4-(4-hydroxypiperidin-1-yl)butanoic acid

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 4-(4-hydroxypiperidin-1-yl)butanoic acid
• 英文别名: 4-(4-Hydroxypiperidin-1-ium-1-yl)butanoate
• 化学式: C₉H₁₇NO₃
• 分子量: 187.239
• InChiKey: YMTDEUMSQQCFCK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.3
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  60.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(4-hydroxypiperidin-1-yl)butanoic acid 、 加替沙星 在 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以39%的产率得到
  参考文献：
  名称：

  加替沙星衍生物及其制备方法和用途

  摘要：

  本发明属于药物化学领域，具体涉及一种加替沙星衍生物及其制备方法和用途。本发明通过对加替沙星7位侧链进行结构修饰得到式I所示化合物，本发明的化合物不但能够对结核分支杆菌及普通细菌所致感染进行治疗，还对细菌持留菌、柑桔致病菌、烟酰胺N‑甲基转移酶(NNMT)、白细胞介素IL‑17 PPI及前蛋白转化酶枯草溶菌素9(PCSK9)具有抑制活性。本发明的化合物制备过程操作简便、条件温和，得到抗菌活性增强、水溶性提高、毒副作用降低的众多化合物，有望减少用药剂量、缩短治疗周期、提高患者依从性，为结核病药物和其他疾病研究提供新的分子类型与研究思路。

  公开号：

  CN107721924B
• 作为产物：
  描述：

  4-羟基哌啶 在 H₂O*(x)HLiO 、 碳酸氢钠 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 4-(4-hydroxypiperidin-1-yl)butanoic acid
  参考文献：
  名称：

  加替沙星衍生物及其制备方法和用途

  摘要：

  本发明属于药物化学领域，具体涉及一种加替沙星衍生物及其制备方法和用途。本发明通过对加替沙星7位侧链进行结构修饰得到式I所示化合物，本发明的化合物不但能够对结核分支杆菌及普通细菌所致感染进行治疗，还对细菌持留菌、柑桔致病菌、烟酰胺N‑甲基转移酶(NNMT)、白细胞介素IL‑17 PPI及前蛋白转化酶枯草溶菌素9(PCSK9)具有抑制活性。本发明的化合物制备过程操作简便、条件温和，得到抗菌活性增强、水溶性提高、毒副作用降低的众多化合物，有望减少用药剂量、缩短治疗周期、提高患者依从性，为结核病药物和其他疾病研究提供新的分子类型与研究思路。

  公开号：

  CN107721924B

文献信息

• Process for production of piperidine derivatives
  申请人：——

  公开号：US20030171590A1

  公开（公告）日：2003-09-11

  The present invention discloses processes for preparing piperidine derivative compounds of the formulae: 1 wherein n is 0 or 1; R 1 is hydrogen or hydroxy; R 2 is hydrogen; or, when n is 0, R 1 and R 2 taken together form a second bond between the carbon atoms bearing R 1 and R 2 , provided that when n is 1, R 1 and R 2 are each hydrogen; R 3 is —COOH or —COOR 4 ; R 4 is an alkyl or aryl moiety; A, B, and D are the substituents of their rings, each of which may be different or the same, and are selected from the group consisting of hydrogen, halogens, alkyl, hydroxy, alkoxy, and other substituents. One process comprises providing a regioisomer of the following formula: 2 wherein Z is —CG 1 G 2 G 3 , 3 m is an integer from 1 to 6; Q and Y are the same or different and are selected from the group consisting of O, S, and NR 5 ; G 1 , G 2 , and G 3 are the same or different and are selected from the group consisting of OR 8 , SR 8 , and NR 8 R 9 ; X 3 is halogen, OR 15 , SR 15 , NR 15 R 16 , OSO 2 R 15 , or NHSO 2 R 15 ; R 6 and R 7 are the same or different and are selected from the group consisting of hydrogen, an alkyl moiety, an aryl moiety, OR 8 , SR 8 , and NR 8 R 9 ; and R 5 , R 8 , R 9 , R 15 , and R 16 are the same or different and are selected from the group consisting of hydrogen, an alkyl moiety, and an aryl moiety and converting the regioisomer to the piperidine derivative compound with a piperidine compound. Another process for producing piperidine derivative compounds comprises providing an &agr;,&agr;-disubstituted-methylbenzene derivative having the formula: 4 wherein X 1 is a halogen, trialkyl or triaryl tin, trialkyl or triaryl borate, trialkyl silicon, alkylhalo silicon, a substituted sulfonic ester, or substituents useful in organometallic coupling reactions and converting the &agr;,&agr;-disubstituted-methylbenzene derivative to the piperidine derivative compound with a piperidine compound. In yet another process, a 4-(&agr;,&agr;-disubstituted)-toluic acid derivative having the formula: 5 wherein X 2 is a halogen; an alkali metal oxide; a moiety having the formula —OR 10 ; a moiety having the formula —SR 10 ; or an amine; and R 10 is selected from the group consisting of hydrogen, an alkyl moiety, and an aryl moiety is provided and converted to the piperidine derivative compound with a piperidine compound.

