右氯谷胺 | 119817-90-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 右氯谷胺
• 英文名称: dexloxiglumide
• 英文别名: (4R)-4-[(3,4-dichlorobenzoyl)amino]-5-[3-methoxypropyl(pentyl)amino]-5-oxopentanoic acid
• CAS: 119817-90-2
• 化学式: C₂₁H₃₀Cl₂N₂O₅
• mdl: MFCD00866773
• 分子量: 461.386
• InChiKey: QNQZBKQEIFTHFZ-GOSISDBHSA-N

物化性质

• 沸点：
  632.2±55.0 °C(Predicted)
• 密度：
  1.233±0.06 g/cm3(Predicted)
• 溶解度：
  DMSO：50 mg/ml，超声处理

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  30
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.571
• 拓扑面积：
  95.9
• 氢给体数：
  2
• 氢受体数：
  5

ADMET

代谢

细胞色素P450（CYP）3A4/5和CYP2C9参与了dexloxiglumide的代谢，生成O-脱甲基dexloxiglumide。这个代谢物进一步氧化为dexloxiglumide羧酸。这两个主要代谢物（占dexloxiglumide消除的50%）已被确定。然而，在人体血浆中，未改变的药物是代谢图谱的主要成分（高达91%）。母药被认为是该化合物疗效的主要贡献者，因为其主要代谢物在药理上是无效的。

Cytochrome P450 (CYP) 3A4/5 and CYP2C9 have been implicated in the metabolism of dexloxiglumide to produce O-demethyl dexloxi-glumide. This metabolite is further oxidised to dexloxiglumide carboxylic acid. These two major metabolites (accounting for up to 50% of dexloxiglumide elimination) have been identified. However, in human plasma the unchanged drug represents the major (up to 91%) component of the metabolic profile. The parent drug is believed to be the major contributor to the efficacy of the compound, since its major metabolites are pharmacologically inactive.

来源:DrugBank

代谢

.dexloxiglumide 已知的人类代谢物包括 4-[(3,4-二氯苯甲酰)氨基]-5-[3-羟基丙基(戊基)氨基]-5-氧代戊酸。

Dexloxiglumide has known human metabolites that include 4-[(3,4-Dichlorobenzoyl)amino]-5-[3-hydroxypropyl(pentyl)amino]-5-oxopentanoic acid.

来源:NORMAN Suspect List Exchange

毒理性

• 蛋白质结合

百分之九十四至九十八

94-98%

来源:DrugBank

吸收、分配和排泄

• 吸收

单次口服给药后，在人体内迅速而广泛地被吸收，绝对生物利用度为48%。不完全的生物利用度是由于吸收不完全和肝脏的首过效应共同造成的。

Rapidly and extensively absorbed after single oral administration in humans with an absolute bioavailability of 48%. The incomplete bioavailability is due to both incomplete absorption and hepatic first-pass effect.

来源:DrugBank

安全信息

• 危险品标志：
  Xn,Xi
• 危险类别码：
  R20/21/22,R36/37/38

制备方法与用途

生物活性方面，dexloxiglumide 是一种选择性胆囊收缩素 A 型（CCKA）受体拮抗剂。它属于 loxiglumide 的活性对映体，能够有效抑制由胆囊收缩素-八肽（CCK-8）诱导的平滑肌细胞收缩。

反应信息

• 作为产物：
  描述：

  Boc-D-谷氨酸-5-苄酯 在 N-甲基吗啉 、 5%-palladium/activated carbon 、 氢气 、 sodium carbonate 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 甲醇 为溶剂， -10.0~20.0 ℃ 、400.01 kPa 条件下， 反应 10.33h， 生成 右氯谷胺
  参考文献：
  名称：

  一种右氯谷胺的制备方法

  摘要：

  本发明公开了一种右氯谷胺的制备方法，包括：N‑叔丁氧羰基‑D‑谷氨酸‑5‑苄酯与N‑(3‑甲氧基丙基)‑戊胺经混合酸酐法反应酰化后再脱除叔丁氧羰基，得到再与3,4‑二氯苯甲酰氯反应生成最后脱苄基，即得到右氯谷胺。与现有技术相比，本发明的方法操作更简单、收率更高。

  公开号：

  CN108912007B

文献信息

• Alpha,beta-unsaturated esters and acids by stereoselective dehydration
  申请人：Deng Xiaohu

  公开号：US20060004195A1

  公开（公告）日：2006-01-05

  There are provided by the present invention certain pyrazole based CCK-1 receptor modulators which have the general formula: wherein Ar is an aromatic or heteroaromatic group, X is a hydrocarbon linker, Y is a bond or hydrocarbon linker and R 1 , R 2 , R 3 , R 4 and R 5 are certain organic substituents, methods for making the same, and stereoselective dehydration methods for generally making α,β-unsaturated esters, acids and their derivatives.

