DL-缬氨酰-L-亮氨酰-N-(4-硝基苯基)-L-精氨酰胺 | 117961-22-5

• 物质功能分类: 生物化工 - 多肽
• 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
• 中文名称: DL-缬氨酰-L-亮氨酰-N-(4-硝基苯基)-L-精氨酰胺
• 英文名称: H-DL-Val-Leu-Arg-pNA
• 英文别名: (2S)-2-[(2-amino-3-methylbutanoyl)amino]-N-[(2S)-5-(diaminomethylideneamino)-1-(4-nitroanilino)-1-oxopentan-2-yl]-4-methylpentanamide
• CAS: 117961-22-5
• 化学式: C23H38N8O5
• 分子量: 506.6
• InChiKey: ZNKZJCICBFSACN-ADUPEVMXSA-N

物化性质

• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  36
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  224
• 氢给体数：
  6
• 氢受体数：
  7

文献信息

• Use of carprofen and derivatives therof for treating or preventing articular degeneration
  申请人：Pfizer Products Inc.

  公开号：EP0970694A2

  公开（公告）日：2000-01-12

  Treating or preventing the early stages of degeneration of articular cartilage or subchondral bone in the affected joint of a mammal is accomplished by administering a chondroprotective compound of Formula (I): wherein where A is hydroxy, (C1 - C4)alkoxy, amino, hydroxy-amino, mono-(C1 -C2)alkylamino, di-(C1-C2)alkylamino; X and Y are independently H or (C1 - C2)alkyl; and n is 1 or 2; R6 is halogen, (C1 - C3)alkyl, trifluoromethyl, or nitro; R9 is H; (C1 - C2)alkyl; phenyl or phenyl-(C1 - C2)alkyl, where phenyl is optionally mono-substituted by fluoro or chloro; -C(=O)-R, where R is (C1-C2)alkyl or phenyl, optionally mono-substituted by fluoro or chloro; or -C(=O)-O-R1 , where R1 is (C1 - C2)alkyl. This treatment ameliorates, diminishes, actively treats, reverses or prevents any injury, damage or loss of articular cartilage or subchondral bone subsequent to said early stage of said degeneration. Whether or not a mammal needs such treatment is determined by whether or not it exhibits a statistically significant deviation from normal standard values in synovial fluid or membrane from the affected joint, with respect to at least five of the following substances: increased interleukin-1 beta (IL-1β); increased tumor necrosis factor alpha (TNFα); increased ratio of IL-1β to IL-1 receptor antagonist protein (IRAP); increased expression of p55 TNF receptors (p55 TNF-R); increased interleukin-6 (IL-6); increased leukemia inhibitory factor (LIF); decreased insulin-like growth factor-1 (IGF-1); decreased transforming growth factor beta (TGFβ); decreased platelet-derived growth factor (PDGF); decreased basic fibroblast growth factor (b-FGF); increased keratan sulfate; increased stromelysin; increased ratio of stromelysin to tissue inhibitor of metalloproteases (TIMP); increased osteocalcin; increased alkaline phosphatase; increased cAMP responsive to hormone challenge; increased urokinase plasminogen activator (uPA); increased cartilage oligomeric matrix protein; and increased collagenase.

