tert-butyl [(1R)-1-(5-bromo-3-fluoropyridin-2-yl)ethyl]-carbamate | 858414-25-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: tert-butyl [(1R)-1-(5-bromo-3-fluoropyridin-2-yl)ethyl]-carbamate
• 英文别名: tert-butyl N-[(1R)-1-(5-bromo-3-fluoropyridin-2-yl)ethyl]carbamate
• CAS: 858414-25-2
• 化学式: C₁₂H₁₆BrFN₂O₂
• 分子量: 319.174
• InChiKey: HKXACTQRBSSCDB-SSDOTTSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl [(1R)-1-(5-bromo-3-fluoropyridin-2-yl)ethyl]-carbamate 、 联硼酸频那醇酯 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Novel small molecule bradykinin B1 receptor antagonists. Part 1: Benzamides and semicarbazides

  摘要：

  The synthesis and SAR of two series of bradykinin B-1 receptor antagonists is described. The benzamide moiety proved to be a suitable replacement for the aryl ester functionality of biaryl based antagonists. In addition, it was found that semicarbazides can effectively replace cyclopropyl amino acids. The compounds with the best overall pro. le were biaryl semicarbazides which display high antagonistic activity, low Caco-2 efflux and high oral bioavailability in the rat. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.11.119
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 盐酸 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 21.0h， 生成 tert-butyl [(1R)-1-(5-bromo-3-fluoropyridin-2-yl)ethyl]-carbamate
  参考文献：
  名称：

  [EN] ALPHA-HYDROXY AMIDES AS BRADYKININ ANTAGONISTS OR INVERSE AGONISTS
  [FR] ALPHA-HYDROXY AMIDES UTILISES COMME ANTAGONISTES OU AGONISTES INVERSES DE LA BRADYKININE

  摘要：

  通用公式（I）的α-羟基酰胺衍生物是布雷肯肽B1拮抗剂或逆向激动剂，在治疗或预防与布雷肯肽B1途径相关的疼痛和炎症症状方面很有用。R2a从（1）Ra组中选择。 （2）（CH2）nNRbC（O）Ra。（3）（CH2）nNRbSO2Rd。（4）（CH2）nNRbCO2Ra。（5）（CH2）k-杂环，可选择地取代为1到3个独立选择的卤素，硝基，氰基，ORa，SRa，C1-4烷基和C1-3卤代烷基，其中所述杂环是（a）具有N，O和S中选择的环杂原子的5元杂芳环，并且可选地具有多达3个额外的环氮原子，其中所述环可选地与苯融合；或（b）含有1到3个环氮原子和其N-氧化物的6元杂芳环。其中所述环可选地与苯融合。（6）（CH2）kCO2Ra和（7）（CH2）C（O）NRbRc。 R2b是OH或从R2a选择的组；或R2a和R2b与它们连接的碳原子一起形成一个3到7个成员的碳环，可选择地取代为1到4个独立选择的卤素，ORa，C1-4烷基和C1-4卤代烷基；

  公开号：

  WO2005063690A1

文献信息

• [EN] ALPHA-HYDROXY AMIDES AS BRADYKININ ANTAGONISTS OR INVERSE AGONISTS<br/>[FR] ALPHA-HYDROXY AMIDES UTILISES COMME ANTAGONISTES OU AGONISTES INVERSES DE LA BRADYKININE
  申请人：MERCK & CO INC

