N-(2-呋喃甲基)-2-吗啉-4-基乙胺二盐酸盐 | 880813-53-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: N-(2-呋喃甲基)-2-吗啉-4-基乙胺二盐酸盐
• 中文别名: (呋喃-2-甲基)[2-(吗啉-4-基)乙基]胺
• 英文名称: furan-2-ylmethyl-(2-(morpholin-4-yl)ethyl)amine
• 英文别名: N-(Furan-2-ylmethyl)-2-morpholinoethanamine；N-(furan-2-ylmethyl)-2-morpholin-4-ylethanamine
• CAS: 880813-53-6
• 化学式: C₁₁H₁₈N₂O₂
• mdl: MFCD07410488
• 分子量: 210.276
• InChiKey: XODQIXKMHPJBFF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.636
• 拓扑面积：
  37.6
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  N-(2-呋喃甲基)-2-吗啉-4-基乙胺二盐酸盐 在 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 3.0h， 生成 2-(2-Morpholin-4-yl-ethyl)-3-oxo-2,3-dihydro-1H-isoindole-4-carboxylic acid
  参考文献：
  名称：

  Discovery of 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118): A Potent, Orally Available, and Highly Selective PARP-1 Inhibitor for Cancer Therapy

  摘要：

  The nuclear protein poly(ADP-ribose) polymerase-1 (PARP-1) has a well-established role in the signaling and repair of DNA and is a prominent target in oncology, as testified by the number of candidates in clinical testing that unselectively target both PARP-1 and its closest isoform PARP-2. The goal of our program was to find a PARP-1 selective inhibitor that would potentially mitigate toxicities arising from cross-inhibition of PARP-2. Thus, an HTS campaign on the proprietary Nerviano Medical Sciences (NMS) chemical collection, followed by SAR optimization, allowed us to discover 2-[1-4,4-difluorocyclohexyl)piperidin-4-yl] -6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118, 20by). NMS-P118 proved to be a potent, orally available, and highly selective PARP-1 inhibitor endowed with excellent ADME and pharmacokinetic profiles and high efficacy in vivo both as a single agent and in combination with Temozolomide in MDA-MB-436 and Capan-1 xenograft models, respectively. Cocrystal structures of 20by with both PARP-1 and PARP-2 catalytic domain proteins allowed rationalization of the observed selectivity.

  DOI：

  10.1021/acs.jmedchem.5b00680
• 作为产物：
  描述：

  N-(2-氨基乙基)吗啉 、 糠醛 在 sodium tetrahydroborate 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 8.0h， 生成 N-(2-呋喃甲基)-2-吗啉-4-基乙胺二盐酸盐
  参考文献：
  名称：

  Discovery of 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118): A Potent, Orally Available, and Highly Selective PARP-1 Inhibitor for Cancer Therapy

  摘要：

  The nuclear protein poly(ADP-ribose) polymerase-1 (PARP-1) has a well-established role in the signaling and repair of DNA and is a prominent target in oncology, as testified by the number of candidates in clinical testing that unselectively target both PARP-1 and its closest isoform PARP-2. The goal of our program was to find a PARP-1 selective inhibitor that would potentially mitigate toxicities arising from cross-inhibition of PARP-2. Thus, an HTS campaign on the proprietary Nerviano Medical Sciences (NMS) chemical collection, followed by SAR optimization, allowed us to discover 2-[1-4,4-difluorocyclohexyl)piperidin-4-yl] -6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118, 20by). NMS-P118 proved to be a potent, orally available, and highly selective PARP-1 inhibitor endowed with excellent ADME and pharmacokinetic profiles and high efficacy in vivo both as a single agent and in combination with Temozolomide in MDA-MB-436 and Capan-1 xenograft models, respectively. Cocrystal structures of 20by with both PARP-1 and PARP-2 catalytic domain proteins allowed rationalization of the observed selectivity.

