(2S,3S)-2-amino-1-(3,4-dihydro-1H-isoquinolin-2-yl)-3-methylpentan-1-one | 134015-52-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S,3S)-2-amino-1-(3,4-dihydro-1H-isoquinolin-2-yl)-3-methylpentan-1-one
• CAS: 134015-52-4
• 化学式: C₁₅H₂₂N₂O
• mdl: MFCD13211342
• 分子量: 246.352
• InChiKey: CSGUIEXSWZMONM-FZMZJTMJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.533
• 拓扑面积：
  46.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (2S,3S)-2-amino-1-(3,4-dihydro-1H-isoquinolin-2-yl)-3-methylpentan-1-one 、 丁氧羰基--环乙基-丙氨酸-羟基盐酸盐 在 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Novel Agonists and Antagonists for Human Protease Activated Receptor 2

  摘要：

  Human protease activated receptor 2 (PAR2) is a G protein-coupled receptor that is associated with inflammatory diseases and cancers. PAR2 is activated by serine proteases that cleave its N-terminus and by synthetic peptides corresponding to the new N-terminus. Peptide agonists are widely used to characterize physiological roles for PAR2 but typically have low potency (e.g., SLICK V-NH2, SLIGRL-NH2), uncertain target selectivity, and poor bioavailability, limiting their usefulness for specifically interrogating PAR2 in vivo. Structure-activity relationships were used to derive new PAR2 agonists and antagonists containing nonpeptidic moieties. Agonist GB110 (19, EC50 0.28 mu M) selectively induced PAR2-, but not PAR1-, mediated intracellular Ca2+ release in HT29 human colorectal carcinoma cells. Antagonist GB83 (36, IC50 2 mu M) is the first compound at micromolar concentrations to reversibly inhibit PAR2 activation by both proteases and other PAR2 agonists (e.g., trypsin, 2f-furoyl-LIGRLO-NH2, 19). The new compounds are selective for PAR2 over PAR1, serum stable, and suitable for modulating PAR2 in disease models.

  DOI：

  10.1021/jm100984y
• 作为产物：
  描述：

  tert-butyl N-[(2S,3S)-1-(3,4-dihydro-1H-isoquinolin-2-yl)-3-methyl-1-oxopentan-2-yl]carbamate 在 三氟乙酸 、 碳酸氢钠 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 1.0h， 生成 (2S,3S)-2-amino-1-(3,4-dihydro-1H-isoquinolin-2-yl)-3-methylpentan-1-one
  参考文献：
  名称：

  Novel Agonists and Antagonists for Human Protease Activated Receptor 2

  摘要：

  Human protease activated receptor 2 (PAR2) is a G protein-coupled receptor that is associated with inflammatory diseases and cancers. PAR2 is activated by serine proteases that cleave its N-terminus and by synthetic peptides corresponding to the new N-terminus. Peptide agonists are widely used to characterize physiological roles for PAR2 but typically have low potency (e.g., SLICK V-NH2, SLIGRL-NH2), uncertain target selectivity, and poor bioavailability, limiting their usefulness for specifically interrogating PAR2 in vivo. Structure-activity relationships were used to derive new PAR2 agonists and antagonists containing nonpeptidic moieties. Agonist GB110 (19, EC50 0.28 mu M) selectively induced PAR2-, but not PAR1-, mediated intracellular Ca2+ release in HT29 human colorectal carcinoma cells. Antagonist GB83 (36, IC50 2 mu M) is the first compound at micromolar concentrations to reversibly inhibit PAR2 activation by both proteases and other PAR2 agonists (e.g., trypsin, 2f-furoyl-LIGRLO-NH2, 19). The new compounds are selective for PAR2 over PAR1, serum stable, and suitable for modulating PAR2 in disease models.

  DOI：

  10.1021/jm100984y

文献信息

• Imidazole-containing inhibitors of farnesyl protein transferase
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：EP0675112A1

