4-[4-(1-ethoxycarbonyl-1-methylethoxy)phenyl]-butyric acid | 425675-42-9

• 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: 4-[4-(1-ethoxycarbonyl-1-methylethoxy)phenyl]-butyric acid
• 英文别名: 4-(2-ethoxy-1,1-dimethyl-2-oxoethoxy)benzenebutanoic acid；4-(4-((1-ethoxy-2-methyl-1-oxopropan-2-yl)oxy)phenyl)butanoic acid；4-(4-(2-ethoxy-1,1-dimethyl-2-oxoethoxy)phenyl)butanoic acid；4-[4-(1-Ethoxycarbonyl-1-methylethoxy)phenyl]butyric acid；4-[4-(1-ethoxy-2-methyl-1-oxopropan-2-yl)oxyphenyl]butanoic acid
• CAS: 425675-42-9
• 化学式: C₁₆H₂₂O₅
• 分子量: 294.348
• InChiKey: UIEHADJKDNEJJF-UHFFFAOYSA-N

物化性质

• 熔点：
  119-122 °C
• 沸点：
  423.4±25.0 °C(Predicted)
• 密度：
  1.132±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-[4-(1-ethoxycarbonyl-1-methylethoxy)phenyl]-butyric acid 在 吡啶 、 草酰氯 、 camphor-10-sulfonic acid 、 sodium hydroxide 作用下， 以 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 13.5h， 生成 2-[4-[3-[2,5-二氢-1-[(4-甲基苯基)甲基]-5-氧代-1H-1,2,4-T噻唑-3-基]丙基]苯氧基]-2-甲基-丙酸
  参考文献：
  名称：

  PPARα激动剂LY518674的收敛千克级合成：新型酸介导的三唑酮合成的发现

  摘要：

  描述了PPARα激动剂LY518674（1）的第一公斤级合成。从头聚合方法包括偶联两个快速组装的组分，通过新型的酸促进的环化反应形成三唑酮和最后一步皂化，通过八步共六步最长的线性顺序，以32.5％的总收率递送该化合物。在4-羟基苯基丁酸的二价阴离子上进行区域选择性烷基化，可以直接制备会聚偶联伙伴之一的羧酸12，并且非常规的溶剂作用使脲基可以在受保护的肼上安装，从而可以对苯二酚进行区域特异性制备。其他偶合剂，甲磺酸氨基脲17。发现磺酸以实现所需的三唑酮环的形成，得到25从耦合前体酰基氨基脲23。以下的皂化25至1，乙酸乙酯提取物之间的宽溶解性差异1和溶液1于无水乙酸乙酯在最后结晶步骤以提供高收率和高纯度的最终化合物利用。在一系列其他底物上进一步评估了新型酸介导的三唑酮的形成，显示出该新方法与现有的碱介导的三唑酮合成在很大程度上互补。

  DOI：

  10.1021/op700040v
• 作为产物：
  描述：

  2-溴-2-甲基丙酸乙酯 、 4-(4-羟基苯基)丁酸 在 sodium ethanolate 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 反应 1.5h， 以95.5%的产率得到4-[4-(1-ethoxycarbonyl-1-methylethoxy)phenyl]-butyric acid
  参考文献：
  名称：

  PPARα激动剂LY518674的收敛千克级合成：新型酸介导的三唑酮合成的发现

  摘要：

  描述了PPARα激动剂LY518674（1）的第一公斤级合成。从头聚合方法包括偶联两个快速组装的组分，通过新型的酸促进的环化反应形成三唑酮和最后一步皂化，通过八步共六步最长的线性顺序，以32.5％的总收率递送该化合物。在4-羟基苯基丁酸的二价阴离子上进行区域选择性烷基化，可以直接制备会聚偶联伙伴之一的羧酸12，并且非常规的溶剂作用使脲基可以在受保护的肼上安装，从而可以对苯二酚进行区域特异性制备。其他偶合剂，甲磺酸氨基脲17。发现磺酸以实现所需的三唑酮环的形成，得到25从耦合前体酰基氨基脲23。以下的皂化25至1，乙酸乙酯提取物之间的宽溶解性差异1和溶液1于无水乙酸乙酯在最后结晶步骤以提供高收率和高纯度的最终化合物利用。在一系列其他底物上进一步评估了新型酸介导的三唑酮的形成，显示出该新方法与现有的碱介导的三唑酮合成在很大程度上互补。

