(1-甲基-1H-咪唑-2-基)-乙酸 | 118054-54-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: (1-甲基-1H-咪唑-2-基)-乙酸
• 英文名称: 1-methyl-4-imidazoleacetic acid
• 英文别名: (1-methyl-1H-imidazol-2-yl)acetic acid；(1H-1-methylimidazol-2-yl)acetic acid；(1-Methyl-1h-imidazol-2-yl)-acetic acid；2-(1-methylimidazol-2-yl)acetic acid
• CAS: 118054-54-9
• 化学式: C₆H₈N₂O₂
• 分子量: 140.142
• InChiKey: MGIKMFCKRKDEIK-UHFFFAOYSA-N

物化性质

• 熔点：
  112 - 117°C
• 溶解度：
  可溶于DMSO（略微加热）、甲醇（略微加热）

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933290090

反应信息

• 作为反应物：
  描述：

  (1-甲基-1H-咪唑-2-基)-乙酸 在 磷酸 、 三氯化磷 作用下， 以 氯苯 为溶剂， 反应 3.0h， 以46%的产率得到2-(1-methylimidazol-2-yl)-1-hydroxyethane-1,1-diphosphonic acid
  参考文献：
  名称：

  Highly Potent Geminal Bisphosphonates. From Pamidronate Disodium (Aredia) to Zoledronic Acid (Zometa)

  摘要：

  Bisphosphonates (BP) are pyrophosphate analogues in which the oxygen in P-O-P has been replaced by a carbon, resulting in a metabolically stable P-C-P structure. Pamidronate (1b, Novartis), a second-generation BP, was the starting point for extensive SAR studies. Small changes of the structure of pamidronate lead to marked improvements of the inhibition of osteoclastic resorption potency. Alendronate (1c, MSD), with an extra methylene group in the N-alkyl chain, and olpadronate (1h, Gador), the N,N-dimethyl analogue, are about 10 times more potent than pamidronate. Extending one of the N-methyl groups of olpadronate to a pentyl substituent leads to ibandronate (1k, Roche, Boehringer-Mannheim), which is the most potent close analogue of pamidronate. Even slightly better antiresorptive potency is achieved with derivatives having a phenyl group linked via a short aliphatic tether of three to four atoms to nitrogen, the second substituent being preferentially a methyl group (e.g., 4g, 4j, 5d, or 5r). The most potent BPs are found in the series containing a heteroaromatic moiety (with at least one nitrogen atom), which is linked via a single methylene group to the geminal bisphosphonate unit. Zoledronic acid (6i), the most potent derivative, has an ED50 of 0.07 mg/kg in the TPTX in vivo assay after sc administration. It not only shows by far the highest therapeutic ratio when comparing resorption inhibition with undesired inhibition of bone mineralization but also exhibits superior renal tolerability. Zoledronic acid (6i) has thus been selected for clinical development under the registered trade name Zometa. The results of the clinical trials indicate that low doses are both efficacious and safe for the treatment of tumor-induced hypercalcemia, Paget's disease of bone, osteolytic metastases, and postmenopausal osteoporosis.

  DOI：

  10.1021/jm020819i

文献信息

• [EN] SPIRO-FUSED TRICYCLIC MAP4K1 INHIBITORS<br/>[FR] INHIBITEURS DE MAP4K1 TRICYCLIQUES SPIRO FUSIONNÉS
  申请人：BAYER AG

  公开号：WO2021074279A1

  公开（公告）日：2021-04-22

  The present invention relates to Map4K1 inhibitors of formula (I) to pharmaceutical compositions and combinations comprising the compounds according to the invention, and to the prophylactic and therapeutic use of the inventive compounds, respectively to the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular for neoplastic disorders, repectively cancer or conditions with dysregulated immune responses or other disorders associated with aberrant MAP4K1 signaling, as a sole agent or in combination with other active ingredients. The present invention further relates to the use, respectively to the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of protein inhibitors in benign hyperplasias, atherosclerotic disorders, sepsis, autoimmune disorders, vascular disorders, viral infections, in neurodegenerative disorders, in inflammatory disorders, in atherosclerotic disorders and in male fertility control.

  本发明涉及式(I)的Map4K1抑制剂，以及包含根据本发明的化合物的药物组合物和组合物，以及创新化合物的预防性和治疗性用途，分别用于制造用于治疗或预防疾病的药物组合物，特别是用于肿瘤性疾病，癌症或与异常MAP4K1信号相关的其他紊乱免疫反应或其他紊乱的疾病，作为单一药剂或与其他活性成分组合使用。本发明还涉及使用，分别用于制造用于治疗或预防良性增生、动脉粥样硬化疾病、败血症、自身免疫疾病、血管疾病、病毒感染、神经退行性疾病、炎症性疾病、动脉粥样硬化疾病和男性生育控制的蛋白抑制剂的药物组合物的用途。
• Inhibitors of protein isoprenyl transferases
  申请人：University of Pittsburgh

