5-chloro-3-methoxy-[1,2,4]thiadiazole | 41218-40-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-chloro-3-methoxy-[1,2,4]thiadiazole
• 英文别名: 5-chloro-3-methoxy-1,2,4-thiadiazole
• CAS: 41218-40-0
• 化学式: C₃H₃ClN₂OS
• 分子量: 150.589
• InChiKey: GYGNJEASCVSRLC-UHFFFAOYSA-N

物化性质

• 沸点：
  218.4±23.0 °C(Predicted)
• 密度：
  1.486±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  8
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  63.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  甘氨酸甲酯盐酸盐 、 5-chloro-3-methoxy-[1,2,4]thiadiazole 在 四丁基溴化铵 、 三乙胺 作用下， 以 正己烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 以60.1%的产率得到(3-methoxy-[1,2,4]thiadiazol-5-ylamino)-acetic acid methyl ester
  参考文献：
  名称：

  Thiadiazole compounds useful as inhibitors of cysteine activity

  摘要：

  提供了新颖的1,2,4-噻二唑化合物，这些化合物作为半胱氨酸活性依赖酶的抑制剂，特别是半胱氨酸蛋白酶的抑制剂具有有效性。这些化合物可用于通过抑制转谷氨酰胺酶治疗痤疮，通过抑制人类鼻病毒3C蛋白酶治疗普通感冒，通过抑制半胱氨酸蛋白酶治疗炎症性关节疾病。本发明的化合物是一般式（I）的3,5-二取代的1,2,4-噻二唑：其中Z是含有酶识别序列的氮基团，Y是调节抑制剂对半胱氨酸活性依赖酶硫醇基团反应性的取代基。Y基团也可用于识别。

  公开号：

  US06162791A1
• 作为产物：
  描述：

  trichloromethyl mercaptan 、 O-甲基异脲 半硫酸盐 在 sodium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 1.0h， 以42%的产率得到5-chloro-3-methoxy-[1,2,4]thiadiazole
  参考文献：
  名称：

  Synthesis and evaluation of novel dipeptide-bound 1,2,4-Thiadiazoles as irreversible inhibitors of guinea pig liver transglutaminase

  摘要：

  Herein we report the synthesis and evaluation of 14 novel peptides as potential irreversible inactivators of guinea pig liver transglutaminase (TGase). These peptides were designed to resemble Cbz-L-Gln-Gly, known to be a good TGase substrate, and to include a 1,2,4-thiadiazole group. The side chain length of the amino acid residue bearing the inhibitor group was also varied in order to permit investigation of this effect. Their inactivation rate constants were measured using a direct continuous spectrophotometric method and were found to vary between 0.330 to 0.89 muM min(-1). (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00228-0

文献信息

• Synthesis and muscarinic activities of 1,2,4-thiadiazoles
  作者：Angus M. MacLeod、Raymond Baker、Stephen B. Freedman、Shailendra Patel、Kevin J. Merchant、Michael Roe、John Saunders

  DOI：10.1021/jm00169a041

  日期：1990.7

  synthesized by reaction of the lithium enolate of the 3-methoxycarbonyl compounds followed by ester hydrolysis and decarboxylation. The receptor-binding affinity and efficacy of these compounds as muscarinic ligands was assessed by radioligand binding assays using [3H]-N-methylscopolamine and [3H]oxotremorine-M. Optimal agonist affinity was observed for 3'-methyl compounds. Smaller substituents (H) retained

  制备了一系列在C5带有单或双环胺的新型1,2,4-噻二唑。通过3-甲氧基羰基化合物的烯醇锂反应，然后进行酯水解和脱羧反应，合成了奎尼丁和1-氮杂双环[2.2.1]庚烷衍生物。这些化合物作为毒蕈碱配体的受体结合亲和力和功效通过使用[3H] -N-甲基东pol碱和[3H]氧代短发胺-M的放射性配体结合测定法进行评估。对于3'-甲基化合物观察到最佳激动剂亲和力。较小的取代基（H）保留了较低亲和力的功效，而较大的基团则导致实质上较低的功效。观察到的结合亲和力受围绕C3-C5'键旋转的构象能以及单环或双环胺的空间要求的影响。
• 1,2,4-Thiadiazole: A novel Cathepsin B inhibitor
  作者：Regis Leung-Toung、Jolanta Wodzinska、Wanren Li、Jayme Lowrie、Rahul Kukreja、Denis Desilets、Khashayar Karimian、Tim Fat Tam

  DOI：10.1016/j.bmc.2003.09.040

  日期：2003.12

  inhibitor in this series. The enhanced inhibitory potency of 3a is a consequence of its increased enzyme binding affinity (lower K(i)) rather than its increased intrinsic reactivity (higher k(i)). In addition, 3a is inactive against Cathepsin S, is a poor inhibitor of Cathepsin H and is >100-fold more selective for Cat B over papain.

