1-(3-吡啶基羰基)-L-脯氨酸 | 59834-37-6

• 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: 1-(3-吡啶基羰基)-L-脯氨酸
• 英文名称: N-(Pyridine-3-carbonyl)-L-proline
• 英文别名: (2S)-1-(pyridine-3-carbonyl)pyrrolidine-2-carboxylic acid
• CAS: 59834-37-6
• 化学式: C₁₁H₁₂N₂O₃
• mdl: MFCD09757454
• 分子量: 220.228
• InChiKey: VHACSPGAMLSZBK-VIFPVBQESA-N

物化性质

• 熔点：
  169-171 °C
• 沸点：
  458.7±35.0 °C(Predicted)
• 密度：
  1.357±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  70.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(3-吡啶基羰基)-L-脯氨酸 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 96.5h， 生成 trigonellyl-Pro-Pro-Tyr-Lys(Boc) cholesteryl ester
  参考文献：
  名称：

  Strategies To Target Kyotorphin Analogues to the Brain

  摘要：

  The design, synthesis, and pharmacological evaluation of brain-targeted chemical delivery systems (CDS) for a kyotorphin analogue (Tyr-Lys) are described. The brain-targeted compound contains the active peptide in a packaged, disguised form, flanked between the lipophilic cholesteryl ester on the C-terminus and the 1,4-dihydrotrigonellyl redox targetor, attached to the N-terminus through strategically selected L-amino acid(s) spacer. It was found that for successful brain targeting, the epsilon-amine of Lys needs to be also converted to a Lipophilic function. Through sequential enzymatic bioactivation, the Tyr-Lys dipeptide is released in a sustained manner, producing significant and prolonged analgesic activity as demonstrated by the rat tail latency test. An alternate strategy was also employed. Lys was replaced by a redox amino acid pair, Nys(+) <-> Nys, the nicotinamide <-> 1,4-dihydronicotinamide analogues of Lys (Nys(+) is 2-amino-6-(3-carbamoyl-1-pyridiniumyl)hexanoic acid). The Nys form is lipophilic and facilitates delivery in addition to the C- and N-terminal lipophilic functions, Enzymatic oxidation to Nys(+) provides the lock-in, followed by removal;of the lipophilic groups, releasing Tyr-Nys(+) from the brain-targeted analogue (BTRA). Nys(+) was shown to be an effective substitution for Arg or Lys. The activities of the CDS and BTRA, respectively,were antagonized by naloxone, supporting the designed brain-targeted processes. The mst potent compound is the two-proline spacer containing CDS (CDS-PP), followed by the BTRA.

  DOI：

  10.1021/jm970715l
• 作为产物：
  描述：

  氯化烟碱盐酸盐 在 TEA 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 1-(3-吡啶基羰基)-L-脯氨酸
  参考文献：
  名称：

  Brain-Targeted Delivery of a Leucine-enkephalin Analogue by Retrometabolic Design

  摘要：

  A brain-targeted chemical delivery system (CDS) based on retrometabolic drug design was applied to a Leu-enkephalin analogue, Tyr-D-Ala-Gly-Phe-D-Leu (DADLE). The molecular architecture of the peptide CDS disguises its peptide nature from neuropeptide-degrading enzymes and provides lipophilic, bioreversible functions for the penetration through the blood-brain barrier. These functions were provided by a targetor, a 1,4-dihydrotrigonellyl group, on the N-terminus and a bulky, lipophilic ester group on the C-terminus. A spacer amino acid residue was also inserted between the targetor and the parent peptide to assure the release of DADLE by specific enzymes. Four CDSs were synthesized by segment-coupling method that proved to be superior to sequential elongation in obtaining this type of peptide conjugates. Intravenous injection of the compounds produced a significant and long-lasting response in rats monitored by the tail-flick latency measurements. CDSs having the bulkier cholesteryl group showed a better efficacy than those having the smaller 1-adamantaneethyl ester. The spacer was the most important factor to manipulate the rate of DADLE release and, thus, the pharmacological activity; proline as a spacer produced more potent analgesia than alanine. The antinociceptive effect of the CDSs was naloxone-reversible and methylnaloxonium-irreversible, confirming that central opiate receptors were solely responsible for mediating analgesia induced by the peptide CDS that delivered, retained, and then released the peptide in the brain.

  DOI：

  10.1021/jm960356e

文献信息

• Hepatitis C virus polymerase inhibitors
  申请人：Blaney Jeffrey Mark

  公开号：US20080200512A1

  公开（公告）日：2008-08-21

  The invention provides a compound of formula: and methods for making and using the same, where R 1 and R 2 are independently hydrogen, C 1-6 alkyl or C 1-6 haloalkyl; R 3 is hydrogen, halogen, C 1-6 alkyl or C 1-6 alkoxy; R 4 is hydrogen or halogen; and R 5 is a mono- or di-amino acid moiety, a succinic acid moiety, a urea moiety, or a derivative thereof. The invention also provides pharmaceutical compositions comprising a compound of formula I, and methods for making and using the same.