  本发明披露了制备以下式的哌啶衍生物化合物的过程：其中n为0或1；R1为氢或羟基；R2为氢；或者当n为0时，R1和R2在承载R1和R2的碳原子之间形成第二个键，但当n为1时，R1和R2分别为氢；R3为—COOH或—COOR4；R4为烷基或芳基基团；A、B和D为它们的环的取代基，每个取代基可以不同或相同，并且从氢、卤素、烷基、羟基、烷氧基和其他取代基的群中选择。其中一种过程包括提供以下式的区域异构体：其中Z为—CG1G2G3，3m为1到6的整数；Q和Y相同或不同，选自O、S和NR5的群；G1、G2和G3相同或不同，选自OR8、SR8和NR8R9的群；X3为卤素、OR15、SR15、NR15R16、OSO2R15或NHSO2R15；R6和R7相同或不同，选自氢、烷基基团、芳基基团、OR8、SR8和NR8R9；以及R5、R8、R9、R15和R16相同或不同，选自氢、烷基基团和芳基基团，并将区域异构体转化为哌啶衍生物化合物。另一种制备哌啶衍生物化合物的方法包括提供具有以下式的α，α-二取代甲基苯衍生物：其中X1为卤素、三烷基或三芳基锡、三烷基或三芳基硼酸酯、三烷基硅、烷基卤硅、取代磺酸酯或有机金属偶合反应中有用的取代基，并用哌啶化合物将α，α-二取代甲基苯衍生物转化为哌啶衍生物化合物。在另一种方法中，提供具有以下式的4-（α，α-二取代）-甲苯酸衍生物：其中X2为卤素；碱金属氧化物；具有式—OR10的基团；具有式—SR10的基团；或者胺；并用哌啶化合物将其转化为哌啶衍生物化合物。
• PROCESS FOR PRODUCTION OF PIPERIDINE DERIVATIVES
  申请人：D'AMBRA Thomas E.

  公开号：US20100010227A1

  公开（公告）日：2010-01-14

  The present invention discloses a process for preparing the piperidine derivative compound 4-[4-[4-hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylphenylacetic acid of formula comprising the sequential steps of: (1) reacting 4-bromo-α,α-dimethyl-α-(4,4-dimethylisoxazolin-2-yl)toluene with 4-chlorobutyryl chloride to provide 4-(4-chloro-1-oxobutyl)-α,α-dimethyl-α-(4,4-dimethylisoxazolin-2-yl)toluene; (2) hydrolyzing said 4-(4-chloro-1-oxobutyl)-α,α-dimethyl-α-(4,4-dimethylisoxazolin-2-yl)toluene to provide 4-(4-chloro-1-oxobutyl)-α,α-dimethylphenylacetic acid; (3) reacting said 4-(4-chloro-1-oxobutyl)-α,α-dimethylphenylacetic acid with methanol to provide methyl 4-(4-chloro-1-oxobutyl)-α,α-dimethylphenylacetate; (4) reacting said methyl 4-(4-chloro-1-oxobutyl)-α,α-dimethylphenylacetate with 4-(α,α-diphenyl)piperidinemethanol to provide methyl 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-oxobutyl]-α,α-dimethylphenylacetate; (5) reducing said methyl 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-oxobutyl]-α,α-dimethylphenylacetate to provide methyl 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylphenylacetate; and (6) hydrolyzing said methyl 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylphenylacetate to provide said 4-[4-[4-hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylphenylacetic acid.

