- Preparation method of R-N-Boc-3-pyrrolidine acetic acid
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The invention provides a preparation method of R-N-Boc-3-pyrrolidine acetic acid, which comprises the following steps: by using N-Boc-3-pyrrolidone and trimethyl phosphonyl acetate as raw materials, carrying out wittig reaction, asymmetric reduction hydrogenation reaction and hydrolysis reaction to obtain the R-N-Boc-3-pyrrolidine acetic acid. The preparation method starts from a low-price racemicmixture N-Boc-3-pyrrolidone, the reaction conditions are mild, use of dangerous materials is not needed, the reaction steps are few, the process is simple, the single product R-N-Boc-3-pyrrolidine acetic acid with a target chiral structure can be finally obtained, the product has high purity, an optical activity ee value of more than 99% and high yield, and industrial scale-up production is facilitated.
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Paragraph 0056-0060; 0070-0073; 0078-0081; 0086-0088
(2020/09/12)
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- CYANOPYRROLIDINE DERIVATIVES WITH ACTIVITY AS INHIBITORS OF USP30
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The present invention relates to substituted-cyanopyrrolidines of Formula (I) with activity as inhibitors of deubiquitilating enzymes, in particular, ubiquitin C-terminal hydrolase 30 or ubiquitin specific peptidase 30 (USP30), having utility in a variety
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Page/Page column 58-59
(2018/06/16)
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- Synthesis and structure-activity relationship of a novel sulfone series of TNF-α converting enzyme inhibitors
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Replacement of the amide functionality in IM491 (N-hydroxy-(5S,6S)-1- methyl-6-{[4-(2-methyl-4-quinolinylmethoxy)anilinyl]carbonyl} -5-piperidinecarboxamide) with a sulfonyl group led to a new series of α,β-cyclic and β,β-cyclic γ-sulfonyl hydroxamic acids, which were potent TNF-α converting enzyme (TACE) inhibitors. Among them, inhibitor 4b (N-hydroxy-(4S,5S)-1-methyl-5-{[4-(2-methyl-4- quinolinylmethoxy)phenyl]sulfonylmethyl}-4-pyrrolidinecarboxamide) exhibited IC50 values of 1 nM and 180 nM in porcine TACE (pTACE) and cell assays, respectively, with excellent selectivity over MMP-1, -2, -9 and -13 and was orally bioavailable with an F value of 46% in mice.
- Xue, Chu-Biao,Chen, Xiao-Tao,He, Xiaohua,Roderick, John,Corbett, Ronald L.,Ghavimi, Bahman,Liu, Rui-Qin,Covington, Maryanne B.,Qian, Mingxin,Ribadeneira, Maria D.,Vaddi, Krishna,Trzaskos, James,Newton, Robert C.,Duan, James J.-W.,Decicco, Carl P.
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p. 4453 - 4459
(2007/10/03)
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