sodium 3-(1-methyl-1-phenylethyl)benzenesulfonate

• 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: sodium 3-(1-methyl-1-phenylethyl)benzenesulfonate
• 英文别名: 3-(α,α-dimethylbenzyl)benzenesulphonic acid sodium salt；3-(alpha,alpha-Dimethylbenzyl)benzenesulphonic acid sodium salt；sodium;3-(2-phenylpropan-2-yl)benzenesulfonate
• 化学式: C₁₅H₁₅O₃S*Na
• 分子量: 298.338
• InChiKey: HZQVROVQGNKIPZ-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -0.08
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  65.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  sodium 3-(1-methyl-1-phenylethyl)benzenesulfonate 在 氯化亚砜 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 5-guanidino-2(S)-[3-(1-methyl-1-phenylethyl)benzenesulfonylamino]pentanoic acid
  参考文献：
  名称：

  Design and Synthesis of Thrombin Inhibitors:  Analogues of MD-805 with Reduced Stereogenicity and Improved Potency

  摘要：

  Mitsubishi's MD-805, a potent and selective inhibitor of thrombin which contains four stereogenic centers, has been the starting point for an optimization program. A systematic synthetic study resulted in thrombin inhibit;ors achiral at P2 and P3 but with a 10-fold increase in potency over the original lead. A number of 4-substituted piperidines were synthesized and examined as replacements for 2-carboxy-4-methylpiperidine at P2; 4-fluoroethylpiperidine (FEP) among others provided inhibitors (e.g. 45g) of increased potency. An enantioselective route was developed to 3(R)-methyl-1,2,3,4-tetrahydroquinolinesulfonyl chloride. Inhibitors containing this enantiomerically pure P3 (42d) had similar potency to the racemic material and provided support, with modeling studies, for the preparation of the gem 3,3-disubstituted compounds. A series of inhibitors containing the novel 3,3-dimethyl-1,2,3,4-tetrahydroquinolinesulfonyl (DMTHQS) P3 (Table 5) were synthesized and showed a similar activity profile as the monomethyl series. The combination of P3-DMTHQS, PB-FEP, and P1-arginine (45g) had a K-i of 6 nM (MD-805 K-i = 85 nM). In animal models of both venous and arterial thrombosis, one inhibitor (42e) was shown to produce a dose-dependent inhibition of thrombus formation that in some situations was superior to that of MD-805.

  DOI：

  10.1021/jm9811209
• 作为产物：
  描述：

  次磷酸 、 2-amino-3-(1-methyl-1-phenylethyl)benzenesulfonic acid 在 盐酸 、 sodium hydroxide 、 sodium chloride 、 sodium nitrite 作用下， 以 (2S)-N-methyl-1-phenylpropan-2-amine hydrate 、 水 、 丙酮 为溶剂， 生成 sodium 3-(1-methyl-1-phenylethyl)benzenesulfonate
  参考文献：
  名称：

  Peptide derivatives corresponding to the carboxy terminal sequence of

  摘要：

  化合物的新结构如下：其中R.sup.1和R.sup.2为氢、C.sub.1 -C.sub.4烷基或连接形成C.sub.3 -C.sub.7环烷基，而R.sup.3、R.sup.4和R.sup.5相同或不同，可以是氢、C.sub.1 -C.sub.4烷基、羟基、OR.sup.6、SR.sup.6、卤素、NR.sup.7 R.sup.8、NO.sub.2、CN、CONR.sup.7 R.sup.8或CO.sub.2 R.sup.9，其中R.sup.6为C.sub.1 -C.sub.4烷基或C.sub.7 -C.sub.10芳基烷基，而R.sup.7、R.sup.8和R.sup.9相同或不同，可以是氢、C.sub.1 -C.sub.4烷基或C.sub.7 -C.sub.10芳基烷基，或者R.sup.7和R.sup.8与它们连接的氮原子形成5或6元杂环烷基或氧杂环烷基；Arg为精氨酸\x9bNH--CH(CH.sub.2 CH.sub.2 CH.sub.2 NH--C(.dbd.NH)--NH.sub.2)--CO!；X为甲烷CH或氮；n为0到7的整数；L为肽链连接剂，H为蛭素的羧基末端，以及其盐。这些新化合物可用于医学治疗或预防血栓形成或由血栓形成引起的疾病，也可用于血液中凝血酶的检测作为诊断试剂。