  本发明揭示了一种制备式为4-[4-[4-羟基二苯甲基)-1-哌啶基]-1-羟基丁基]-α，α-二甲基苯乙酸的哌啶衍生物化合物的方法，包括以下步骤：(1)将4-溴-α,α-二甲基-α-(4,4-二甲基异恶唑-2-基)甲苯与4-氯丁酰氯反应，得到4-(4-氯-1-氧代丁基)-α,α-二甲基-α-(4,4-二甲基异恶唑-2-基)甲苯；(2)水解所述的4-(4-氯-1-氧代丁基)-α,α-二甲基-α-(4,4-二甲基异恶唑-2-基)甲苯，得到4-(4-氯-1-氧代丁基)-α,α-二甲基苯乙酸；(3)将所述的4-(4-氯-1-氧代丁基)-α,α-二甲基苯乙酸与甲醇反应，得到甲基4-(4-氯-1-氧代丁基)-α,α-二甲基苯乙酸酯；(4)将所述的甲基4-(4-氯-1-氧代丁基)-α,α-二甲基苯乙酸酯与4-(α,α-二苯基)哌啶甲醇反应，得到甲基4-[4-[4-(羟基二苯甲基)-1-哌啶基]-1-氧代丁基]-α,α-二甲基苯乙酸酯；(5)将所述的甲基4-[4-[4-(羟基二苯甲基)-1-哌啶基]-1-氧代丁基]-α，α-二甲基苯乙酸酯还原，得到甲基4-[4-[4-(羟基二苯甲基)-1-哌啶基]-1-羟基丁基]-α，α-二甲基苯乙酸酯；(6)水解所述的甲基4-[4-[4-(羟基二苯甲基)-1-哌啶基]-1-羟基丁基]-α，α-二甲基苯乙酸酯，得到所述的4-[4-[4-羟基二苯甲基)-1-哌啶基]-1-羟基丁基]-α，α-二甲基苯乙酸。
• Characterization of Photodegradation Products of Bepotastine Besilate and In Silico Evaluation of Their Physicochemical, Absorption, Distribution, Metabolism, Excretion and Toxicity Properties
  作者：Dilip Kumar Singh、Archana Sahu、Aabid Abdullah Wani、Prasad V. Bharatam、Asit K. Chakraborti、Sanjeev Giri、Saranjit Singh

  DOI：10.1016/j.xphs.2020.03.004

  日期：2020.6

  Bepotastine (BPT) is a H-1-receptor antagonist. It is used as a besilate salt in ophthalmic solution for allergic conjunctivitis and orally for the treatment of allergic rhinitis and urticaria/pruritus. Its systematic forced degradation study is unreported. The same was carried out in different conditions prescribed by International Conference on Harmonisation. The stressed solutions were subjected to reversed phase liquid chromatographic analysis, and BPT was observed to be labile under photobasic condition only, yielding 5 photodegradation products. The structures of the latter were elucidated from data generated by liquid chromatography-high-resolution mass spectrometry and multistage mass spectrometry. Of the 5, 4 products were further isolated and subjected to nuclear magnetic resonance spectroscopy to justify the proposed structures. Two of them, with similar accurate mass, were additionally and unambiguously characterized from their heteronuclear multiple bond correlation data, hydrogen deuterium exchange mass data, and quantum chemical analysis using density functional theory calculations. One degradation product had a structure that could only be explained by unusual rearrangement involving conversions of N-oxide into hydroxylamine, similar to Meisenheimer rearrangement. The physicochemical, as well as absorption, distribution, metabolism, excretion, and toxicity properties of BPT and its characterized photodegradation products were evaluated in silico by ADMET Predictor (TM) software. (C) 2020 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
• EP0877733A4
  申请人：——

  公开号：EP0877733A4

  公开（公告）日：1999-03-31
• US6201124B1
  申请人：——

  公开号：US6201124B1

  公开（公告）日：2001-03-13