2-[[[4-[(4-methylbenzoyl)amino]phenyl]sulfonyl]amino]acetic acid

• 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: 2-[[[4-[(4-methylbenzoyl)amino]phenyl]sulfonyl]amino]acetic acid
• 英文别名: N-[[4-(p-Toluoylamino)phenyl]sulfonyl]glycine；2-[[4-[(4-Methylbenzoyl)amino]phenyl]sulfonylamino]acetic acid
• 化学式: C₁₆H₁₆N₂O₅S
• 分子量: 348.379
• InChiKey: NRXRBGIDIOEMOF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  121
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-氨基-1,2,4-二噻唑-5-硫酮 、 2-[[[4-[(4-methylbenzoyl)amino]phenyl]sulfonyl]amino]acetic acid 在 N-甲基吗啉 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 生成 4-methyl-N-[4-[[[2-oxo-2-[(3-thioxo-3H-1,2,4-dithiazol-5-yl)amino]ethyl]amino]sulfonyl]phenyl]benzamide
  参考文献：
  名称：

  DITHIAZOLE COMPOUNDS, MATRIX METALLOPROTEASE INHIBITORS AND EXTERNAL PREPARATIONS FOR THE SKIN

  摘要：

  公开号：

  EP1422224B1
• 作为产物：
  描述：

  tert-butyl 2-[[[4-[(4-methylbenzoyl)amino]phenyl]sulfonyl]amino]acetate 以 水 、 三氟乙酸 为溶剂， 生成 2-[[[4-[(4-methylbenzoyl)amino]phenyl]sulfonyl]amino]acetic acid
  参考文献：
  名称：

  Sulfonylamino acid derivatives

  摘要：

  本发明涉及:(i)包含式(Ia)的磺酰氨基酸衍生物的基质金属蛋白酶抑制剂:其中R1是氢，C1-4烷基; R是氢，C1-8烷基等; E是—CONR3—，其中R3是氢，C1-4烷基等，—NR3CO—，—CO—O—，—O—CO—等; A是氢，C1-8烷基，C3-7环烷基或Ar; J是键，C2-4烷基等; G是—(CH2)m—，其中m为2, 3或4，或其中R6和R7是氢，C1-8烷基等; 及其非毒性盐，(ii)式(Ib)的新型磺酰氨基酸衍生物:其中所有符号的含义与(i)相同; 及其非毒性盐，和(iii)制备式(Ib)化合物的方法。式(Ia)的化合物对于预防和/或治疗由MMP过度表达和过度活性引起的疾病是有用的。例如，上述疾病包括类风湿、关节炎、异常骨吸收、骨质疏松症、牙周炎、间质性肾炎、动脉粥样硬化、肺气肿、肝硬化、角膜损伤、转移、肿瘤细胞的侵袭或生长、自身免疫性疾病（克罗恩病、干燥综合征等）、由白细胞的血管移行或浸润引起的疾病、动脉化等。

  公开号：

  US06177466B1

文献信息

• Sulfonylamino acid derivatives
  申请人：Ono Pharmaceutical Co., Ltd.

  公开号：US06177466B1

  公开（公告）日：2001-01-23

  The present invention is related to: (i) matrix metalloproteinase inhibitors containing sulfonylamino acid derivatives of the formula (Ia): wherein R1 is hydrogen, C1-4 alkyl; R is hydrogen, C1-8 alkyl etc.; E is —CONR3—, in which R3 is hydrogen, C1-4 alkyl etc., —NR3CO—, —CO—O—, —O—CO— etc.; A is hydrogen, C1-8 alkyl, C3-7 cycloalkyl, or Ar; J is bond, C2-4 alkylene etc.; G is —(CH2)m— in which m is 2, 3 or 4, or in which R6 and R7 is hydrogen, C1-8 alkyl etc.; and non-toxic salts thereof, (ii) novel sulfonylamino acid derivatives of the formula (Ib): wherein all the symbols are the same meaning as (i); and non-toxic salts thereof, and (iii) process for the preparation of the compound of the formula (Ib). The compounds of the formula (Ia) are useful for prevention and/or treatment of diseases induced by overexpression and excess activity of MMP. The diseases such as above, for example, are rheumatoid, arthrosteitis, unusual bone resorption, osteoporosis, periodontitis, interstitial nephritis, arteriosclerosis, pulmonary emphysema, cirrhosis, cornea injury, metastasis of, invasion of or growth of tumor cell, autoimmune disease (Crohn's disease, Sjogren's syndrome etc.), disease caused by vascular emigration or infiltration of leukocytes, arterialization.

