1,3-bis(bromomethyl)-5-chlorobenzene | 781616-32-8

• 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: 1,3-bis(bromomethyl)-5-chlorobenzene
• CAS: 781616-32-8
• 化学式: C₈H₇Br₂Cl
• 分子量: 298.405
• InChiKey: XZHUMKMJIWMDNH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  0

反应信息

• 作为反应物：
  描述：

  1,3-bis(bromomethyl)-5-chlorobenzene 在 lithium aluminium tetrahydride 、 sodium azide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 6.0h， 生成 3-aminomethyl-5-chlorobenzylamine
  参考文献：
  名称：

  Acyl Guanidine Inhibitors of β-Secretase (BACE-1): Optimization of a Micromolar Hit to a Nanomolar Lead via Iterative Solid- and Solution-Phase Library Synthesis

  摘要：

  This report describes the discovery and optimizition of a BACE-1 inhibitor series containing an unusual acyl guanidine chemotype that was originally synthesized as part of a 6041-membered solid-phase library. The synthesis of multiple follow-up solid- and solution-phase libraries facilitated the optimization of the original micromolar hit into a single-digit nanomolar BACE-1 inhibitor in both radioligand binding and cell-based functional assay formats. The X-ray structure of representative inhibitors bound to BACE-1 revealed a number of key ligand:protein interactions, including a hydrogen bond between the side chain amide of flap residue Gln73 and the acyl guanidine carbonyl group, and a cation-pi interaction between Arg235 and the isothiazole 4-methoxyphenyl substituent. Following subcutaneous administration in rats, an acyl guanidine inhibitor with single-digit nanomolar activity in cells afforded good plasma exposures and a dose-dependent reduction in plasma A beta levels, but poor brain exposure was observed (likely due to Pgp-mediated efflux), and significant reductions in brain A beta levels were not obtained.

  DOI：

  10.1021/jm300931y
• 作为产物：
  描述：

  5-氯间二甲苯 在 偶氮二异丁腈 N-溴代丁二酰亚胺(NBS) 作用下， 以 四氯化碳 为溶剂， 生成 1,3-bis(bromomethyl)-5-chlorobenzene
  参考文献：
  名称：

  Aminoacetamide acyl guanidines as beta-secretase inhibitors

  摘要：

  提供了一系列的取代酰基胍类化合物，符合以下化学式（Ik）或其立体异构体；或其药学上可接受的盐，其中R2、R3、R4、R5、R25、R26和R27如本文所定义，它们的药物组合物和使用方法。这些化合物抑制β-分泌酶对淀粉样前体蛋白（APP）的加工，更具体地说，抑制Aβ肽的产生。本公开涉及对β-淀粉样蛋白产生相关的神经疾病的治疗有用的化合物，如阿尔茨海默氏病和其他受抗淀粉样活性影响的病症。

  公开号：

  US20060287287A1

文献信息

• Aminoacetamide acyl guanidines as beta-secretase inhibitors
  申请人：Gerritz Samuel

  公开号：US20060287287A1

  公开（公告）日：2006-12-21

  There is provided a series of substituted acyl guanidines of Formula (Ik) or a stereoisomer; or a pharmaceutically acceptable salt thereof, wherein R 2 , R 3 , R 4 , R 5 , R 25 , R 26 and R 27 as defined herein, their pharmaceutical compositions and methods of use. These compounds inhibit the processing of amyloid precursor protein (APP) by β-secretase and, more specifically, inhibit the production of Aβ-peptide. The present disclosure is directed to compounds useful in the treatment of neurological disorders related to β-amyloid production, such as Alzheimer's disease and other conditions affected by anti-amyloid activity.