  本发明提供了一些基于吡唑的CCK-1受体调节剂，其具有以下一般式： 其中Ar是芳香族或杂环芳基，X是碳氢链，Y是键或碳氢链，R1、R2、R3、R4和R5是某些有机取代基，以及制备这些化合物的方法，以及用于通常制备α，β-不饱和酯，酸及其衍生物的立体选择性脱水方法。
• NOVEL PYRAZOLE-3-CARBOXAMIDE DERIVATIVE HAVING 5-HT2B RECEPTOR ANTAGONIST ACTIVITY
  申请人：Yamagishi Tatsuya

  公开号：US20110275628A1

  公开（公告）日：2011-11-10

  Disclosed is a compound represented by general formula (I) or a pharmaceutically acceptable salt thereof, which is useful as a selective antagonist of a 5-HT 2B receptor. The compound and salt are useful for treatment or prevention of various diseases and conditions associated with a 5-HT 2B receptor.

  揭示的是由通式（I）表示的化合物或其药用可接受盐，其作为5-HT2B受体的选择性拮抗剂是有用的。该化合物和盐可用于治疗或预防与5-HT2B受体相关的各种疾病和症状。
• Sulfonamide compounds
  申请人：Allison Brett

  公开号：US20060069286A1

  公开（公告）日：2006-03-30

  Certain sulfonamide compounds are dual CCK1/CCK2 inhibitors useful in the treatment of CCK1/CCK2 mediated diseases.

  某些磺酰胺化合物是双CCK1/CCK2抑制剂，在治疗CCK1/CCK2介导的疾病中很有用。
• [EN] INHIBITORS OF NHE-MEDIATED ANTIPORT<br/>[FR] INHIBITEURS D'ANTIPORT À MÉDIATION PAR NHE
  申请人：ARDELYX INC

  公开号：WO2018129557A1

  公开（公告）日：2018-07-12

  The present disclosure is directed to compounds (Ι') and to their use in 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 (Ι') and their use in methods for the treatment of hypertension. The present disclosure is also directed to compounds (Ι') and to their use in 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(Ι')及其在治疗与液体潴留或盐超负荷相关的疾病的方法中的用途，例如心力衰竭（尤其是充血性心力衰竭）、慢性肾病、终末期肾病、肝病以及过氧化物酶体增殖物激活受体（PPAR）gamma激动剂引起的液体潴留。本公开还涉及化合物(Ι')及其在治疗高血压的方法中的用途。本公开还涉及化合物(Ι')及其在治疗胃肠道疾病的方法中的用途，包括治疗或减少与胃肠道疾病相关的疼痛。
• [EN] COMPOUNDS AND METHODS FOR INHIBITING NHE-MEDIATED ANTIPORT IN THE TREATMENT OF DISORDERS ASSOCIATED WITH FLUID RETENTION OR SALT OVERLOAD AND GASTROINTESTINAL TRACT DISORDERS<br/>[FR] COMPOSÉS ET PROCÉDÉS DESTINÉS À INHIBER UN ANTIPORT MÉDIÉ PAR NHE DANS LE TRAITEMENT DES TROUBLES ASSOCIÉS À UNE RÉTENTION DE FLUIDE OU À UNE SURCHARGE DE SEL ET DES TROUBLES DU TRACTUS GASTRO-INTESTINAL
  申请人：ARDELYX INC

  公开号：WO2014029984A1

  公开（公告）日：2014-02-27

  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治疗与液体潴留或盐过多有关的疾病的方法，例如心力衰竭（特别是充血性心力衰竭）、慢性肾病、晚期肾病、肝病和过氧化物酶体增殖物激活受体（PPAR）γ激动剂诱导的液体潴留。本公开还涉及化合物和治疗高血压的方法。本公开还涉及化合物和治疗胃肠道疾病的方法，包括治疗或减轻与胃肠道疾病相关的疼痛。