biphenyl-4-carboxylic acid [1-acetyl-4-(4-hydroxyphenyl)-2,2,4-trimethyl-1,2,3,4-tetrahydroquinolin-6-yl]amide | 487064-99-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: biphenyl-4-carboxylic acid [1-acetyl-4-(4-hydroxyphenyl)-2,2,4-trimethyl-1,2,3,4-tetrahydroquinolin-6-yl]amide
• 英文别名: 1-Acetyl-4-(4-hydroxyphenyl)-6-(4-phenylbenzoyl)amino-1,2,3,4-tetrahydro-2,2,4-trimethylquinoline；N-[1-acetyl-4-(4-hydroxyphenyl)-2,2,4-trimethyl-3H-quinolin-6-yl]-4-phenylbenzamide
• CAS: 487064-99-3
• 化学式: C₃₃H₃₂N₂O₃
• 分子量: 504.629
• InChiKey: BOSIOWJWBMFJNH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  38
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  69.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  biphenyl-4-carboxylic acid [1-acetyl-4-(4-hydroxyphenyl)-2,2,4-trimethyl-1,2,3,4-tetrahydroquinolin-6-yl]amide 、 二甲氨基氯乙烷盐酸 在 caesium carbonate 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 生成 biphenyl-4-carboxylic acid {1-acetyl-4-[4-(2-dimethylamino-ethoxy)-phenyl]-2,2,4-trimethyl-1,2,3,4-tetrahydroquinolin-6-yl}-amide
  参考文献：
  名称：

  [EN] TETRAHYDROQUINOLINE DERIVATIVES AND THEIR USE AS FSH RECEPTOR MODULATORS
  [FR] DERIVES DE TETRAHYDROQUINOLINE

  摘要：

  公开号：

  WO2004056779A3
• 作为产物：
  描述：

  特定基氨基甲酸脂酶 在 吡啶 、 三氯化铝 、 碘 、 乙酸酐 、 三溴化硼 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 59.0h， 生成 biphenyl-4-carboxylic acid [1-acetyl-4-(4-hydroxyphenyl)-2,2,4-trimethyl-1,2,3,4-tetrahydroquinolin-6-yl]amide
  参考文献：
  名称：

  Identification of Substituted 6-Amino-4-phenyltetrahydroquinoline Derivatives:  Potent Antagonists for the Follicle-Stimulating Hormone Receptor

  摘要：

  Substituted 6-amino-4-phenyl-tetrahydroquinoline derivatives are described that are antagonists for the G(s)-protein-coupled human follicle-stimulating hormone (FSH) receptor. These compounds show high antagonistic efficacy in vitro using a CHO cell line expressing the human FSH receptor. Antagonist 10 also showed a submicromolar IC50 in a more physiologically relevant rat granulosa cell assay and was found to significantly inhibit follicle growth and ovulation in an ex vivo mouse model. This compound class may open the way toward a novel, nonsteroidal approach for contraception.

  DOI：

  10.1021/jm049676l

文献信息

• TSH receptor antagonizing tetrahydroquinoline compounds
  申请人：Karstens Willem Frederik Johan

  公开号：US09174940B2

  公开（公告）日：2015-11-03

  The present invention relates the use of a compound, a pharmaceutical composition, compounds and a kit for treating or preventing disorders in a mammal responsive to TSH receptor mediated pathways, including disorders such as hyperthyroidism, Graves' disease, Graves Ophthalmopathy, Graves' associated pretibial dermopathy, nodular goitre and thyroid cancer comprising administering to said mammal an effective amount of a tetrahydroquinoline compound of Formula (I) or an pharmaceutically acceptable salt thereof.

  本发明涉及使用一种化合物、一种药物组合物、化合物和一种用于治疗或预防对TSH受体介导途径敏感的哺乳动物中的疾病的工具包，包括治疗甲状腺功能亢进、格雷夫斯病、格雷夫斯眼病、格雷夫斯相关的胫部皮肤病、结节性甲状腺肿和甲状腺癌等疾病，包括向该哺乳动物施用式(I)的四氢喹啉化合物或其药学上可接受的盐的有效量。
• Tetrahydroquinoline derivatives
  申请人：——

