4-[[5-(氨基磺酰基)-1,3,4-噻二唑]氨基]-4-氧丁酸 | 78851-85-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 4-[[5-(氨基磺酰基)-1,3,4-噻二唑]氨基]-4-氧丁酸
• 英文名称: 4-oxo-4-((5-sulfamoyl-1,3,4-thiadiazol-2-yl)amino)butanoic acid
• 英文别名: 4-oxo-4-[(5-sulfamoyl-1,3,4-thiadiazol-2-yl)amino]butanoic acid
• CAS: 78851-85-1
• 化学式: C₆H₈N₄O₅S₂
• 分子量: 280.285
• InChiKey: VEHPJMWKEUDKJE-UHFFFAOYSA-N

物化性质

• 密度：
  1.807±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  189
• 氢给体数：
  3
• 氢受体数：
  9

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  室温下应存放在干燥密封的容器中。

反应信息

• 作为反应物：
  描述：

  4-[[5-(氨基磺酰基)-1,3,4-噻二唑]氨基]-4-氧丁酸 在 sodium ascorbate 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.58h， 生成
  参考文献：
  名称：

  종양 표적화 광역학 치료제

  摘要：

  本发明涉及一种包含如下化合物的肿瘤靶向光动力疗法药物：[化学式 1]。

  公开号：

  KR102009601B1
• 作为产物：
  描述：

  5-((methoxysuccinyl)amino)-1,3,4-thiadiazole-2-sulfonyl chloride 在 sodium hydroxide 、 氨 作用下， 反应 0.5h， 生成 4-[[5-(氨基磺酰基)-1,3,4-噻二唑]氨基]-4-氧丁酸
  参考文献：
  名称：

  Acetazolamide-like carbonic anhydrase inhibitors with topical ocular hypotensive activity

  摘要：

  New carbonic anhydrase (EC 4.2.1.1) inhibitors were synthesized as potential drugs for the topical treatment of glaucoma. They were obtained by substituting the acetyl group of acetazolamide and methazolamide with bicarboxylic acids of different chain length (C4-C6). The terminal carboxyl was either kept free or esterified with alcohols of different size (C1-C12). A gamma-aminovaleric derivative was also prepared. All compounds proved active as carbonic anhydrase inhibitors in vitro, with an average IC50 of about 0.5-mu-M. Some proved also to be topically active in vivo in lowering the artificially elevated intraocular pressure in rabbits. The most active compound, carrying a succinic acid side chain, is the most soluble in aqueous buffers. Its duration of action is about 8 h and it is under evaluation as a topical antiglaucoma drug. It is hypothesized that the duration of action could be longer in compounds having both the same high water solubility and partition coefficient.

  DOI：

  10.1021/jm00092a021

文献信息

• Acetazolamide-based [ 18 F]-PET tracer: In vivo validation of carbonic anhydrase IX as a sole target for imaging of CA-IX expressing hypoxic solid tumors
  作者：Kunal N. More、Jun Young Lee、Dong-Yeon Kim、Nam-Chul Cho、Ayoung Pyo、Misun Yun、Hyeon Sik Kim、Hangun Kim、Kwangseok Ko、Jeong-Hoon Park、Dong-Jo Chang

  DOI：10.1016/j.bmcl.2018.01.060

  日期：2018.3

  Carbonic anhydrase IX is overexpressed in many solid tumors including hypoxic tumors and is a potential target for cancer therapy and diagnosis. Reported imaging agents targeting CA-IX are successful mostly in clear cell renal carcinoma as SKRC-52 and no candidate was approved yet in clinical trials for imaging of CA-IX. To validate CA-IX as a valid target for imaging of hypoxic tumor, we designed

  碳酸酐酶IX在许多实体瘤（包括低氧肿瘤）中过表达，并且是癌症治疗和诊断的潜在靶标。报道的靶向CA-IX的显像剂主要在透明细胞肾癌中作为SKRC-52获得成功，并且尚未在临床试验中批准用于CA-IX显像的候选药物。为了验证CA-IX作为低氧肿瘤成像的有效靶标，我们基于乙酰唑胺（一种著名的CA-IX抑制剂）设计并合成了新型[ 18 F] -PET示踪剂（1），并在2002年进行了成像研究除SKRC-52外，CA-IX在体内模型中将缺氧肿瘤模型表达为4T1和HT-29 。[ 18 F]-乙酰唑胺（1）被发现不足以在表达CA-IX的肿瘤中特异性积聚。这项研究可能有助于了解乙酰唑酰胺PET示踪剂的体内行为，并有助于将来成功开发针对CA-IX的PET成像剂。需要进一步的研究来理解CA-IX靶向性差的机制，好像CA-IX作为表达低氧性实体瘤的CA-IX成像的唯一目标并不可靠。
• Compounds for diagnosis, treatment and prevention of bone injury and metabolic disorders
  申请人：Pierce M. William

  公开号：US20050143366A1

  公开（公告）日：2005-06-30

  The present invention relates to compounds of the formula or pharmaceutically acceptable salts thereof useful for the prophylaxis and treatment of degenerative bone disorders and for the acceleration of bone healing.

