CGS 27023 hydrochloride | 169799-04-6

• 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: CGS 27023 hydrochloride
• 英文别名: MMI-270；N-hydroxy-2(R)-{[(4-methoxyphenyl)sulfonyl](3-picolyl)amino}-3-methylbutanamide hydrochloride；Butanamide, N-hydroxy-2-(((4-methoxyphenyl)sulfonyl)(3-pyridinylmethyl)amino)-3-methyl-, hydrochloride (1:1), (2R)-；(2R)-N-hydroxy-2-[(4-methoxyphenyl)sulfonyl-(pyridin-3-ylmethyl)amino]-3-methylbutanamide;hydrochloride
• CAS: 169799-04-6
• 化学式: C₁₈H₂₃N₃O₅S*ClH
• 分子量: 429.925
• InChiKey: ZVYIZSNCEAHMCF-UNTBIKODSA-N

物化性质

• 熔点：
  156-158 °C

计算性质

• 辛醇/水分配系数(LogP)：
  2.23
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  117
• 氢给体数：
  3
• 氢受体数：
  7

制备方法与用途

CGS 27023A(MMI 270)是一种有效的口服活性MMP抑制剂，其对MMP1、MMP2、MMP3和MMP9的Ki值在8至43纳摩尔之间。

反应信息

• 作为产物：
  描述：

  D-缬氨酸 在 N-甲基吗啉 、 盐酸 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 103.0h， 生成 CGS 27023 hydrochloride
  参考文献：
  名称：

  Discovery of CGS 27023A, a Non-Peptidic, Potent, and Orally Active Stromelysin Inhibitor That Blocks Cartilage Degradation in Rabbits

  摘要：

  Structure-activity relationships of a lead hydroxamic acid inhibitor of recombinant human stromelysin were systematically defined by taking advantage of a concise synthesis that allowed diverse functionality to be explored at each position in a template. An ex vivo rat model and an in vivo rabbit model of stromelysin-induced cartilage degradation were used to further optimize these analogs for oral activity and duration of action. The culmination of these modifications resulted in CGS 27023A, a potent, orally active stromelysin inhibitor that blocks the erosion of cartilage matrix.

  DOI：

  10.1021/jm960871c

文献信息

• [EN] ARYLSULFONAMIDO-SUBSTITUTED HYDROXAMIC ACIDS AS MATRIX METALLOPROTEINASE INHIBITORS<br/>[FR] ACIDES HYDROXAMIQUES SUBSTITUES PAR ARYLSULFONAMINO UTILISES COMME INHIBITEURS DE METALLOPROTEINASES MATRICIELLES
  申请人：CIBA-GEIGY AG

  公开号：WO1996000214A1

  公开（公告）日：1996-01-04

  (EN) Compounds of formula (I) wherein R, R1, R2 and Ar are as defined in the specification, have valuable pharmaceutical properties and are effective especially as matrix metalloproteinase inhibitors, for example for the treatment of arthritis. They are prepared in a manner known per se.(FR) L'invention se rapporte à des composés de la formule (I) dans laquelle R, R1, R2 et Ar sont tels que définis dans la demande. Ces composés ont de précieuses propriétés pharmaceutiques et sont notamment efficaces comme inhibiteurs de métalloprotéinases matricielles, par exemple, dans le traitement de l'arthrite. Ils sont préparés d'une manière connue en soi.

  (EN) 公式(I)中的化合物，其中R、R1、R2和Ar的定义如规范中所述，具有有价值的药物特性，特别是作为基质金属蛋白酶抑制剂，例如用于治疗关节炎。它们以已知的方式制备。 (FR) 公式(I)中的化合物，其中R、R1、R2和Ar的定义如申请中所述，具有有价值的药物特性，特别是作为基质金属蛋白酶抑制剂，例如用于治疗关节炎。它们以已知的方式制备。
• Arylsulfonamido-substituted hydroxamix acids
  申请人：Ciba-Geigy Corporation

  公开号：US05646167A1

  公开（公告）日：1997-07-08

  Disclosed are compounds of formula I ##STR1## wherein R, R.sub.1, R.sub.2 and Ar have meanings as defined; pharmaceutically acceptable prodrug derivatives and pharmaceutically acceptable salts thereof; methods for preparation thereof; pharmaceutical compositions comprising said compounds; and methods of inhibiting matrix-degrading metalloproteinase and of treating matrix-degrading metalloproteinase dependent conditions in mammals using such compounds.

  本文揭示了式I的化合物，其中R，R1，R2和Ar具有定义的含义；药学上可接受的前药衍生物和其药学上可接受的盐；其制备方法；包括所述化合物的制药组合物；以及使用这些化合物抑制基质降解金属蛋白酶和治疗哺乳动物中基质降解金属蛋白酶依赖的情况的方法。
• THERAPEUTIC BENEFIT OF SUBOPTIMALLY ADMINISTERED CHEMICAL COMPOUNDS
  申请人：BROWN Dennis M.

