5-piperidin-1-ylmethyl-furan-2-carboxylic acid

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-piperidin-1-ylmethyl-furan-2-carboxylic acid
• 英文别名: 5-(Piperidin-1-ium-1-ylmethyl)furan-2-carboxylate
• 化学式: C₁₁H₁₅NO₃
• mdl: MFCD00455269
• 分子量: 209.245
• InChiKey: FOMTWLBLESUJEU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.545
• 拓扑面积：
  53.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-piperidin-1-ylmethyl-furan-2-carboxylic acid 、 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， 反应 16.0h， 生成
  参考文献：
  名称：

  Identification of non-peptidic cysteine reactive fragments as inhibitors of cysteine protease rhodesain

  摘要：

  Rhodesain, the major cathepsin L-like cysteine protease in the protozoan Trypanosoma brucei rhodesiense, the causative agent of African sleeping sickness, is a well-validated drug target. In this work, we used a fragment-based approach to identify inhibitors of this cysteine protease, and identified inhibitors of T. brucei. To discover inhibitors active against rhodesain and T. brucei, we screened a library of covalent fragments against rhodesain and conducted preliminary SAR studies. We envision that in vitro enzymatic assays will further expand the use of the covalent tethering method, a simple fragment-based drug discovery technique to discover covalent drug leads. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.08.074

文献信息

• PHARMACEUTICAL COMBINATIONS OF 1-CYCLOPROPYL-3- [3-(5-M0RPHOOLIN-4-YL-METHYL-1H-BENZOIMIDAZOL-2-YL)- LH-1-PYRAZOL-4-YL]- UREA
  申请人：Curry Jayne Elizabeth

  公开号：US20100055094A1

  公开（公告）日：2010-03-04

  The invention provides combinations of an ancillary compound and a compound which is a salt of 1-cyclopropyl-3-[3-(5-morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-1H-pyrazol-4-yl]-urea selected from the lactate and citrate salts and mixtures thereof. Also provided are crystalline forms of the salts, methods for making the salts and their uses in treating cancers. The invention further provides combinations of an ancillary compound and a compound of the formula (I) as defined in PCT/GB2004/002824 (WO 2005/002552) or a compound of the formula (I′) or a salt, solvate, tautomer or N-oxide thereof, wherein R 1 , E, A and M are as defined in the claims.

  该发明提供了一种辅助化合物和一种盐化合物的组合物，所述盐化合物为1-环丙基-3-[3-(5-吗啉-4-基甲基-1H-苯并咪唑-2-基)-1H-吡唑-4-基]-脲的盐，所述盐选自乳酸盐和柠檬酸盐及其混合物。还提供了所述盐的晶型形式，制备所述盐的方法以及它们在治疗癌症中的用途。该发明进一步提供了一种辅助化合物和根据PCT/GB2004/002824（WO 2005/002552）中定义的式（I）或式（I'）的化合物的组合物，或者其盐、溶剂化合物、互变异构体或N-氧化物，其中R1、E、A和M如权利要求中所定义。
• [EN] PHARMACEUTICAL COMPOSITION COMPRISING A BENZODIAZEPINE DERIVATIVE AND A INHIBITOR OF THE RSV FUSION PROTEIN<br/>[FR] COMPOSITION PHARMACEUTIQUE COMPRENANT UN DERIVE DE BENZODIAZEPINE ET UN INHIBITEUR DE LA PROTEINE DE FUSION DU VIRUS RESPIRATOIRE SYNCYTIAL
  申请人：ARROW THERAPEUTICS LTD

  公开号：WO2005089771A1

  公开（公告）日：2005-09-29

  A pharmaceutical composition which comprises a pharmaceutically acceptable carrier or diluent and: (a) an inhibitor of the RSV fusion protein; and (b) a benzodiazepine derivative capable of inhibiting RSV replication is found to be highly active against RSV.

