(S)-3-methyl-2-[(pyridine-3-carbonyl)amino]butyric acid | 17274-86-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-3-methyl-2-[(pyridine-3-carbonyl)amino]butyric acid
• 英文别名: L-Methyl-2-nicotinoylamino-buttersaeure；N-(3-pyridinylcarbonyl)-L-valine；(2S)-3-methyl-2-[(pyridin-3-yl)formamido]butanoic acid；(2S)-3-methyl-2-(pyridine-3-carbonylamino)butanoic acid
• CAS: 17274-86-1
• 化学式: C₁₁H₁₄N₂O₃
• mdl: MFCD00455384
• 分子量: 222.244
• InChiKey: QBWUAJGXNZOAQO-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  79.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(4-(4-bromobutoxy)phenyl)-3H-1,2-dithiole-3-thione 、 (S)-3-methyl-2-[(pyridine-3-carbonyl)amino]butyric acid 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 以47%的产率得到N-nicotinoylvaline 4-[4-(3H-1,2-dithiole-3-thione-5-yl)phenoxy]butyl ester
  参考文献：
  名称：

  新型硫化氢释放烟酸衍生物的合成及生物评价

  摘要：

  合成了十二种新的缓释硫化氢供体ADT-OH与烟酸结合的杂种。所有结构均通过1 H NMR确证，131 H NMR和MS光谱。用MTT分析评估目标化合物对谷氨酸诱导的损伤对海马神经元HT22细胞的神经保护作用，并在100μM浓度对未经谷氨酰胺处理的HT22细胞的毒性。在永久性大脑中动脉闭塞（pMCAO）小鼠模型中，在缺血后3小时通过腹膜内注射进一步研究了该活性化合物对缺血性梗死体积的影响。结果表明，所有化合物在大多数实验浓度下均能显着保护HT22细胞免受谷氨酸诱导的损伤，并且在高浓度下对正常HT22细胞没有或只有很少的神经毒性。更重要的是，化合物A6在pMCAO模型中显着减少了梗塞体积。这些结果表明，化合物A6可能有望用于进一步评估对脑缺血损伤的干预。

  DOI：

  10.1016/j.bmc.2016.08.060
• 作为产物：
  描述：

  N-(3-pyridinylcarbonyl)-L-valine phenylmethyl ester 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 5.0h， 以97%的产率得到(S)-3-methyl-2-[(pyridine-3-carbonyl)amino]butyric acid
  参考文献：
  名称：

  Microwave-assisted synthesis of pyridylpyrroles from N-acylated amino acids

  摘要：

  A small library of 3- and 4-pyridyl-substituted pyrroles was prepared from N-acylated amino acids. Nicotinoyl or isonicotinoyl chloride was used for the N-acylation of benzyl esters of amino acids. Debenzylation by palladium-catalyzed hydrogenation gave N-acylated amino acids. Dehydration of the acylated amino acids gave cyclic intermediates, manchnones or aziactones, which were treated in situ with alkynes in 1,3-dipolar cycloadditions. The starting materials were prepared in a parallel fashion, and microwave irradiation was used to facilitate the cycloaddition reactions. The regiochemistry of the cycloaddition was studied. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2009.09.094

文献信息

• PIPERIDINE-2, 6-DIONE DERIVATIVES AND THEIR USE AS TUMOR NECROSIS FACTOR INHIBITORS
  申请人：ZHANG Hesheng

  公开号：US20080051432A1

  公开（公告）日：2008-02-28

  This invention is directed to derivatives of piperidine-2,6-dione, or their organic or inorganic salts thereof, a methods of synthesis of these derivatives, and their application as active pharmaceutical ingredient as inhibitors of TNFα releasing in cells, the derivative of piperidine-2,6-dione being of the general formula (I): wherein n represents 1, 2, 3, 4, 5 or 6; R 1 represents from one to four of the same or different substituents selected from F, Cl, Br, C 1-4 alkyl, OH, OC 1-4 alkyl, NO 2 , NHC(O)C 1-4 alkyl, NH 2 , NH(C 1-4 alkyl), N(C 1-4 alkyl) 2 ; R 2 represents OR 3 , NR 3 R 4 , N(R 3 )COR 4 , O 2 CR 5 ; R 3 and R 4 represent independently and at each occurrence H or C 1-4 alkyl; R 5 represents CHR 6 NR 7 R 8 , CHR 6 NR 9 C(O)CHR 10 NR 7 R 8 , a heterocycle W or CHR 6 NR 9 C(O)W; R 6 , R 9 , R 10 represent independently and at each occurrence H, or C 1-4 alkyl; R 7 and R 8 represent independently and at each occurrence H, C 1-4 alkyl, or R 7 and R 8 taken together represent 1,3-propylene, 1,4-butylene, 1,5-pentylene, or 1,6-hexylene; W represents four-membered, five-membered, six-membered, seven-membered, or eight-membered saturated or unsaturated heterocycle.