  公开号：

  US05686564A1

文献信息

• PEPTIDE DERIVATIVES CORRESPONDING TO THE CARBOXY TERMINAL SEQUENCE OF HIRUDIN
  申请人：CIBA-GEIGY AG

  公开号：EP0637318A1

  公开（公告）日：1995-02-08
• US5686564A
  申请人：——

  公开号：US5686564A

  公开（公告）日：1997-11-11
• [EN] PEPTIDE DERIVATIVES CORRESPONDING TO THE CARBOXY TERMINAL SEQUENCE OF HIRUDIN<br/>[FR] DERIVES PEPTIDIQUES CORRESPONDANT A LA SEQUENCE CARBOXY TERMINALE D'HIRUDINE
  申请人：CIBA-GEIGY AG

  公开号：WO1993022344A1

  公开（公告）日：1993-11-11

  (EN) Novel compounds of formula (I) in which R1 and R2 are hydrogen, C1-C4 alkyl or are linked to form C3-C7 cycloalkyl and R3, R4 and R5 are the same or different and are hydrogen, C1-C4 alkyl, hydroxy, OR6, SR6, halogen, NR7R8, NO2, CN, CONR7R8 or CO2R9 wherein R6 is C1-C4 alkyl or C7-C10 aralkyl and R7, R8 and R9 are the same or different and are hydrogen, C1-C4 alkyl or C7-C10 aralyl or R7 and R8 together with the nitrogen atom to which they are bound form 5 or 6 membered azacyloalkyl or oxazacyloalkyl; Arg is arginine [NH-CH(CH2CH2CH2NH-C(=NH)-NH2)-CO]; X is methine CH or nitrogen; n is an integer from 0 to 7; L is a peptide linker, and H is the carboxy terminal end of hirudin, and salts thereof, are provided. The novel compounds are useful for the medical treatment or prevention of thrombosis or diseases caused by thrombosis or can be used for the determination of thrombin in blood as diagnostic reagents.(FR) L'invention concerne de nouveaux composés de la formule (I) dans laquelle R1 et R2 représentent hydrogène, alkyle C1-C4 ou sont liés pour former cycloalkyle C3-C7, et R3, R4 et R5 sont identiques ou différents et représentent hydrogène, alkyle C1-C4, hydroxy, OR6, SR6, halogène, NR7R8, NO2, CN, CONR7R8 ou CO2R9 où R6 représente alkyle C1-C4 ou aralkyle C7-C10 et R7, R8 ainsi que R9 sont identiques ou différents et représentent hydrogène, alkyle C1-C4 ou aralkyle C7-C10, ou R7 ainsi que R8 avec l'atome d'azote auquel ils sont liés forment azacycloalkyle ou oxazacycloalkyle à cinq ou six éléments; Arg représente arginine [NH-CH(CH2CH2CH2NH-C(=NH)-NH2)-CO]; X représente méthine CH ou azote; n représente un nombre entier compris entre 0 et 7; L représente une liaison peptidique, et H représente l'extrémité carboxy terminale d'hirudine, ainsi que leurs sels. Les nouveaux composés sont utiles dans le traitement ou la prévention médicale de la thrombose ou de maladies provoquées par thrombose, ou bien ils peuvent être utilisés dans la détermination de thrombine dans le sang comme réactifs de diagnostic.
• Design and Synthesis of Thrombin Inhibitors:  Analogues of MD-805 with Reduced Stereogenicity and Improved Potency
  作者：Derek Brundish、Alice Bull、Vera Donovan、Joseph D. Fullerton、Sheila M. Garman、Judy F. Hayler、Diana Janus、Peter D. Kane、Mark McDonnell、Garrick P. Smith、Robert Wakeford、Clive V. Walker、Graham Howarth、William Hoyle、Mark C. Allen、John Ambler、Keith Butler、Mark D. Talbot

