5-oxo-5-[(2-phenylethyl)amino]pentanoic acid | 119627-14-4

• 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: 5-oxo-5-[(2-phenylethyl)amino]pentanoic acid
• 英文别名: 5-Oxo-5-[2-phenylethylamino]pentanoic acid；4-[(2-Phenylethyl)carbamoyl]butanoic acid；5-oxo-5-(2-phenylethylamino)pentanoic acid
• CAS: 119627-14-4
• 化学式: C₁₃H₁₇NO₃
• mdl: MFCD00029859
• 分子量: 235.283
• InChiKey: YDQWOZQRRHREID-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.384
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-oxo-5-[(2-phenylethyl)amino]pentanoic acid 在 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.5h， 生成 5-oxo-N-phenethyl-5-(2-propylhydrazineyl)pentanamide
  参考文献：
  名称：

  Marine Cytotoxin Santacruzamate A Derivatives as Potent HDAC1-3 Inhibitors and Their Synergistic Anti-Leukemia Effects with Venetoclax

  摘要：

  Acute myeloid leukemia (AML) is a hematologic malignancy characterized by infiltration of the blood and bone marrow, exhibiting a low remission rate and high recurrence rate. Current research has demonstrated that class I HDAC inhibitors can downregulate anti-apoptotic proteins, leading to apoptosis of AML cells. In the present investigation, we conducted structural modifications of marine cytotoxin Santacruzamate A (SCA), a compound known for its inhibitory activity towards HDACs, resulting in the development of a novel series of potent class I HDACs hydrazide inhibitors. Representative hydrazide-based compound 25c exhibited concentration-dependent induction of apoptosis in AML cells as a single agent. Moreover, 25c exhibited a synergistic anti-AML effect when combined with Venetoclax, a clinical Bcl-2 inhibitor employed in AML therapy. This combination resulted in a more pronounced downregulation of anti-apoptotic proteins Mcl-1 and Bcl-xL, along with a significant upregulation of the pro-apoptotic protein cleaved-caspase3 and the DNA double-strand break biomarker γ-H2AX compared to monotherapy. These results highlighted the potential of 25c as a promising lead compound for AML treatment, particularly when used in combination with Venetoclax.

  DOI：

  10.3390/md22060250
• 作为产物：
  描述：

  2-苯乙胺 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.5h， 生成 5-oxo-5-[(2-phenylethyl)amino]pentanoic acid
  参考文献：
  名称：

  Marine Cytotoxin Santacruzamate A Derivatives as Potent HDAC1-3 Inhibitors and Their Synergistic Anti-Leukemia Effects with Venetoclax

  摘要：

  Acute myeloid leukemia (AML) is a hematologic malignancy characterized by infiltration of the blood and bone marrow, exhibiting a low remission rate and high recurrence rate. Current research has demonstrated that class I HDAC inhibitors can downregulate anti-apoptotic proteins, leading to apoptosis of AML cells. In the present investigation, we conducted structural modifications of marine cytotoxin Santacruzamate A (SCA), a compound known for its inhibitory activity towards HDACs, resulting in the development of a novel series of potent class I HDACs hydrazide inhibitors. Representative hydrazide-based compound 25c exhibited concentration-dependent induction of apoptosis in AML cells as a single agent. Moreover, 25c exhibited a synergistic anti-AML effect when combined with Venetoclax, a clinical Bcl-2 inhibitor employed in AML therapy. This combination resulted in a more pronounced downregulation of anti-apoptotic proteins Mcl-1 and Bcl-xL, along with a significant upregulation of the pro-apoptotic protein cleaved-caspase3 and the DNA double-strand break biomarker γ-H2AX compared to monotherapy. These results highlighted the potential of 25c as a promising lead compound for AML treatment, particularly when used in combination with Venetoclax.

