N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide | 210826-40-7

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide
• 英文别名: 1-(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)-3-[4-(1-hydroxy-1-methyl-ethyl)-furan-2-sulfonyl]urea；N-(1,2,3,5,6,7-Hexahydro-s-indacen-4-ylcarbamoyl)-4-(2-hydroxy-2-propanyl)-2-furansulfonamide；MCC-950；MCC950；CRID3；1-(1,2,3,5,6,7-Hexahydro-s-indacen-4-yl)-3-[4-(1-hydroxy-1-methyl-ethyl)-furan-2-sulfonyl]-urea；1-(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)-3-[4-(2-hydroxypropan-2-yl)furan-2-yl]sulfonylurea
• CAS: 210826-40-7
• 化学式: C₂₀H₂₄N₂O₅S
• 分子量: 404.487
• InChiKey: HUUSXLKCTQDPGL-UHFFFAOYSA-N

物化性质

• 熔点：
  239 °C
• 密度：
  1.396±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（高达40mg/ml）或水（高达30mg/ml）

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  117
• 氢给体数：
  3
• 氢受体数：
  5

制备方法与用途

生物活性

MCC950（CP-456773，CRID3）是一种有效的NLRP3选择性抑制剂，在BMDMs和HMDMs中的IC50值分别为7.5 nM和8.1 nM。

靶点

Target	Value
NLRP3 (BMDM-based)	7.5 nM
NLRP3 (HMDM-based)	8.1 nM

反应信息

• 作为产物：
  描述：

  茚满 在 盐酸 、 三氯化铝 、 硫酸 、 硝酸 、 sodium methylate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， -10.0~60.0 ℃ 、344.74 kPa 条件下， 反应 67.0h， 生成 N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide
  参考文献：
  名称：

  1-(1,2,3,5,6,7-Hexahydro-s-indacen-4-yl)-3-[4-(1-hydroxy-1-methyl-ethyl)-furan-2-的新合成磺酰]脲，抗炎剂

  摘要：

  摘要 抗炎剂 1-(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)-3-[4-(1-hydroxy-1-methyl-描述了乙基)-呋喃-2-磺酰基]脲1。从 3-糠酸乙酯 2 开始制备磺酰胺 5。关键步骤是在二氯甲烷中用氯磺酸进行一锅磺酰化，然后形成吡啶盐并与五氯化磷反应以提供 2-（氯磺酰基）-4-糠酸乙酯 7。该磺酰氯用碳酸氢铵处理以形成磺酰胺 8，然后用过量的甲基氯化镁处理以提供 4-(1-羟基-1-甲基-乙基)-呋喃-2-磺酰胺 5。4-异氰酸根合-1， 2,3,5,6,7-六氢-s-吲哚16 由茚满分五步制备。

  DOI：

  10.1081/scc-120021029

文献信息

• [EN] SULFONYLUREAS AND RELATED COMPOUNDS AND USE OF SAME<br/>[FR] SULFONYLURÉES ET COMPOSÉS APPARENTÉS ET LEUR UTILISATION
  申请人：UNIV QUEENSLAND

  公开号：WO2017140778A1

  公开（公告）日：2017-08-24

  The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts, solvates and prodrugs thereof: Formula (I) wherein Q is selected from O, S and Se; J is S or Se; W1 and W2, when present, are independently selected from N and C; R1 and R2 are independently selected from the group consisting of hydrogen, C1-C12alkyl, C2-C12alkenyl, C2-C12alkynyl, aryl, heterocyclyl, heteroaryl, cycloalkyl, cycloalkenyl, amino, amido, alkylthio, acyl, arylalkyl and acylamido, all of which may be optionally substituted; and wherein at least one of W1 and W2 is present and is a nitrogen atom and when R1 and R2 are cyclic then the respective W1 or W2 may form part of the ring structure. The present invention also relates to pharmaceutical compositions including such compounds, to methods of treatment using such compounds, in particular in relation to NLRP3 inflammasome mediated disorders, and to associated diagnostic uses.

