- Synthesis ofN-Boc-α-amino Acids from Carbon Dioxide by Electrochemical Carboxylation ofN-Boc-α-aminosulfones
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Electrochemical reduction ofN-Boc-α-aminosulfones in DMF using an undivided cell equipped with a Pt plate cathode and an Mg rod anode under atmospheric pressure of bubbling carbon dioxide through the solution under constant current conditions resulted in a reductive C-S bond cleavage with elimination of benzenesulfinate ion generating the corresponding anion species followed by fixation of carbon dioxide to give the correspondingN-Boc-α-amino acids in moderate to good yields.
- Senboku, Hisanori,Minemura, Yoshihito,Suzuki, Yuto,Matsuno, Hidetoshi,Takakuwa, Mayu
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p. 16077 - 16083
(2021/10/12)
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- Extensive investigation of benzylic N-containing substituents on the pyrrolopyrimidine skeleton as Akt inhibitors with potent anticancer activity
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Continuous optimization of benzylic substituents on 1-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazin-1-yl)-2-phenylethan-1-one structure as Akt inhibitors was described in this paper. Particularly, compounds 8 and 14g exhibited high enzymatic potency against all Akt isoforms and antiproliferative effects in mantle cell lymphoma cell lines, as well as favorable cytotoxicities in patient primary cancer cells. Low micromolar doses of both 8 and 14g dose-dependently induced cell apoptosis and G2/M cell cycle arrest, also suppressed the phosphorylation level of Akt downstream targets GSK3β and S6.
- Chen, Xin,Guo, Kaiwen,Liu, Yang,Ran, Fansheng,Zhang, Zhen,Zhao, Guisen
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- Substituted p-chlorophenyl acetylpiperazine-containing compound as well as preparation method and application thereof
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The application provides a substituted p-chlorophenyl acetylpiperazine-containing compound as well as a preparation method and application of the substituted p-chlorophenyl acetylpiperazine-containingcompound. The compound has the structure shown in the formula (I), and has better Akt1 inhibitory activity or growth inhibitory activity to MCL cell lines.
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Paragraph 0101; 0112; 0156; 0157
(2019/01/06)
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- CIS-MORPHOLINONE AND OTHER COMPOUNDS AS MDM2 INHIBITORS FOR THE TREATMENT OF CANCER
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The present invention provides MDM2 inhibitor compounds of Formula (I), or the pharmaceutically acceptable salts thereof, wherein the variables are defined above, which compounds are useful as therapeutic agents, particularly for the treatment of cancers. The present invention also relates to pharmaceutical compositions that contain an MDM2 inhibitor.
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Page/Page column 102-103
(2014/09/03)
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- Rational design and binding mode duality of MDM2-p53 inhibitors
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Structural analysis of both the MDM2-p53 protein-protein interaction and several small molecules bound to MDM2 led to the design and synthesis of tetrasubstituted morpholinone 10, an MDM2 inhibitor with a biochemical IC 50 of 1.0 μM. The cocrystal structure of 10 with MDM2 inspired two independent optimization strategies and resulted in the discovery of morpholinones 16 and 27 possessing distinct binding modes. Both analogues were potent MDM2 inhibitors in biochemical and cellular assays, and morpholinone 27 (IC50 = 0.10 μM) also displayed suitable PK profile for in vivo animal experiments. A pharmacodynamic (PD) experiment in mice implanted with human SJSA-1 tumors showed p21WAF1 mRNA induction (2.7-fold over vehicle) upon oral dosing of 27 at 300 mg/kg.
- De Turiso, Felix Gonzalez-Lopez,Sun, Daqing,Rew, Yosup,Bartberger, Michael D.,Beck, Hilary P.,Canon, Jude,Chen, Ada,Chow, David,Correll, Tiffany L.,Huang, Xin,Julian, Lisa D.,Kayser, Frank,Lo, Mei-Chu,Long, Alexander M.,McMinn, Dustin,Oliner, Jonathan D.,Osgood, Tao,Powers, Jay P.,Saiki, Anne Y.,Schneider, Steve,Shaffer, Paul,Xiao, Shou-Hua,Yakowec, Peter,Yan, Xuelei,Ye, Qiuping,Yu, Dongyin,Zhao, Xiaoning,Zhou, Jing,Medina, Julio C.,Olson, Steven H.