  治疗或预防哺乳动物受影响关节的关节软骨或软骨下骨退化的早期阶段，可通过施用式 (I) 的软骨保护化合物来实现： 其中 其中 A 是羟基、(C1 - C4)烷氧基、氨基、羟基氨基、单-(C1 -C2)烷基氨基、二-(C1 -C2)烷基氨基；X 和 Y 独立地是 H 或(C1 - C2)烷基；n 是 1 或 2；R6 是卤素、(C1 - C3)烷基、三氟甲基或硝基；R9 是 H；(C1-C2)烷基；苯基或苯基-(C1-C2)烷基，其中苯基任选被氟或氯单取代；-C(＝O)-R，其中 R 是(C1-C2)烷基或苯基，任选被氟或氯单取代；或-C(＝O)-O-R1，其中 R1 是(C1-C2)烷基。 这种治疗方法可以改善、减轻、积极治疗、逆转或预防所述退化早期阶段之后关节软骨或软骨下骨的任何损伤、损坏或损失。哺乳动物是否需要此类治疗，取决于其受影响关节的滑液或滑膜中是否至少有以下五种物质在统计学上明显偏离正常标准值：白细胞介素-1β（IL-1β）增加；肿瘤坏死因子α（TNFα）增加；IL-1β与IL-1受体拮抗蛋白（IRAP）的比值增加；p55 TNF受体（p55 TNF-R）表达增加；白细胞介素-6（IL-6）增加；白血病抑制因子（LIF）增加；胰岛素样生长因子-1（IGF-1）减少；转化生长因子β（TGFβ）减少；血小板衍生生长因子（PDGF）减少；碱性成纤维细胞生长因子（b-FGF）减少；角蛋白硫酸盐增加；基质溶蛋白增加；基质溶蛋白与组织金属蛋白酶抑制剂（TIMP）的比率增加；骨钙素增加；碱性磷酸酶增加；对激素挑战反应的 cAMP 增加；尿激酶纤溶酶原激活剂（uPA）增加；软骨寡聚基质蛋白增加；胶原酶增加。
• TREATING OR PREVENTING THE EARLY STAGES OF DEGENERATION OF ARTICULAR CARTILAGE OR SUBCHONDRAL BONE IN MAMMALS USING CARPROFEN AND DERIVATIVES
  申请人：——

  公开号：US20010002401A1

  公开（公告）日：2001-05-31

  Treating or preventing the early stages of degeneration of articular cartilage or subchondral bone in the affected joint of a mammal is accomplished by administering a chondroprotective compound of Formula (I): 1 where A is hydroxy, (C 1 -C 4 )alkoxy, amino, hydroxy-amino, mono-(C 1 -C 2 )alkylamino, di-(C 1 -C 2 )alkylamino; X and Y are independently H or (C 1 -C 2 )alkyl; and n is 1 or 2; R 6 is halogen, (C 1 -C 3 )alkyl, trifluoromethyl, or nitro; R 9 is H; (C 1 -C 2 )alkyl; phenyl or phenyl-(C 1 -C 2 )alkyl, where phenyl is optionally mono-substituted by fluoro or chloro; —C(═O)-R, where R is (C 1 -C 2 )alkyl or phenyl, optionally mono-substituted by fluoro or chloro; or —C(═O)—O-R′, where R 1 is (C 1 -C 2 )alkyl. This treatment ameliorates, diminishes, actively treats, reverses or prevents any injury, damage or loss of articular cartilage or subchondral bone subsequent to said early stage of said degeneration. Whether or not a mammal needs such treatment is determined by whether or not it exhibits a statistically significant deviation from normal standard values in synovial fluid or membrane from the affected joint, with respect to at least five of the following substances: increased interleukin-1 beta (IL-1&bgr;); increased tumor necrosis factor alpha (TNF&agr;); increased ratio of IL-1&bgr; to IL-1 receptor antagonist protein (IRAP); increased expression of p55 TNF receptors (p55 TNF-R); increased interleukin-6 (IL-6); increased leukemia inhibitory factor (LIF); decreased insulin-like growth factor-1 (IGF-1); decreased transforming growth factor beta (TGF&bgr;); decreased platelet-derived growth factor (PDGF); decreased basic fibroblast growth factor (b-FGF); increased keratan sulfate; increased stromelysin; increased ratio of stromelysin to tissue inhibitor of metalloproteases (TIMP); increased osteocalcin; increased alkaline phosphatase; increased cAMP responsive to hormone challenge; increased urokinase plasminogen activator (uPA); increased cartilage oligomeric matrix protein; and increased collagenase.