  本发明涉及化合物的公式（I），以及其药学上可接受的盐、溶剂化合物和前药：公式（I）其中Q从O、S和Se中选择；J为S或Se；当存在时，W1和W2独立地从N和C中选择；R1和R2独立地从氢、C1-C12烷基、C2-C12烯基、C2-C12炔基、芳基、杂环烷基、杂芳基、环烷基、环烯基、氨基、酰胺基、烷基硫基、酰基、芳基烷基和酰胺基中选择，其中所有这些基团可能是可选地取代的；其中W1和W2中至少有一个存在且为氮原子，当R1和R2为环时，相应的W1或W2可能构成环结构的一部分。本发明还涉及包括这些化合物的药物组合物，使用这些化合物的治疗方法，特别是与NLRP3炎症小体介导的疾病相关的治疗方法，以及相关的诊断用途。
• A synthesis of furan sulfonamide compounds useful in the synthesis of IL-1 inhibitors
  申请人：Pfizer Products Inc.

  公开号：EP0976742A1

  公开（公告）日：2000-02-02

  An efficent synthesis of furan sulfonamide compounds of formula    comprising reacting a compound of formula II with a Grignard reagent in a reaction inert solvent, wherein R' is (C1-C6)alkyl. The compound of formula II is prepared by reacting a compound of formula III with a compound of formula IV wherein R' is (C1-C6)alkyl with a chorinating reagent and an acid scaverger in an inert solvent. The invention also includes a novel compound of the formula    wherein R' is (C1-C6)alkyl and Q is halo, hydroxy or amino.

  一种有效的合成呋喃磺酰胺化合物的方法，包括在反应惰性溶剂中，将式II化合物与Grignard试剂反应，其中R'为(C1-C6)烷基。式II化合物是通过在惰性溶剂中，将式III化合物与式IV化合物反应而制备的，其中R'为(C1-C6)烷基，使用氯化试剂和酸性清除剂。该发明还包括一种新的化合物，其化学式为，其中R'为(C1-C6)烷基，Q为卤素、羟基或氨基。
• AMIDE DERIVATIVE AND PREPARATION METHOD THEREFOR AND APPLICATION THEREOF IN MEDICINE
  申请人：Chengdu Baiyu Pharmaceutical Co., Ltd.

  公开号：EP4059930A1

  公开（公告）日：2022-09-21

  The present invention relates to an amide derivative and use thereof in medicine, and specifically to an amide derivative shown as general formula (I) or a stereoisomer, sol vate, metabolite, deuteride, prodrug, pharmaceutically acceptable salt or cocrystal thereo f, a pharmaceutical composition containing the same, and use of the compound or the composition disclosed herein in preparing an NLRP3 inhibitor

  本发明涉及一种酰胺衍生物及其在医学上的用途，具体而言，涉及一种通式（I）或其立体异构体、溶剂化物、代谢物、氘代物、前药、药学上可接受的盐或共晶体的酰胺衍生物，以及含有该衍生物的药物组合物，以及本发明所披露的化合物或组合物在制备NLRP3抑制剂时的用途。
• 4-Substituted furan-2-sulfonamide and its use in the preparation of sulfonyl urea derivatives
  申请人：PFIZER INC.

