRe)nCN, -(CReRe)nC(O)5-8 membered heterocycloalkyl, etc.; any heteroaryl or heterocycloalkyl group has one or more heteroatoms independently selected from O, N or S; any cycloalkyl, heterocycloalkyl, heteroaryl or aryl group can be unsubstituted or substituted; R3 = H or C1-6alkyl; R4 = C6-8 aryl or 5-9 membered heteroaryl; R5 = C6-8 aryl or 5-9 membered heteroaryl; R6, R7 = H or C1-6alkyl; Ra = independently H, C1-6alkyl, C2-6alkenyl, (CReRe)nC3-8cycloalkyl, or (CReRe)nC6-8aryl, wherein any cycloalkyl or aryl group can be unsubstituted or substituted; Re, Rf = independently H, C1-6alkyl , or OH; n, m = independently 0-4; provided that R2 and R3 are not both H] or pharmaceutically acceptable salts thereof were prepared These compounds including morpholinone and 2,5,6,8-tetrahydro-3H-imidazo[2,1-c][1,4]oxazine derivatives are inhibitors of MDM2 (oncoprotein) and are useful as therapeutic agents, particularly for the treatment of cancers. The cancer is selected from bladder, breast, colon, rectum, kidney, liver, small cell lung cancer, non-small-cell lung cancer, esophagus, gall bladder, ovary, pancreas, stomach, cervix, thyroid, prostate, skin, acute lymphocytic leukemia, chronic myelogenous leukemia, acute lymphoblastic leukemia, B-cell lymphoma, T-cell lymphoma, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, hairy cell lymphoma, Burkitt’s lymphoma, acute and chronic myelogenous leukemia, melanoma, endometrial cancer, head and neck cancer, glioblastoma, or osteosarcoma. Thus, cyclocondensation of rel-(1R,2S)-1,2-bis(4-bromophenyl)-2-(methylamino)ethanol with 2-chloroacetyl chloride in the presence of Et3N in THF at 0掳 for 1 h gave rel-(5R,6S)-5,6-Bis(4-bromophenyl)-4-methylmorpholin-3-one which was treated with sodium bis(trimethylsilyl)amide in THF at -78掳 for 20 min and then underwent benzylation with benzyl bromide at -78掳 for 30 min and at room temperature for 30 min to give rel-(2S,5R,6S)-2-benzyl-5,6-bis(4-bromophenyl)-4-methylmorpholin-3-one (II). II and 2-[rel-(2S,5R,6S)-4-benzyl-6-(3-chlorophenyl)-5-(4-chlorophenyl)-3-oxomorpholin-2-yl]acetic acid (III) showed IC50 of 1.96 and 0.0399 渭M, resp., for inhibiting the interaction of GST-hMDM2 and biotinylated-p53 in an homogeneous time-resolved fluorescence assay (HTRF1 assay). The experimental process involved the reaction of 1-(Bromomethyl)-4-fluoro-2-iodobenzene(cas: 70931-59-8).Related Products of 70931-59-8
The Article related to mdm2 oncoprotein inhibitor morpholinone tetrahydroimidazooxazine, morpholinone tetrahydroimidazooxazine preparation treatment cancer, Heterocyclic Compounds (More Than One Hetero Atom): Pyrazines and Quinoxalines (Including Piperazines) and other aspects.Related Products of 70931-59-8
Referemce:
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com