tert-butyl 4-(3-hydroxy-4-nitrophenyl)piperazine-1-carboxylate | 932372-93-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: tert-butyl 4-(3-hydroxy-4-nitrophenyl)piperazine-1-carboxylate
• CAS: 932372-93-5
• 化学式: C₁₅H₂₁N₃O₅
• 分子量: 323.349
• InChiKey: SUZQEWNTJYFKHO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  98.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(3-hydroxy-4-nitrophenyl)piperazine-1-carboxylate 在 盐酸 、 4-二甲氨基吡啶 、 palladium 10% on activated carbon 、 氢气 、 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 23.0h， 生成 6-(4-isobutylpiperazin-1-yl)-2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3-carboxamide
  参考文献：
  名称：

  Lead Optimization of Benzoxazolone Carboxamides as Orally Bioavailable and CNS Penetrant Acid Ceramidase Inhibitors

  摘要：

  Sphingolipids (SphLs) are a diverse class of molecules that are regulated by a complex network of enzymatic pathways. A disturbance in these pathways leads to lipid accumulation and initiation of several SphL-related disorders. Acid ceramidase is one of the key enzymes that regulate the metabolism of ceramides and glycosphingolipids, which are important members of the SphL family. Herein, we describe the lead optimization studies of benzoxazolone carboxamides resulting in piperidine 22m, where we demonstrated target engagement in two animal models of neuropathic lysosomal storage diseases (LSDs), Gaucher's and Krabbe's diseases. After daily intraperitoneal administration at 90 mg kg(-1), 22m significantly reduced the brain levels of the toxic lipids glucosylsphingosine (GluSph) in 4L;C* mice and galactosylsphingosine (GalSph) in Twitcher mice. We believe that 22m is a lead molecule that can be further developed for the correction of severe neurological LSDs where GluSph or GalSph play a significant role in disease pathogenesis.

  DOI：

  10.1021/acs.jmedchem.9b02004
• 作为产物：
  描述：

  5-氟-2-硝基苯酚 、 N-Boc-哌嗪 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以78%的产率得到tert-butyl 4-(3-hydroxy-4-nitrophenyl)piperazine-1-carboxylate
  参考文献：
  名称：

  [EN] SMALL MOLECULE INHIBITORS OF GALECTIN-3
  [FR] INHIBITEURS À PETITES MOLÉCULES DE GALECTINE-3

  摘要：

  本公开涉及Formula (I)的化合物，该化合物抑制Gal-3，并包括药用盐、含有此类化合物的组合物，以及使用和制备此类化合物和组合物的方法。

  公开号：

  WO2021231243A1

文献信息

• [EN] SUBSTITUTED N-HETEROCYCLIC CARBOXAMIDES AS ACID CERAMIDASE INHIBITORS AND THEIR USE AS MEDICAMENTS<br/>[FR] CARBOXAMIDES N-HÉTÉROCYCLIQUES SUBSTITUÉS UTILISÉS EN TANT QU'INHIBITEURS DE LA CÉRAMIDASE ACIDE ET LEUR UTILISATION EN TANT QUE MÉDICAMENTS
  申请人：BIAL BIOTECH INVEST INC

  公开号：WO2021055627A1

  公开（公告）日：2021-03-25

  The invention provides substituted N-heterocyclic carboxamides and related compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat a medical disorder, e.g., cancer, lysosomal storage disorder, neurodegenerative disorder, inflammatory disorder, in a patient.

  这项发明提供了替代的N-杂环羧酰胺和相关化合物，含有这些化合物的组合物，医疗工具包，以及使用这些化合物和组合物治疗患者的医疗疾病（例如癌症、溶酶体贮积症、神经退行性疾病、炎症性疾病）的方法。
• 2-Alkynyl-and 2-alkenyl-pyrazolo-[4,3-e]-1,2,4-triazolo-[1,5-c]-pyrimidine adenosine A2a receptor antagonists
  申请人：Schering Corporation

  公开号：US20040220194A1

  公开（公告）日：2004-11-04

  Compounds having the structural formula I 1 or a pharmaceutically acceptable salt thereof, wherein R is 2 R 1 , R 2 , R 3 , R 4 and R 5 are H, alkyl or alkoxyalkyl; R 6 is H, alkyl, hydroxyalkyl or —CH 2 F; R 7 , R 8 and R 9 are H, alkyl, alkoxy, alkylthio, alkoxyalkyl, halo or —CF 3 ; and Z is optionally substituted aryl, heteroaryl or heteroaryl-alkyl are disclosed. Also disclosed is the use of compounds of formula I in the treatment of central nervous system diseases, in particular Parkinson's disease, alone or in combination with other agents for treating Parkinson's disease, and pharmaceutical compositions comprising them.

  具有结构式I或其药用可接受盐的化合物，其中R是R1，R2，R3，R4和R5为H，烷基或烷氧基烷基；R6为H，烷基，羟基烷基或—CH2F；R7，R8和R9为H，烷基，烷氧基，烷硫基，烷氧基烷基，卤素或—CF3；以及Z是可选择地取代的芳基，杂环芳基或杂环芳基烷基。还公开了化合物I的应用于治疗中枢神经系统疾病，特别是帕金森病，单独或与其他治疗帕金森病的药剂联合使用，以及包含它们的药物组合物。
• [EN] SMALL MOLECULE INHIBITORS OF GALECTIN-3<br/>[FR] INHIBITEURS À PETITES MOLÉCULES DE GALECTINE-3
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2021231243A1

  公开（公告）日：2021-11-18

  The present disclosure relates to compounds of Formula (I), which inhibit Gal-3, and include pharmaceutically acceptable salts, compositions comprising such compounds, and methods using and making such compounds and compositions. (Formula (I))

  本公开涉及Formula (I)的化合物，该化合物抑制Gal-3，并包括药用盐、含有此类化合物的组合物，以及使用和制备此类化合物和组合物的方法。
• SULFONAMIDE DERIVATIVE HAVING PGD2 RECEPTOR ANTAGONISTIC ACTIVITY
  申请人：Shionogi&Co., Ltd.