  提供了一系列的取代酰基胍类化合物，符合以下化学式（Ik）或其立体异构体；或其药学上可接受的盐，其中R2、R3、R4、R5、R25、R26和R27如本文所定义，它们的药物组合物和使用方法。这些化合物抑制β-分泌酶对淀粉样前体蛋白（APP）的加工，更具体地说，抑制Aβ肽的产生。本公开涉及对β-淀粉样蛋白产生相关的神经疾病的治疗有用的化合物，如阿尔茨海默氏病和其他受抗淀粉样活性影响的病症。
• PYRROLOBENZODIAZEPINES AND CONJUGATES THEREOF
  申请人：GENENTECH, INC.

  公开号：US20140294868A1

  公开（公告）日：2014-10-02

  Conjugate compounds of formula (A): wherein: R 2 is where R 36a and R 36b are independently selected from H, F, C 1-4 saturated alkyl, C 2-3 alkenyl, which alkyl and alkenyl groups are optionally substituted by a group selected from C 1-4 alkyl amido and C 1-4 alkyl ester or, when one of R 36a and R 36b is H, the other is selected from nitrile and a C 1-4 alkyl ester; R 6 and R 9 are independently selected from H, R, OH, OR, SH, SR, NH 2 , NHR, NRR′, NO 2 , Me 3 Sn and halo; R 7 is independently selected from H, R, OH, OR, SH, SR, NH 2 , NHR, NRR′, NO 2 , Me 3 Sn and halo; Y is selected from formulae A1, A2, A3, A4, A5 and A6: L is a linker connected to a cell binding agent; CBA is the cell binding agent; n is an integer selected in the range of 0 to 48; R A4 is a C 1-6 alkylene group; either (a) R 10 is H, and R 11 is OH, OR A , where R A is C 1-4 alkyl; or (b) R 10 and R 11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound; or (c) R 10 is H and R 11 is OSO z M, where z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation; R and R′ are each independently selected from optionally substituted C 1-12 alkyl, C 3-20 heterocyclyl and C 5-20 aryl groups, and optionally in relation to the group NRR′, R and R′ together with the nitrogen atom to which they are attached form an optionally substituted 4-, 5-, 6- or 7-membered heterocyclic ring; wherein R 16 , R 17 , R 19 , R 20 , R 21 and R 22 are as defined for R 6 , R 7 , R 9 , R 10 , R 11 and R 2 respectively; wherein Z is CH or N; wherein T and T′ are independently selected from a single bond or a C 1-9 alkylene, which chain may be interrupted by one or more heteroatoms e.g. O, S, N(H), NMe, provided that the number of atoms in the shortest chain of atoms between X and X′ is 3 to 12 atoms; and X and X′ are independently selected from O, S and N(H).

  将公式（A）的共轭化合物变形：其中：R2是其中R36a和R36b分别独立选择自H、F、C1-4饱和烷基、C2-3烯基，所述烷基和烯基基团可以选择性地被C1-4烷基酰胺和C1-4烷基酯中的一种基团取代，或者当R36a和R36b中的一个是H时，另一个选择自腈和C1-4烷基酯；R6和R9独立选择自H、R、OH、OR、SH、SR、NH2、NHR、NRR′、NO2、Me3Sn和卤素；R7独立选择自H、R、OH、OR、SH、SR、NH2、NHR、NRR′、NO2、Me3Sn和卤素；Y选择自公式A1、A2、A3、A4、A5和A6；L是连接到细胞结合剂的连接剂；CBA是细胞结合剂；n是选择在0到48范围内的整数；RA4是C1-6烷基基团；要么（a）R10是H，而R11是OH、ORA，其中RA是C1-4烷基；或者（b）R10和R11在氮和碳原子之间形成氮-碳双键；或者（c）R10是H，而R11是OSOzM，其中z为2或3，M是一价的药用可接受阳离子；R和R′各自独立选择自选择性取代的C1-12烷基、C3-20杂环基和C5-20芳基，并且在NRR′基团方面，R和R′与它们连接的氮原子一起形成一个可选择取代的4-、5-、6-或7-成员杂环环；其中R16、R17、R19、R20、R21和R22如R6、R7、R9、R10、R11和R2所定义；其中Z为CH或N；其中T和T′独立选择自单键或C1-9烷基，该链可能被一个或多个杂原子（如O、S、N(H)、NMe）中断，前提是在X和X′之间原子最短链中原子的数量为3到12个原子；X和X′独立选择自O、S和N(H)。
• [EN] IMMUNOCONJUGATES COMPRISING ANTI-HER2 ANTIBODIES AND PYRROLOBENZODIAZEPINES<br/>[FR] IMMUNOCONJUGUÉS COMPRENANT DES ANTICORPS ANTI-HER2 ET DES PYRROLOBENZODIAZÉPINES
  申请人：GENENTECH INC