  公开号：US20020193596A1

  公开（公告）日：2002-12-19

  Compounds having the formula 1 or a pharmaceutically acceptable salt thereof wherein R 1 is (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkoxy, (e) thioalkoxy, (f) halo, (g) haloalkyl, (h) aryl-L 2 —, and (i) heterocyclic-L 2 —; R 2 is selected from (a) 2 (b) —C(O)NH—CH(R 14 )—C(O)OR 15 , (c) 3 (d) —C(O)NH—CH(R 14 )—C(O)NHSO 2 R 16 (e) —C(O)NH—CH(R 14 )-tetrazolyl, (f) —C(O)NH-heterocyclic, and (g) —C(O)NH—CH(R 14 )—C(O)NR 17 R 18 ; R 3 is heterocyclic, aryl, substituted or unsubstituted cycloalkyl; R 4 is hydrogen, lower alkyl, haloalkyl, halogen, aryl, arylakyl, heterocyclic, or (heterocyclic)alkyl; L 1 is absent or is selected from (a) —L 4 —N(R 5 )—L 5 —, (b) —L 4 —O—L 5 —, (c) —L 4 —S(O) n —L 5 — (d) —L 4 -L 6 —C(W)—N(R 5 )—L 5 —, (e) —L 4 -L 6 —S(O) m —N(R 5 )—L 5 —, (f) —L 4 —N(R 5 )—C(W)—L 7 -L 5 —, (g) —L 4 —N(R 5 )—S(O) p —L 7 —L 5 —, (h) optionally substituted alkylene, (i) optionally substituted alkenylene, and (j) optionally substituted alkynylene are inhibitors of protein isoprenyl transferases. Also disclosed are protein isoprenyl transferase inhibiting compositions and a method of inhibiting protein isoprenyl transferases.

  具有以下公式的化合物或其药学上可接受的盐，其中R1为(a)氢，(b)较低的烷基，(c)烯基，(d)烷氧基，(e)硫代烷氧基，(f)卤素，(g)卤代烷基，(h)芳基-L2—，以及(i)杂环-L2—；R2从(a)中选择，(b) -C(O)NH-CH(R14)-C(O)OR15，(c)中选择，(d) -C(O)NH-CH(R14)-C(O)NHSO2R16，(e) -C(O)NH-CH(R14)-四唑基，(f) -C(O)NH-杂环，以及(g) -C(O)NH-CH(R14)-C(O)NR17R18；R3为杂环，芳基，取代或未取代的环烷基；R4为氢，较低烷基，卤代烷基，卤素，芳基，芳基烷基，杂环基，或(杂环)烷基；L1为空缺或从(a) -L4-N(R5)-L5-，(b) -L4-O-L5-，(c) -L4-S(O)n-L5-，(d) -L4-L6-C(W)-N(R5)-L5-，(e) -L4-L6-S(O)m-N(R5)-L5-，(f) -L4-N(R5)-C(W)-L7-L5-，(g) -L4-N(R5)-S(O)p-L7-L5-，(h)可选择取代的烷基，(i)可选择取代的烯基，以及(j)可选择取代的炔基是蛋白异戊二烯转移酶的抑制剂。还公开了蛋白异戊二烯转移酶抑制组合物和抑制蛋白异戊二烯转移酶的方法。
• CYCLIC AMINE DERIVATIVE AND MEDICAL USE THEREOF
  申请人：Toray Industries, Inc.

  公开号：US20180370916A1

  公开（公告）日：2018-12-27

  A compound has retinoid-related orphan receptor γ antagonist activity and shows a therapeutic effect or a preventive effect on autoimmune diseases such as multiple sclerosis or psoriasis or allergic diseases, including allergic dermatitis or the like, such as contact dermatitis or atopic dermatitis. The cyclic amine derivative is represented by the formula or a pharmacologically acceptable salt thereof.

  一种化合物具有类视黄醇相关孤儿受体γ拮抗活性，并对自身免疫性疾病如多发性硬化或牛皮癣或过敏性疾病，包括过敏性皮炎等，如接触性皮炎或特应性皮炎等，显示治疗效果或预防效果。该环胺衍生物由以下公式或其药理学可接受的盐表示。
• THERAPEUTIC PIPERAZINES
  申请人：Kaplan Alan P.

  公开号：US20110065691A1

  公开（公告）日：2011-03-17

  The invention includes a compound of formula I: wherein R 1 , Y, A, n, R 4 and Z have any of the values described herein, as well as salts of such compounds, compositions comprising such compounds, and therapeutic methods that comprise the administration of such compounds. The compounds are inhibitors of PDE4 function and are useful for improving cognitive function and/or treating cognitive disorders or impairment, traumatic and/or ischemic injuries of the central and peripheral nervous system and/or psychiatric disorders in animals, especially humans.

  本发明涉及公式I的化合物：其中R1，Y，A，n，R4和Z具有本文所述的任何值，以及这些化合物的盐，包含这些化合物的组合物和治疗方法，包括给予这些化合物的管理。这些化合物是PDE4功能抑制剂，对于改善认知功能和/或治疗动物（特别是人类）的认知障碍或损伤、中枢和周围神经系统的创伤性和/或缺血性损伤和/或精神障碍非常有用。
• Carbostyril derivatives, process for preparing them, pharmaceutical composition, and use
  申请人：OTSUKA PHARMACEUTICAL CO., LTD.

  公开号：EP0240015A2

  公开（公告）日：1987-10-07

  Carbostyril derivatives and salts thereof represented by the general formula (1), including some known compounds, possess activities for inhibiting adhesion of thrombocytes. Some carbostyril derivatives having chemical structural formulas similar to those of carbostyril derivatives and salts thereof represented by the general formula (1) have been known in the prior art references, however above-mentioned pharmacological activities have not been known yet up to the date. Processes for preparing carbostyril derivatives offormu- la (1), a pharmaceutical composition containing them, or a salt thereof, as active ingredient, and their use in the preparation of a medicament for inhibiting adhesion of thrombocytes are also disclosed.

  通式(1)代表的羧基吡啶衍生物及其盐类，包括一些已知化合物，具有抑制血小板粘附的活性。 一些羧基吡啶衍生物的化学结构式与通式(1)代表的羧基吡啶衍生物及其盐类相似，在现有技术参考文献中已为人所知，但上述药理活性至今尚未为人所知。 本发明还公开了制备通式(1)代表的羧基吡啶衍生物、含有它们或其盐类作为活性成分的药物组合物的工艺，以及它们在制备抑制血小板粘附的药物中的用途。