  公开（公告）日：1995-10-04

  Inhibition of farnesyl transferase, which is an enzyme involved in ras oncogene expression, is effected by compounds of the formula their enantiomers, diastereomers, and pharmaceutically acceptable salts, prodrugs, and solvates, wherein:    G is    G¹ is    G² is or -NR¹⁰-CH(Q¹)-;    J, K and L are each, independently, N, NR⁹, O, S or CR¹⁰ with the provisos that only one of the groups J, K and L can be O or S, and at least one of the groups J or L must be N, NR⁹, O or S to form a fused five-membered heteroring; the bond between J and K or K and L may also form one side of a phenyl ring fused to the fused five-membered heteroring;    Q is aryl;    Q¹, A¹ and A² are each, independently, H, alkyl, substituted alkyl, phenyl or substituted phenyl;    G³ is R¹¹, -C(O)OR¹¹, -C(O)NR¹¹R¹², 5-tetrazolyl, -C(O)N(R¹³)OR¹¹, -C(O)NHSO₂R¹⁴ or -CH₂OR¹¹;    G⁴ is attached at the 1, 2, 4 or 5 position and optionally substituted, at any of the available position or positions on the ring, with halo, alkyl or substituted alkyl having 1 to 20 carbon atoms, alkoxy, aryl, aralkyl, hydroxy, alkanoyl, alkanoyloxy, amino, alkylamino, dialkylamino, alkanoylamino, thiol, alkylthio, alkylthiono, alkylsulfonyl, sulfonamido, nitro, cyano, carboxy, carbamyl, N-hydroxycarbamyl, N-alkylcarbamyl, N-dialkylcarbamyl, alkoxycarbonyl, phenyl, substituted phenyl, or a combinaton of these groups;    Y and Z are each, independently, -CH₂- or -C(O)-;    R¹ - R¹⁴ are each, independently, H or alkyl having 1 to 20 carbon atoms;    R⁷, R⁸ and R¹⁴ may also be aryl or aralkyl, and R³, R⁹, R¹¹, R¹² and R¹³ may also be aralkyl;    m, n and p are each, independently, 0 or an integer from 1 to 2;    q is 0 or an integer from 1 to 4; and    the dotted line represents an optional double bond.

  抑制法尼醇转移酶是一种参与ras癌基因表达的酶，其受化合物的影响，其化合物包括其对映异构体、非对映异构体和药用可接受的盐、前药和溶剂化合物，其中： G为G¹为G²为或-NR¹⁰-CH(Q¹)-；J、K和L分别独立地为N、NR⁹、O、S或CR¹⁰，但有以下规定：J、K和L中只有一个可以是O或S，且J或L中至少有一个必须是N、NR⁹、O或S以形成融合的五元杂环；J和K之间的键或K和L之间的键也可以形成与融合的五元杂环融合的苯环的一侧；Q为芳基；Q¹、A¹和A²分别独立地为H、烷基、取代烷基、苯基或取代苯基；G³为R¹¹、-C(O)OR¹¹、-C(O)NR¹¹R¹²、5-四唑基、-C(O)N(R¹³)OR¹¹、-C(O)NHSO₂R¹⁴或-CH₂OR¹¹；G⁴附着在1、2、4或5位，并可选择地取代在环上的任何可用位置或位置，取代基为卤素、烷基或取代烷基（碳原子数为1至20）、烷氧基、芳基、芳基烷基、羟基、烷酰基、烷酰氧基、氨基、烷基氨基、二烷基氨基、烷酰氨基、硫醇基、烷基硫基、烷基硫酰基、磺酰胺基、硝基、氰基、羧基、氨基甲酰基、N-羟基氨基甲酰基、N-烷基氨基甲酰基、N-二烷基氨基甲酰基、烷氧基羰基、苯基、取代苯基或上述基团的组合；Y和Z分别独立为-CH₂-或-C(O)-；R¹-R¹⁴分别独立为H或烷基（碳原子数为1至20）；R⁷、R⁸和R¹⁴也可以是芳基或芳基烷基，R³、R⁹、R¹¹、R¹²和R¹³也可以是芳基烷基；m、n和p分别独立地为0或1至2的整数；q为0或1至4的整数；虚线表示可选的双键。
• Amino acid derivatives
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0386611A2

  公开（公告）日：1990-09-12

  Compounds of the formula wherein R¹ represents alkoxycarbonyl, aralkoxycarbonyl, alkanoyl, aralkanoyl, aroyl, cycloalkylcarbonyl, heterocyclylcarbonyl, heterocyclyl-alkanoyl, 6-(dibenzylcarbamoyl)-4-oxohexanoyl or an acyl group of an α-amino acid in which the amino group is substituted by alkoxycaronyl, aralkoxycarbonyl, diaralkylcarbamoyl, diaralkylalkanoyl or aralkanoyl; R² represents alkyl, cycloalkylalkyl or aralkyl; R³ represents hydrogen or alkyl; R⁴ represents alkyl; and one of R⁵ and R⁶ represents hydrogen and the other represents hydrogen, alkyl, aryl, aralkyl, 1-alkoxycarbonyl-2-phenylethyl, 1-alkoxycarbonyl-2-(imidazol-4-yl)ethyl, 2-(imidazol-1-yl)ethyl, indanyl, heterocyclyl-alkyl, carboxyalkyl, alkoxycarbonylalkyl, aryloxycarbonylalkyl, aralkoxycarbonylalkyl or a group of the formula -A-N(Ra)(Rb) in which A represents alkylene and Ra and Rb each represent alkyl or Ra and Rb together represent a pentamethylene group in which one methylene group can be replaced by NH, N-alkyl, N-alkanoyl, N-aralkoxy carbonyl, O, S, SO or SO₂; or R⁵ and R⁶ together with the nitrogen atom to which they are attached represent a 1,2,3,4-tetrahydroisoquinoline ring; one of W and X represents hydrogen and the other represents hydroxy or amino or W and X together represent hydroxyimino and Y represents hydrogen or, where one of W and X represents hydrogen and the other represents hydroxy, Y can also represent hydroxy, and pharmaceutically acceptable acid addition salts thereof can be used as medicaments for the treatment and prophylaxis of viral infections, particularly of infections caused by HIV and other retroid viruses. They can be manufactured according to generally known procedures.

