4-(diethylamino)butyric acid hydrochloride | 42060-21-9

• 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-(diethylamino)butyric acid hydrochloride
• 英文别名: 4-Diaethylamino-buttersaeure; Hydrochlorid；4-(diethylamino)butanoic acid;hydrochloride
• CAS: 42060-21-9
• 化学式: C₈H₁₇NO₂*ClH
• 分子量: 195.689
• InChiKey: ZRHAADCYUIHWGZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.61
• 重原子数：
  12
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(diethylamino)butyric acid hydrochloride 、 多西他赛 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 42.0h， 以63%的产率得到2’-O-(4-(N,N-diethylamino)butanoyl)docetaxel hydrochloride
  参考文献：
  名称：

  [EN] TREATING EPHRIN RECEPTOR A2 (EPHA2) POSITIVE CANCER WITH TARGETED DOCETAXEL-GENERATING NANO-LIPOSOME COMPOSITIONS
  [FR] TRAITEMENT DU CANCER POSITIF AU RÉCEPTEUR DE L'ÉPHRINE A2 (EPHA2) AVEC DES COMPOSITIONS DE NANOLIPOSOMES CIBLÉS DE GÉNÉRATION DE DOCÉTAXEL

  摘要：

  EphA2靶向阿霉素生成的纳米脂质体在治疗过表达EphA2的癌症方面非常有用，可以单独使用，也可以与吉西他滨或卡铂等化疗药物联合使用。

  公开号：

  WO2017161071A1
• 作为产物：
  描述：

  4-(二乙基氨基)丁酸乙酯 在 盐酸 作用下， 以 水 为溶剂， 反应 8.0h， 生成 4-(diethylamino)butyric acid hydrochloride
  参考文献：
  名称：

  Formulation optimization of an ephrin A2 targeted immunoliposome encapsulating reversibly modified taxane prodrugs

  摘要：

  Ephrin A2 targeted immunoliposomes incorporating pH-sensitive taxane prodrugs were developed for sustained delivery of active drug to solid tumors. Here we describe the systematic formulation development and characterization of these immunoliposomes. We synthesized both paclitaxel and docetaxel prodrugs to formulate as ephrin A2-targeted liposomes stabilized in the aqueous core with sucroseoctasulfate (SOS). The optimized lipid formulation was comprised of egg-sphingomyelin, cholesterol, and polyethylene glycol distearoyl glycerol (PEG-DSG). The formulations examined had a high efficiency of prodrug encapsulation (as high as 114 mol% taxane per mole phospholipid) and subsequent stability (> 3 years at 2-8 degrees C). The taxane prodrug was stabilized with extraliposomal citric acid and subsequently loaded into liposomes containing a gradient of SOS, resulting in highly stable SOS-drug complexes being formed inside the liposome. The internal prodrug and SOS concentrations were optimized for their impact on in vivo drug release and drug degradation. Cryo-electron microscope images revealed dense prodrug-SOS complex in the aqueous core of the immunoliposomes. Ephrin A2-targeted taxane liposomes exhibited sub-nanomolar (0.69 nM) apparent equilibrium dissociation constant toward the extracellular domain of the ephrin A2 receptor, long circulation half-life (8-12 h) in mouse plasma, a release rate dependent on intraliposomal drug concentration and stable long-term storage. At an equitoxic dose of 50 mg taxane/kg, ephrin A2-targeted liposomal prodrug showed greater antitumor activity than 10 mg/kg of docetaxel in A549 non-small cell lung, as well as MDA-MB-436 and SUM149 triple negative breast cancer xenograft models. The lead molecule entered a Phase I clinical trial in patients with solid tumors (NCT03076372).

