3-[(cyclopropylcarbonyl)amino]-N-[2-(dimethylamino)ethyl]-4-[4-(5-methyl-1h-imidazol-4-yl)piperidin-1-yl]benzamide

• 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: 3-[(cyclopropylcarbonyl)amino]-N-[2-(dimethylamino)ethyl]-4-[4-(5-methyl-1h-imidazol-4-yl)piperidin-1-yl]benzamide
• 英文别名: 3-(cyclopropanecarbonylamino)-N-[2-(dimethylamino)ethyl]-4-[4-(5-methyl-1H-imidazol-4-yl)piperidin-1-yl]benzamide
• 化学式: C₂₄H₃₄N₆O₂
• 分子量: 438.6
• InChiKey: LKWFNDRVIMYKDZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  93.4
• 氢给体数：
  3
• 氢受体数：
  5

文献信息

• [EN] 4-[(1H-IMIDAZOL-4-YL)PIPERIDIN-1-YL]ANILIDE DERIVATIVES, THEIR PREPARATION AND APPLICATION IN THERAPY<br/>[FR] DERIVES DE 4-[(1H-IMIDAZOL-4-YL)PIPERIDIN-1-YL]ANILIDE, LEUR PREPARATION ET LEUR APPLICATION EN THERAPEUTIQUE
  申请人：SANOFI-SYNTHELABO

  公开号：WO1999000379A1

  公开（公告）日：1999-01-07

  (EN) The invention concerns compounds of formula (I) in which R1 represents a hydrogen atom or a linear or branched (C1-C4) alkyl group; R2 represents a linear or branched (C1-C6) alkyl, cyclo(C3-C7) alkyl or cyclo(C3-C7)alkyl(C1-C5) alkyl group; R3 represents a -OR4, -O(CH2)nNR5R6, -NHC(NH)NH2, -NHC(NH)N(CH3)2, -NR5R6, -NR5(CH2)nNR6R7 group, a group (a), X being selected among the oxygen and sulphur atoms and the -CHR8, -NR8, -SO- and -SO2- groups; R4, R5, R6, R7 and R8 being a hydrogen atom, a linear or branched (C1-C6)alkyl, cyclo (C3-C7)alkyl, cyclo(C3-C7)alkyl(C1-C5)alkyl, phenyl, phenyl(C1-C6)alkyl or heteroaryl group; m = 1 or 2 and n = 2, 3 or 4. The invention is applicable in therapy.(FR) Composés de formule (I) dans laquelle R1 représente un atome d'hydrogène ou un groupe (C1-C4)alkyle droit ou ramifié, R2 représente un groupe (C1-C6)alkyle droit ou ramifié, cyclo(C3-C7)alkyle ou cyclo(C3-C7)alkyle(C1-C5)alkyle et R3 représente un groupe -OR4, -O(CH2)nNR5R6, -NHC(NH)NH2, -NHC(NH)N(CH3)2, -NR5R6, -NR5(CH2)nNR6R7, un groupe (a), X étant choisi parmi les atomes d'oxygène et de soufre et les groupes -CHR8, -NR8, -SO- et -SO2-, R4, R5, R6, R7 et R8 étant un atome d'hydrogène, un groupe (C1-C6)alkyle droit ou ramifié, cyclo(C3-C7)alkyle, cyclo(C3-C7)alkyle(C1-C5)alkyle, phényle, phényl(C1-C6)alkyle ou hétéroaryle, m = 1 ou 2 et n = 2, 3 ou 4. Application en thérapeutique.