  DOI：

  10.3390/md22060250

文献信息

• AMIDE COMPOUNDS, METHODS FOR PREPARATION, AND USE THEREOF AS AGENTS FOR THE TREATMENT AND PREVENTION OF DISEASES CAUSED BY RNA- AND/OR DNA-CONTAINING VIRUSES, AND CONCOMITANT DISEASES
  申请人：OBSCHESTVO S OGRANICHENNOI OTVETSTVENNOSTIYU "PHARMENTERPRISES"

  公开号：US20170183318A1

  公开（公告）日：2017-06-29

  The present invention relates to medicine and includes a method for preventing and treating diseases caused by RNA- and DNA-containing viruses, and concomitant diseases, wherein the method comprises the use of an effective amount of compounds of general formula I or pharmaceutically acceptable salts thereof. The invention also relates to methods for preparing said compounds, pharmaceutical compositions for the prevention or treatment of diseases caused by RNA- and DNA-containing viruses, said compositions comprising an effective amount of a compound of formula I or a pharmaceutically acceptable salt thereof. The invention addresses the object of providing a novel agent effective in the treatment of diseases caused by an RNA-containing virus belonging to the Enterovirus, Metapneumovirus, Pneumovirus, Respirovirus, or Alfa-coronavirus genus, and/or by a DNA-containing virus belonging to the Adenoviridae and/or Herpesviridae family, and in the prevention and treatment of asthma exacerbation, chronic obstructive pulmonary disease, mucoviscidosis, conjunctivitis, gastroenteritis, hepatitis, myocarditis; in the prevention and treatment of rhinorrhea, acute and infectious rhinitis, pharyngitis, nasopharyngitis, tonsillitis, laryngitis, laryngotracheitis, laryngotracheobronchitis, bronchitis, bronchiolitis, pneumonia, or airway obstructive syndrome.

  本发明涉及医学，包括一种用于预防和治疗由RNA-和DNA-含病毒引起的疾病以及相关疾病的方法，其中该方法包括使用通式I的化合物或其药用可接受盐的有效量。该发明还涉及制备上述化合物的方法，用于预防或治疗由RNA-和DNA-含病毒引起的疾病的药物组合物，该组合物包括通式I的化合物或其药用可接受盐的有效量。该发明解决了提供一种新型药剂的目标，用于治疗属于肠病毒、副呼吸道病毒、呼吸道病毒、呼吸道病毒或阿尔法冠状病毒属的RNA-含病毒引起的疾病，和/或属于腺病毒科和/或疱疹病毒科的DNA-含病毒引起的疾病，并在预防和治疗哮喘急性发作、慢性阻塞性肺疾病、黏液囊病、结膜炎、胃肠炎、肝炎、心肌炎；在预防和治疗流涕、急性和感染性鼻炎、咽炎、鼻咽炎、扁桃体炎、喉炎、喉气管炎、喉气管支气管炎、支气管炎、支气管炎、肺炎或气道梗阻综合征方面具有有效性。
• 2-(3,4-Dihydroxyphenyl ethyl amines, their preparation and use as pharmaceutical compounds
  申请人：FISONS plc

  公开号：EP0292202A1

  公开（公告）日：1988-11-23

  There are described compounds of formula I,     in which     one of R₃₀ and R₄₀ represents a group Ra,     and the other of R₃₀ and R₄₀ represents hydrogen or halogen,     R₅₀ and R₆₀, which may be the same or different, each independently represent hydrogen or alkyl C 1 to C6; in addition R₆₀ may represent a group Rb,     wherein X represents a C2 to C8 alkylene chain optionally interrupted by a double bond or by S(0)n, wherein n is 0, 1 or 2, Z represents a C 1 to C3 alkylene chain, each of X and Z being optionally substituted by OH or one or more alkyl C 1 to C6,     R₇₀ represents hydrogen, alkyl C 1 to C6 or (CH₂)qR₁₁,     R₁₀ and R₁₁ independently represent phenyl substituted by one or more substituents R₂₃, which may be the same or different; or R₁₀ represents a saturated carbocyclic group,     R₁₅ represents hydrogen, alkyl C 1 to C6, or together with R₂₃ forms a (CH₂)p chain, wherein p represents 0, 1 or 2,     R₂₀, R₂₁, R₂₂ and R₂₃ independently represent hydrogen, alkyl C 1 to C6, NHR₂₅, SH, NO₂, halogen, CF₃, SO₂R₂₆, CH₂₀H or OH, wherein R₂₅ represents hydrogen, alkyl C 1 to C6 or alkanoyl C 1 to C6 and R₂₆ represents alkyl C 1 to C6 or NH₂     l represents 2, 3 or 4,     q represents an integer from 1 to 6 inclusive,     provided that when R₄₀, R₅₀ and R₇₀ each represent hydrogen and R₆₀ represents Rb,     then Ra represents 2(3-hydroxyphenyl)ethyl, R₁₅ represents hydrogen and either a) X represents (CH₂)p, in which p is 3, 5, 7 or 8 or b) at least one of X and Z is substituted by either OH or one or more alkyl C 1 to C6,     and pharmaceutically acceptable salts and solvates thereof. There are also described processes for the preparation of the compounds of formula I and pharmaceutical compositions containing them. The compounds of the invention may be used in the treatment or prophylaxis of renal failure or cardiovascular disorders.

