1-amidino-3,5-dimethylpyrazole acetate | 78060-73-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-amidino-3,5-dimethylpyrazole acetate
• 英文别名: Acetic acid;3,5-dimethylpyrazole-1-carboximidamide
• CAS: 78060-73-8
• 化学式: C₂H₄O₂*C₆H₁₀N₄
• 分子量: 198.225
• InChiKey: TXXQKMIEBUHQGW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.33
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-amidino-3,5-dimethylpyrazole acetate 、 H-Tyr-D-Arg-Gly-4-nitro-L-phenylalanyl-Pro-NH2 diacetate 在 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 以42%的产率得到N1-amidino-L-tyrosyl-D-arginylglycyl-L-4-nitrophenylalanyl-L-prolinamide diacetate
  参考文献：
  名称：

  Peripherally acting enkephalin analogs. 1. Polar pentapeptides

  摘要：

  The design, synthesis, and biological activity of a series of highly polar enkephalin-related pentapeptides are reported. These analogues incorporate structural features that exclude them from the central nervous system and thereby restrict their action to peripherally located receptors. Hydrophilic analogues were obtained by introduction of polar D-amino acid residues at position 2 and, in certain cases, by conversion of the N-terminal amino group of the Tyr residue to a guanidino function. The peptides were synthesized by classical solution methods. All compounds demonstrated in vitro opioid activity in the GPI and all were shown to possess antinociceptive activity in chemically induced writhing models. The analgesic effects were shown to be predominantly peripherally mediated by antagonism of antinociception with the peripheral antagonist N-methylnalorphine. Comparative data obtained in writhing and hot-plate tests were also supportive of a peripheral mode of action. Compound 13a, L-tyrosyl-D-arginylglycyl-L-4-nitrophenylalanyl-L-prolinamide (BW 443C), was identified as having a favorable pharmacological profile, indicating a high level of peripheral selectivity, and worthy of further investigation.

  DOI：

  10.1021/jm00400a012
• 作为试剂：
  描述：

  ((S)-2-{(R)-2-[(S)-2-Amino-3-(4-hydroxy-phenyl)-propionylamino]-propionylamino}-3-phenyl-propionylamino)-acetic acid methyl ester; compound with acetic acid 在 1-amidino-3,5-dimethylpyrazole acetate 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 ((S)-2-{(R)-2-[(S)-2-Guanidino-3-(4-hydroxy-phenyl)-propionylamino]-propionylamino}-3-phenyl-propionylamino)-acetic acid methyl ester
  参考文献：
  名称：

  Salvadori; Sarto; Tomatis, European Journal of Medicinal Chemistry, 1983, vol. 18, # 6, p. 489 - 493

  摘要：

  DOI：

文献信息

• Pharmaceutical compounds, preparation, use and intermediates therefor and their preparation
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0085963A2

  公开（公告）日：1983-08-17

  Novel peptides of formula (I) and salts thereof, wherein X is hydrogen or an amidino group and X2 is a radical selected from D-S-methylmethionyl and D-arginyl, have a selectively peripheral analgesic effect when administered to mammals. The compounds also exhibit antidiarrhoeal and antitussive activity and may thus be used in human or veterinary medicine for the relief or prevention of pain, for the treatment of diarrhoea or dysentery and for the suppression of cough.

  式(I)的新型多肽及其盐类，其中 X 是氢或脒基，X2 是选自 D-S-甲基蛋氨酰和 D-精氨酰的基团，在给哺乳动物用药时具有选择性外周镇痛作用。 这些化合物还具有止泻和止咳活性，因此可用于人类或兽医领域，以缓解或预防疼痛、治疗腹泻或痢疾以及抑制咳嗽。
• Pharmaceutical peptides, preparation, use and intermediates
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0127154A2

