(7S,9S)-7-[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione;[(19S)-10,19-diethyl-19-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaen-7-yl] 4-piperidin-1-ylpiperidine-1-carboxylate

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 蒽环类药物
• 英文名称: (7S,9S)-7-[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione;[(19S)-10,19-diethyl-19-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaen-7-yl] 4-piperidin-1-ylpiperidine-1-carboxylate
• 化学式: C60H67N5O17
• 分子量: 1130.2
• InChiKey: NVNPKCYNNLSIPM-GSVMOBEQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.09
• 重原子数：
  82
• 可旋转键数：
  10
• 环数：
  12.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  319
• 氢给体数：
  7
• 氢受体数：
  20

文献信息

• [EN] CYCLIC PEPTIDES AND THEIR CONJUGATES FOR ADDRESSING ALPHA-V-BETA-6 INTEGRIN IN VIVO<br/>[FR] PEPTIDES CYCLIQUES ET LEURS CONJUGUÉS POUR L'ADRESSAGE D'UNE INTÉGRINE ALPHA-V-BÊTA-6 IN VIVO
  申请人：UNIV MUENCHEN TECH

  公开号：WO2021180969A1

  公开（公告）日：2021-09-16

  The invention provides conjugates of cyclic peptides as ligands for cellular surface receptors, in particular, as ligands for αvβ6-integrin. The conjugates further contain effector moieties and are suitable for use as therapeutic agent, diagnostic agent, agent for imaging, targeting moiety and as biomolecular research tool. The invention specifically relates to the use of conjugates with signalling moieties or radionuclides for in-vivo addressing of αvβ6-integrin.

  本发明提供了环肽的共轭物，作为细胞表面受体的配体，特别是作为αvβ6整合素的配体。这些共轭物还含有效应物质，适用于作为治疗剂、诊断剂、成像剂、靶向分子和生物分子研究工具。本发明特别涉及使用带有信号物质或放射性核素的共轭物来体内定位αvβ6整合素。
• Ligands for integrin αvβ6, synthesis and uses thereof
  申请人：Technische Universitat Munchen

  公开号：US10562936B2

  公开（公告）日：2020-02-18

  Disclosed are compound exhibiting highly active and selective binding to αvβ6 integrin, which are represented by the following general formula (I): Cyclo-(Arg-X1-Asp-X2-X3-X4-X5-X6-X7) (I) wherein the variables groups X to X have the following meanings X1: Ser, Gly, Thr, X2: Leu, lie, Nle, Val, Phe, X3: Gly, Ala, X4: Leu, He, Nle, Val, Phe, Lys, Tyr, Trp, Arg, X5: D-Pro, N-Me-D-lipophilic amino acids, X6: Pro, N-Me-amino acids, N-Me-Lys, N-Me-Lys(Ac), and X7; Ala, Leu, He, Nle, Val, Phe, Tyr, Trp or wherein the sub-sequence -X5-X6- represents a β-turn mimetic differing from the meanings above, or pharmaceutically acceptable salts, esters, solvates, polymorphs or modified forms thereof represented by the following general formula (II): (X0)n1L(X8)n2 wherein Xo represents the compound of the general formula (I) as specified above (excluding one hydrogen atom to allow bonding to the linker), L represents a linker, X8 represents the effector moiety and wherein n1 and n2 are each independently selected from the range of 1 to 5, wherein n1+n2 represents the number of valencies of the linker and is preferably in the range of from 2 to 6, more preferably 3-5, with the proviso that each of n1 and n2 is at least 1, as well as uses therefore in therapy and imaging.

  所公开的化合物对 αvβ6 整合素具有高活性和选择性结合，由以下通式 (I) 表示：环-（Arg-X1-Asp-X2-X3-X4-X5-X6-X7） (I) 其中变量基团 X 至 X 的含义如下 X1：Ser, Gly, Thr, X2: Leu, lie, Nle, Val, Phe, X3: Gly, Ala, X4: Leu, He, Nle, Val, Phe, Lys, Tyr, Trp, Arg, X5: D-Pro, N-Me-D-lipophilic amino acids, X6：Pro、N-Me-氨基酸、N-Me-Lys、N-Me-Lys(Ac)，以及 X7；Ala、Leu、He、Nle、Val、Phe、Tyr、Trp 或其中子序列 -X5-X6- 代表不同于上述含义的 β-匝数模拟物，或其药学上可接受的盐、酯、溶液剂、多晶型或改进型，由下式通式 (II) 代表：(X0)n1L(X8)n2其中 Xo 代表上述通式(I)的化合物（不包括一个氢原子，以便与连接体结合），L 代表连接体，X8 代表效应分子，其中 n1 和 n2 各自独立地选自 1 至 5 的范围、其中 n1+n2 代表连接体的价数，优选在 2-6 之间，更优选在 3-5 之间，但 n1 和 n2 中的每一个至少为 1，以及因此在治疗和成像中的用途。
• Ligands for integrin αVβ8, synthesis and uses thereof
  申请人：Technische Universitat Munchen