  公开号：US20040236109A1

  公开（公告）日：2004-11-25

  The present invention relates to tetrahydroquinoline derivatives having general formula (I) or a pharmaceutically acceptable salt thereof, wherein R 1 is formyl, (1-6C)alkylcarbonyl or (1-6C)alkylsulfonyl; R 2 and R 3 are H or (1-4C)alkyl; R 4 is phenyl; R 5 is (1-4C)alkyl; Y—X is (CO)—O, (SO) 2 —O, NHC(O)—O, NHC(S)—O, OC(O)—O, bond-O, C(O)—NH, S(O) 2 —NH, NHC(O)—NH, NHC(S)—NH, OC(O)—NH, bond-NH, NH—C(O), O—C(O), NH—S(O) 2 , or O—S(O) 2 or Y—X is a bond; R 6 is H, trifluormethyl, (1-6C)alkyl, 1- or 2-adamantyl(1-4C)alkyl, (2-6C)alkenyl, (3-9C)heteroaryl, (3-6C)cycloalkyl, (2-6C)heterocycloalkyl, (1-4C)alkylthio(1-4C)alkyl, (6-10C)aryl(1-4C)alkyl, (3-9C)heteroaryl(1-4C)alkyl, (3-6C)cycloalkyl(1-4C)alkyl, (2-6C)heterocycloalkyl(1-4C)alkyl, R 8 , R 9 -aminocarbonyl(1-4C)alkyl, R 8 , R 9 -amino(1-4C)alkyl, R 8 -oxycarbonyl(1-4C)alkyl, R 8 -oxy(1-4C)alkyl, R 8 -carbonyl(1-4C)alkyl or (6-10C)aryl; R 7 is H, (1-4C)alkyl, (1-4C)alkoxy, halogen, trifluoromethyl, cyano, nitro hydroxyl; and R 8 and/or R 9 is H, (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (6-10C)aryl, (3-9C)heteroaryl, (6-10C)aryl(1-4C)alkyl, (3-9C)heteroaryl(1-4C)alkyl, (3-6C)cycloalkyl(1-4C)alkyl, (2-6C)heterocycloalkyl(1-4C)alkyl, (1-4C)(di)alkylamino(1-4C)alkyl, (1-4C)alkoxy(1-4C)alkyl, (1-4C)alkylthio(1-4C)alkyl, (1-4C)alkylcarbonylamino(1-4C)alkyl, (1-4C)alkoxycarbonyl(1-4C)alkyl, (1-4C)alkoxycarbonylamino(1-4C)alkyl, (3-6C)cycloalkyl, (2-6C)heterocycloylkyl, or R 8 and R 9 may be joined in a (2-6C)heterocycloalkyl ring. The present invention also relates to pharmaceutical compositions comprising said derivatives and the use of these derivatives to control fertility. 1

  本发明涉及具有一般式（I）或其药学上可接受的盐的四氢喹啉衍生物，其中R1是甲酰基，（1-6C）烷基羰基或（1-6C）烷基磺酰基; R2和R3是H或（1-4C）烷基; R4是苯基; R5是（1-4C）烷基; Y-X是（CO）-O，（SO）2-O，NHC（O）-O，NHC（S）-O，OC（O）-O，键-O，C（O）-NH，S（O）2-NH，NHC（O）-NH，NHC（S）-NH，OC（O）-NH，键-NH，NH-C（O），O-C（O），NH-S（O）2或O-S（O）2，或Y-X是键; R6是H，三氟甲基，（1-6C）烷基，1-或2-金刚烷基（1-4C）烷基，（2-6C）烯基，（3-9C）杂环芳基，（3-6C）环烷基，（2-6C）杂环环烷基，（1-4C）烷基硫（1-4C）烷基，（6-10C）芳基（1-4C）烷基，（3-9C）杂环芳基（1-4C）烷基，（3-6C）环烷基（1-4C）烷基，（2-6C）杂环环烷基（1-4C）烷基，R8，R9-氨基羰基（1-4C）烷基，R8，R9-氨基（1-4C）烷基，R8-氧羰基（1-4C）烷基，R8-氧（1-4C）烷基，R8-羰基（1-4C）烷基或（6-10C）芳基; R7是H，（1-4C）烷基，（1-4C）烷氧基，卤素，三氟甲基，氰基，硝基羟基; R8和/或R9是H，（1-4C）烷基，（2-4C）烯基，（2-4C）炔基，（6-10C）芳基，（3-9C）杂环芳基，（6-10C）芳基（1-4C）烷基，（3-9C）杂环芳基（1-4C）烷基，（3-6C）环烷基（1-4C）烷基，（2-6C）杂环环烷基（1-4C）烷基，（1-4C）（二）烷基氨基（1-4C）烷基，（1-4C）烷氧基（1-4C）烷基，（1-4C）烷基硫（1-4C）烷基，（1-4C）烷基羰基氨基（1-4C）烷基，（1-4C）烷氧基羰基（1-4C）烷基，（1-4C）烷氧基羰基氨基（1-4C）烷基，（3-6C）环烷基，（2-6C）杂环环烷基，或R8和R9可以连接在（2-6C）杂环环烷基环中。本发明还涉及包含所述衍生物的制药组合物以及使用这些衍生物控制生育的方法。
• TETRAHYDROQUINOLINE DERIVATIVES
  申请人：Van Straten Nicole Corine Renée