  公开号：EP1939175A1

  公开（公告）日：2008-07-02

  The present invention provides an sulfonamide derivative having DP receptor antagonistic activity and a pharmaceutical composition comprising the said compound as an active ingredient, and further a therapeutic agent for treating allergic diseases. A compound of the general formula (II): wherein the ring A is an aromatic carbocyclic ring etc.; the ring B is a nitrogen-containing non-aromatic heterocyclic ring etc.; the ring C is an aromatic carbocyclic ring etc.; R1 is carboxy etc.; R2 is independently a halogen atom etc.; R3 is optionally substituted alkyloxy etc.; R4 is independently a halogen atom etc.; R5 is independently optionally substituted alkyl etc.; M is sulfonyl etc.; Y is a single bond etc.; L1 is a single bond etc.; L2 is a single bond etc.; k is 0, 1, 2, 3 or 4; n is 0, 1 or 2; and q is 0, 1, 2 or 3; provided that a) k is not 0 when the ring B is a 6-membered nitrogen-containing heterocyclic ring containing one or two nitrogen atom(s) and the ring C is a benzene ring, etc.; a pharmaceutically acceptable salt or a hydrate thereof.

  本发明提供了一种具有DP受体拮抗活性的磺酰胺衍生物和一种包含上述化合物作为活性成分的药物组合物，并进一步提供了一种治疗过敏性疾病的治疗剂。 通式(II)的化合物： 其中环 A 是芳香碳环等；环 B 是含氮非芳香杂环等；环 C 是芳香碳环等；R1 是羧基等；R2 独立地是卤素原子等；R3 是任选取代的烷氧基等；R4 独立地是卤素原子等；R5 独立地是任选取代的烷基等；M 是磺酰基等。M是磺酰基等；Y是单键等；L1是单键等；L2是单键等；k是0、1、2、3或4；n是0、1或2；q是0、1、2或3；条件是 a) 当环 B 是含有一个或两个氮原子的 6 元含氮杂环且环 C 是苯环等时，k 不是 0； 药学上可接受的盐或其水合物。
• PGD2 receptor antagonist
  申请人：Shionogi & Co., Ltd.

  公开号：EP2407453A1

  公开（公告）日：2012-01-18

  A compound of the general formula (I) for use in the treatment of diseases associated with a PGD2 receptor: wherein the ring A is an aromatic carbocyclic ring etc.; the ring B is a nitrogen-containing non-aromatic heterocyclic ring etc.; the ring C is an aromatic carbocyclic ring etc.; R1 is hydroxyalkyl etc.; R2 is independently a halogen atom etc.; R3 is a hydrogen atom etc.; R4 is independently a halogen atom etc.; R5 is independently a halogen atom etc.; M is carbonyl etc.; Y is a single bond etc.; L1, L2 and L3 are independently a single bond etc.; R6 and R7 are independently a hydrogen atom etc.; k is 0, 1, 2, 3 or 4; n is 0, 1 or 2; and q is 0, 1, 2 or 3; provided that a) k is not 0 when the ring B is a 6-membered nitrogen-containing heterocyclic ring containing one or two nitrogen atom(s), and the ring C is a benzene ring, b) the ring C is not an indole ring or an azaindole ring, c) R1 is not carboxy when the ring C is a benzene ring, -L3- is - (O-alkylene)-, and the substituting position of L3 and Y is an ortho-position each other in the ring C, and d) the substituting position of L3 and Y is not a para-position in the ring C when the ring B is a thiazolidine ring and the ring C is a benzene ring; a pharmaceutically acceptable salt or solvate thereof.

  用于治疗与 PGD2 受体相关疾病的通式 (I) 化合物： 其中，环 A 是芳香碳环等；环 B 是含氮非芳香杂环等；环 C 是芳香碳环等；R1 是羟烷基等；R2 独立地是卤素原子等；R3 是氢原子等；R4 独立地是卤素原子等；R5 独立地是卤素原子等。R3 是氢原子等；R4 独立地是卤素原子等；R5 独立地是卤素原子等；M 是羰基等；Y 是单键等；L1、L2 和 L3 独立地是单键等；R6 和 R7 独立地是氢原子等。k 为 0、1、2、3 或 4；n 为 0、1 或 2；q 为 0、1、2 或 3；条件是：a) 当环 B 是含有一个或两个氮原子的 6 元含氮杂环且环 C 是苯环时，k 不是 0；b) 环 C 不是吲哚环或氮杂吲哚环；c) 当环 C 是苯环时，R1 不是羧基、-当环 B 是噻唑烷环而环 C 是苯环时，-L3- 是-(O-烯烃)-，并且 L3 和 Y 的取代位置在环 C 中互为正交位置，以及 d) L3 和 Y 的取代位置在环 C 中不是对位； 其药学上可接受的盐或溶液。