  一种包含药用可接受载体或稀释剂以及：(a) RSV融合蛋白抑制剂；和(b) 能够抑制RSV复制的苯二氮䓬类衍生物的药物组合物被发现对RSV具有很高的活性。
• [EN] THERAPEUTIC COMBINATIONS OF A BTK INHIBITOR, A PI3K INHIBITOR, A JAK-2 INHIBITOR AND/OR A CDK 4/6 INHIBITOR<br/>[FR] COMBINAISONS THÉRAPEUTIQUES D'UN INHIBITEUR DE LA BTK, D'UN INHIBITEUR DE LA PI3K, D'UN INHIBITEUR DE LA JAK-2 ET/OU D'UN INHIBITEUR DE LA CDK 4/6
  申请人：ACERTA PHARMA BV

  公开号：WO2016024232A1

  公开（公告）日：2016-02-18

  Therapeutic combinations of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms (PI3K-γ,δ, PI3K-γ, and PI3K-δ, a Janus kinase-2 (JAK-2) inhibitor, a cyclin-dependent kinase- 4/6 (CDK4/6) inhibitor, and/or a Bruton's tyrosine kinase (BTK) inhibitor are described. In certain embodiments, the invention includes therapeutic combinations of a cyclin-dependent kinase-4/6 (CDK4/6) inhibitor and a BTK inhibitor, a PI3K-δ inhibitor and a BTK inhibitor, a JAK-2 and a BTK inhibitor, and a JAK-2, PI3K-δ, and BTK inhibitor.

  描述了磷脂酰肌醇3-激酶（PI3K）抑制剂的治疗组合，包括选择性作用于γ-和δ-异构体以及同时选择γ-和δ-异构体（PI3K-γ,δ, PI3K-γ和PI3K-δ）的PI3K抑制剂，一种Janus激酶-2（JAK-2）抑制剂，一种细胞周期依赖性激酶-4/6（CDK4/6）抑制剂，和/或一种Bruton氏酪氨酸激酶（BTK）抑制剂。在某些实施例中，该发明包括细胞周期依赖性激酶-4/6（CDK4/6）抑制剂和BTK抑制剂的治疗组合，PI3K-δ抑制剂和BTK抑制剂，JAK-2和BTK抑制剂，以及JAK-2、PI3K-δ和BTK抑制剂的治疗组合。
• [EN] THERAPEUTIC COMBINATIONS OF A BTK INHIBITOR, A PI3K INHIBITOR, A JAK-2 INHIBITOR, AND/OR A BCL-2 INHIBITOR<br/>[FR] COMBINAISONS THÉRAPEUTIQUES D'UN INHIBITEUR DE BTK, D'UN INHIBITEUR DE PI3K, D'UN INHIBITEUR DE JAK-2, ET/OU D'UN INHIBITEUR DE BCL-2
  申请人：ACERTA PHARMA BV

  公开号：WO2016024230A1

  公开（公告）日：2016-02-18

  Therapeutic combinations of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms (PI3K-γ,δ, PI3K-γ, and PI3K-δ), a Janus kinase-2 (JAK-2) inhibitor, a Bruton's tyrosine kinase (BTK) inhibitor, and/or a B-cell lymphoma-2 (BCL-2) inhibitor are described. In some embodiments, the invention provides therapeutic combinations of a PI3K-δ inhibitor and a BTK inhibitor, a JAK-2 and a BTK inhibitor, and a BCL-2 and BTK inhibitor.

  本发明描述了磷脂酰肌醇3-激酶（PI3K）抑制剂的治疗组合，包括选择性作用于γ-和δ-异构体以及同时选择性作用于γ-和δ-异构体（PI3K-γ,δ, PI3K-γ和PI3K-δ）的PI3K抑制剂，一种Janus激酶-2（JAK-2）抑制剂，一种Bruton酪氨酸激酶（BTK）抑制剂，和/或一种B细胞淋巴瘤-2（BCL-2）抑制剂。在一些实施例中，本发明提供了PI3K-δ抑制剂和BTK抑制剂、JAK-2和BTK抑制剂、以及BCL-2和BTK抑制剂的治疗组合。
• Pharmaceutical Compounds
  申请人：Berdini Valerio