  公开号：WO2005063690A1

  公开（公告）日：2005-07-14

  α-Hydroxy amide derivatives of the general formula (I) are bradykinin B1 antagonists or inverse agonists useful in the treatment or prevention of symptoms such as pain and inflammation associated with the bradykinin B1 pathway. R2a is selected from (1) a group selected from Ra. (2) (CH2)nNRbC(O)Ra. (3)(CH2)nNRbSO2Rd.(4)(CH2)nNRbCO2Ra.(5)(CH2)k-heterocycle optionally substituted with 1 to 3 groups independently selected from halogen.nitro, cyano.ORa.SRa.C1-4 alkyl and C1-3 haloakyl wherein said heterocycle is (a) a 5-membered heteroaromatic ring having a ring heteroatom selected from N.O and S. and optionally having up to 3 additional ring nitrogen atoms wherein said ring is optionally benzo-fused; or(b) a 6-membered heteromatic ring containing from 1 to 3 ring nitrogen atoms and N-oxydes thereof. Wherein said ring is optionally benzo-fused. (6)(CH2)kCO2Ra.and (7)(CH2)C(O)NRbRc. R2b is OH or a group selected from R2a; or R2a and R2b together with the carbon atom to which they are attached form a 3-to 7-membered carbocyclic ring optionally substituted with 1 to 4 groups independently selected from halogen. ORa. C1-4 alkyl and C1-4 haloalkyl;

  通用公式（I）的α-羟基酰胺衍生物是布雷肯肽B1拮抗剂或逆向激动剂，在治疗或预防与布雷肯肽B1途径相关的疼痛和炎症症状方面很有用。R2a从（1）Ra组中选择。 （2）（CH2）nNRbC（O）Ra。（3）（CH2）nNRbSO2Rd。（4）（CH2）nNRbCO2Ra。（5）（CH2）k-杂环，可选择地取代为1到3个独立选择的卤素，硝基，氰基，ORa，SRa，C1-4烷基和C1-3卤代烷基，其中所述杂环是（a）具有N，O和S中选择的环杂原子的5元杂芳环，并且可选地具有多达3个额外的环氮原子，其中所述环可选地与苯融合；或（b）含有1到3个环氮原子和其N-氧化物的6元杂芳环。其中所述环可选地与苯融合。（6）（CH2）kCO2Ra和（7）（CH2）C（O）NRbRc。 R2b是OH或从R2a选择的组；或R2a和R2b与它们连接的碳原子一起形成一个3到7个成员的碳环，可选择地取代为1到4个独立选择的卤素，ORa，C1-4烷基和C1-4卤代烷基；
• 1-Hydroxycycloalkanecarboxamide derivatives
  申请人：Kuduk Scott D.

  公开号：US20090062349A1

  公开（公告）日：2009-03-05

  α-Hydroxycycloalkanecarboxamide derivatives of formula (I) or a pharmaceutically acceptable salt thereof, wherein formula (a) is a single or double bond; R 1 , R 2 and R 3 are each independently selected from H, halogen and OH; or R 1 and R 2 attached to the same carbon atom together represent oxo; R 4 is H or methyl; R 5 is Cl or I 2 ; R 6 is selected from —CO 2 —C 3-4 alkyl, —O—C 1-4 alkyl, —O—C 1-4 haloalkyl, 2-methyltetrazol-5-yl, 5-methyl-1,2,4-oxadiazol-3-yl, 3-methyl-1,2,4-oxadiazol-5-yl, 5-halomethyl-1,2,4-oxadiazol-3-yl, 3-halomethyl-1,2,4-oxadiazol-5-yl, tetrazol-5-yl, 5-halomethyl-1,2,3-triazolyl, and 5-methyl-1,2,3-triazolyl; R 7 and R 8 are each independently Cl or I 2 ; and n is 0 or 1, are bradykinin B1 antagonists or inverse agonists useful in the treatment or prevention of symptoms such as pain and inflammation associated with the bradykinin B1 pathway.

