(3-bromo-phenyl)-(3,5-dimethoxy-phenyl)-methanone | 951892-07-2

• 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: (3-bromo-phenyl)-(3,5-dimethoxy-phenyl)-methanone
• 英文别名: 3-Bromo-3',5'-dimethoxybenzophenone；(3-bromophenyl)-(3,5-dimethoxyphenyl)methanone
• CAS: 951892-07-2
• 化学式: C₁₅H₁₃BrO₃
• 分子量: 321.17
• InChiKey: AKGVNYWTZQPUEZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3-bromo-phenyl)-(3,5-dimethoxy-phenyl)-methanone 在 对甲苯磺酸 作用下， 以 甲醇 、 氘代二甲亚砜 为溶剂， 反应 169.0h， 生成 [(Z)-[(3-bromophenyl)-(3,5-dimethoxyphenyl)methylidene]amino]thiourea
  参考文献：
  名称：

  组织蛋白酶L的铅抑制剂KGP94的水溶性磷酸盐前药盐和结构类似物的合成和生物学评估

  摘要：

  组织蛋白酶L的表达量通常在肿瘤微环境中上调，与某些肿瘤的侵袭性和转移性有关。组织蛋白酶L的抑制代表一种治疗转移性癌症的新兴策略。组织蛋白酶L的有效的小分子抑制剂（称为KGP94），并合成了新的KGP94类似物。（3,5-二溴苯基）-（3-羟基苯基）酮硫代半碳酸盐（22）的IC 50值为202 nM，与KGP94相比，对组织蛋白酶L的抑制活性相似（IC 50 = 189 nM）。由于KGP94在水中的溶解度有限，因此制备了水溶性磷酸盐（KGP420），以便于将来进行体内研究。用碱性磷酸酶（ALP）进行酶水解表明，磷酸盐前药KGP420易于转化为母体化合物KGP94。

  DOI：

  10.1016/j.bmcl.2016.12.039
• 作为产物：
  描述：

  (3-溴-苯基)-(3,5-二甲氧基-苯基)-甲醇 在 Celite 、 pyridinium chlorochromate 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以63.6%的产率得到(3-bromo-phenyl)-(3,5-dimethoxy-phenyl)-methanone
  参考文献：
  名称：

  Exploring the substituent effects on a novel series of C1′-dimethyl-aryl Δ8-tetrahydrocannabinol analogs

  摘要：

  The synthesis and characterization of novel C1'-phenyl-substituted Delta(8)-THC analogs were previously reported by our laboratory. Within this small series of compounds, the C1'-dimethyl phenyl group was found to impart 13.5-fold selectivity for the CB2 receptor with a K-i 0.91 nM. The current study expands on the previous report by evaluating the effects of aromatic ring substitution on CB1 and CB2 receptor subtype binding and selectivity. The ring substituents synthesized in this study include aliphatic, halogen, nitrile, and acetamido functional groups. In addition, the isosteric replacement of the phenyl group by thiophene was evaluated. The anti-glioma activities of selected compounds were evaluated in vitro and compared to the lead compound 2. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.05.034

文献信息

• [EN] COMPOSITIONS AND METHODS FOR INHIBITION OF CATHEPSINS<br/>[FR] COMPOSITIONS ET PROCÉDÉS D'INHIBITION DE CATHEPSINES
  申请人：MATEON THERAPEUTICS INC

  公开号：WO2017030983A1

  公开（公告）日：2017-02-23

  This present disclosure is directed to compound of Formula I and methods of using these compounds in the treatment of conditions in which modulation of a cathepsin, particularly cathepsin L, cathepsin K, and/or cathepsin B, will be therapeutically useful. Formula I: or a solvate or pharmaceutically acceptable salt thereof. Each of Rl -Rl 0 are independently selected from the group consisting of: hydrogen, alkoxy, halo, hydroxy, phosphate, phosphate salts, disodium phosphate, diphosphate dimer, diphosphate dimer salt, and sodium diphosphate dimer with at least one of R1 -R10 is a phosphate or diphosphate dimer group.