  DOI：

  10.1016/j.jconrel.2019.08.006

文献信息

• [EN] EPHRIN RECEPTOR A2 (EPHA2)-TARGETED DOCETAXEL-GENERATING NANO-LIPOSOME COMPOSITIONS<br/>[FR] COMPOSITIONS DE NANOLIPOSOMES GÉNÉRANT DU DOCÉTAXEL ET CIBLANT LE RÉCEPTEUR DE L'ÉPHRINE A2 (EPHA2)
  申请人：MERRIMACK PHARMACEUTICALS INC

  公开号：WO2017161067A1

  公开（公告）日：2017-09-21

  EphA2-targeted immunoliposomes for delivering docetaxel are useful in the treatment of certain types of cancer. The immunoliposomes can include an EphA2 targeting moiety (e.g., a scFv) and encapsulate a docetaxel prodrug in a stable salt form within a liposome having an average size of about 100 nm. Novel docetaxel prodrugs suitable for loading into nanoliposomes (including immunoliposomes) are provided, along with novel and other useful EphA2 targeting moieties for preparation of EphA2-targeted doxorubicin-generating immunoliposome therapies. Pharmaceutical compositions can be prepared that include nanoliposomes encapsulating one or more docetaxel prodrugs, and/or immunoliposomes or nanoparticles comprising an EphA2 binding moiety and encapsulating one or more docetaxel prodrugs. The pharmaceutical compositions are useful for administration to a patient for the treatment of cancer.

  EphA2靶向免疫脂质体用于输送紫杉醇在治疗某些类型的癌症中是有用的。这些免疫脂质体可以包括EphA2靶向基团（例如，scFv），并在平均大小约为100纳米的脂质体内以稳定的盐形式封装紫杉醇前药。提供了适合装载到纳米脂质体（包括免疫脂质体）中的新型紫杉醇前药，以及用于制备EphA2靶向阿霉素生成免疫脂质体疗法的新型和其他有用的EphA2靶向基团。可以制备包含封装一个或多个紫杉醇前药的纳米脂质体和/或包含EphA2结合基团并封装一个或多个紫杉醇前药的免疫脂质体或纳米粒子的药物组合物。这些药物组合物对于用于治疗癌症的患者是有用的。
• [EN] IONIZABLE LIPIDS FOR NUCLEIC ACID DELIVERY<br/>[FR] LIPIDES IONISABLES POUR ADMINISTRATION D'ACIDES NUCLÉIQUES
  申请人：PREC NANOSYSTEMS INC

  公开号：WO2020252589A1

  公开（公告）日：2020-12-24

  The present document describes compounds, or pharmaceutically acceptable salt thereof, of a core formula (I) where R1 features an amine group, particularly useful in the formulation of lipid particles including nucleic acid therapeutic agents, or proteins, or both, and for delivery of nucleic acid and protein therapeutics to cells in vivo or ex vivo, including anticancer and vaccine applications.

  本文件描述了核心公式（I）的化合物或其药用可接受的盐，其中R1特征为胺基，特别适用于制备包括核酸治疗剂或蛋白质在内的脂质颗粒，并用于将核酸和蛋白质治疗剂递送到体内或体外的细胞中，包括抗癌和疫苗应用。
• Fumarate salt of
  申请人：——

  公开号：US05498419A1

  公开（公告）日：1996-03-12

  The present invention provides the fumarate salt of 4-(diethyl-3-(1-methyloctyl)-7,8,9,10-tetrahydro-6,6,9-trimethyl-6H-dibenz o[b,d]pyran-1-ol, 4-diethyl-amino)butyric acid ester, i.e. the compound having the following structure (I): ##STR1## and methods of treatment, particularly treatment of glaucoma, and pharmaceutical compositions that utilize or comprise the fumarate salt (I).

  本发明提供了4-（二乙基-3-（1-甲基辛基）-7,8,9,10-四氢-6,6,9-三甲基-6H-二苯并[b,d]吡喃-1-醇，4-二乙氨基）丁酸酯的富马酸盐，即具有以下结构（I）的化合物：##STR1##以及治疗方法，特别是治疗青光眼的制剂和利用或包含富马酸盐（I）的制药组合物。
• Intermediates for the preparation of thienobenzopyrans and
  申请人：Arthur D. Little, Inc.