  公开号：US20120202996A1

  公开（公告）日：2012-08-09

  The present invention relates to tetrahydroquinoline derivatives having general formula I: or a pharmaceutically acceptable salt thereof, wherein R1 is formyl, (1-6C)alkylcarbonyl or (1-6C)alkylsulfonyl; R2 and R3 are H or (1-4C)alkyl; R4 is phenyl; R5 is (1-4C)alkyl; Y—X is C(O)—O, S(O)2-O, NHC(O)—O, NHC(S)—O, OC(O)—O, bond-O, C(O)—NH, S(O)2-NH, NHC(O)—NH, NHC(S)—NH, OC(O)—NH, bond-NH, NH—C(O), O—C(O), NH—S(O)2, or O—S(O)2 or Y—X is a bond; R6 is H, trifluoromethyl, (1-6C)alkyl, 1- or 2-adamantyl(1-4C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (3-9C)heteroaryl, (3-6C)cycloalkyl, (2-6C)heterocycloalkyl, (1-4C)alkylthio(1-4C)alkyl, (6-10C)aryl(1-4C)alkyl, (3-9C)heteroaryl(1-4C)alkyl, (3-6C)cycloalkyl(1-4C)alkyl, (2-6C)heterocycloalkyl(1-4C)alkyl, R8,R9-aminocarbonyl(1-4C)alkyl, R8,R9-amino(1-4C)alkyl, R8-oxycarbonyl(1-4C)alkyl, R8-oxy(1-4C)alkyl, R8-carbonyl(1-4C)alkyl or (6-10C)aryl; R7 is H, (1-4C)alkyl, (1-4C)alkoxy, halogen, trifluoromethyl, cyano, nitro, hydroxyl; and R8 and/or R9 is H, (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (6-10C)aryl, (3-9C)heteroaryl, (6-10C)aryl(1-4C)alkyl, (3-9C)heteroaryl(1-4C)alkyl, (3-6C)cycloalkyl(1-4C)alkyl, (2-6C)heterocycloalkyl(1-4C)alkyl, (1-4C)(di)alkylamino(1-4C)alkyl, (1-4C)alkoxy(1-4C)alkyl, (1-4C)alkylthio(1-4C)alkyl, (1-4C)alkylcarbonylamino(1-4C)alkyl, (1-4C)alkoxycarbonyl(1-4C)alkyl, (1-4C)alkoxycarbonylamino(1-4C)alkyl, (3-6C)cycloalkyl, (2-6C)heterocycloalkyl, or R8 and R9 may be joined in a (2-6C)heterocycloalkyl ring. The present invention also relates to pharmaceutical compositions comprising said derivatives and the use of these derivatives to control fertility.

  本发明涉及通式I的四氢喹啉衍生物或其药学上可接受的盐，其中R1为甲酰基，(1-6C)烷基羰基或(1-6C)烷基磺酰基; R2和R3为H或(1-4C)烷基; R4为苯基; R5为(1-4C)烷基; Y-X为C(O)-O、S(O)2-O、NHC(O)-O、NHC(S)-O、OC(O)-O、键-O、C(O)-NH、S(O)2-NH、NHC(O)-NH、NHC(S)-NH、OC(O)-NH、键-NH、NH-C(O)、O-C(O)、NH-S(O)2或O-S(O)2，或Y-X为键; R6为H、三氟甲基、(1-6C)烷基、1-或2-金刚烷基(1-4C)烷基、(2-6C)烯基、(2-6C)炔基、(3-9C)杂环芳基、(3-6C)环烷基、(2-6C)杂环环烷基、(1-4C)烷基硫(1-4C)烷基、(6-10C)芳基(1-4C)烷基、(3-9C)杂环芳基(1-4C)烷基、(3-6C)环烷基(1-4C)烷基、(2-6C)杂环环烷基(1-4C)烷基、R8，R9-氨基羰基(1-4C)烷基、R8，R9-氨基(1-4C)烷基、R8-氧羰基(1-4C)烷基、R8-氧(1-4C)烷基、R8-羰基(1-4C)烷基或(6-10C)芳基; R7为H、(1-4C)烷基、(1-4C)烷氧基、卤素、三氟甲基、氰基、硝基、羟基; R8和/或R9为H、(1-4C)烷基、(2-4C)烯基、(2-4C)炔基、(6-10C)芳基、(3-9C)杂环芳基、(6-10C)芳基(1-4C)烷基、(3-9C)杂环芳基(1-4C)烷基、(3-6C)环烷基(1-4C)烷基、(2-6C)杂环环烷基(1-4C)烷基、(1-4C)(二)烷基氨基(1-4C)烷基、(1-4C)烷氧基(1-4C)烷基、(1-4C)硫基(1-4C)烷基、(1-4C)烷基羰基氨基(1-4C)烷基、(1-4C)烷氧羰基(1-4C)烷基、(1-4C)烷氧羰基氨基(1-4C)烷基、(3-6C)环烷基、(2-6C)杂环环烷基，或R8和R9可以在一个(2-6C)杂环环烷基环中连接。本发明还涉及包含所述衍生物的制药组合物以及使用这些衍生物控制生育的方法。
• TETRAHYDROQUINOLINE DERIVATIVES
  申请人：Akzo Nobel N.V.

  公开号：EP1406628B1

  公开（公告）日：2006-03-08
• TSH RECEPTOR ANTAGONIZING TETRAHYDROQUINOLINE COMPOUNDS
  申请人：N.V. Organon

  公开号：EP2197445A2

  公开（公告）日：2010-06-23