  公开号：US11332498B2

  公开（公告）日：2022-05-17

  Disclosed are compounds represented by the following general formula (I): Cyclo-(Arg-Gly-Asp-X1-X2-X3-X4-X5) (I) wherein the variables groups X1 to X5 have the following meanings X1: Leu, Ile, Nle, Val, Tyr, Phe; X2: D-amino acid such as D-Pro, N-Me-D-Phe; X3: Pro, N-Me-amino acid such as N-Me-Lys, N-Me-Lys(Ac); Pro-Rx3, N-Me-Lys-Rx4; X4: Gly, Ala, Ser, Thr; X5: Leu, Ala, Tyr, His, Ile, Nle, Val, Phe wherein Pro-Rx3 represents a proline residue that carries at the C-3, C-4 or C-5 carbon atom and preferably the C-4 carbon atom a functional group selected from —NH2, —OH, —NH—Ac, —NH-hexyne, and wherein Lys-Rx4 represents a lysine residue, wherein the ω-amino nitrogen atom carries a group of the formula -L4-R4, wherein L4 is selected from the group consisting of covalent bond, —C(O)—, and —C(O)—O—, . . . , and wherein R4 is selected from the group consisting of —(CH2)n-C≡CH with n=0, 1, 2, 3, 4, 5, 6, 7 or 8, or wherein the sub-sequence -X2-X3- represents a β-turn mimetic diffeωωring from the meanings above, or pharmaceutically acceptable salts, esters, solvates, polymorphs or modified forms thereof represented by the following general formula (II): (X0)n1L(X8)n2 wherein X0 represents the compound of the general formula (I) as specified above (excluding one hydrogen atom to allow bonding to the linker), L represents a linker, X8 represents the effector moiety and wherein n1 and n2 are each independently selected from the range of 1 to 5, preferably such that each of n1 and n2 represents 1, wherein n1+n2 represents the number of valencies of the linker and is preferably in the range of from 2 to 6, more preferably 2-5, with the proviso that each of n1 and n2 is at least 1, as well as uses therefore in therapy and imaging.

  公开了由以下通式 (I) 所代表的化合物：环-(Arg-Gly-Asp-X1-X2-X3-X4-X5) (I) 其中变量基团 X1 至 X5 具有以下含义 X1：Leu、Ile、Nle、Val、Tyr、Phe；X2：D-氨基酸，如 D-Pro、N-Me-D-Phe；X3：Pro、N-Me-氨基酸，如 N-Me-Lys、N-Me-Lys(Ac)；Pro-Rx3、N-Me-Lys-Rx4；X4：Gly、Ala、Ser、Thr；X5：其中 Pro-Rx3 代表脯氨酸残基，该残基在 C-3、C-4 或 C-5 碳原子上，最好在 C-4 碳原子上带有选自-NH2、-OH、-NH-Ac、-其中 Lys-Rx4 代表赖氨酸残基，其中 ω-氨基氮原子带有式 -L4-R4 的基团，其中 L4 选自由共价键、-C(O)- 和 -C(O)-O-、.. .，其中 R4 选自由 n=0、1、2、3、4、5、6、7 或 8 的-(CH2)n-C≡CH 所组成的组，或其中子序列 -X2-X3- 代表与上述含义不同的 β-回转模拟物ωω环，或其药学上可接受的盐类、酯类、溶液剂、多晶型或改进型，由下式通式 (II) 代表：(X0)n1L(X8)n2其中 X0 代表上述通式(I)的化合物（不包括一个氢原子，以便与连接体结合），L 代表连接体，X8 代表效应分子，其中 n1 和 n2 各自独立地选自 1 至 5 的范围、其中 n1+n2 代表连接体的价数，优选在 2 到 6 的范围内，更优选 2 到 5，但 n1 和 n2 中的每一个至少为 1，以及因此在治疗和成像中的用途。
• LIGANDS FOR INTEGRIN AVBETA6, SYNTHESIS AND USES THEREOF
  申请人：Technische Universität München

  公开号：EP3350222A1

  公开（公告）日：2018-07-25
• LIGANDS FOR INTEGRIN AVß6, SYNTHESIS AND USES THEREOF
  申请人：Technische Universitat Munchen

  公开号：US20180265548A1

  公开（公告）日：2018-09-20

  Disclosed are compound exhibiting highly active and selective binding to ανβ6 integrin, which are represented by the following general formula (I): Cyclo-(Arg-X 1 -Asp-X 2 -X 3 -X 4 -X 5 -X 6 -X 7 ) (I) wherein the variables groups X to X have the following meanings X 1 : Ser, Gly, Thr, X 2 : Leu, Ile, Nle, Val, Phe, X 3 : Gly, Ala, X 4 : Leu, He, Nle, Val, Phe, Lys, Tyr, Trp, Arg, X 5 : D-Pro, N-Me-D-lipophilic amino acids, X 6 : Pro, N-Me-amino acids, N-Me-Lys, N-Me-Lys(Ac), and X 7 ; Ala, Leu, He, Nle, Val, Phe, Tyr, Trp or wherein the sub-sequence -X 5 -X 6 - represents a β-turn mimetic differing from the meanings above, or pharmaceutically acceptable salts, esters, solvates, polymorphs or modified forms thereof represented by the following general formula (II): (X 0 ) n1 L(X 8 ) n2 wherein X 0 represents the compound of the general formula (I) as specified above (excluding one hydrogen atom to allow bonding to the linker), L represents a linker, X 8 represents the effector moiety and wherein n1 and n2 are each independently selected from the range of 1 to 5, wherein n1+n2 represents the number of valencies of the linker and is preferably in the range of from 2 to 6, more preferably 3-5, with the proviso that each of n1 and n2 is at least 1, as well as uses therefore in therapy and imaging.