tert-butyl (4aR,7aR)-7a-(5-(5-fluoropicolinamido)-2-fluorophenyl)-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-2-ylcarbamate | 1415208-91-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl (4aR,7aR)-7a-(5-(5-fluoropicolinamido)-2-fluorophenyl)-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-2-ylcarbamate
• 英文别名: tert-butyl ((4aR,7aR)-7a-(2-fluoro-5-(5-fluoropicolinamido)phenyl)-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-2-yl)carbamate；tert-butyl N-[(4aR,7aR)-7a-[2-fluoro-5-[(5-fluoropyridine-2-carbonyl)amino]phenyl]-4,4a,5,6-tetrahydrofuro[2,3-d][1,3]thiazin-2-yl]carbamate
• CAS: 1415208-91-1
• 化学式: C₂₃H₂₄F₂N₄O₄S
• 分子量: 490.531
• InChiKey: RNYHALIWDQXXLY-ZAMGYDSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  127
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  tert-butyl (4aR,7aR)-7a-(5-(5-fluoropicolinamido)-2-fluorophenyl)-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-2-ylcarbamate 在 三氟乙酸 作用下， 生成 (+/-)-N-(3-((4aR,7aR)-2-amino-4a,5,6,7a-tetrahydro-4H-furo[2,3-d] [1,3]thiazin-7a-yl)-4-fluorophenyl)-5-fluoropicolinamide
  参考文献：
  名称：

  Discovery of furo[2,3- d ][1,3]thiazinamines as beta amyloid cleaving enzyme-1 (BACE1) inhibitors

  摘要：

  This Letter describes the synthesis and structure-activity relationships of a series of furo[2,3-d][1,3] thiazinamine BACE1 inhibitors. The co-crystal structure of a representative thiazinamine 2e bound with the BACE1 active site displayed a binding mode driven by interactions with the catalytic aspartate dyad and engagement of the biaryl amide toward the S1 and S3 pockets. This work indicates that furo[2,3-d] thiazine can serve as a viable bioisostere of the known furo[3,4-d] thiazine. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.10.055
• 作为产物：
  描述：

  tert-butyl ((4aR,7aR)-7a-(5-bromo-2-fluorophenyl)-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-2-yl)carbamate 在 sodium azide 、 copper(ll) sulfate pentahydrate 、 palladium on activated charcoal 、 (1R,2R)-(-)-N,N'-二甲基-1,2-环己二胺 、 氢气 、 1-羟基苯并三唑 、 sodium ascorbate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 为溶剂， 生成 tert-butyl (4aR,7aR)-7a-(5-(5-fluoropicolinamido)-2-fluorophenyl)-4a,5,6,7a-tetrahydro-4H-furo[2,3-d][1,3]thiazin-2-ylcarbamate
  参考文献：
  名称：

  Discovery of furo[2,3- d ][1,3]thiazinamines as beta amyloid cleaving enzyme-1 (BACE1) inhibitors

  摘要：

  This Letter describes the synthesis and structure-activity relationships of a series of furo[2,3-d][1,3] thiazinamine BACE1 inhibitors. The co-crystal structure of a representative thiazinamine 2e bound with the BACE1 active site displayed a binding mode driven by interactions with the catalytic aspartate dyad and engagement of the biaryl amide toward the S1 and S3 pockets. This work indicates that furo[2,3-d] thiazine can serve as a viable bioisostere of the known furo[3,4-d] thiazine. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.10.055

文献信息

• [EN] COMPOUNDS FOR THE REDUCTION OF BETA-AMYLOID PRODUCTION<br/>[FR] COMPOSÉS DESTINÉS À LA RÉDUCTION DE LA PRODUCTION DE BÊTA-AMYLOÏDES
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2012162334A1

  公开（公告）日：2012-11-29

  Compounds of formula (I), including pharmaceutically acceptable salts thereof, are set forth herein: wherein R1, R2, R3, R4, R5, and R6 are independently hydrogen, C1-C6 alkyl or C1-C6 cycloalkyl; Y and Z are independently a C6-C10- aryl group or a 5-10 membered heterocyclic group, wherein each Y and Z group can be optionally substituted with from 0-3 substituents selected from halogen, amino, C1-4alkylamino, C1-4dialkylamino, haloC1-4 alkyl, OH, CN, C1-C6 alkyl or cycloalkyl, C1-C6 alkoxy, and C2-C4 alkynyl; L is either a bond or is -NHCO-; L and Z together can be absent; and m is 1, 2 or 3.