  该发明涉及式（I）的化合物，其中R1代表氢原子或线性或支链（C1-C4）烷基；R2代表线性或支链（C1-C6）烷基，环（C3-C7）烷基或环（C3-C7）烷基（C1-C5）烷基；R3代表-OR4，-O（CH2）nNR5R6，-NHC（NH）NH2，-NHC（NH）N（CH3）2，-NR5R6，-NR5（CH2）nNR6R7基团，一个（a）基团，其中X被选自氧原子和硫原子以及-CHR8，-NR8，-SO-和-SO2-基团；R4，R5，R6，R7和R8为氢原子，线性或支链（C1-C6）烷基，环（C3-C7）烷基，环（C3-C7）烷基（C1-C5）烷基，苯基，苯基（C1-C6）烷基或杂环基团；m = 1或2，n = 2，3或4。该发明适用于治疗。
• COMPOUNDS AND METHODS FOR INHIBITING NHE-MEDIATED ANTIPORT IN THE TREATMENT OF DISORDERS ASSOCIATED WITH FLUID RETENTION OR SALT OVERLOAD AND GASTROINTESTINAL TRACT DISORDERS
  申请人：Charmot Dominique

  公开号：US20120263670A1

  公开（公告）日：2012-10-18

  The present disclosure is directed to compounds and methods for the treatment of disorders associated with fluid retention or salt overload, such as heart failure (in particular, congestive heart failure), chronic kidney disease, end-stage renal disease, liver disease, and peroxisome proliferator-activated receptor (PPAR) gamma agonist-induced fluid retention. The present disclosure is also directed to compounds and methods for the treatment of hypertension. The present disclosure is also directed to compounds and methods for the treatment of gastrointestinal tract disorders, including the treatment or reduction of pain associated with gastrointestinal tract disorders.

  本公开涉及化合物和方法，用于治疗与液体潴留或盐过载相关的疾病，如心力衰竭（特别是充血性心力衰竭）、慢性肾脏病、终末期肾脏病、肝病和过氧化物酶体增殖物激活受体（PPAR）γ激动剂引起的液体潴留。本公开还涉及化合物和方法，用于治疗高血压。本公开还涉及化合物和方法，用于治疗胃肠道疾病，包括治疗或减轻与胃肠道疾病相关的疼痛。
• COMPOUNDS AND METHODS FOR INHIBITING NHE-MEDIATED ANTIPORT IN THE TREATMENT OF DISORDERS ASSOCIATED WITH FLUID RETENTION OR SALT OVERLOAD AND GASTROINTESTINAL TRACT DISORDER
  申请人：Ardelyx, Inc.

  公开号：US20150190389A1

  公开（公告）日：2015-07-09

  The present disclosure is directed to compounds of the structure (X): CoreL-NHE) n (X) wherein: n is 2 or 3; NHE has the structure wherein: R 1 is H or —SO 2 —NR 7 R 8 —; R 2 is selected from H, —NR 7 (CO)R 8 , —SO 2 —NR 7 R 8 — and —NR 7 R 8 ; R 3 is hydrogen; R 7 is hydrogen; R 8 is a bond linking to L; L is a polyalkylene glycol linker; and Core has the following structure: wherein: X is selected from the group consisting of a bond, —O—, —NH—, NHC(═O)—, —NHC(═O)NH— and —NHSO 2 —; and Y is selected from the group consisting of a bond, optionally substituted C 1-6 alkylene, optionally substituted benzene, pyridinyl, a polyethylene glycol linker and —(CH 2 ) 1-6 O(CH 2 ) 1-6 —, and methods of using such compounds for the treatment of irritable bowel syndrome, chronic kidney disease and end-stage renal disease.

  本公开涉及结构为（X）：CoreL-NHE)n（X）的化合物，其中：n为2或3；NHE具有以下结构：其中：R1为H或—SO2—NR7R8—；R2选自H，—NR7（CO）R8，—SO2—NR7R8—和—NR7R8；R3为氢；R7为氢；R8为连接到L的键；L为多聚乙二醇连接剂；Core具有以下结构：其中：X选自由键，—O—，—NH—，NHC（═O）—，—NHC（═O）NH—和—NHSO2—；Y选自键，可选择性地取代的C1-6烷基，可选择性地取代的苯，吡啶基，聚乙二醇连接剂和—（CH2）1-6O（CH2）1-6—，以及使用这种化合物治疗肠易激综合征、慢性肾脏病和终末期肾脏疾病的方法。
• NHE3-binding compounds and methods for inhibiting phosphate transport
  申请人：ARDELYX, INC.

