[³H]-methyl tosylate | 807620-15-1

• 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: [³H]-methyl tosylate
• 英文别名: Tritritiomethyl 4-methylbenzenesulfonate
• CAS: 807620-15-1
• 化学式: C₈H₁₀O₃S
• 分子量: 192.208
• InChiKey: VUQUOGPMUUJORT-BHTRQJOGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  12
• 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：
  51.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Ethyl 6-bromo-8-[[4-[tert-butyl(dimethyl)silyl]oxybenzoyl]amino]-4-oxochromene-2-carboxylate 、 [³H]-methyl tosylate 在 potassium fluoride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成
  参考文献：
  名称：

  6-Bromo-8-(4-[³H]methoxybenzamido)-4-oxo-4H-chromene-2-carboxylic Acid: A Powerful Tool for Studying Orphan G Protein-Coupled Receptor GPR35

  摘要：

  The potent and selective GPR35 agonist 6-bromo-8-(4-methoxybenzamido)-4-oxo-4H-chromene-2-carboxylic acid (12) was obtained in tritium-labeled form, designated [H-3]PSB-13253, with a specific activity of 36 Ci (1.33 TBq)/mmol. Radiolabeling was achieved by methylation of ethyl 6-bromo-8-(4-((tert-butyldimethylsilyl)oxy)benzamido)-4-oxo-4H-Chromene-2-carboxylate (19) with [H-3]methyl tosylate followed by ester hydrolysis. The radioligand was characterized by kinetic, saturation, and competition assays at membrane preparations of Chinese hamster ovary cells recombinantly expressing the human GPR35. [H-3]12 labeled the receptor with high affinity (K-D = 5.27 nM). Binding was saturable (B-max = 12.6 pmol/mg of protein) and reversible. Affinities of selected standard ligands and a library of amidochromen-4-one-2-carboxylates were determined. Binding data mostly correlated with potencies determined in beta-arrestin assays. On the basis of the test results, several new fluorine-substituted 6-bromo-8-benzamidochromen-4-one-2-carboxylic acids were obtained, which represent the most potent GPR35 agonists known to date. 6-Bromo-8-(2,6-difluoro-4-methoxybenzamido)-4-oxo-4H-chromene-2-carboxylic acid (83; K-i = 0.589 nM, EC50 = 5.54 nM) showed the highest affinity with a K-i value in the subnanomolar range.

  DOI：

  10.1021/jm4009373

文献信息

• ISOTOPICALLY LABELED CHEMICALLY STABLE REAGENTS AND PROCESS FOR THE SYNTHESIS THEREOF
  申请人：Pounds Jerry Scot

  公开号：US20120004413A1

  公开（公告）日：2012-01-05

  A radioisotope labeled reagent includes a compound having the general formula (I), L-( a C b H 2 ) n a C 5b H 3 (I) where a in each occurrence independently is a carbon mass number between 11 and 14 inclusive, b in each occurrence independently is a hydrogen mass number between 1 and 3 inclusive, such that a in each occurrence is not 12 simultaneously with b in each occurrence being 1; L is a leaving group R 1 SO 2 —O—, R 1 —S—, 12 C 1 H 3 ( 12 C 1 H 2 ) n —S—R 1 C(O)O—, NC—, (R 1 ) 3 P—, XMg— and Li—, where n is an integer between 0 and 3 inclusive, where X is chloro, bromo or iodine, where R 1 is H, aryl, a substituent containing aryl, C 1 -C 20 alkyl, a substituent containing C 1 -C 20 alkyl, C 2 -C 20 alkenyl, a substituent containing C 2 -C 20 alkenyl, C 2 -C 20 alkynyl, and a substitute containing C 2 -C 20 alkynyl with the proviso that when n is 0, a is 13 and b is 2 and R 1 in R 1 —S is not aryl.
• 6-Bromo-8-(4-[³H]methoxybenzamido)-4-oxo-4<i>H</i>-chromene-2-carboxylic Acid: A Powerful Tool for Studying Orphan G Protein-Coupled Receptor GPR35
  作者：Dominik Thimm、Mario Funke、Anne Meyer、Christa E. Müller

  DOI：10.1021/jm4009373

  日期：2013.9.12

  The potent and selective GPR35 agonist 6-bromo-8-(4-methoxybenzamido)-4-oxo-4H-chromene-2-carboxylic acid (12) was obtained in tritium-labeled form, designated [H-3]PSB-13253, with a specific activity of 36 Ci (1.33 TBq)/mmol. Radiolabeling was achieved by methylation of ethyl 6-bromo-8-(4-((tert-butyldimethylsilyl)oxy)benzamido)-4-oxo-4H-Chromene-2-carboxylate (19) with [H-3]methyl tosylate followed by ester hydrolysis. The radioligand was characterized by kinetic, saturation, and competition assays at membrane preparations of Chinese hamster ovary cells recombinantly expressing the human GPR35. [H-3]12 labeled the receptor with high affinity (K-D = 5.27 nM). Binding was saturable (B-max = 12.6 pmol/mg of protein) and reversible. Affinities of selected standard ligands and a library of amidochromen-4-one-2-carboxylates were determined. Binding data mostly correlated with potencies determined in beta-arrestin assays. On the basis of the test results, several new fluorine-substituted 6-bromo-8-benzamidochromen-4-one-2-carboxylic acids were obtained, which represent the most potent GPR35 agonists known to date. 6-Bromo-8-(2,6-difluoro-4-methoxybenzamido)-4-oxo-4H-chromene-2-carboxylic acid (83; K-i = 0.589 nM, EC50 = 5.54 nM) showed the highest affinity with a K-i value in the subnanomolar range.