  本发明涉及:(i)包含式(Ia)的磺酰氨基酸衍生物的基质金属蛋白酶抑制剂:其中R1是氢，C1-4烷基; R是氢，C1-8烷基等; E是—CONR3—，其中R3是氢，C1-4烷基等，—NR3CO—，—CO—O—，—O—CO—等; A是氢，C1-8烷基，C3-7环烷基或Ar; J是键，C2-4烷基等; G是—(CH2)m—，其中m为2, 3或4，或其中R6和R7是氢，C1-8烷基等; 及其非毒性盐，(ii)式(Ib)的新型磺酰氨基酸衍生物:其中所有符号的含义与(i)相同; 及其非毒性盐，和(iii)制备式(Ib)化合物的方法。式(Ia)的化合物对于预防和/或治疗由MMP过度表达和过度活性引起的疾病是有用的。例如，上述疾病包括类风湿、关节炎、异常骨吸收、骨质疏松症、牙周炎、间质性肾炎、动脉粥样硬化、肺气肿、肝硬化、角膜损伤、转移、肿瘤细胞的侵袭或生长、自身免疫性疾病（克罗恩病、干燥综合征等）、由白细胞的血管移行或浸润引起的疾病、动脉化等。
• Hydroxamic acid derivatives
  申请人：ONO Pharmaceutical Co., Ltd.

  公开号：US06022893A1

  公开（公告）日：2000-02-08

  The present invention relates to: (i) hydroxamic acid derivative of the formula (I): ##STR1## wherein R.sup.1 is hydrogen, or C1-4 alkyl; R.sup.2 is hydrogen, C1-8 alkyl, phenyl, C1-4 alkyl substituted by phenyl; E is --CONR.sup.3 --, in which R.sup.3 is hydrogen, C1-4 alkyl, etc., --NR.sup.3 CO--, --CO--O--, --O--CO--etc.; A is hydrogen, C1-8 alkyl, C3-7 cycloalkyl, or Ar; J is bond, C2-4 alkylene etc.; G is --(CH.sub.2).sub.m --, in which m is 2, 3 or 4, or ##STR2## in which R.sup.6 and R.sup.7 is hydrogen, C1-8 alkyl etc.; and non-toxic salts thereof, ii) processes for the preparation thereof, and iii) pharmaceutical agents containing them. The compounds of formula (I) are useful for prevention and/or treatment of diseases induced by overexpression or excess activity of gelatinases, for example, rheumatoid diseases, arthrosteitis, unusual bone resorption, osteoporosis, periodontitis, interstitial nephritis, arteriosclerosis, pulmonary emphysema, cirrhosis, cornea injury, metastasis of, invasion of or growth of tumor cells, autoimmune disease (Crohn's disease, Sjogren's syndrome), disease caused by vascular emigration or infiltration of leukocytes or arterialization in animals including human beings, especially human beings.

  本发明涉及以下内容：（i）式（I）的羟肟酸衍生物：##STR1##其中R.sup.1为氢或C1-4烷基；R.sup.2为氢、C1-8烷基、苯基、C1-4烷基取代的苯基；E为--CONR.sup.3--，其中R.sup.3为氢、C1-4烷基等，--NR.sup.3 CO--，--CO--O--，--O--CO--等；A为氢、C1-8烷基、C3-7环烷基或Ar；J为键、C2-4烷基等；G为--（CH.sub.2）.sub.m--，其中m为2、3或4，或##STR2##其中R.sup.6和R.sup.7为氢、C1-8烷基等；以及其非毒性盐，（ii）其制备方法，以及（iii）含有它们的药物制剂。式（I）的化合物对于预防和/或治疗由明胶酶过度表达或过度活性引起的疾病有用，例如风湿性疾病、关节炎、异常骨吸收、骨质疏松症、牙周炎、间质性肾炎、动脉硬化、肺气肿、肝硬化、角膜损伤、肿瘤细胞的转移、侵袭或生长、自身免疫性疾病（Crohn病、Sjogren综合征）、由动物包括人类的白细胞或动脉化引起的疾病。
• Dithiazole compounds, matrix metalloprotease inhibitors and external preparations for the skin
  申请人：——