  这项发明涉及哌啶-2,6-二酮的衍生物，或其有机或无机盐，以及这些衍生物的合成方法，以及它们作为细胞中TNFα释放抑制剂的活性药用成分的应用，其中哌啶-2,6-二酮的衍生物为通式（I）： 其中n代表1、2、3、4、5或6；R1代表从一个到四个相同或不同的取代基，所选自F、Cl、Br、C1-4烷基、OH、OC1-4烷基、NO2、NHC(O)C1-4烷基、NH2、NH(C1-4烷基)、N(C1-4烷基)2；R2代表OR3、NR3R4、N(R3)COR4、O2CR5；R3和R4独立地且在每次出现时代表H或C1-4烷基；R5代表CHR6NR7R8、CHR6NR9C(O)CHR10NR7R8、杂环W或CHR6NR9C(O)W；R6、R9、R10独立地且在每次出现时代表H，或C1-4烷基；R7和R8独立地且在每次出现时代表H、C1-4烷基，或R7和R8一起代表1,3-丙二烯基、1,4-丁二烯基、1,5-戊二烯基或1,6-己二烯基；W代表四元、五元、六元、七元或八元饱和或不饱和杂环。
• Retroviral protease inhibiting compounds
  申请人：ABBOTT LABORATORIES

  公开号：EP0402646A1

  公开（公告）日：1990-12-19

  A retroviral protease inhibiting compound of the formula or a pharmaceutical acceptable salt, prodrug or ester thereof, wherein X is a linking group; A is (1) substituted amino, (2) substituted carbonyl, (3) functionalized imino, (4) functionalized alkyl, (5) functionalized acyl, (6) functionalized heterocyclic or (7) functionalized (heterocyclic)alkyl; and B is (1) substituted carbonyl independently defined as herein, (2) substituted amino independently defined as herein, (3) functionalized imino independently defined as herein, (4) functionalized alkyl independently defined as herein, (5) functionalized acyl independently defined as herein, (6) functionalized heterocyclic independently defined as herein or (7) functionalized (heterocyclic)alkyl independently defined as herein.

  式中的逆转录病毒蛋白酶抑制化合物 或其药物可接受的盐、原药或酯，其中 X 是连接基团； A 是 (1) 取代的氨基 (2) 取代的羰基 (3) 官能化亚氨基 (4) 官能化烷基 (5) 官能化酰基 (6) 官能化杂环或 (7) 官能化（杂环）烷基；且 B 是 (1) 如本文所独立定义的取代的羰基、 (2) 如本文所独立定义的取代氨基 (3) 如本文所独立定义的官能化亚氨基 (4) 如本文所独立定义的官能化烷基、 (5) 如本文所独立定义的官能化酰基、 (6) 如本文所独立定义的官能化杂环，或 (7) 本文独立定义的官能化（杂环）烷基。
• Intermediates for preparating non-peptide retroviral protease inhibitors
  申请人：ABBOTT LABORATORIES

  公开号：EP0839798A2

  公开（公告）日：1998-05-06

  Intermediates, for preparing non-peptide retroviral protease inhibitors, said intermediates having the formula: or an acid addition salt thereof or an N-protected derivative thereof wherein at each occurrence the N-protecting group is independently selected from the group consisting of formyl, acetyl, pivaloyl, t-butylacetyl, t-butyloxycarbonyl, benzyloxycarbonyl, benzyl and isopropylaminocarbonyl; or said intermediates being selected from: (2S,3R,4S,5S)-2,5-di-(N-(Cbz-valinyl)amino)-3,4-dihydroxy-1,6-diphenylhexane; (2S,3S,4S,5S)-2,5-di-(N-(Cbz-valinyl)amino)-3,4-dihydroxy-1,6-diphenylhexane; (2S,3R,4R,5S)-2,5-di-(N-(Cbz-valinyl)amino)-3,4-dihydroxy-1,6-diphenylhexane; (2S,3S,4S,5S)-2,5-di-(N-(valinyl)amino)-3,4-dihydroxy-1,6-diphenylhexane; (2S,3R,4S,5S)-2,5-di-(N-(valinyl)amino)-3,4-dihydroxy-1,6-diphenylhexane; (2S,3R,4R,5S)-2,5-di-(N-(valinyl)amino)-3,4-dihydroxy-1,6-diphenylhexane; (2S,3S,4R,5S)-2-(N-(t-butyloxy)carbonyl)amino)-5-(N-(Cbz-valinyl)amino)-3,4-dihydroxy-1,6-diphenylhexane; 2-(N-benzyl-N-(benzyloxycarbonyl)amino)-5-(t-butyloxycarbonylamino)-1,6-diphenyl-3-hexene-3,4-oxide; 2-amino-5-(t-butyloxycarbonylamino)-1,6-diphenyl-3-hexene-3,4-oxide; and 2,5-di-(t-butyloxycarbonylamino)-1,6-diphenyl-3-hexene-3,4-oxide; or an acid addition salt thereof.