  式(I)中，α-羟基环烷基羧酰胺衍生物或其药学上可接受的盐，其中式(a)为单键或双键；R1、R2和R3各自独立地选自H、卤素和OH；或者R1和R2结合到同一碳原子上表示氧代基；R4为H或甲基；R5选自Cl或I2；R6选自—CO2—C3-4烷基、—O—C1-4烷基、—O—C1-4卤代烷基、2-甲基四唑-5-基、5-甲基-1,2,4-噁二唑-3-基、3-甲基-1,2,4-噁二唑-5-基、5-卤代甲基-1,2,4-噁二唑-3-基、3-卤代甲基-1,2,4-噁二唑-5-基、四唑-5-基、5-卤代甲基-1,2,3-三唑基和5-甲基-1,2,3-三唑基；R7和R8各自独立地选自Cl或I2；n为0或1。这些化合物是Bradykinin B1拮抗剂或反向激动剂，可用于治疗或预防与Bradykinin B1通路相关的疼痛和炎症症状。
• 1-hydroxycycloalkanecarboxamide derivatives
  申请人：Merck Sharp & Dohme Corp.

  公开号：US07816380B2

  公开（公告）日：2010-10-19

  α-Hydroxycycloalkanecarboxamide derivatives of formula (I) or a pharmaceutically acceptable salt thereof, wherein formula (a) is a single or double bond; R1, R2 and R3 are each independently selected from H, halogen and OH; or R1 and R2 attached to the same carbon atom together represent oxo; R4 is H or methyl; R5 is Cl or I2; R6 is selected from —CO2—C1-4alkyl, —O—C1-4alkyl, —O—C1-4haloalkyl, 2-methyltetrazol-5-yl, 5-methyl-1,2,4-oxadiazol-3-yl, 3-methyl-1,2,4-oxadiazol-5-yl, 5-halomethyl-1,2,4-oxadiazol-3-yl, 3-halomethyl-1,2,4-oxadiazol-5-yl, tetrazol-5-yl, 5-halomethyl-1,2,3-triazolyl, and 5-methyl-1,2,3-triazolyl; R7 and R8 are each independently Cl or I2; and n is 0 or 1, are bradykinin B1 antagonists or inverse agonists useful in the treatment or prevention of symptoms such as pain and inflammation associated with the bradykinin B1 pathway.

  式(I)或其药学上可接受的盐，其中式(a)表示单键或双键；R1、R2和R3各自独立地选择自H、卤素和OH；或者R1和R2结合到同一碳原子上表示氧代；R4为H或甲基；R5为Cl或I2；R6选择自—CO2—C1-4烷基、—O—C1-4烷基、—O—C1-4卤代烷基、2-甲基四唑-5-基、5-甲基-1,2,4-噁二唑-3-基、3-甲基-1,2,4-噁二唑-5-基、5-卤代甲基-1,2,4-噁二唑-3-基、3-卤代甲基-1,2,4-噁二唑-5-基、四唑-5-基、5-卤代甲基-1,2,3-三唑基和5-甲基-1,2,3-三唑基；R7和R8各自独立地为Cl或I2；n为0或1。这些化合物是Bradykinin B1拮抗剂或反向激动剂，用于治疗或预防与Bradykinin B1通路相关的疼痛和炎症等症状。
• WO2006/132837
  申请人：——

  公开号：——

  公开（公告）日：——
• Novel small molecule bradykinin B1 receptor antagonists. Part 1: Benzamides and semicarbazides
  作者：Marco Schaudt、Elsa Locardi、Gunther Zischinsky、Roland Stragies、Jochen R. Pfeifer、Christoph Gibson、Dirk Scharn、Uwe Richter、Holger Kalkhof、Klaus Dinkel、Karsten Schnatbaum

  DOI：10.1016/j.bmcl.2009.11.119

  日期：2010.2

  The synthesis and SAR of two series of bradykinin B-1 receptor antagonists is described. The benzamide moiety proved to be a suitable replacement for the aryl ester functionality of biaryl based antagonists. In addition, it was found that semicarbazides can effectively replace cyclopropyl amino acids. The compounds with the best overall pro. le were biaryl semicarbazides which display high antagonistic activity, low Caco-2 efflux and high oral bioavailability in the rat. (C) 2009 Elsevier Ltd. All rights reserved.