  公开号：US10272079B2

  公开（公告）日：2019-04-30

  Provided are NHE3-binding and/or NHE3-modulating agents having activity as phosphate transport inhibitors, including inhibitors of phosphate transport in the gastrointestinal tract and the kidneys, and methods for their use as therapeutic or prophylactic agent.

  本文提供了具有磷酸盐转运抑制剂活性的 NHE3 结合剂和/或 NHE3 调节剂，包括胃肠道和肾脏磷酸盐转运抑制剂，以及将其用作治疗或预防剂的方法。
• Compounds and methods for inhibiting NHE-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders
  申请人：Ardelyx, Inc.

  公开号：US11318129B2

  公开（公告）日：2022-05-03

  The present disclosure is directed to compounds and methods for the treatment of disorders associated with fluid retention or salt overload, such as heart failure (in particular, congestive heart failure), chronic kidney disease, end-stage renal disease, liver disease, and peroxisome proliferator-activated receptor (PPAR) gamma agonist-induced fluid retention. The present disclosure is also directed to compounds and methods for the treatment of hypertension. The present disclosure is also directed to compounds and methods for the treatment of gastrointestinal tract disorders, including the treatment or reduction of pain associated with gastrointestinal tract disorders. The methods generally comprise administering to a mammal in need thereof a pharmaceutically effective amount of a compound, or a pharmaceutical composition comprising such a compound, that is designed to be substantially active in the gastrointestinal (GI) tract to inhibit NHE-mediated antiport of sodium ions and hydrogen ions therein. More particularly, the method comprises administering to a mammal in need thereof a pharmaceutically effective amount of a compound, or a pharmaceutical composition comprising such a compound, that inhibits NHE-3, -2 and/or -8 mediated antiport of sodium and/or hydrogen ions in the GI tract and is designed to be substantially impermeable to the layer of epithelial cells, or more specifically the epithelium of the GI tract. As a result of the compound being substantially impermeable, it is not absorbed and is thus essentially systemically non-bioavailable, so as to limit the exposure of other internal organs (e.g., liver, heart, brain, etc.) thereto. The present disclosure is still further directed to a method wherein a mammal is administered such a compound with a fluid-absorbing polymer, such that the combination acts as described above and further provides the ability to sequester fluid and/or salt present in the GI tract.

  本公开内容涉及用于治疗与体液潴留或盐负荷过重相关的疾病的化合物和方法，如心力衰竭（尤其是充血性心力衰竭）、慢性肾病、终末期肾病、肝病和过氧化物酶体增殖激活受体（PPAR）γ激动剂诱导的体液潴留。本公开还涉及治疗高血压的化合物和方法。本公开还涉及治疗胃肠道疾病的化合物和方法，包括治疗或减轻与胃肠道疾病相关的疼痛。这些方法一般包括向有需要的哺乳动物施用药学上有效量的化合物或包含这种化合物的药物组合物，这种化合物在胃肠道中基本具有活性，可抑制其中钠离子和氢离子的NHE介导的反转运。更具体地说，该方法包括向有需要的哺乳动物施用药学上有效量的化合物或包含该化合物的药物组合物，该化合物可抑制胃肠道中NHE-3、-2和/或-8介导的钠离子和/或氢离子的反转运，且设计成基本上不渗透上皮细胞层，或更具体地说不渗透胃肠道上皮细胞。由于该化合物基本上不渗透，因此不会被吸收，从而基本上不会被全身生物利用，从而限制了其他内脏器官（如肝脏、心脏、大脑等）对该化合物的接触。本公开内容还进一步涉及一种方法，在这种方法中，哺乳动物与吸液聚合物一起服用这种化合物，从而使这种组合起到如上所述的作用，并进一步提供封存存在于消化道中的液体和/或盐的能力。