  公开号：WO2016044396A1

  公开（公告）日：2016-03-24

  The invention provides immunoconjugates comprising anti-HER2 antibodies and methods of using the same. An immunoconjugate is provided, which comprises an antibody and a cytotoxic agent, wherein the cytotoxic agent is a center-linked pyrrolobenzodiazepine. The immunoconjugate has the formula Ab-(L-D)p, wherein: a) Ab is the antibody of any one of claim 1 to 16; b) L is a linker; c) D is a center-linked pyrrolobenzodiazepine; and d) p ranges from 1-8.

  该发明提供了包含抗HER2抗体的免疫结合物及其使用方法。提供了一种免疫结合物，其中包括一种抗体和一种细胞毒性剂，其中该细胞毒性剂是一个中心连接的吡咯苯并二氮杂环。该免疫结合物的公式为Ab-(L-D)p，其中：a) Ab是权利要求1至16中的任一抗体；b) L是一个连接物；c) D是一个中心连接的吡咯苯并二氮杂环；d) p的取值范围为1-8。
• Acyl guanidines as beta-secretase inhibitors
  申请人：Gerritz Samuel

  公开号：US20070015754A1

  公开（公告）日：2007-01-18

  There is provided a series of substituted acyl guanidines of Formula (I) or a stereoisomer; or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , R 4 and R 5 as defined herein, their pharmaceutical compositions and methods of use. These compounds inhibit the processing of amyloid precursor protein (APP) by β-secretase and, more specifically, inhibit the production of Aβ-peptide. The present disclosure is directed to compounds useful in the treatment of neurological disorders related to β-amyloid production, such as Alzheimer's disease and other conditions affected by anti-amyloid activity.

  提供了一系列的取代酰基鸟氨酸化合物（I）或其立体异构体；或其药学上可接受的盐，其中R1、R2、R3、R4和R5如本文所定义，以及它们的药物组合物和使用方法。这些化合物抑制β-分泌酶对淀粉样前体蛋白（APP）的加工，更具体地抑制Aβ-肽的产生。本公开涉及用于治疗与β-淀粉样蛋白产生有关的神经系统疾病，例如阿尔茨海默病和其他受抗淀粉样蛋白活性影响的疾病的化合物。
• 一种含硫类青蒿素二聚体、其制备方法和应用
  申请人：云南苏理生物医药科技有限公司

  公开号：CN115073496A

  公开（公告）日：2022-09-20

  本发明涉及一种含硫类青蒿素二聚体、其制备方法和应用，属于药物化学技术领域。所述含硫类青蒿素二聚体的化学结构式如式Ⅰ表示的化合物或其药学上可接受的盐： 其中，W表示为：S、SO和SO2中的任意一种；Z表示为：S、SO、SO2、O、NR1和CR12中的任意一种；Y表示为：单键、烷基、芳基、环基、醚和氨中的任意一种；R1表示为：氢、卤素、烷基、芳基、环基、醚和氨中的任意一种；n和m各自独立的选自：0～15的整数。本发明还公开了含硫类青蒿素二聚体的制备方法。本发明的含硫类青蒿素二聚体对人癌细胞株的生长具有选择性的抑制作用。