  公开号：US20160045502A1

  公开（公告）日：2016-02-18

  The present invention describes methods and compositions for improving the therapeutic efficacy of therapeutic agents previously limited by suboptimal therapeutic performance by either improving efficacy as monotherapy or reducing side effects. Such methods and compositions are particularly applicable to mustard-based alkylating agents such as uracil mustard and analogs, derivatives, or prodrugs thereof, including 6-methyluracil mustard and 6-ethyluracil mustard.

  本发明描述了一种改善先前受到治疗性能不佳限制的治疗剂的治疗效果的方法和组合物，通过改善单药疗法的功效或减少副作用。这种方法和组合物特别适用于芥子碱基烷基化剂，例如尿嘧啶芥和其类似物、衍生物或前药，包括6-甲基尿嘧啶芥和6-乙基尿嘧啶芥。
• THERAPEUTIC AGENTS FOR ALLERGIC DISEASES
  申请人：FUJI YAKUHIN KOGYO KABUSHIKI KAISHA

  公开号：EP1101496A1

  公开（公告）日：2001-05-23

  Disclosed are anti-inflammatory agents, antiallergic agents, particularly prophylactically and/or therapeutically effective drugs for type I and/or IV allergic conditions, and further pharmaceutical drugs for prophylactically and/or therapeutically treating bronchial asthma, atopic diseases, etc. The inventive drugs comprising a prophylactically and/or therapeutically effective amount of a metalloproteinase inhibitor are active in the prophylaxis and/or therapy of allergy, especially type I and/or IV allergy, etc. The drugs are active in prophylactically and/or therapeutically treating inflammation, rhinitis, conjunctivitis, bronchial asthma, atopic diseases (including dermatitis, enteritis, etc.), or allergic gastroenterocolitis (allergic inflammation in digestive tract). The application of such drugs leads to (A) reduction of cells (such as lymphocytes, neutrophils, mast cells, eosinophils, basophils, macrophages and monocytes) at a diseased site, and/or (B) alleviation of inflammatory symptoms caused by migration, infiltration or accumulation of cells (such as lymphocytes, neutrophils, mast cells, eosinophils, basophils, macrophages and monocytes) to (or at) the diseased site, (C) inhibition of pathophysiological functions in cells (such as lymphocytes, neutrophils, mast cells, eosinophils, basophils, macrophages, monocytes, Langerhans cell and dendritic cells), and/or (D) reducing the blood level or inhibiting the production, of antibodies, especially IgE. Accordingly, the drugs are useful in the prophylaxis and/or therapy of diseases, disorders or ill conditions at the site.

  本发明公开了抗炎剂、抗过敏剂，特别是预防和/或治疗 I 型和/或 IV 型过敏症的有效药物，以及预防和/或治疗支气管哮喘、特应性疾病等的进一步药物。包含预防和/或治疗有效量金属蛋白酶抑制剂的本发明药物在预防和/或治疗过敏症，尤其是 I 型和/或 IV 型过敏症等方面具有活性。这些药物在预防和/或治疗炎症、鼻炎、结膜炎、支气管哮喘、特应性疾病（包括皮炎、肠炎等）或过敏性胃肠炎（消化道过敏性炎症）方面具有活性。使用这类药物可(A)减少患病部位的细胞（如淋巴细胞、中性粒细胞、肥大细胞、嗜酸性粒细胞、嗜碱性粒细胞、巨噬细胞和单核细胞），和/或(B)减轻细胞（如淋巴细胞、中性粒细胞、肥大细胞、嗜酸性粒细胞、嗜碱性粒细胞、巨噬细胞和单核细胞）迁移、浸润或积聚引起的炎症症状、(C) 抑制细胞（如淋巴细胞、中性粒细胞、肥大细胞、嗜酸性粒细胞、嗜碱性粒细胞、巨噬细胞、单核细胞、朗格汉斯细胞和树突状细胞）的病理生理功能，和/或 (D) 降低血液中抗体，尤其是 IgE 的水平或抑制其产生。因此，这些药物可用于预防和/或治疗该部位的疾病、失调或病症。
• REMEDIES FOR DEGENERATIVE ARTHRITIS
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP1293202A1

  公开（公告）日：2003-03-19

  A treatment and/or prevention agent for osteoarthritis comprising N-hydroxy-5-ethoxymethyloxy-2(S)-methyl-4(S)-(4-phenoxybenzoyl)amino pentanamide having an inhibitory activity of matrix metalloproteinases, or a non-toxic salt thereof as active ingredient.

  一种治疗和/或预防骨关节炎的药物，其活性成分包括具有基质金属蛋白酶抑制活性的 N-羟基-5-乙氧基甲氧基-2(S)-甲基-4(S)-(4-苯氧基苯甲酰基)氨基戊酰胺或其无毒盐。