  公开号：EP1270565A1

  公开（公告）日：2003-01-02

  The invention relates to a compound, 4-(1-hydroxy-1-methyl-ethyl)furan-2-sulfonamide, and its use as an intermediate in the preparation of a compound of the formula wherein R1 and R2 are as defined in the description, useful in the treatment and condition selected from the group consisting of meningitis and salpingitis, septic shock, disseminated intravascular coagulation, and/or adult respiratory distress syndrome, acute or chronic inflammation, arthritis, cholangitis, colitis, encephalitis, endocarditis, glomerulonephritis, hepatitis, myocarditis, pancreatitis, pericarditis, reperfusion injury, vasculitis, acute and delayed hypersensitivity, graft rejection, and graft-versus-host disease, auto-immune diseases including Type 1 diabetes mellitus and multiple sclerosis, periodonate diseases, interstitial pulmonary fibrosis, cirrhosis, systemic sclerosis, keloid formation, tumors which produce IL-1 as an autocrine growth factor, cachexia, Alzheimers disease, percussion injury, depression, atherosclerosis (including cardiomyopathy, myocarditis and heart failure) and osteoporosis in a mammal, including a human.

  本发明涉及一种化合物，4-(1-羟基-1-甲基-乙基)呋喃-2-磺酰胺，及其在制备 式化合物中作为中间体的用途，其中 R1 和 R2 如描述中所定义。 其中 R1 和 R2 如描述中所定义，可用于治疗选自以下组别的疾病：脑膜炎和输卵管炎、脓毒性休克、弥散性血管内凝血和/或成人呼吸窘迫综合征、急性或慢性炎症、关节炎、胆管炎、结肠炎、脑炎、心内膜炎、肾小球肾炎、肝炎、心肌炎、胰腺炎、心包炎、再灌注损伤、血管炎、急性和迟发性超敏反应、移植物排斥和移植物抗宿主疾病、自身免疫性疾病（包括 1 型糖尿病和多发性硬化症）、牙周病、间质性肺纤维化、肝硬化、系统性硬化症、瘢痕疙瘩的形成、产生 IL-1 作为自分泌生长因子的肿瘤、恶病质、老年痴呆症、叩击伤、抑郁症、动脉粥样硬化（包括心肌病、心肌炎和心力衰竭）以及哺乳动物（包括人类）骨质疏松症。
• Sulfonyl urea derivatives and their use in the control of interleukin-1 activity
  申请人：PFIZER INC.

  公开号：EP1270554A1

  公开（公告）日：2003-01-02

  The invention relates to a compound of the formula wherein R1 and R2 are as defined in the description, useful in the treatment and condition selected from the group consisting of meningitis and salpingitis, septic shock, disseminated intravascular coagulation, and/or adult respiratory distress syndrome, acute or chronic inflammation, arthritis, cholangitis, colitis, encephalitis, endocarditis, glomerulonephritis, hepatitis, myocarditis, pancreatitis, pericarditis, reperfusion injury, vasculitis, acute and delayed hypersensitivity, graft rejection, and graft-versus-host disease, auto-immune diseases including Type 1 diabetes mellitus and multiple sclerosis, periodonate diseases, interstitial pulmonary fibrosis, cirrhosis, systemic sclerosis, keloid formation, tumors which produce IL-1 as an autocrine growth factor, cachexia, Alzheimers disease, percussion injury, depression, atherosclerosis (including cardiomyopathy, myocarditis and heart failure) and osteoporosis in a mammal, including a human.

  本发明涉及一种如下式的化合物 其中 R1 和 R2 如描述中所定义，可用于治疗选自以下组别的疾病：脑膜炎和输卵管炎、脓毒性休克、弥散性血管内凝血和/或成人呼吸窘迫综合征、急性或慢性炎症、关节炎、胆管炎、结肠炎、脑炎、心内膜炎、肾小球肾炎、肝炎、心肌炎、胰腺炎、心包炎、再灌注损伤、血管炎、急性和迟发性超敏反应、移植物排斥和移植物抗宿主疾病、自身免疫性疾病（包括 1 型糖尿病和多发性硬化症）、牙周病、间质性肺纤维化、肝硬化、系统性硬化症、瘢痕疙瘩的形成、产生 IL-1 作为自分泌生长因子的肿瘤、恶病质、老年痴呆症、叩击伤、抑郁症、动脉粥样硬化（包括心肌病、心肌炎和心力衰竭）以及哺乳动物（包括人类）骨质疏松症。