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p. 4053 - 4070
(2013/06/27)
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- HETEROCYCLIC COMPOUNDS AS MDM2 INHIBITORS FOR THE TREATMENT OF CANCER
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The present invention provides MDM2 inhibitor compounds of Formula I or II, or the pharmaceutically acceptable salts thereof, wherein the variables are defined above, which compounds are useful as therapeutic agents, particularly for the treatment of cancers. The present invention also relates to pharmaceutical compositions that contain an MDM2 inhibitor.
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Page/Page column 88
(2013/04/13)
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- GLYCINE DERIVATIVES AND THEIR USE AS MUSCARINIC RECEPTOR ANTAGONISTS
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The present invention relates to alkaloid aminoester derivatives acting as muscarinic receptor antagonists, processes for their preparation, compositions comprising them and therapeutic uses thereof.
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Page/Page column 60-61
(2012/06/15)
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- GLYCINE DERIVATIVES AND MEDICINAL COMPOSITIONS THEREOF
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Alkaloid aminoester derivatives according to formula (I) and (VI) act as muscarinic receptor antagonists.
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Page/Page column 28
(2012/06/16)
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- Synthesis of arylglycine and mandelic acid derivatives through carboxylations of α-amido and α-acetoxy stannanes with carbon dioxide
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Incorporation reactions of carbon dioxide (CO2) with N-Boc-α-amido and α-acetoxy stannanes were developed using CsF as a mild tin activator. Monoprotected α-amido stannanes could be used, and the corresponding arylglycine derivatives were obtained in moderate-to-high yields under 1 MPa (10 atm) of CO2 pressure. α-Acetoxy stannanes also underwent carboxylation to afford mandelic acid derivatives in excellent yields under ambient CO2 pressure. Both transformations enabled the synthesis of α-tertiary and α-quaternary carboxylic acid derivatives. In addition, the chirality of (S)-N-tert-butylsulfonyl-α- amido stannanes was transferred with up to 90% inversion of configuration at 100 °C.
- Mita, Tsuyoshi,Sugawara, Masumi,Hasegawa, Hiroyuki,Sato, Yoshihiro
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experimental part
p. 2159 - 2168
(2012/06/01)
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- One-pot synthesis of α-amino acids from imines through CO2 incorporation: An alternative method for strecker synthesis
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Itas a gas: A novel one-pot process for the synthesis of α-amino acids from imine equivalents using CO2 gas as a carbon source has been developed. This reaction was made possible by the reagent combination of TMSSnBu3 and CsF (see scheme). Three successive reactions (imine formation, stannylation, and carboxylation) proceeded in the same flask under these conditions to give products in up to 79 % yield. Boc=tert-butoxycarbonyl, TMS=trimethylsilyl.
- Mita, Tsuyoshi,Chen, Jianyang,Sugawara, Masumi,Sato, Yoshihiro
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p. 1393 - 1396
(2011/04/22)
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- ARYLPYRAZINONE DERIVATIVES INSULIN SECRETION STIMULATORS, METHODS FOR OBTAINING THEM AND USE THEREOF FOR THE TREATMENT OF DIABETES
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The present invention relates to arylpyrazinone derivatives of formula (I), wherein R1, R2, R3 and A are as defined in claim 1, as insulin secretion stimulators. The invention also relates to the preparation and use of these pyrazinone derivatives for the
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Page/Page column 32
(2009/12/05)
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- SUBSTITUTED PIPERAZINES AS CB1 ANTAGONISTS
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Compounds of Formula (I): or pharmaceutically acceptable salts, solvates, or esters thereof, are useful in treating diseases or conditions mediated by CB1 receptors, such as metabolic syndrome and obesity, neuroinflammatory disorders, cognitive disorders and psychosis, addiction (e.g., smoking cessation), gastrointestinal disorders, and cardiovascular conditions.
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Page/Page column 140
(2009/03/07)
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