  DOI：10.1021/jm9811209

  日期：1999.11.1

  Mitsubishi's MD-805, a potent and selective inhibitor of thrombin which contains four stereogenic centers, has been the starting point for an optimization program. A systematic synthetic study resulted in thrombin inhibit;ors achiral at P2 and P3 but with a 10-fold increase in potency over the original lead. A number of 4-substituted piperidines were synthesized and examined as replacements for 2-carboxy-4-methylpiperidine at P2; 4-fluoroethylpiperidine (FEP) among others provided inhibitors (e.g. 45g) of increased potency. An enantioselective route was developed to 3(R)-methyl-1,2,3,4-tetrahydroquinolinesulfonyl chloride. Inhibitors containing this enantiomerically pure P3 (42d) had similar potency to the racemic material and provided support, with modeling studies, for the preparation of the gem 3,3-disubstituted compounds. A series of inhibitors containing the novel 3,3-dimethyl-1,2,3,4-tetrahydroquinolinesulfonyl (DMTHQS) P3 (Table 5) were synthesized and showed a similar activity profile as the monomethyl series. The combination of P3-DMTHQS, PB-FEP, and P1-arginine (45g) had a K-i of 6 nM (MD-805 K-i = 85 nM). In animal models of both venous and arterial thrombosis, one inhibitor (42e) was shown to produce a dose-dependent inhibition of thrombus formation that in some situations was superior to that of MD-805.
• Peptide derivatives corresponding to the carboxy terminal sequence of
  申请人：Novartis Corporation

  公开号：US05686564A1

  公开（公告）日：1997-11-11

  Novel compounds of the formula I ##STR1## in which R.sup.1 and R.sup.2 are hydrogen, C.sub.1 -C.sub.4 alkyl or are linked to form C.sub.3 -C.sub.7 cycloalkyl and R.sup.3, R.sup.4 and R.sup.5 are the same or different and are hydrogen, C.sub.1 -C.sub.4 alkyl, hydroxy, OR.sup.6, SR.sup.6, halogen, NR.sup.7 R.sup.8, NO.sub.2, CN, CONR.sup.7 R.sup.8 or CO.sub.2 R.sup.9 wherein R.sup.6 is C.sub.1 -C.sub.4 alkyl or C.sub.7 -C.sub.10 aralkyl and R.sup.7, R.sup.8 and R.sup.9 are the same or different and are hydrogen, C.sub.1 -C.sub.4 alkyl or C.sub.7 -C.sub.10 aralkyl or R.sup.7 and R.sup.8 together with the nitrogen atom to which they are bound form 5 or 6 membered azacycloalkyl or oxazacycloalkyl; Arg is arginine \x9bNH--CH(CH.sub.2 CH.sub.2 CH.sub.2 NH--C(.dbd.NH)--NH.sub.2)--CO!; X is methine CH or nitrogen; n is an integer from 0 to 7; L is a peptide linker, and H is the carboxy terminal end of hirudin, and salts thereof, are provided. The novel compounds are useful for the medical treatment or prevention of thrombosis or diseases caused by thrombosis or can be used for the determination of thrombin in blood as diagnostic reagents.

  化合物的新结构如下：其中R.sup.1和R.sup.2为氢、C.sub.1 -C.sub.4烷基或连接形成C.sub.3 -C.sub.7环烷基，而R.sup.3、R.sup.4和R.sup.5相同或不同，可以是氢、C.sub.1 -C.sub.4烷基、羟基、OR.sup.6、SR.sup.6、卤素、NR.sup.7 R.sup.8、NO.sub.2、CN、CONR.sup.7 R.sup.8或CO.sub.2 R.sup.9，其中R.sup.6为C.sub.1 -C.sub.4烷基或C.sub.7 -C.sub.10芳基烷基，而R.sup.7、R.sup.8和R.sup.9相同或不同，可以是氢、C.sub.1 -C.sub.4烷基或C.sub.7 -C.sub.10芳基烷基，或者R.sup.7和R.sup.8与它们连接的氮原子形成5或6元杂环烷基或氧杂环烷基；Arg为精氨酸\x9bNH--CH(CH.sub.2 CH.sub.2 CH.sub.2 NH--C(.dbd.NH)--NH.sub.2)--CO!；X为甲烷CH或氮；n为0到7的整数；L为肽链连接剂，H为蛭素的羧基末端，以及其盐。这些新化合物可用于医学治疗或预防血栓形成或由血栓形成引起的疾病，也可用于血液中凝血酶的检测作为诊断试剂。