Boc Tyr D.Met OH | 108329-67-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Boc Tyr D.Met OH
• 英文别名: N-(tert-Butyloxycarbonyl)-L-tyrosyl-D-methionine；N-[N-[(1,1-dimethylethoxy)carbonyl]-L-tyrosyl]-D-methionine；(2R)-2-[[(2S)-3-(4-hydroxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]-4-methylsulfanylbutanoic acid
• CAS: 108329-67-5
• 化学式: C₁₉H₂₈N₂O₆S
• 分子量: 412.507
• InChiKey: AXWCTMRSTMTNHF-CABCVRRESA-N

物化性质

• 熔点：
  76 °C (decomp)
• 沸点：
  706.3±60.0 °C(Predicted)
• 密度：
  1.250±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  150
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Boc Tyr D.Met OH 在 sodium hydroxide 、 水 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 formamide 、 N,N-二甲基甲酰胺 为溶剂， 生成 Boc Tyr D.Met Gly Phe Pro OMe
  参考文献：
  名称：

  Audigier; Mazarguil; Gout, European Journal of Medicinal Chemistry, 1980, vol. 15, # 2, p. 173 - 177

  摘要：

  DOI：
• 作为产物：
  描述：

  D-methionine methyl ester 在 sodium hydroxide 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 Boc Tyr D.Met OH
  参考文献：
  名称：

  Peripherally acting enkephalin analogs. 2. Polar tri- and tetrapeptides

  摘要：

  The design, synthesis, and biological activity of a series of D-Arg2-enkephalin-derived tetrapeptide amides and tripeptide aralkylamides are reported. These polar analogues were designed to be excluded from the central nervous system with their action thus limited to peripheral opioid receptors. The effects of the nature of the aromatic ring, aryl ring substitution, and aralkylamine chain length on activity were investigated; in a number of cases the N-terminal amino group of Tyr1 was converted to a guanidino group to further increase hydrophilicity. The peptides were all synthesized by classical solution methodology. The opioid activity of the peptides was assessed in vitro on the guinea pig ileum and their antinociceptive activity was determined in vivo in chemically induced writhing models (peripheral activity) and in the hot-plate test (central activity), in rodents. That the analgesic effects were predominantly mediated in the periphery was demonstrated by antagonism of antinociception by the peripheral opioid antagonist N-methylnalorphine and by comparison of the activities in the writhing and hot-plate tests. As a class, the tetrapeptides were more potent than the tripeptides; N alpha-amidination generally increased activity. A number of compounds exhibited very potent opioid activity and had the desired pharmacological profile, indicating a high degree of peripheral selectivity.

  DOI：

  10.1021/jm00125a028

文献信息

• Sulfide, sulfinyl and sulfone dipeptide amides
  申请人：G. D. Searle & Co.

  公开号：US04757153A1

  公开（公告）日：1988-07-12

  The invention relates to novel substituted tyrosyl alanine dipeptide amides of the formula: ##STR1## and the pharmaceutically acceptable acid addition salts thereof wherein R.sup.1 is hydrogen, lower alkyl, hydroxy, lower alkoxy, --O(CH.sub.2).sub.n phenyl with the phenyl optionally substituted by halogen, --NO.sub.2, --CN, --NH.sub.2 or lower alkyl wherein n is 1 to 4; R.sup.2 and R.sup.3 represent lower alkyl, halogen, or lower alkoxy, or either one of R.sup.2 or R.sup.3 is hydrogen and the other is lower alkyl, lower alkoxy or halogen; R.sup.4, R.sup.5, R.sup.6, and R.sup.9 may be the same or different and represent hydrogen, lower alkyl, cycloalkyl having 3 to 8 carbons, unsaturated lower alkyl, or --(CH.sub.2).sub.m cycloalkyl with the cycloalkyl having 3 to 8 carbons and m is 1 to 4; R.sup.10 is hydrogen or --(CH.sub.2).sub.p phenyl or with the phenyl optionally substituted with --NH.sub.2, --OH, halogen, --NO.sub.2, or lower alkyl or --(CH.sub.2).sub.p thienyl wherein p is 1 to 4; one of R.sup.7 or R.sup.8 is --(CH.sub.2).sub.f --S(O).sub.z --(CH.sub.2).sub.q --CH.sub.3 where f is 1 to 3 and q is 0 to 3, z is 0, 1 or 2 and the other is hydrogen or lower alkyl, or R.sup.7 and R.sup.8 together with carbon w is ##STR2## where x and y are independently 1 to 3 and z is 0, or 2. V represents an asymmetric carbon that may be recemic or have the D or L configuration; W represents an asymmetric carbon when R.sup.7 and R.sup.8 are not the same that may be recemic or have the D or L configuration. The compounds of this invention are useful as analgesic and/or antihypertensive agents.