  DOI：

  10.1021/op700040v

文献信息

• [EN] PYRAZOLONE COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS À BASE DE PYRAZOLONE ET LEURS UTILISATIONS
  申请人：INCEPTION 2 INC

  公开号：WO2015123133A1

  公开（公告）日：2015-08-20

  The invention disclosed herein is directed to compounds of Formula I [Formula should be entered here] and pharmaceutically acceptable salts thereof, which are useful in the treatment of prostate, breast, colon, pancreatic, human chronic lymphocytic leukemia, acute or chronic myeloid leukemia, melanoma, and other cancers. The invention also includes pharmaceutical compositions comprising a therapeutically effective amount of compound of Formula I, or a pharmaceutically acceptable salt thereof. The invention disclosed herein is also directed to methods of treating prostate, breast, ovarian, liver, kidney, colon, pancreatic, human chronic lymphocytic leukemia, acute or chronic myeloid leukemia, melanoma and other cancers. The invention disclosed herein is further directed to methods of treating prostate, breast, ovarian, liver, kidney, colon, pancreatic, human chronic lymphocytic leukemia, acute or chronic myeloid leukemia, melanoma and other cancers through the administration of a therapeutically effective amount of a selective PPARα antagonist. The compounds and pharmaceutical compositions of the invention are also useful in the treatment of viral infections, such as HCV infections and HIV infections.

  本发明涉及一种具有化学式I的化合物及其药学上可接受的盐，该化合物在前列腺、乳腺、结肠、胰腺、人类慢性淋巴细胞白血病、急性或慢性髓细胞白血病、黑色素瘤和其他癌症的治疗中有用。该发明还包括包含化合物I的治疗有效量或其药学上可接受的盐的药物组合物。本发明还涉及治疗前列腺、乳腺、卵巢、肝脏、肾脏、结肠、胰腺、人类慢性淋巴细胞白血病、急性或慢性髓细胞白血病、黑色素瘤和其他癌症的方法。本发明还涉及通过给予选择性PPARα拮抗剂的治疗有效量来治疗前列腺、乳腺、卵巢、肝脏、肾脏、结肠、胰腺、人类慢性淋巴细胞白血病、急性或慢性髓细胞白血病、黑色素瘤和其他癌症的方法。该发明的化合物和药物组合物还可用于治疗病毒感染，如HCV感染和HIV感染。
• Peroxisome proliferator activated receptor alpha agonists
  申请人：——

  公开号：US20040102500A1

  公开（公告）日：2004-05-27

  The present invention is directed to compounds represented by the following structural formula, and pharmaceutically acceptable salts, solvates and hydrates thereof, R1 is a substituted or unsubstituted group selected from C 1 -C 8 alkyl, aryl-C 0-2 -alkyl, heteroaryl-C 0-2 -alkyl, C 3 -C 6 cycloalkylaryl-C 0-2 -alkyl or phenyl. W is O or S. R2 is H or a substituted or unsubstituted group selected from C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl and heteroaryl. X is a C 2 -C 5 alkylene linker wherein one carbon atom of the linker may be replaced with O, NH or S. Y is C, O, S, NH or a single bond. Furthermore, E is (CH 2 ) n COOH, wherein n is 0, 1, 2 or 3, or C(R3)(R4)A, wherein A is an acidic functional group such as carboxyl, carboxamide substituted or unsubstituted sulfonamide, or substituted or unsubstituted tetrazole. R3 is H, saturated or unsaturated C 1 -C 5 alkyl, C 1 -C 5 alkoxy. Additionally, R4 is H, halo, a substituted or unsubstituted group selected from C 1 -C 5 alkyl, C 1 -C 5 alkoxy, C 3 -C 6 cycloalkyl, arylC 0 -C 4 alkyl and phenyl, or R3 and R4 are combined to form a C 3 -C 4 cycloalkyl.