  治疗或预防哺乳动物受影响关节的关节软骨或软骨下骨退化的早期阶段，可通过施用式（I）的软骨保护化合物来实现： 1 其中 A 是羟基，(C 1 -C 4 烷氧基、氨基、羟基氨基、单-(C 1 -C 2 )烷基氨基、二-(C 1 -C 2 )烷基氨基；X 和 Y 独立地为 H 或(C 1 -C 2 )烷基；n 是 1 或 2；R 6 是卤素、(C 1 -C 3 烷基、三氟甲基或硝基；R 9 是 H 1 -C 2 烷基；苯基或苯基-(C 1 -C 2 )烷基，其中苯基可选择被氟或氯单取代； -C(═O)-R，其中 R 是 (C 1 -C 2) 1 -C 2 )烷基或苯基，可选被氟或氯单取代；或 -C(═O)-O-R′，其中 R 1 是（C 1 -C 2 )烷基。 这种治疗方法可改善、减轻、积极治疗、逆转或预防所述退化早期阶段之后关节软骨或软骨下骨的任何损伤、损坏或损失。哺乳动物是否需要此类治疗，取决于其受影响关节的滑液或滑膜中是否至少有以下五种物质在统计学上明显偏离正常标准值：白细胞介素-1β（IL-1&bgr；）增加；肿瘤坏死因子α（TNF&agr；）增加；IL-1&bgr；与 IL-1 受体拮抗蛋白（IRAP）的比率增加；p55 TNF 受体（p55 TNF-R）表达增加；白细胞介素-6（IL-6）增加；白血病抑制因子（LIF）增加；胰岛素样生长因子-1（IGF-1）减少；转化生长因子 beta（TGF&bgr;）减少；血小板衍生生长因子（PDGF）减少；碱性成纤维细胞生长因子（b-FGF）减少；角蛋白硫酸盐增加；基质溶蛋白增加；基质溶蛋白与组织金属蛋白酶抑制剂（TIMP）的比率增加；骨钙素增加；碱性磷酸酶增加；对激素挑战反应的 cAMP 增加；尿激酶纤溶酶原激活剂（uPA）增加；软骨寡聚基质蛋白增加；胶原酶增加。
• Treating or preventing the early stages of degeneration of articular cartilage or subchondral bone in mammals using carprofen and derivatives
  申请人：——

  公开号：US20030008911A1

  公开（公告）日：2003-01-09

  Treating or preventing the early stages of degeneration of articular cartilage or subchondral bone in the affected joint of a mammal is accomplished by administering a chondroprotective compound of Formula (I): 1 where A is hydroxy, (C 1 -C 4 )alkoxy, amino, hydroxy-amino, mono-(C 1 -C 2 )alkylamino, di-(C 1 -C 2 )alkylamino; X and Y are independently H or (C 1 -C 2 )alkyl; and n is 1 or 2; R 6 is halogen, (C 1 - C 3 )alkyl, trifluoromethyl, or nitro; R 9 is H; (C 1 -C 2 )alkyl; phenyl or phenyl-(C 1 - C 2 )alkyl, where phenyl is optionally mono-substituted by fluoro or chloro; —C(═O)—R, where R is (C 1 -C 2 )alkyl or phenyl, optionally mono-substituted by fluoro or chloro; or —C(═O)—O—R 1 , where R 1 is (C 1 - C 2 )alkyl. This treatment ameliorates, diminishes, actively treats, reverses or prevents any injury, damage or loss of articular cartilage or subchondral bone subsequent to said early stage of said degeneration. Whether or not a mammal needs such treatment is determined by whether or not it exhibits a statistically significant deviation from normal standard values in synovial fluid or membrane from the affected joint, with respect to at least five of the following substances: increased interleukin-1 beta (IL-1&bgr;), increased tumor necrosis factor alpha (TNF&agr;); increased ratio of IL-1&bgr; to IL-1 receptor antagonist protein (IRAP); increased expression of p55 TNF receptors (p55 TNF-R), increased interleukin-6 (IL-6); increased leukemia inhibitory factor (LIF); decreased insulin-like growth factor-1 (IGF-1); decreased transforming growth factor beta (TGF&bgr;); decreased platelet-derived growth factor (PDGF); decreased basic fibroblast growth factor (b-FGF); increased keratan sulfate; increased stromelysin; increased ratio of stromelysin to tissue inhibitor of metalloproteases (TIMP); increased osteocalcin; increased alkaline phosphatase; increased cAMP responsive to hormone challenge; increased urokinase plasminogen activator (uPA); increased cartilage oligomeric matrix protein; and increased collagenase.