  公开号：US03940421A1

  公开（公告）日：1976-02-24

  Novel thienobenzopyrans and thiopyranobenzopyrans represented by the formula ##SPC1## Wherein m and n are each 0, 1, 2 or 3 and m + n is 2 or 3; R.sub.1 is loweralkyl; R.sub.2 is alkyl or cycloalkylloweralkyl and R.sub.3 is hydrogen, loweralkyl, loweralkanoyl, carbamyl, N-loweralkylcarbamyl, N,N-diloweralkylcarbamyl, phosphonyl, hemisuccinate or an ester of another such acid, phosphate, dialkylaminoalkyl of the structure ##EQU1## or acid addition salt thereof, or dialkylaminoalkylanoyl of the structure ##EQU2## or acid addition salt thereof, wherein x is 1 through 6 and R.sub.4 and R.sub.5 are loweralkyl; the loweralkyl groups containing from 1 through 6 carbon atoms, the alkyl groups containing from 1 through 20 carbon atoms and the cycloalkyl groups containing from 3 through 8 ring carbon atoms. Novel intermediates for the synthesis of these compounds are also disclosed as well as methods for making the compounds.

  该专利涉及一种新型的噻吩并苯并吡喃和噻吩并苯并噻吩喹啉类化合物，其化学式为##SPC1##其中m和n分别为0、1、2或3，且m+n为2或3；R.sub.1为低碳基；R.sub.2为烷基或环烷基低碳基，R.sub.3为氢、低碳基、低碳酰基、氨基甲酰基、N-低碳基氨基甲酰基、N,N-二低碳基氨基甲酰基、磷酸酯、半琥珀酸或另一种酸的酯、磷酸酯、结构为##EQU1##的二烷基氨基烷基或其酸加成盐，或结构为##EQU2##的二烷基氨基烷酰基或其酸加成盐，其中x为1到6，R.sub.4和R.sub.5为低碳基；低碳基含1到6个碳原子，烷基含1到20个碳原子，环烷基含3到8个环碳原子。该专利还公开了合成这些化合物的新型中间体以及制备这些化合物的方法。
• Tetrahydropyrid-4-yl-chroman-5-ol derivatives
  申请人：Beecham Group Limited

  公开号：US03960880A1

  公开（公告）日：1976-06-01

  Compounds of the formula: ##SPC1## And their pharmaceutically acceptable non-toxic salts, wherein R.sub.1 is alkyl of 5 to 8 carbon atoms which is straight chained or .alpha.-substituted by a methyl group or .alpha.,.alpha.-disubstituted by methyl groups and R.sub.5 is hydrogen, R.sub.6 or CO.R.sub.6 wherein R.sub.6 is alkyl of 1 to 4 carbon atoms or alkyl of 1 to 4 carbon atoms substituted by NR.sub.7 R.sub.8 wherein R.sub.7 and R.sub.8 are each hydrogen or alkyl of 1 to 4 carbon atoms or NR.sub.7 R.sub.8 is pyrrolidino, piperidino or morpholino, have been found to possess good antihypertensive activity while being of low-toxicity and substantially free of sedative side effects.

  式子为：##SPC1##及其药学上可接受的无毒盐，其中R.sub.1是5到8个碳原子的直链或α-取代甲基或α，α-二取代甲基的烷基，R.sub.5是氢，R.sub.6或CO.R.sub.6，其中R.sub.6是1到4个碳原子的烷基或1到4个碳原子的烷基，其被NR.sub.7 R.sub.8取代，其中R.sub.7和R.sub.8均为氢或1到4个碳原子的烷基，或NR.sub.7 R.sub.8为吡咯烷基，哌啶基或吗啉基。发现这些化合物具有良好的降压活性，同时毒性低，基本没有镇静副作用。