  用于制备非肽类逆转录病毒蛋白酶抑制剂的中间体，所述中间体具有以下式子： 或其酸加成盐或其 N-保护衍生物，其中每次出现时，N-保护基独立选自甲酰、乙酰、特戊酰、叔丁基乙酰、叔丁氧羰基、苄氧羰基、苄基和异丙氨基羰基组成的组；或所述中间体选自以下物质 (2S,3R,4S,5S)-2,5-二(N-(Cbz-缬氨酰)氨基)-3,4-二羟基-1,6-二苯基己烷； (2S,3S,4S,5S)-2,5-二(N-苄氧羰基缬氨酰氨基)-3,4-二羟基-1,6-二苯基己烷； (2S,3R,4R,5S)-2,5-二(N-苄氧羰基缬氨酰氨基)-3,4-二羟基-1,6-二苯基己烷； (2S,3S,4S,5S)-2,5-二(N-(缬氨酰)氨基)-3,4-二羟基-1,6-二苯基己烷； (2S,3R,4S,5S)-2,5-二(N-(缬氨酰)氨基)-3,4-二羟基-1,6-二苯基己烷； (2S,3R,4R,5S)-2,5-二(N-(缬氨酰)氨基)-3,4-二羟基-1,6-二苯基己烷； (2S,3S,4R,5S)-2-(N-(叔丁氧基)羰基)氨基)-5-(N-(Cbz-缬氨酰)氨基)-3,4-二羟基-1,6-二苯基己烷； 2-(N-苄基-N-(苄氧羰基)氨基)-5-(叔丁氧羰基氨基)-1,6-二苯基-3-己烯-3,4-氧化物； 2-氨基-5-(叔丁氧羰基氨基)-1,6-二苯基-3-己烯-3,4-氧化物；以及 2,5-二（叔丁氧羰基氨基）-1,6-二苯基-3-己烯-3,4-氧化物； 或其酸加成盐。
• Piperidine-2, 6-dione derivatives and their use as tumor necrosis factor inhibitors
  申请人：Tianjin Hemay Bio-Tech Co., Ltd.

  公开号：US10166222B2

  公开（公告）日：2019-01-01

  This invention is directed to derivatives of piperidine-2,6-dione, or their organic or inorganic salts thereof, a methods of synthesis of these derivatives, and their application as active pharmaceutical ingridient as inhibitors of TNFα releasing in cells, the derivative of piperidine-2,6-dione being of the general formula (I): wherein n represents 1, 2, 3, 4, 5 or 6; R1 represents from one to four of the same or different substituents selected from F, Cl, Br, C1-4 alkyl, OH, OC1-4 alkyl, NO2, NHC(O)C1-4 alkyl, NH2, NH(C1-4 alkyl), N(C1-4 alkyl)2; R2 represents OR3, NR3R4, N(R3)COR4, O2CR5; R3 and R4 represent independently and at each occurrence H or C1-4 alkyl; R5 represents CHR6NR7R8, CHR6NR9C(O)CHR10NR7R8, a heterocycle W or CHR6NR9C(O)W; R6, R9, R10 represent independently and at each occurrence H, or C1-4 alkyl; R7 and R8 represent independently and at each occurrence H, C1-4 alkyl, or R7 and R8 taken together represent 1,3-propylene, 1,4-butylene, 1,5-pentylene , or 1,6-hexylene; W represents four-membered, five-membered, six-membered, seven-membered, or eight-membered saturated or unsaturated heterocycle.

  本发明涉及哌啶-2,6-二酮的衍生物，或它们的有机盐或无机盐，这些衍生物的合成方法，以及它们作为抑制细胞中 TNFα 释放的活性药物锭剂的应用，哌啶-2,6-二酮的衍生物为通式 (I)： 其中 n 代表 1、2、3、4、5 或 6；R1 代表 1 至 4 个相同或不同的取代基，选自 F、Cl、Br、C1-4 烷基、OH、OC1-4 烷基、NO2、NHC(O)C1-4 烷基、NH2、NH(C1-4 烷基)、N(C1-4 烷基)2；R2 代表 OR3、NR3R4、N(R3)COR4、O2CR5；R3 和 R4 独立地且在每次出现时代表 H 或 C1-4 烷基；R5 代表 CHR6NR7R8、CHR6NR9C(O)CHR10NR7R8、杂环 W 或 CHR6NR9C(O)W；R6、R9、R10 独立地且在每次出现时代表 H 或 C1-4 烷基；R7 和 R8 独立地且在每次出现时代表 H、C1-4 烷基，或 R7 和 R8 合在一起代表 1,3-丙烯、1,4-丁烯、1,5-戊烯或 1,6-己烯；W 代表四元、五元、六元、七元或八元饱和或不饱和杂环。
• High concentration protein formulations with reduced viscosity
  申请人：Bhami's Research Laboratory, Pvt. Ltd.

  公开号：US10646569B2

  公开（公告）日：2020-05-12

  The present disclosure, among other things, provides low-viscosity, high concentration therapeutic protein agent formulations.

  本公开的内容包括提供低粘度、高浓度的治疗性蛋白制剂。