  DOI：

  10.1021/acs.jmedchem.5b00680

文献信息

• SUBSTITUTED 1,2,3,4-TETRAHYDROISOQUINOLINE DERIVATIVES FOR THE TREATMENT OF HORMONE-DEPENDENT DISEASES
  申请人：UNIVERSITÉ LAVAL

  公开号：US20160200685A1

  公开（公告）日：2016-07-14

  Provided are compounds of general formula A and A′, wherein X 1 and X 2 are each C, CH or N; R 3 and R 4 are each H, optionally substituted C 1 -C 30 saturated or unsaturated chemical group, or together form an optionally substituted C 5 -C 8 cycle; Z 1 ; Z 2 and Z 3 are each N or CH; V is C═O, C═S or CH 2 ; n is from 1 to 12; W 1 and W 2 are each H, CH 2 , O or S; and R 1 and R 2 are each H, Cr 1 C 6 alkyl, C 1 C 6 aryl, C 1 C 12 alkylaryl, optionally substituted phenyl, C 1 C 6 alkoxy, C 1 C 6 thioalkoxy, F, Cl, Br or I. These compounds inhibit steroid sulfatase (STS), act as selective estrogen receptor modulators (SERMs), increase alkaline phosphatase (ALP) activity, and are useful in the treatment of medical conditions involving hormones such as breast cancer, prostate cancer, endometriosis, osteoporosis, benign prostatic hyperplasia and endometrial cancer.

  提供了一般式为A和A'的化合物，其中X1和X2分别为C、CH或N；R3和R4分别为H、可选取代的C1-C30饱和或不饱和化学基团，或共同形成可选取代的C5-C8环；Z1、Z2和Z3分别为N或CH；V为C═O、C═S或CH2；n为1至12；W1和W2分别为H、CH2、O或S；R1和R2分别为H、Cr1C6烷基、C1C6芳基、C1C12烷基芳基、可选取代的苯基、C1C6烷氧基、C1C6硫代烷氧基、F、Cl、Br或I。这些化合物抑制类固醇磺酸酯酶（STS），作为选择性雌激素受体调节剂（SERMs），增加碱性磷酸酶（ALP）活性，并可用于治疗涉及激素的医疗条件，如乳腺癌、前列腺癌、子宫内膜异位症、骨质疏松症、良性前列腺增生和子宫内膜癌。
• US9708305B2
  申请人：——

  公开号：US9708305B2

  公开（公告）日：2017-07-18
• Discovery of 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1<i>H</i>-isoindole-4-carboxamide (NMS-P118): A Potent, Orally Available, and Highly Selective PARP-1 Inhibitor for Cancer Therapy
  作者：Gianluca Papeo、Helena Posteri、Daniela Borghi、Alina A. Busel、Francesco Caprera、Elena Casale、Marina Ciomei、Alessandra Cirla、Emiliana Corti、Matteo D’Anello、Marina Fasolini、Barbara Forte、Arturo Galvani、Antonella Isacchi、Alexander Khvat、Mikhail Y. Krasavin、Rosita Lupi、Paolo Orsini、Rita Perego、Enrico Pesenti、Daniele Pezzetta、Sonia Rainoldi、Federico Riccardi-Sirtori、Alessandra Scolaro、Francesco Sola、Fabio Zuccotto、Eduard R. Felder、Daniele Donati、Alessia Montagnoli

  DOI：10.1021/acs.jmedchem.5b00680

  日期：2015.9.10

  The nuclear protein poly(ADP-ribose) polymerase-1 (PARP-1) has a well-established role in the signaling and repair of DNA and is a prominent target in oncology, as testified by the number of candidates in clinical testing that unselectively target both PARP-1 and its closest isoform PARP-2. The goal of our program was to find a PARP-1 selective inhibitor that would potentially mitigate toxicities arising from cross-inhibition of PARP-2. Thus, an HTS campaign on the proprietary Nerviano Medical Sciences (NMS) chemical collection, followed by SAR optimization, allowed us to discover 2-[1-4,4-difluorocyclohexyl)piperidin-4-yl] -6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118, 20by). NMS-P118 proved to be a potent, orally available, and highly selective PARP-1 inhibitor endowed with excellent ADME and pharmacokinetic profiles and high efficacy in vivo both as a single agent and in combination with Temozolomide in MDA-MB-436 and Capan-1 xenograft models, respectively. Cocrystal structures of 20by with both PARP-1 and PARP-2 catalytic domain proteins allowed rationalization of the observed selectivity.