  本发明涉及以下结构式所代表的化合物，以及其药用可接受的盐、溶剂化合物和水合物，其中R1是从C1-C8烷基、芳基-C0-2-烷基、杂环芳基-C0-2-烷基、C3-C6环烷基芳基-C0-2-烷基或苯基中选择的取代或未取代基团。W是O或S。R2是H或从C1-C6烷基、C3-C6环烷基和杂环芳基中选择的取代或未取代基团。X是一个C2-C5烷基亚甲基连接物，其中连接物的一个碳原子可以被O、NH或S取代。Y是C、O、S、NH或一个单键。此外，E是(CH2)nCOOH，其中n为0、1、2或3，或C(R3)(R4)A，其中A是酸性官能团，如羧基、羧酰胺取代或未取代的磺酰胺，或取代或未取代的四唑。R3是H、饱和或不饱和的C1-C5烷基、C1-C5烷氧基。另外，R4是H、卤素、从C1-C5烷基、C1-C5烷氧基、C3-C6环烷基、芳基-C0-C4烷基和苯基中选择的取代或未取代基团，或者R3和R4组合形成一个C3-C4环烷基。
• PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA AGONISTS
  申请人：Cano Ivan Collado

  公开号：US20090062358A1

  公开（公告）日：2009-03-05

  The present invention is directed to compounds represented by the following structural formula, and pharmaceutically acceptable salts, solvates and hydrates thereof, R1 is a substituted or unsubstituted group selected from C 1 -C 8 alkyl, aryl-C 0-2 -alkyl, heteroaryl-C 0-2 -alkyl, C3-C6 cycloalkylaryl-C 0-2 -alkyl or phenyl. W is O or S. R2 is H or a substituted or unsubstituted group selected from C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl and heteroaryl. X is a C 2 -C 5 alkylene linker wherein one carbon atom of the linker may be replaced with O, NH or S. Y is C, O, S, NH or a single bond. Furthermore, E is (CH 2 ) n COOH, wherein n is 0, 1, 2 or 3, or C(R3)(R4)A, wherein A is an acidic functional group such as carboxyl, carboxamide substituted or unsubstituted sulfonamide, or substituted or unsubstituted tetrazole. R3 is H, saturated or unsaturated C 1 -C 5 alkyl, C 1 -C 5 alkoxy. Additionally, R4 is H, halo, a substituted or unsubstituted group selected from C 1 -C 5 alkyl, C 1 -C 5 alkoxy, C 3 -C 6 cycloalkyl, arylC 0 -C 4 alkyl and phenyl, or R3 and R4 are combined to form a C 3 -C 4 cycloalkyl.

  本发明涉及以下结构式所代表的化合物，以及其药学上可接受的盐、溶剂合物和水合物，其中，R1是C1-C8烷基、芳基-C0-2-烷基、杂芳基-C0-2-烷基、C3-C6环烷基芳基-C0-2-烷基或苯基的取代或未取代基团。W为O或S。R2为H或C1-C6烷基、C3-C6环烷基和杂芳基的取代或未取代基团。X为C2-C5烷基链，在链中的一个碳原子可以被O、NH或S取代。Y为C、O、S、NH或单键。此外，E为(CH2)nCOOH，其中n为0、1、2或3，或C(R3)(R4)A，其中A为酸性功能基团，如羧基、羧酰基取代或未取代的磺酰胺基、取代或未取代的四唑基。R3为H、饱和或不饱和的C1-C5烷基、C1-C5烷氧基。此外，R4为H、卤素、C1-C5烷基、C1-C5烷氧基、C3-C6环烷基、芳基C0-C4烷基和苯基的取代或未取代基团，或R3和R4结合形成C3-C4环烷基。
• [EN] PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA AGONISTS<br/>[FR] AGONISTES DE RECEPTEURS ALPHA ACTIVES DE LA PROLIFERATION DES PEROXYSOMES
  申请人：LILLY CO ELI