  本公开涉及化合物I的公式以及在治疗需要调节蛋白酶的情况下使用这些化合物的方法，特别是蛋白酶L、蛋白酶K和/或蛋白酶B。公式I：或其溶剂或药用可接受盐。R1-R10中的每一个独立地选择自羟基、烷氧基、卤素、羟基、磷酸酯、磷酸盐、二钠磷酸盐、二磷酸二聚体、二磷酸二聚体盐和含有R1-R10中至少一个为磷酸酯或二磷酸二聚体基团的羟基。
• COMPOSITIONS AND METHODS FOR INHIBITION OF CATHEPSINS
  申请人：Mateon Therapeutics, Inc.

  公开号：US20190010173A1

  公开（公告）日：2019-01-10

  This present disclosure is directed to compound of Formula I and methods of using these compounds in the treatment of conditions in which modulation of a cathepsin, particularly cathepsin L, cathepsin K, and/or cathepsin B, will be therapeutically useful. Formula I: or a solvate or pharmaceutically acceptable salt thereof. Each of R1-R10 are independently selected from the group consisting of: hydrogen, alkoxy, halo, hydroxy, phosphate, phosphate salts, disodium phosphate, diphosphate dimer, diphosphate dimer salt, and sodium diphosphate dimer with at least one of R1-R10 is a phosphate or diphosphate dimer group.
• Synthesis and biological evaluation of a water-soluble phosphate prodrug salt and structural analogues of KGP94, a lead inhibitor of cathepsin L
  作者：Erica N. Parker、Samuel O. Odutola、Yifan Wang、Tracy E. Strecker、Rajeswari Mukherjee、Zhe Shi、David J. Chaplin、Mary Lynn Trawick、Kevin G. Pinney

  DOI：10.1016/j.bmcl.2016.12.039

  日期：2017.3

  inhibitor (referred to as KGP94) of cathepsin L, and new KGP94 analogues were synthesized. (3,5-Dibromophenyl)-(3-hydroxyphenyl) ketone thiosemicarbazone (22), with an IC50 value of 202 nM, exhibited similar inhibitory activity against cathepsin L compared to KGP94 (IC50 = 189 nM). Due to limited aqueous solubility of KGP94, a water-soluble phosphate salt (KGP420) was prepared in order to facilitate future

  组织蛋白酶L的表达量通常在肿瘤微环境中上调，与某些肿瘤的侵袭性和转移性有关。组织蛋白酶L的抑制代表一种治疗转移性癌症的新兴策略。组织蛋白酶L的有效的小分子抑制剂（称为KGP94），并合成了新的KGP94类似物。（3,5-二溴苯基）-（3-羟基苯基）酮硫代半碳酸盐（22）的IC 50值为202 nM，与KGP94相比，对组织蛋白酶L的抑制活性相似（IC 50 = 189 nM）。由于KGP94在水中的溶解度有限，因此制备了水溶性磷酸盐（KGP420），以便于将来进行体内研究。用碱性磷酸酶（ALP）进行酶水解表明，磷酸盐前药KGP420易于转化为母体化合物KGP94。
• Exploring the substituent effects on a novel series of C1′-dimethyl-aryl Δ8-tetrahydrocannabinol analogs
  作者：Mathangi Krishnamurthy、Steven Gurley、Bob M. Moore II

  DOI：10.1016/j.bmc.2008.05.034

  日期：2008.7.1

  The synthesis and characterization of novel C1'-phenyl-substituted Delta(8)-THC analogs were previously reported by our laboratory. Within this small series of compounds, the C1'-dimethyl phenyl group was found to impart 13.5-fold selectivity for the CB2 receptor with a K-i 0.91 nM. The current study expands on the previous report by evaluating the effects of aromatic ring substitution on CB1 and CB2 receptor subtype binding and selectivity. The ring substituents synthesized in this study include aliphatic, halogen, nitrile, and acetamido functional groups. In addition, the isosteric replacement of the phenyl group by thiophene was evaluated. The anti-glioma activities of selected compounds were evaluated in vitro and compared to the lead compound 2. (c) 2008 Elsevier Ltd. All rights reserved.