  公开（公告）日：1984-12-05

  Novel peptides of formula (I) wherein R' is hydrogen, alkyl of 1 or 2 carbon atoms or an amidino group, R2 is alkyl of 1 or 2 carbon atoms, R3 is hydrogen or carbamyl, X2 is a D-radical having the structure: Z1 and Z2 are the same or different and each is hydrogen, halo, nitro or trifluoromethyl and at least one is other than hydrogen, m is 2, 3 or 4 and n is 0,1 or 2, provided that when R' is carbamyl then n is always 1; and salts thereof. The compounds have a selectively peripheral analgesic effect when administered to mammals and also exhibit antidiarrhoeal and antitussive activity and may thus be used in human or veterinary medicine for the relief or prevention of pain, for the treatment of diarrhoea or dysentery and for the suppression of cough.

  式(I)的新型多肽 其中 R' 是氢、1 或 2 个碳原子的烷基或脒基、 R2 是 1 或 2 个碳原子的烷基 R3 是氢或氨甲酰、 X2 是具有以下结构的 D-自由基 Z1 和 Z2 相同或不同，各自为氢、卤素、硝基或三氟甲基，且至少有一个不是氢、 m 是 2、3 或 4，以及 n 为 0、1 或 2、 但当 R' 为氨基甲酰基时，n 始终为 1；及其盐类。 这些化合物对哺乳动物具有选择性外周镇痛作用，还具有止泻和止咳活性，因此可用于人类或兽医领域，以缓解或预防疼痛、治疗腹泻或痢疾以及抑制咳嗽。
• Peripherally acting enkephalin analogs. 2. Polar tri- and tetrapeptides
  作者：George W. Hardy、Lawrence A. Lowe、Gail Mills、Pang Yih Sang、Dean S. A. Simpkin、Rhonda L. Follenfant、Clare Shankley、Terence W. Smith

  DOI：10.1021/jm00125a028

  日期：1989.5

  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.
• Synthesis and activity profiles of new dermorphin-(1-4) peptide analogs
  作者：Mauro Marastoni、Severo Salvadori、Gianfranco Balboni、Pier Andrea Borea、Giuliano Marzola、Roberto Tomatis

  DOI：10.1021/jm00392a002

  日期：1987.9

  A new series of 12 dermorphin tetrapeptides, W-Tyr-D-MetO-Phe-Xaa-Y (W = H, H2NC = (NH); Xaa = Gly, Sar, D-Ala; Y = OH, OCH3, NH2) were prepared by traditional methods in solution and tested for opioid activity. In binding studies based on displacement of mu, delta, and kappa opioid receptor selective radiolabels from guinea pig brain membranes, the new analogues showed a negligible affinity for the kappa binding site and a preference for mu- over delta-receptors with an evident dependence on N- and/or C-terminal modifications; H-Tyr-D-MetO-Phe-Gly-OCH3 was shown to be one of the most selective mu-receptor ligands reported to date. All these tetrapeptides display dose-related naloxone-reversible antinociceptive effects following intracerebroventricular (icv) or subcutaneous (sc) administrations in mice. In comparison to morphine, H-Tyr-D-MetO-Phe-Sar-NH2 and the guanidino derivative H2NC = (NH)-Tyr-D-MetO-Phe-Gly-NH2 showed lower affinity for mu, delta, and kappa sites but exceptionally stronger analgesia: respectively they are 560 and 1550 times as potent an analgesic as morphine. Among analogues tested after sc administration, H-Tyr-D-MetO-Phe-Sar-NH2 and H-Tyr-D-MetO-Phe-D-Ala-OH displayed the highest activities; they were respectively 22 and 30 times more potent than morphine on a molar basis. These results indicate that N- or C-terminal modifications and substitution at position 2 or 4 of dermorphin-(1-4) peptide do not only influence the affinity of the resulting analogues to opioid receptors but also may favorably alter their pharmacokinetic properties.
• Marastoni; Balboni; Tomatis, Il Farmaco, 1989, vol. 44, # 11, p. 1083 - 1093
  作者：Marastoni、Balboni、Tomatis、Salvadori、Borea、Uccelli

  DOI：——

  日期：——