  式中的化合物 其中 R¹ 代表烷氧基羰基、烷氧基羰基、烷酰基、烷酰基、芳酰基、环烷基羰基、杂环烷基羰基、杂环烷酰基、6-(二苄基氨基甲酰基)-4-氧代己酰基或 α-氨基酸的酰基，其中氨基被烷氧基羰基、烷氧基羰基、二烷基氨基甲酰基、二烷基烷酰基或芳酰基取代；R² 代表烷基、环烷基烷基或芳烷基； R³ 代表氢或烷基； R⁴ 代表烷基；R⁵ 和 R⁶ 中的一个代表氢，另一个代表氢、烷基、芳基、芳烷基、1-烷氧基羰基-2-苯基乙基、1-烷氧基羰基-2-(咪唑-4-基)乙基、2-(咪唑-1-基)乙基、茚基、杂环烷基、羧基、烷氧基羰基烷基、芳氧基羰基烷基、烷氧基羰基烷基、芳氧基羰基烷基、芳氧基羰基烷基、芳氧基羰基烷基、芳氧基羰基烷基、芳氧基羰基烷基或 R⁵ 和 R⁶ 与它们所连接的氮原子一起代表 1，2，3，4-四氢异喹啉环； W 和 X 中的一个代表氢，另一个代表羟基或氨基，或 W 和 X 一起代表羟基亚氨基，Y 代表氢，或 W 和 X 中的一个代表氢，另一个代表羟基，Y 也可以代表羟基、 及其药学上可接受的酸加成盐可用作治疗和预防病毒感染的药物，特别是由 HIV 和其他逆转录病毒引起的感染。它们可以按照一般已知的程序制造。
• Inhibitors of farnesyl protein transferase
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：EP0696593A2

  公开（公告）日：1996-02-14

  Inhibition of farnesyl transferase, which is an enzyme involved in ras oncogene expression, is effected by compounds of the formula their enantiomers, diastereomers, and pharmaceutically acceptable salts, prodrugs, and solvates, wherein:    G is    when G is it is optionally substituted, at any available position or positions, with halo, alkyl or substituted alkyl having 1 to 20 carbon atoms, alkoxy, or a combination of these groups;    G¹ is optionally substituted, at any of the available position or positions on the ring, with halo, alkyl or substituted alkyl having 1 to 20 carbon atoms, alkoxy, aryl, aralkyl, hydroxy, alkanoyl, alkanoyloxy, amino, alkylamino, dialkylamino, alkanoylamino, thiol, alkylthio, alkylthiono, alkylsulfonyl, sulfonamido, nitro, cyano, carboxy, carbamyl, N-hydroxycarbamyl, N-alkylcarbamyl, N-dialkylcarbamyl, alkoxycarbonyl, phenyl, substituted phenyl, or a combination of these groups;    G² is or -NR⁶-CH(Q¹)-;    J, K and L are each, independently, N, NR⁷, O, S or CR⁶ with the provisos that only one of the groups J, K and L can be O or S, and at least one of the groups J or L must be N, NR⁷, O or S to form a fused five-membered heteroring; the bond between J and K or K and L may also form one side of a phenyl ring fused to the fused five-membered heteroring;    Q is is alkyl, cycloalkyl, substituted alkyl, aryl, pyrrolyl, furyl, thiophenyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, pyrrolidyl or pyridyl;    Q¹, A¹ and A² are each, independently, H, alkyl, substituted alkyl, phenyl or substituted phenyl;    G³ is R⁸, -C(O)OR⁸, -C(O)NR⁸R⁹, -C(O)N(R¹⁰)OR⁸, -C(O)NHSO₂R¹¹ or -CH₂OR⁸;    X is -SH, -OH or -NHR¹²;    X¹ is -NR¹³-, -CH₂- or -CH(NHR¹⁴)-;    Y and Z are each, independently, -CH₂- or -C(O)-;    R¹ - R¹⁴ are each, independently, H or alkyl having 1 to 20 carbon atoms;    R³ may also be substituted alkyl or cycloalkyl; R⁴, R⁵ and R¹¹ may also be aryl or aralkyl; R⁷, R⁸, R⁹ and R¹⁰ may also be aralkyl; and R¹², R¹³ and R¹⁴ may also be substituted alkyl or aralkyl;    m is 0 or an integer from 1 to 2;    q is 0 or an integer from 1 to 3;    t is an integer from 1 to 2; and    the dotted line represents an optional double bond.