  公开号：US20100004232A1

  公开（公告）日：2010-01-07

  The use of a compound for the manufacture of a medicament for the prophylaxis or treatment of: A. a disease state or condition mediated by a kinase which is BCR-abl, VEGFR, PDGFR, EGFR, Flt3, JAK (e.g. JAK2 or JAK3), C-abl, PDK1, Chk (e.g. Cbk1 or Chk2), FGFR (e.g. FGFR3), Ret, Eph (e.g. EphB2 or EphB4), or Src (e.g. cSrc); or B. a cancer in which the cancer cells thereof contain a drug resistant kinase mutation which is: (a) a threonine gatekeeper mutation; or (b) a drug-resistant gatekeeper mutation; or (c) an imatinib resistant mutation; or (d) a nilotinib resistant mutation; or (e) a dasatinib resistant mutation; or (f) a T670I mutation in KIT; or (g) a T674I mutation in PDGFR; or (h) T790M mutation in EGFR; or (i) a T315I mutation in abl; or C. a cancer which expresses a mutated molecular target which is a mutated form of BCRabl, c-kit, PDGF, EGF receptor or ErbB2; or D. a disease mediated by a kinase containing a mutation in a region of the protein that binds to or interacts with other cancer agents but does not bind to or interact with the compounds of formula (I) or (I′), for example a mutated kinase selected from c-abl, c-kit, PDGFR including PDGFR-beta and PDGFR-alpha, and ErbB family members such as EGFR (ErbB1), HER2 (ErbB2), ErbB3, and ErbB4, members of the Ephrin receptor family including EphA1, EphA2, EphA3, EphA4, EphA5, EphA8, EphA10, EphB1, EphB2, EphB3, EphB5, EphB6, c-Src and kinases of the JAK family such as TYK2; wherein the compound is a compound of the formula (I or I′): or a salt, solvate, tautomer or N-oxide thereof wherein R 0′ , R 1 , R 1′ , R 2′ , R 3′ , R 4′ , A′, X′, E, A and M are as defined in the claims.

  使用该化合物制造药物，用于预防或治疗以下疾病状态或条件：A. 由激酶介导的疾病状态或条件，其中激酶是BCR-abl、VEGFR、PDGFR、EGFR、Flt3、JAK（例如JAK2或JAK3）、C-abl、PDK1、Chk（例如Cbk1或Chk2）、FGFR（例如FGFR3）、Ret、Eph（例如EphB2或EphB4）或Src（例如cSrc）；或B. 癌症，其癌细胞含有耐药激酶突变，该耐药激酶突变是：（a）苏氨酸门卫突变；或（b）耐药门卫突变；或（c）伊马替尼耐药突变；或（d）尼洛替尼耐药突变；或（e）达沙替尼耐药突变；或（f）KIT中的T670I突变；或（g）PDGFR中的T674I突变；或（h）EGFR中的T790M突变；或（i）abl中的T315I突变；或C. 表达突变分子靶点的癌症，该突变分子靶点是BCRabl、c-kit、PDGF、EGF受体或ErbB2的突变形式；或D. 由激酶介导的疾病，其中激酶在与其他癌症药物结合或相互作用的蛋白质区域中具有突变，但不与式（I）或（I'）化合物结合或相互作用，例如选择自c-abl、c-kit、PDGFR（包括PDGFR-beta和PDGFR-alpha）和ErbB家族成员，如EGFR（ErbB1）、HER2（ErbB2）、ErbB3和ErbB4，包括Ephrin受体家族成员，如EphA1、EphA2、EphA3、EphA4、EphA5、EphA8、EphA10、EphB1、EphB2、EphB3、EphB5、EphB6、c-Src和JAK家族的激酶；其中该化合物是式（I或I'）的化合物：或其盐、溶剂合物、互变异构体或N-氧化物，其中R0'、R1、R1'、R2'、R3'、R4'、A'、X'、E、A和M如权利要求所定义。