  这项发明涉及一种新型的取代基酪氨酸丙氨酸二肽酰胺，其化学式为：##STR1##以及其药用可接受的酸盐，其中R.sup.1为氢、较低烷基、羟基、较低烷氧基、--O(CH.sub.2).sub.n苯基，其中苯基可选择地被卤素、--NO.sub.2、--CN、--NH.sub.2或较低烷基取代，其中n为1到4；R.sup.2和R.sup.3代表较低烷基、卤素或较低烷氧基，或者R.sup.2或R.sup.3中的一个为氢，另一个为较低烷基、较低烷氧基或卤素；R.sup.4、R.sup.5、R.sup.6和R.sup.9可以相同或不同，代表氢、较低烷基、具有3到8个碳的环烷基、不饱和较低烷基，或--(CH.sub.2).sub.m环烷基，其中环烷基具有3到8个碳，m为1到4；R.sup.10为氢或--(CH.sub.2).sub.p苯基，或者该苯基可选择地被--NH.sub.2、--OH、卤素、--NO.sub.2或较低烷基或--(CH.sub.2).sub.p噻吩基取代，其中p为1到4；R.sup.7或R.sup.8中的一个为--(CH.sub.2).sub.f --S(O).sub.z --(CH.sub.2).sub.q --CH.sub.3，其中f为1到3，q为0到3，z为0、1或2，另一个为氢或较低烷基，或者R.sup.7和R.sup.8连同碳w为##STR2##其中x和y独立地为1到3，z为0或2。V代表一个可能是外消旋的或具有D或L构型的不对称碳；W代表一个不对称碳，当R.sup.7和R.sup.8不相同时，可能是外消旋的或具有D或L构型的。本发明的化合物可用作镇痛和/或降压剂。
• Substituted dipeptide amides
  申请人：G.D. Searle & Co.

  公开号：EP0212550A2

  公开（公告）日：1987-03-04

  The invention relates to novel substituted tyrosyl alanine dipeptide amides of the formula: and the pharmaceutically acceptable acid addition salts thereof wherein R¹ is hydrogen, lower alkyl, hydroxy, lower alkoxy, -O(CH₂)nphenyl with the phenyl optionally substituted by halogen, -NO₂, -CN, -NH₂ or lower alkyl wherein n is 1 to 4; R² and R³ represent lower alkyl, halogen, or lower alkoxy, or either one of R² or R³ is hydrogen and the other is lower alkyl, lower alkoxy or halogen; R⁴, R⁵, R⁶, and R⁹ may be the same or different and represent hydrogen, lower alkyl, cycloalkyl having 3 to 8 carbons, unsaturated lower alkyl, or -(CH₂)mcycloalkyl with the cycloalkyl having 3 to 8 carbons and m is 1 to 4; R10 is hydrogen or -(CH₂)pphenyl or with the phenyl optionally substituted with -NH₂, -OH, halogen, -NO₂, or lower alkyl or -(CH₂)p thienyl wherein p is 1 to 4; one of R⁷ or R⁸ is -(CH₂)f-S(O)z-(CH₂)q-CH₃ where f is 1 to 3 and q is 0 to 3, z is 0, 1 or 2 and the other is hydrogen or lower alkyl, or R⁷ and R⁸ together with carbon w is where x and y are independently 1 to 3 and z is 0, or 2. V represents an asymmetric carbon that may be recemic or have the D or L configuration; W represents an asymmetric carbon when R⁷ and R⁸ are not the same that may be recemic or have the D or L configuration. The compounds of this invention are useful as analgesic and/or antihypertensive agents.

  本发明涉及式如下的新型取代酪氨丙氨酸二肽酰胺： 及其药学上可接受的酸加成盐 其中 R¹ 是氢、低级烷基、羟基、低级烷氧基、-O(CH₂)n 苯基，其中苯基可选择被卤素、-NO₂、-CN、-NH₂ 或低级烷基取代，其中 n 是 1 至 4；R² 和 R³ 代表低级烷基、卤素或低级烷氧基，或者 R² 或 R³ 中的一个是氢，另一个是低级烷基、低级烷氧基或卤素；R⁴、R⁵、R⁶ 和 R𠞙 可以相同或不同，代表氢、低级烷基、具有 3 至 8 个碳原子的环烷基、不饱和低级烷基或-(CH₂)m 环烷基，其中环烷基具有 3 至 8 个碳原子，m 为 1 至 4；R10 是氢或-(CH₂)对苯基或被-NH₂、-OH、卤素、-NO₂或低级烷基或-(CH₂)p 噻吩基任选取代的苯基，其中 p 为 1 至 4；R⁷ 或 R⁸ 中的一个是-(CH₂)f-S(O)z-(CH₂)q-CH₃，其中 f 为 1 至 3，q 为 0 至 3，z 为 0、1 或 2，另一个是氢或低级烷基，或 R⁷ 和 R⁸ 连同碳 w 是 其中 x 和 y 独立地为 1 至 3，z 为 0 或 2。V 代表不对称碳，可以是可接受的或具有 D 或 L 构型；W 代表 R⁷ 和 R⁸ 不相同时的不对称碳，可以是可接受的或具有 D 或 L 构型。 本发明的化合物可用作镇痛剂和/或抗高血压剂。
• HANSEN, DONALD W. (JR);PILIPAUSKAS, DANIEL R.;CLARE, MICHAEL
  作者：HANSEN, DONALD W. (JR)、PILIPAUSKAS, DANIEL R.、CLARE, MICHAEL

  DOI：——

  日期：——
• HARDY, GEORGE W.;LOWE, LAWRENCE A.;MILLS, GAIL;PANG, YIH SANG;SIMPKIN, DE+, J. MED. CHEM., 32,(1989) N, C. 1108-1118
  作者：HARDY, GEORGE W.、LOWE, LAWRENCE A.、MILLS, GAIL、PANG, YIH SANG、SIMPKIN, DE+

  DOI：——

  日期：——
• US4757153A
  申请人：——

  公开号：US4757153A

  公开（公告）日：1988-07-12