  式中的化合物可抑制法尼基转移酶，该酶是一种参与 ras 肿瘤基因表达的酶。 它们的对映体、非对映体以及药学上可接受的盐、原药和溶液，其中： G 是 当 G 为 在任何一个或多个可用位置被卤代、具有 1 至 20 个碳原子的烷基或取代烷基、烷氧基或这些基团的组合任选取代； G¹ 是 在环上的任何一个或多个可用位置被卤代、烷基或具有 1 至 20 个碳原子的取代烷基、烷氧基、芳基、芳烷基、羟基、烷酰基、烷酰氧基、氨基、烷基氨基、二烷基氨基、烷酰氨基、硫醇、烷基酰胺、烷氧基、烷氧基酰胺、烷氧基酰胺、烷氧基酰胺或这些基团的组合任选取代烷酰氨基、硫醇、烷硫基、烷硫基、烷基磺酰基、磺酰氨基、硝基、氰基、羧基、氨基甲酰基、N-羟基氨基甲酰基、N-烷基氨基甲酰基、N-二烷基氨基甲酰基、烷氧基羰基、苯基、取代苯基或这些基团的组合； G² 是 或-NR⁶-CH(Q¹)-； J、K 和 L 各自独立地为 N、NR⁷、O、S 或 CR⁶，但 J、K 和 L 中只能有一个基团为 O 或 S，且 J 或 L 中至少有一个基团必须为 N、NR⁷、O 或 S，以形成融合的五元杂环；J 和 K 或 K 和 L 之间的键还可以形成与融合的五元杂环相融合的苯基环的一侧； Q 是烷基、环烷基、取代烷基、芳基、吡咯基、呋喃基、噻吩基、咪唑基、噁唑基、噻唑基、吡唑基、吡咯烷基或吡啶基； Q¹、A¹ 和 A² 各自独立地为 H、烷基、取代的烷基、苯基或取代的苯基； G³ 是 R⁸、-C(O)OR⁸、-C(O)NR⁸R⁹、-C(O)N(R¹⁰)OR⁸、-C(O)NHSO₂R¹ 或 -CH₂OR⁸； X 是-SH、-OH 或-NHR¹²； X¹是-NR¹³-、-CH₂-或-CH(NHR¹⁴)-； Y和Z各自独立地为-CH₂-或-C(O)-； R¹-R¹⁴各自独立地为 H 或具有 1-20 个碳原子的烷基； R³也可以是取代的烷基或环烷基；R⁴、R⁵和R¹¹也可以是芳基或芳烷基；R⁷、R⁸、R⁹和R¹⁰也可以是芳烷基；R¹²、R¹³和R¹⁴也可以是取代的烷基或芳烷基； m 为 0 或 1 至 2 的整数； q 是 0 或 1 至 3 的整数 t 是 1 至 2 的整数；以及 虚线代表任选双键。
• Novel Agonists and Antagonists for Human Protease Activated Receptor 2
  作者：Grant D. Barry、Jacky Y. Suen、Giang T. Le、Adam Cotterell、Robert C. Reid、David P. Fairlie

  DOI：10.1021/jm100984y

  日期：2010.10.28

  Human protease activated receptor 2 (PAR2) is a G protein-coupled receptor that is associated with inflammatory diseases and cancers. PAR2 is activated by serine proteases that cleave its N-terminus and by synthetic peptides corresponding to the new N-terminus. Peptide agonists are widely used to characterize physiological roles for PAR2 but typically have low potency (e.g., SLICK V-NH2, SLIGRL-NH2), uncertain target selectivity, and poor bioavailability, limiting their usefulness for specifically interrogating PAR2 in vivo. Structure-activity relationships were used to derive new PAR2 agonists and antagonists containing nonpeptidic moieties. Agonist GB110 (19, EC50 0.28 mu M) selectively induced PAR2-, but not PAR1-, mediated intracellular Ca2+ release in HT29 human colorectal carcinoma cells. Antagonist GB83 (36, IC50 2 mu M) is the first compound at micromolar concentrations to reversibly inhibit PAR2 activation by both proteases and other PAR2 agonists (e.g., trypsin, 2f-furoyl-LIGRLO-NH2, 19). The new compounds are selective for PAR2 over PAR1, serum stable, and suitable for modulating PAR2 in disease models.