  公开号：WO2002038553A2

  公开（公告）日：2002-05-16

  he present invention is directed to compounds represented by the following structural formula (I'), and pharmaceutically acceptable salts, solvates and hydrates thereof, R1 is a substituted or unsubstituted group selected from C1-C8 alkyl, aryl-C0-2-alkyl, heteroaryl-C0-2-alkyl, C3-C6 cycloalkylaryl-C0-2-alkyl or phenyl. W is O or S. R2 is H or a substituted or unsubstituted group selected from C1-C6 alkyl, C3-C6 cycloalkyl and heteroaryl. X is a C2-C5 alkylene linker wherein one carbon atom of the linker may be replaced with O, NH or S. Y is C, O, S, NH or a single bond. Furthermore, E is (CH2)nCOOH, wherein n is 0, 1, 2 or 3, or C(R3)(R4)A, wherein A is an acidic functional group such as carboxyl, carboxamide substituted or unsubstituted sulfonamide, or substituted or unsubstituted tetrazole. R3 is H, saturated or unsaturated C1-C5 alkyl, C1-C5 alkoxy. Additionally, R4 is H, halo, a substituted or unsubstituted group selected from C1-C5 alkyl, C1-C5 alkoxy, C3-C6 cycloalkyl, arylC0-C4alkyl and phenyl, or R3 and R4 are combined to form a C3-C4 cycloalkyl.

  本发明涉及如下所示结构式(I')表示的化合物及其药学上可接受的盐、溶剂化物和水合物。R1是自C1-C8烷基、C0-2烷基芳基、C0-2烷基杂芳基、C3-C6环烷基芳基-C0-2烷基或苯基中选择的取代或未取代基团。W是O或S。R2是H，或自C1-C6烷基、C3-C6环烷基和杂芳基中选择的取代或未取代基团。X是C2-C5亚烷基连接基团，其中连接基团的一个碳原子可被O、NH或S替换。Y是C、O、S、NH或单键。此外，E是(CH2)nCOOH，其中n=0、1、2或3，或C(R3)(R4)A，其中A为酸性功能基团，如羧基、羧酸酰胺、取代或未取代磺酰胺，或取代或未取代的四氮唑。R3是H、饱和或不饱和C1-C5烷基、C1-C5烷氧基。另外，R4是H、卤素、自C1-C5烷基、C1-C5烷氧基、C3-C6环烷基、C0-C4烷基芳基和苯基中选择的取代或未取代基团，或R3和R4结合形成C3-C4环烷基。
• The Role of New Technologies in Defining a Manufacturing Process for PPARα Agonist LY518674
  作者：Mark D. Argentine、Timothy M. Braden、Jeffrey Czarnik、Edward W. Conder、Steven E. Dunlap、Jared W. Fennell、Mark A. LaPack、Roger R. Rothhaar、R. Brian Scherer、Christopher R. Schmid、Jeffrey T. Vicenzi、Jeffrey G. Wei、John A. Werner、Robert T. Roginski

  DOI：10.1021/op8002486

  日期：2009.3.20

  The impact of several new technologies on the development of a manufacturing process for LV518674 is described. Extensive use of process analytical technology (PAT) throughout development, both at laboratory and pilot-plant scale, enabled data-rich experiments, shortened development cycle times, and obviated the requirement of PAT for process control at larger scale. In situ ReactIR was used to develop a kinetic model for a one-pot preparation of a semicarbazide intermediate. Parallel crystallizers fitted with online focused-beam reflectance measurement (FBRM) and particle vision and measurement (PVM) probes were used in the development of several challenging crystallization processes. Application of the process knowledge afforded by these technologies, combined with the principles of Quality by Design, resulted in excellent purity control throughout the four-step process. A single, 5-min, MS-friendly method capable of separating over 30 components was developed using a combination of chromatography modeling software, sub-2 mu m column technology, and higher-pressure LC equipment. The method was used across all four processing steps, greatly facilitating impurity tracking, and reducing assay time and solvent use by 85% and 93%, respectively.