  化合物的化学式（I），包括其药用可接受盐，如下所示：其中R1、R2、R3、R4、R5和R6独立地是氢、C1-C6烷基或C1-C6环烷基；Y和Z独立地是C6-C10芳基或5-10成员杂环基，其中每个Y和Z基可以选择地被0-3个取代基取代，所述取代基选自卤素、氨基、C1-4烷基氨基、C1-4二烷基氨基、卤代C1-4烷基、羟基、氰基、C1-C6烷基或环烷基、C1-C6烷氧基和C2-C4炔基；L要么是一个键，要么是-NHCO-；L和Z可以一起不存在；m为1、2或3。
• Compounds for the reduction of beta-amyloid production
  申请人：Wu Yong-Jin

  公开号：US08598161B2

  公开（公告）日：2013-12-03

  Compounds of formula (I), including pharmaceutically acceptable salts thereof, are set forth herein: wherein R1, R2, R3, R4, R5, and R6 are independently hydrogen, C1-C6 alkyl or C1-C6 cycloalkyl; Y and Z are independently a C6-C10-aryl group or a 5-10 membered heterocyclic group, wherein each Y and Z group can be optionally substituted with from 0-3 substituents selected from halogen, amino, C1-4alkylamino, C1-4dialkylamino, haloC1-4 alkyl, OH, CN, C1-C6 alkyl or cycloalkyl, C1-C6 alkoxy, and C2-C4 alkynyl; L is either a bond or is —NHCO—; L and Z together can be absent; and m is 1, 2 or 3.

  以下列出了公式（I）的化合物，包括其药学上可接受的盐： 其中，R1，R2，R3，R4，R5和R6分别独立表示氢、C1-C6烷基或C1-C6环烷基；Y和Z分别独立表示C6-C10芳基或5-10元杂环基，其中每个Y和Z基可以选择性地被0-3个取代基取代，所述取代基选自卤素、氨基、C1-4烷基氨基、C1-4二烷基氨基、卤代C1-4烷基、羟基、氰基、C1-C6烷基或环烷基、C1-C6烷氧基和C2-C4炔基；L可以是键或—NHCO—；L和Z可以同时不存在；m为1、2或3。
• COMPOUNDS FOR THE REDUCTION OF BETA-AMYLOID PRODUCTION
  申请人：Wu Yong-Jin

  公开号：US20130131049A1

  公开（公告）日：2013-05-23

  Compounds of formula (I), including pharmaceutically acceptable salts thereof, are set forth herein: wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are independently hydrogen, C 1 -C 6 alkyl or C 1 -C 6 cycloalkyl; Y and Z are independently a C 6 -C 10 -aryl group or a 5-10 membered heterocyclic group, wherein each Y and Z group can be optionally substituted with from 0-3 substituents selected from halogen, amino, C 1-4 alkylamino, C 1-4 dialkylamino, haloC 1-4 alkyl, OH, CN, C 1 -C 6 alkyl or cycloalkyl, C 1 -C 6 alkoxy, and C 2 -C 4 alkynyl; L is either a bond or is —NHCO—; L and Z together can be absent; and m is 1, 2 or 3.

  本文列出了公式（I）的化合物，包括其药学上可接受的盐： 其中，R1、R2、R3、R4、R5和R6独立地为氢、C1-C6烷基或C1-C6环烷基；Y和Z独立地为C6-C10芳基或5-10成员杂环基，其中每个Y和Z基可以选择地被0-3个取代基取代，所述取代基选自卤素、氨基、C1-4烷基氨基、C1-4二烷基氨基、卤C1-4烷基、羟基、CN、C1-C6烷基或环烷基、C1-C6烷氧基和C2-C4炔基；L是一个键或者是—NHCO—；L和Z可以同时不存在；m为1、2或3。
• Discovery of furo[2,3- d ][1,3]thiazinamines as beta amyloid cleaving enzyme-1 (BACE1) inhibitors
  作者：Yong-Jin Wu、Jason Guernon、Ramkumar Rajamani、Jeremy H. Toyn、Michael K. Ahlijanian、Charles F. Albright、Jodi Muckelbauer、ChiehYing Chang、Dan Camac、John E. Macor、Lorin A. Thompson

  DOI：10.1016/j.bmcl.2016.10.055

  日期：2016.12

  This Letter describes the synthesis and structure-activity relationships of a series of furo[2,3-d][1,3] thiazinamine BACE1 inhibitors. The co-crystal structure of a representative thiazinamine 2e bound with the BACE1 active site displayed a binding mode driven by interactions with the catalytic aspartate dyad and engagement of the biaryl amide toward the S1 and S3 pockets. This work indicates that furo[2,3-d] thiazine can serve as a viable bioisostere of the known furo[3,4-d] thiazine. (C) 2016 Elsevier Ltd. All rights reserved.