  这项发明提供了一个化合物的公式：以及制备和使用该化合物的方法，其中R1和R2分别是氢、C1-6烷基或C1-6卤代烷基；R3是氢、卤素、C1-6烷基或C1-6烷氧基；R4是氢或卤素；R5是单氨基酸或双氨基酸基团、琥珀酸基团、尿素基团或其衍生物。该发明还提供了包含化合物I的药物组合物，以及制备和使用该药物组合物的方法。
• Nouveaux composés hétérocycliques, leur préparation et les médicaments qui les contiennent
  申请人：RHONE-POULENC SANTE

  公开号：EP0118321A1

  公开（公告）日：1984-09-12

  Noveaux composés de formule (I) dans laquelle m = 1 ou 2, n = 0, 1 ou 2, étant entendu que m + n = 1,2 ou 3, A = S, O, CH2, SO ou SO2, R3 = H, alcoyle ou phényle (éventuellement substitué par halogène, alcoyle, alcoyloxy ou CF3) et a) soit X = 0, S, NH ou NOH, p est égal à 0 ou 1 et Y = -N(R1)R2 dans laquelle R1 = R2 = H ou bien R, = H et R2 = OH, alcoyle (1 à 5 C) substitué par COOH, NH2, alcoylamino, dialcoylamino, hydroxyalcoylamino, morpholino, aimidazo- lyle, pipérazinyle-1[(éventuellement sustitué en position 4 par alcoyle, benzyle (éventuellement substitué par halogène, alcoyle, alcoyloxy ou CF3), phényle (éventuellement substitué par halogène, alcoyle, alcoyloxy ou CF3)], pipéridino, pyrrolidinyle-1 ou bien R2 = phényle substitué par un ou plusieurs radicaux OH, COOH, NH2, alcoylamino ou dialcoylamino, ou bien R1 et R2 forment un cycle à 5 ou 6 chaînons pouvant contenir un autre hétéroatome tel que O, S ou N éventuellement substitué par alcoyle, alcoyloxycarbonyle, hydroxyalcoyle, aminoalcoyle, alcoylaminoalcoyle, dialcoylaminoalcoyle, benzyle (éventuellement substitué par halogène, alcoyle, alcoyloxy ou CF3), pyrrolidinyl-1 carbonylalcoyle, b) soit X = dialcoylhydrazono, Y = NH2 et p = 0 ou 1 c) soit X et Y forment un cycle Δ2-thiazolinyle-2 ou A2-imidazolinyle-2 et p = 0 ou 1. d) soit X = O, Y = H et p = O tous les radicaux alcoyle et portions alcoyle étant en chaîne droite ou ramifiée et contiennent sauf mention spéciale 1 à 4 C, ainsi que les formes tautomères lorsqu'elles existent et les sels d'addition et les sels métalliques. Les produits de formule (1) sont utiles comme antithrom- botiques.

  式 (I) 的新化合物，其中 m = 1 或 2，n = 0、1 或 2，不言而喻，m + n = 1、2 或 3，A = S、O、CH2、SO 或 SO2，R3 = H、烷基或苯基（任选被卤素、烷基、烷氧基或 CF3 取代），以及 a) X = 0、S、NH 或 NOH，p 等于 0 或 1，Y = -N(R1)R2，其中 R1 = R2 = H 或 R，= H 和 R2 = OH、被 COOH、NH2、烷基氨基、二烷基氨基、羟基烷基氨基、吗啉基、咪唑基取代的烷基（1 至 5 C）、1-哌嗪基[（可选择在第 4 位被烷基、苄基（可选择被卤素、烷基、烷氧基或 CF3 取代）、苯基（可选择被卤素、烷基、烷氧基或 CF3 取代）取代）]，哌啶基、吡咯烷-1-基，或 R2 = 被一个或多个 OH、COOH、NH2、烷基氨基或二烷基氨基基取代的苯基，或 R1 和 R2 形成一个 5 或 6 元环，该环可能含有另一个杂原子，如 O、S或N，可任选被烷基、烷氧羰基、羟基烷基、氨基烷基、烷基氨基烷基、二烷基氨基烷基、苄基（可任选被卤素、烷基、烷氧基或CF3取代）、吡咯烷基-1-羰基烷基取代、 b) X = 二烷基肼，Y = NH2，p = 0 或 1 c) 或 X 和 Y 形成Δ2-噻唑啉基-2 或 A2-咪唑啉基-2 环，且 p = 0 或 1。 d) 或 X＝O，Y＝H，p＝O，除非另有说明，所有烷基和烷基部分均为直链或支链且含有 1 至 4 个 C，以及存在的同分异构体形式和加成盐及金属盐。 式（1）的产品可用作抗色素药物。
• KUZNETSOVA, E. A.;VORONINA, T. A.;XROMOVA, I. V.;GARIBOVA, T. L.;TOSINA, +, XIM.-FARMATS. ZH., 23,(1989) N2, S. 1425-1431
  作者：KUZNETSOVA, E. A.、VORONINA, T. A.、XROMOVA, I. V.、GARIBOVA, T. L.、TOSINA, +

  DOI：——

  日期：——
• US4539400A
  申请人：——

  公开号：US4539400A

  公开（公告）日：1985-09-03
• US4546100A
  申请人：——

  公开号：US4546100A

  公开（公告）日：1985-10-08