  公开号：US20040236111A1

  公开（公告）日：2004-11-25

  A dithiazole compound or a salt thereof expressed by formula (I): 1 wherein R 1 is hydrogen atom, alkyl, etc.; R 2 is hydrogen atom, hydroxy, alkyl, aryl, arylalkoxy, arylalkyl, etc.; R 3 is one group of formulae (II), (III) and (IV): 2 This compound has an excellent inhibiting action on matrix metalloprotease (MMPs) activity, and is useful for pharmaceutical, cosmetic and skin external compositions.

  一种由式（I）表示的二噻唑化合物或其盐：其中，R1是氢原子，烷基等；R2是氢原子，羟基，烷基，芳基，芳基烷氧基，芳基烷基等；R3是式（II），（III）和（IV）的一种基团：该化合物对基质金属蛋白酶（MMPs）活性具有出色的抑制作用，并且在制药，化妆品和皮肤外用组合物中非常有用。
• Sulfonylamino acid derivatives as metalloproteinase inhibitors
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP0757037A2

  公开（公告）日：1997-02-05

  The present invention relates to: (i) matrix metalloproteinase (MMP) inhibitors containing sulfonylamino acid derivatives of the formula (Ia): wherein R1 is hydrogen, C1-4 alkyl; R2 is hydrogen, C1-8 alkyl etc.; E is -CONR3-, in which R3 is hydrogen, C1-4 alkyl etc., -NR3CO-, -CO-O-, -O-CO- etc.; A is hydrogen, C1-8 alkyl, C3-7 cycloalkyl, or Ar; J is bond, C2-4 alkylene etc.; G is -(CH2)m-, in which m is 2, 3 or 4, or in which R6 and R7 is hydrogen, C1-8 alkyl etc.; and non-toxic salts thereof, (ii) novel sulfonylamino acid derivatives of the formula (Ib): wherein all the symbols are as defined for formula (Ia), with the exclusion of certain compounds; and non-toxic salts thereof, and (iii) processes for the preparation of the compounds of formula (Ib). The compounds of formulae (Ia) and (Ib) are useful for prevention and/or treatment of diseases induced by overexpression or excess activity of MMP, such as rheumatoid diseases, arthrosteitis, unusual bone resorption, osteoporosis, periodontitis, interstitial nephritis, arteriosclerosis, pulmonary emphysema, cirrhosis, cornea injury, metastasis, invasion or growth of tumor cells, autoimmune diseases (Crohn's disease, Sjogren's syndrome etc.), diseases caused by vascular emigration or infiltration of leukocytes, or arterialization.

  本发明涉及 (i) 含式(Ia)的磺酰基氨基酸衍生物的基质金属蛋白酶(MMP)抑制剂： 其中R1是氢、C1-4烷基；R2是氢、C1-8烷基等；E是-CONR3-，其中R3是氢、C1-4烷基等、-NR3CO-、-CO-O-、-O-CO-等；A是氢、C1-8烷基、C3-7环烷基或Ar；J是键、C2-4亚烷基等；G是-(CH2)m-，其中m是2、3或4，或 其中 R6 和 R7 是氢、C1-8 烷基等；以及它们的无毒盐、 (ii) 式(Ib)的新型磺酰基氨基酸衍生物： 其中所有符号与式 (Ia) 所定义的相同，但某些化合物除外；及其无毒盐，以及 (iii) 式(Ib)化合物的制备工艺。 式(Ia)和(Ib)化合物可用于预防和/或治疗因 MMP 过度表达或活性过强而诱发的疾病，如类风湿病、关节炎、异常骨吸收、骨质疏松症、牙周炎、间质性肾炎、动脉硬化、肺气肿、肝硬化、角膜损伤、肿瘤细胞转移、侵袭或生长、自身免疫性疾病（克罗恩病、Sjogren 综合征等）、血管外流引起的疾病。白细胞的血管迁移或浸润或动脉化引起的疾病。
• Hydroxamic acid derivatives useful for inhibiting gelatinase
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：EP0757984B1

  公开（公告）日：2002-10-30