  已经开发出具有1,2,4-噻二唑杂环作为硫醇捕获药效团的新型组织蛋白酶B抑制剂。在C5位置具有不同二肽识别序列（即P1'-P2'= Leu-Pro-OH或P2-P1 = Cbz-Phe-Ala）且具有不同取代基（即OMe，Ph或COOH）的几种化合物已经合成了1,2,4-噻二唑环的C3位上的化合物，并测试了它们的抑制活性。取代的噻二唑3a-h以时间依赖性，不可逆的方式抑制CatB。提出了基于在活性位点半胱氨酸硫醇和杂环的硫原子之间形成二硫键而使酶的活性位点定向失活的机理。具有C3甲氧基部分和Leu-Pro-OH二肽识别序列的化合物3a（K（i）= 2.6 microM，k（i）K（i）= 5630 M（-1）s（-1）），被发现是该系列中最有效的抑制剂。3a抑制力的增强是其酶结合亲和力提高（K（i）较低）而不是固有反应性提高（k（i）较高）的结果。此外，3a对组织蛋白酶S无活性，对组织蛋白酶H的抑制作用较弱，对Cat
• Design and Synthesis of Novel Derivatives of the Muscarinic Agonist Tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-Methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] Ether (CDD-0304):  Effects of Structural Modifications on the Binding and Activity at Muscarinic Receptor Subtypes and Chimeras
  作者：Frederick R. Tejada、Peter I. Nagy、Min Xu、Cindy Wu、Tricia Katz、Jason Dorsey、Melissa Rieman、Elizabeth Lawlor、Manya Warrier、Messer

  DOI：10.1021/jm0606995

  日期：2006.12.1

  As part of a continuing effort to design and synthesize highly selective muscarinic agonists for different muscarinic receptor subtypes, several tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (1) analogues were prepared and characterized. Different analogues were synthesized having hydrophilic spacers of di-, tri-, tetra-

  作为设计和合成针对不同毒蕈碱受体亚型的高选择性毒蕈碱激动剂的持续努力的一部分，几种四（乙二醇）（3-甲氧基-1,2,5-噻二唑-4-基）[3-（1-甲基制备并表征了-（1,2,5,6-四氢吡啶-3-基）-1,2,5-噻二唑-4-基]醚（1）类似物。合成了具有二，三，四，五（乙二醇）和三（丙二醇）亲水间隔基的不同类似物，该间隔基将1,2,5,6-四氢吡啶环与末端杂环隔开，后者为1 ，2,5-噻二唑或1,2,4-噻二唑环。还进行了嵌合受体和分子建模研究，以确定配体如何与毒蕈碱受体相互作用。研究表明，改变末端噻二唑的距离和甲氧基的位置可以增加对某些毒蕈碱受体亚型的结合亲和力（对于13d的M（2）和对于1d的M（4））并增强在M（ 4）13e和18b的受体。此外，如通过逆转阿扑吗啡诱导的感觉运动门控缺陷所评估的，化合物1显示出抗精神病活性，表明在精神分裂症的治疗中具有潜在的实用性。
• Thiadiazole compounds useful as inhibitors of cysteine activity dependent enzymes
  申请人：Apotex Inc.

  公开号：US06468977B1

  公开（公告）日：2002-10-22

  Novel 1,2,4-thiadiazole compounds are provided, which are effective as inhibitors of cysteine activity-dependent enzymes and in particular of cysteine proteases. The compounds are useful in treating acne by inhibition of transglutaminase, common cold by inhibition of human rhinovirus 3C protease and inflammatory joint disease by inhibition of cathepsins. The compounds of the present invention are 3,5-disubstituted 1,2,4-thiadazole of the general formula (I): where Z is a nitrogen containing group with recognition sequence for the enzyme and Y is a substituent that tunes the reactivity of the inhibitor towards the thiol group of the cysteine activity-dependent enzyme. The Y group may also serve in recognition.

  提供了新型1,2,4-噻二唑化合物，这些化合物可有效作为半胱氨酸活性依赖酶的抑制剂，特别是半胱氨酸蛋白酶的抑制剂。这些化合物可用于通过抑制转谷氨酰胺酶治疗痤疮，通过抑制人类鼻病毒3C蛋白酶治疗普通感冒，通过抑制半胱氨酸蛋白酶治疗炎症性关节疾病。本发明的化合物是通式(I)的3,5-二取代的1,2,4-噻二唑，其中Z是含氮基团，具有对酶的识别序列，Y是调节抑制剂对半胱氨酸活性依赖酶巯基的反应性的取代基。Y基团也可用于识别。
• Thiadiazole compounds useful as inhibitors of H.sup.+ /K.sup.+ atpase
  申请人：Apotex Inc.

  公开号：US06060472A1

  公开（公告）日：2000-05-09

  Novel 3,5-disubstituted 1,2,4-thiadiazole compounds are provided, which are effective in treating peptic ulcers by the inhibition of H.sup.+ /K.sup.+ -ATPase. The compounds of the present invention are 3,5-disubstituted 1,2,4-thiadiazole corresponding to the general formula (I): ##STR1## where R.sup.1 is a group with cell penetration properties for the inhibition of the enzyme in-vitro and in-vivo, and Y is a substituent that tunes the reactivity of the inhibitor towards the cysteine residue of H.sup.+ /K.sup.+ -ATPase. The Y group may also serve in recognition.

  提供了一种新型的3,5-二取代的1,2,4-噻二唑化合物，通过抑制H.sup.+ /K.sup.+ -ATPase来有效治疗消化性溃疡。本发明的化合物是与通用式(I)相对应的3,5-二取代的1,2,4-噻二唑：其中R.sup.1是具有细胞穿透性质的基团，用于体外和体内抑制酶活性，Y是调节抑制剂对H.sup.+ /K.sup.+ -ATPase半胱氨酸残基的反应性的取代基。Y基团也可以用于识别。