  所述化合物为式 I、 其中 R₃₀ 和 R₄₀ 中的一个代表基团 Ra、 而 R₃₀ 和 R₄₀ 的另一个代表氢或卤素、 R₅₀ 和 R₆₀ 可以相同或不同，各自独立地代表氢或 C 1 至 C6 烷基；此外，R₆₀ 可以代表一个基团 Rb、 其中 X 代表任选被双键或 S(0)n（其中 n 为 0、1 或 2）打断的 C2 至 C8 亚烷基链，Z 代表 C 1 至 C3 亚烷基链，X 和 Z 各自任选被 OH 或一个或多个 C 1 至 C6 烷基取代、 R₇₀ 代表氢、C 1 至 C6 烷基或 (CH₂)qR₁₁、 R₁₀ 和 R₁₁ 独立地代表被一个或多个取代基 R₂₃ 取代的苯基，这些取代基可以相同或不同；或者 R₁₀ 代表饱和碳环基团、 R₁₅ 代表氢、C 1 至 C6 烷基，或与 R₂₃ 共同形成 (CH₂)p 链，其中 p 代表 0、1 或 2、 R₂₀、R₂₁、R₂₂ 和 R₂₃ 独立地代表氢、C 1 至 C6 烷基、NHR₂₅、SH、NO₂、卤素、CF₃、SO₂R₂₆、CH₂₀H 或 OH，其中 R₂₅代表氢、C 1 至 C6 烷基或 C 1 至 C6 烷酰基，R₂₆代表 C 1 至 C6 烷基或 NH₂ l 代表 2、3 或 4、 q 代表 1 至 6（包括 6）的整数、 但当 R₄₀、R₅₀ 和 R₇₀ 各自代表氢且 R₆₀ 代表 Rb、 则 Ra 代表 2(3-羟基苯基)乙基，R₁₅ 代表氢，且其中一个 a) X 代表 (CH₂)p，其中 p 为 3、5、7 或 8 或 b) X 和 Z 中至少有一个被 OH 或一个或多个 C 1 至 C6 烷基取代、 及其药学上可接受的盐和溶剂。 此外，还描述了制备式 I 化合物和含有它们的药物组合物的工艺。本发明的化合物可用于治疗或预防肾功能衰竭或心血管疾病。
• AMIDE COMPOUNDS AND METHODS FOR THE PRODUCTION AND USE THEREOF
  申请人：Obschestvo S Ogranichennoi Otvetstennostiyu "Pharmenterprises"

  公开号：EP3118211A1

  公开（公告）日：2017-01-18

  The present invention relates to medicine and includes a method for preventing and treating diseases caused by RNA- and DNA-containing viruses, and concomitant diseases, wherein the method comprises the use of an effective amount of compounds of general formula I or pharmaceutically acceptable salts thereof. The invention also relates to methods for preparing said compounds, pharmaceutical compositions for the prevention or treatment of diseases caused by RNA- and DNA-containing viruses, said compositions comprising an effective amount of a compound of formula I or a pharmaceutically acceptable salt thereof. The invention addresses the object of providing a novel agent effective in the treatment of diseases caused by an RNA-containing virus belonging to the Enterovirus, Metapneumovirus, Pneumovirus, Respirovirus, or Alfa-coronavirus genus, and/or by a DNA-containing virus belonging to the Adenoviridae and/or Herpesviridae family, and in the prevention and treatment of asthma exacerbation, chronic obstructive pulmonary disease, mucoviscidosis, conjunctivitis, gastroenteritis, hepatitis, myocarditis; in the prevention and treatment of rhinorrhea, acute and infectious rhinitis, pharyngitis, nasopharyngitis, tonsillitis, laryngitis, laryngotracheitis, laryngotracheobronchitis, bronchitis, bronchiolitis, pneumonia, or airway obstructive syndrome.