  本发明涉及以下式的化合物或其药用可接受盐，用于预防和治疗退行性骨疾病以及促进骨愈合。
• DUAL-TARGETED CARBONIC ANHYDRASE IX COMPLEX AND CONTRAST AGENT THEREOF
  申请人：Institute of Nuclear Energy Research, Atomic Energy Council, Executive Yuan, R.O.C

  公开号：US20210154334A1

  公开（公告）日：2021-05-27

  Disclosed herein are a dual-targeted carbonic anhydrase IX complex, a contrast agent comprising the same, and a synthesizing method thereof. The dual-targeted carbonic anhydrase IX complex includes a carbonic anhydrase IX (CA9) binding peptide, a sulfonamide derivative, and a metal chelating agent. The dual-targeted carbonic anhydrase IX complex has potential for use as a molecular nuclear drug.

  本文披露了一种双靶向碳酸酐酶IX复合物，包括相同的造影剂和其合成方法。该双靶向碳酸酐酶IX复合物包括碳酸酐酶IX（CA9）结合肽、磺胺衍生物和金属螯合剂。该双靶向碳酸酐酶IX复合物具有作为分子核药物的潜力。
• PEGylated Bis-Sulfonamide Carbonic Anhydrase Inhibitors Can Efficiently Control the Growth of Several Carbonic Anhydrase IX-Expressing Carcinomas
  作者：Suleyman Akocak、M. Raqibul Alam、Ahmed M. Shabana、Rajesh Kishore Kumar Sanku、Daniela Vullo、Harry Thompson、Erik R. Swenson、Claudiu T. Supuran、Marc A. Ilies

  DOI：10.1021/acs.jmedchem.6b00492

  日期：2016.5.26

  tumor-overexpressed CA IX and XII and cytosolic isozymes, identified nanomolar-potent inhibitors against both classes and several compounds with medium isoform selectivity in a detailed structure–activity relationship study. The ability of CA inhibitors to kill tumor cells overexpressing CA IX and XII was tested under normoxic and hypoxic conditions, using 2D and 3D in vitro cellular models. The study identified

  由三个已建立的氨基磺酰胺碳酸酐酶（CA，EC 4.2.1.1）抑制剂药效基团与乙二醇低聚或聚合二胺偶联，合成了一系列芳香族/杂环双磺酰胺，可制得具有短或长（聚合）接头的双磺酰胺。对新型抑制剂及其前体针对一系列膜结合的CA同工型（包括肿瘤过度表达的CA IX和XII和胞质同工酶）的测试，确定了针对两类和几种具有中等同工型选择性的化合物的纳摩尔强效抑制剂，具有详细的结构活性关系研究。使用2D和3D体外细胞模型，在常氧和低氧条件下测试了CA抑制剂杀死过表达CA IX和XII的肿瘤细胞的能力。25）能够显着降低结肠HT-29，乳腺癌MDA-MB231和卵巢SKOV-3癌细胞系的活力，从而揭示了聚合物缀合物在CA抑制和癌症治疗中的潜力。
• [EN] CARBONIC ANHYDRASE IX INHIBITOR CONJUGATES AND USES THEREOF<br/>[FR] CONJUGUÉS D'INHIBITEURS D'ANHYDRASE CARBONIQUE IX ET LEURS UTILISATIONS
  申请人：ENDOCYTE INC

  公开号：WO2017161144A1

  公开（公告）日：2017-09-21

  The present disclosure relates to compositions and methods of carbonic anhydrase IX inhibitors. The present disclosure also relates to targeting conjugates of carbonic anhydrase IX inhibitors as therapeutics and imaging agents. The present disclosure also relates to the use of targeting conjugates of carbonic anhydrase IX inhibitors in imaging methods and cancer therapy.

  本公开涉及碳酸酐酶IX抑制剂的组合物和方法。本公开还涉及碳酸酐酶IX抑制剂的靶向共轭物作为治疗剂和成像剂。本公开还涉及在成像方法和癌症治疗中使用碳酸酐酶IX抑制剂的靶向共轭物。