- A class of α-amino acids-derived multifunctional amidophosphane precatalysts: application to the highly enantio- and diastereoselective silver(I)-catalyzed 1,3-dipolar cycloaddition reaction
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A class of multifunctional amidophosphanes derived from chiral α-amino acids have been developed with two amide bonds, a tertiary amine and a phosphine. In combination with Ag(I) salts, these amidophosphanes have been demonstrated as highly efficient multifunctional catalysts in the asymmetric 1,3-dipolar cycloaddition of azomethine ylides as well as the three-component reaction of the α-iminoesters in situ generated. Under optimal conditions, highly functionalized endo-8 pyrrolidines were obtained with good to excellent yields (up to 99% yield) and enantioselectivities (up to 98% ee).
- Hou, Yihui,Zhou, Zhipeng,Liu, Pingle,Wang, Jiankang,Hou, Qinglin,Wen, Pushan,Wang, Haifei
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p. 930 - 938
(2017/07/11)
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- Discovery of pyrroloaminopyrazoles as novel PAK inhibitors
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The P21-activated kinases (PAK) are emerging antitumor therapeutic targets. In this paper, we describe the discovery of potent PAK inhibitors guided by structure-based drug design. In addition, the efflux of the pyrrolopyrazole series was effectively reduced by applying multiple medicinal chemistry strategies, leading to a series of PAK inhibitors that are orally active in inhibiting tumor growth in vivo.
- Guo, Chuangxing,McAlpine, Indrawan,Zhang, Junhu,Knighton, Daniel D.,Kephart, Susan,Johnson, M. Catherine,Li, Haitao,Bouzida, Djamal,Yang, Anle,Dong, Liming,Marakovits, Joseph,Tikhe, Jayashree,Richardson, Paul,Guo, Lisa C.,Kania, Robert,Edwards, Martin P.,Kraynov, Eugenia,Christensen, James,Piraino, Joseph,Lee, Joseph,Dagostino, Eleanor,Del-Carmen, Christine,Deng, Ya-Li,Smeal, Tod,Murray, Brion W.
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experimental part
p. 4728 - 4739
(2012/07/28)
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- CARBONYLAMINO PYRROLOPYRAZOLES, POTENT KINASE INHIBITORS
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Carbonylamino Pyrrolopyrazole compounds of formula I, compositions including these compounds and methods of their use are provided. Preferred compounds of formula I have activity as protein kinase inhibitors, including as inhibitors of PAK4.
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Page/Page column 63-64
(2009/12/28)
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- 1,3-Dihydro-2H-Indole-2-One Compound and Pyrrolidine-2-One Compound Fused With Aromatic Heterocycle
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It is intended to provide a drug which is efficacious against pathological conditions relating to arginine-vasopressin V1b receptor. More particularly speaking, it is intended to provide a drug which has a therapeutic or preventive effect on depression, anxiety, Alzheimer's disease, Parkinson's disease, Huntington's chorea, eating disorders, hypertension, digestive diseases, drug addiction, epilepsy, brain infarction, brain ischemia, brain edema, head injury, inflammation, immune diseases, alopecia and so on. As the results of intensive studies, a novel 1,3-dihydro-2H-indol-2-one compound and a pyrrolidin-2-one compound fused with a heteroaromatic ring, which are highly selective antagonists of arginine-vasopressin V1b receptor, have high metabolic stabilities and show favorable brain penetration and high plasma concentrations, are found, thereby achieving the above objective.
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Page/Page column 96
(2009/01/24)
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- An Unexpected Transformation of Benzyl Carbamates into α-Azidobenzeneacetamides
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Successive treatment of benzyl carbamates 5 (Z-protected secondary amines) with lithium diisopropylamide (LDA), diphenyl phosphorochloridate (DPPCl), and NaN3 yielded the corresponding α-azidobenzeneacetamides 6 in 45-50% yield (Schemes 2 and 3). In the case of Z-protected diisopropylamine 5b, the phosphate 7 was isolated as a minor product. A reaction mechanism for this unexpected transformation is proposed in Scheme 4, the key step being the ring closure of a benzylic anion to give an oxirane intermediate B. In cursory experiments, it was demonstrated that α-azidobenzeneacetamides 6 can be used as 2-phenylglycine synthons in the formation of dipeptides by using a phosphine-mediated coupling (Scheme 5).
- Straessler, Christoph,Heimgartner, Heinz
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p. 2058 - 2065
(2007/10/03)
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- Stereoselective reactions, 25. Enantioselective deprotonation of prochiral 4-substituted cyclohexanones by chiral chelated lithium amides
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Enantioselective deprotonation of prochiral 4-substituted cyclohexanones (4a-d) by chiral chelated lithium amides (8a-k) in the presence of excess trimethylsilyl chloride was realized to give the corresponding chiral silyl enol ethers (6a-d) in up to 89% ee. It is shown that enantioselectivity of the reaction is dependent on the solvent used, but becomes almost independent on the solvent in the presence of HMPA. The sense of asymmetric induction can be correlated to the configuration at the chiral carbon bearing amide nitrogen of the lithium amide.
- Shirai, Ryuichi,Sato, Daisaku,Aoki, Kazumasa,Tanaka, Masahide,Kawasaki, Hisashi,Koga, Kenji
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p. 5963 - 5972
(2007/10/03)
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- ENANTIOSELECTIVE SYNTHESIS OF β-HYDROXY-α-METHYL CARBONYL COMPOUNDS BY ALDOL REACTION
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The enantioselective aldol reactions of ketone lithium enolates with aldehydes mediated chiral lithium amides were extensively investigated.The chiral amino ethers 4a-4l and diamines 16a,b were prepared from α-amino acids.The reaction conditions and the s
- Ando, Akira,Shioiri, Takayuki
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p. 4969 - 4988
(2007/10/02)
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