  治疗或预防哺乳动物受影响关节的关节软骨或软骨下骨退化的早期阶段，可通过施用式（I）的软骨保护化合物来实现： 1 其中 A 是羟基，(C 1 -C 4 烷氧基、氨基、羟基氨基、单-(C 1 -C 2 )烷基氨基、二-(C 1 -C 2 )烷基氨基；X 和 Y 独立地为 H 或 (C 1 -C 2 )烷基；n 是 1 或 2；R 6 是卤素、(C 1 - C 3 烷基、三氟甲基或硝基；R 9 是 H 1 -C 2 烷基；苯基或苯基-(C 1 - C 2 苯基或苯基-(C 1 C 2)烷基，其中苯基可选地被氟或氯单取代； -C(═O)-R，其中 R 是 (C 1 C 2) 1 -C 2 )烷基或苯基，可选被氟或氯单取代；或-C(═O)-O-R 1 其中 R 1 是（C 1 - C 2 )烷基。 这种治疗方法可以改善、减轻、积极治疗、逆转或预防所述退化早期阶段之后关节软骨或软骨下骨的任何损伤、损坏或损失。哺乳动物是否需要此类治疗，取决于其受影响关节的滑液或滑膜中是否至少有以下五种物质在统计学上明显偏离正常标准值：白细胞介素-1β（IL-1&bgr；）增加、肿瘤坏死因子α（TNF&agr；）增加、IL-1&bgr；与 IL-1 受体拮抗蛋白（IRAP）的比率增加、p55 TNF 受体（p55 TNF-R）表达增加、白细胞介素-6（IL-6）增加；白血病抑制因子（LIF）增加；胰岛素样生长因子-1（IGF-1）减少；转化生长因子 beta（TGF&bgr;）减少；血小板衍生生长因子（PDGF）减少；碱性成纤维细胞生长因子（b-FGF）减少；角蛋白硫酸盐增加；基质溶蛋白增加；基质溶蛋白与组织金属蛋白酶抑制剂（TIMP）的比率增加；骨钙素增加；碱性磷酸酶增加；对激素挑战反应的 cAMP 增加；尿激酶纤溶酶原激活剂（uPA）增加；软骨寡聚基质蛋白增加；胶原酶增加。
• USE OF ANNELLATED PYRROLE COMPOUNDS IN THE TREATMENT OF ARTICULAR CARTILAGE OR SUBCHONDRAL BONE DEGENERATION
  申请人：MERCKLE GMBH

  公开号：EP1427410A1

  公开（公告）日：2004-06-16
• Use of annellated pyrrole compounds in the treatment of articular cartilage or subchondral bone degenaration
  申请人：Pelletier Jean-Pierre

  公开号：US20050004108A1

  公开（公告）日：2005-01-06

  Treating or preventing degeneration or destruction of articular cartilage and/or subchondral bone in the affected joint of a mammal is accomplished by administering a compound of formula (I), wherein the variables have the meanings given in the present description. A preferred compound of formula (I) is formula (II). This treatment ameliorates, diminishes, actively treats, reverses or prevents any injury, damage or loss of articular cartilage or subchondral bone subsequent to said early stage of said degeneration.