  本发明涉及医药，包括一种预防和治疗由含RNA和DNA病毒引起的疾病以及伴随疾病的方法，其中该方法包括使用有效量的通式I化合物或其药学上可接受的盐。本发明还涉及制备所述化合物的方法、用于预防或治疗由含 RNA 和 DNA 病毒引起的疾病的药物组合物，所述组合物包含有效量的通式 I 化合物或其药学上可接受的盐。本发明的目的是提供一种新型制剂，有效治疗由肠病毒属、偏肺病毒属、肺炎病毒属、呼吸道病毒属或阿法-冠状病毒属的含 RNA 病毒引起的疾病、和/或属于腺病毒科和/或疱疹病毒科的含 DNA 病毒，以及预防和治疗哮喘加重、慢性阻塞性肺病、粘液粘稠病、结膜炎、肠胃炎、肝炎、心肌炎；预防和治疗鼻炎、急性和感染性鼻炎、咽炎、鼻咽炎、扁桃体炎、喉炎、喉气管炎、喉气管支气管炎、支气管炎、支气管炎、肺炎或气道阻塞综合征。
• Rational Design of an Indolebutanoic Acid Derivative as a Novel Aldose Reductase Inhibitor Based on Docking and 3D QSAR Studies of Phenethylamine Derivatives
  作者：Won Suck Sun、Yoon Sun Park、Jakyung Yoo、Ki Duk Park、Sung Han Kim、Jung-Han Kim、Hyun-Ju Park

  DOI：10.1021/jm0205346

  日期：2003.12.1

  A series of 45 phenethylamine derivatives were synthesized and evaluated for their inhibitory activity against pig kidney aldose reductase (ALR2, EC 1.1.1.21). Their IC50 values ranged from 400 muM to 24 muM. The binding modes of compounds at the active site of ALR2 were examined using flexible docking. The results indicated that phenethylamine derivatives nicely fit into the active pocket of ALR2 by forming various hydrogen bonding and hydrophobic interactions. 3D-QSAR analysis was also conducted using FlexX-docked alignment of the compounds. The best prediction was obtained by CoMSIA combined with hydrophobic and hydrogen bond donor/acceptor field (q(2) = 0.557, r(2) = 0.934). A new derivative, 4-oxo-4-(4-hydroxyindole)butanoic acid, was designed, taking into account the CoMSIA field and the binding mode derived by FlexX docking. This rationally designed compound exhibits an ALR2 inhibition with an IC50 value of 7.4 muM, which compares favorably to that of a well-known ALR2 inhibitor, tolrestat (IC50 = 16 muM) and represents a potency approximately 240-fold higher than that of an original phenethylamine lead compound, YUA001.
• High affinity ligands and potent antagonists for the α1D-adrenergic receptor. Novel 3,8-disubstituted [1]benzothieno[3,2-d]pyrimidine derivatives
  作者：Giuseppe Romeo、Loredana Salerno、Valeria Pittalà、Maria N. Modica、Maria A. Siracusa、Luisa Materia、Michela Buccioni、Gabriella Marucci、Kenneth P. Minneman

  DOI：10.1016/j.ejmech.2014.06.057

  日期：2014.8

  A new series of high affinity ligands and antagonists for the α1D-adrenergic receptor (AR) has been discovered. New molecules present a [1]benzothieno[3,2-d]pyrimidin-2,4(1H,3H)-dione or a [1]benzothieno[3,2-d]pyrimidin-4(3H)-one scaffold and bear a 2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl moiety in the 3-position and various amide substituents in the 8-position. In binding assays at the three human cloned α1A-, α1B-, and α1D-AR subtypes, they showed high affinity values, particularly for the α1D-AR subtype. Compound 22 (RX18), N(1)-methyl-N(5)-[3-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-2,4-dioxo-1,2,3,4-tetrahydro[1]benzothieno[3,2-d]pyrimidin-8-yl]-N(1)-(phenylmethyl)pentanediamide, was the most interesting in the series displaying very high affinity (pKi = 10.25) and potent antagonism (pKb = 9.15) when tested in a functional assay at the α1D-AR.