4-[[4-(5-methoxy-2-pyridinyl)phenoxy]methyl]-5-methyl-N-[(2-methylphenyl)sulphonyl]-2-furancarboxamide | 1186532-61-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-[[4-(5-methoxy-2-pyridinyl)phenoxy]methyl]-5-methyl-N-[(2-methylphenyl)sulphonyl]-2-furancarboxamide
• 英文别名: 4-((4-(5-methoxypyridin-2-yl)phenoxy)methyl)-5-methyl-N-(o-tolylsulfonyl)furan-2-carboxamide；4-[[4-(5-methoxy-2-pyridyl)phenoxy]methyl]-5-methyl-N-[(2-methylphenyl)sulfonyl]-2-furamide；N-{4-[4-(5-methoxypyridin-2-yl)phenoxymethyl]-5-methylfuran-2-carbonyl}-2-methylbenzenesulphonamide；BGC-20-1531 (free base)；4-[[4-(5-methoxypyridin-2-yl)phenoxy]methyl]-5-methyl-N-(2-methylphenyl)sulfonylfuran-2-carboxamide
• CAS: 1186532-61-5
• 化学式: C₂₆H₂₄N₂O₆S
• 分子量: 492.552
• InChiKey: IXDVRRPNWPOPGV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  116
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-[[4-(5-methoxy-2-pyridinyl)phenoxy]methyl]-5-methyl-N-[(2-methylphenyl)sulphonyl]-2-furancarboxamide 在 碳酸氢钠 作用下， 以 甲醇 、 水 为溶剂， 以95%的产率得到sodium (4-((4-(5-methoxypyridin-2-yl)phenoxy)methyl)-5-methylfuran-2-carbonyl)(o-tolylsulfonyl)amide
  参考文献：
  名称：

  From virtual to clinical: The discovery of PGN-1531, a novel antagonist of the prostanoid EP4 receptor

  摘要：

  In this Letter, we present the results of a hit-finding and lead optimization programme against the EP4 receptor (EP4R). In a short time period, we were able to discover five structurally diverse series of hit compounds using a combination of virtual screening methods. The most favoured hit, compound 6, was demonstrated to be a competitive antagonist of the EP4R. Compound 73 was identified following several rounds of optimization, which centred on improving both the primary EP4R affinity and selectivity against the related EP2R as well as the aqueous solubility. This work culminated in the preparation of PGN-1531, the sodium salt of 73, which showed a marked improvement in solubility (>10 mg/mL). PGN-1531 is a potent and selective antagonist at EP(4)Rs in vitro and in vivo, with the potential to alleviate the symptoms of migraine that result from cerebral vasodilatation. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.02.068
• 作为产物：
  描述：

  2-甲基-3-呋喃甲醇 在 咪唑 、 4-二甲氨基吡啶 、 正丁基锂 、 水 、 甲基磺酰氯 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 二氯甲烷 为溶剂， 反应 58.0h， 生成 4-[[4-(5-methoxy-2-pyridinyl)phenoxy]methyl]-5-methyl-N-[(2-methylphenyl)sulphonyl]-2-furancarboxamide
  参考文献：
  名称：

  From virtual to clinical: The discovery of PGN-1531, a novel antagonist of the prostanoid EP4 receptor

  摘要：

  In this Letter, we present the results of a hit-finding and lead optimization programme against the EP4 receptor (EP4R). In a short time period, we were able to discover five structurally diverse series of hit compounds using a combination of virtual screening methods. The most favoured hit, compound 6, was demonstrated to be a competitive antagonist of the EP4R. Compound 73 was identified following several rounds of optimization, which centred on improving both the primary EP4R affinity and selectivity against the related EP2R as well as the aqueous solubility. This work culminated in the preparation of PGN-1531, the sodium salt of 73, which showed a marked improvement in solubility (>10 mg/mL). PGN-1531 is a potent and selective antagonist at EP(4)Rs in vitro and in vivo, with the potential to alleviate the symptoms of migraine that result from cerebral vasodilatation. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.02.068

文献信息

• [EN] EP4 RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES AUX RECEPTEURS EP4
  申请人：PHARMAGENE LAB LTD

  公开号：WO2004067524A1

  公开（公告）日：2004-08-12

  Compounds of formula (I): wherein: R2 is H or an optionally substituted C1-4 alkyl group; Y is either -(CH2)n-X-, where n is 1 or 2 and X is O, S, S(=O), S(=O)2, or NRN1, where RN1 is selected from H or optionally substituted C1-4 alkyl, or Y is -C(=O)NRN2-, where RN2 is selected from H, and optionally substituted C1-7 alkyl or C5-20 aryl; R3 is an optionally substituted C6 aryl group linked to a further optionally substituted C6 aryl group, wherein if both C6 aryl groups are benzene rings, there may be an oxygen bridge between the two rings, bound adjacent the link on both rings; A is a single bond or a C1-3 alkylene group; and R5 is either:(i) carboxy;(ii) a group of formula (II); or(iii) a group of formula (III):, wherein R is optionally substituted C1-7 alkyl, C5-20 aryl or NRN3RN4, where RN3 and RN4 are independently selected from optionally substituted C1-4 alkyl;(iv) tetrazol-5-yl.

  式(I)的化合物：其中：R2为H或可选择地取代的C1-4烷基基团；Y为-(CH2)n-X-，其中n为1或2，X为O、S、S(=O)、S(=O)2或NRN1，其中RN1从H或可选择地取代的C1-4烷基中选择，或Y为-C(=O)NRN2-，其中RN2从H、可选择地取代的C1-7烷基或C5-20芳基中选择；R3为可选择地取代的C6芳基基团，连接到另一个可选择地取代的C6芳基基团，如果两个C6芳基基团均为苯环，则两个环之间可能有氧桥，在两个环上的连接处相邻结合；A为单键或C1-3烷基基团；R5为以下之一：(i)羧基；(ii)式(II)的基团；或(iii)式(III)的基团：其中R为可选择地取代的C1-7烷基、C5-20芳基或NRN3RN4，其中RN3和RN4独立地从可选择地取代的C1-4烷基中选择；(iv)四唑-5-基。
• COMBINATIONS OF MEDICAMENTS, CONTAINING PDE4-INHIBITORS AND EP4-RECEPTOR-ANTAGONISTS
  申请人：Nickolaus Peter

  公开号：US20130225609A1

  公开（公告）日：2013-08-29

  The present invention relates to new medicament combinations which contain in addition to one or more PDE4-inhibitors (1) at least one EP4 receptor antagonist (2), as well as the use thereof for the treatment of preferably respiratory complaints such as particularly COPD, chronic sinusitis and asthma. The invention relates in particular to those medicament combinations which contain, in addition to one or more, preferably one, PDE4 inhibitor of general formula 1 wherein X is SO or SO 2 , but preferably SO, and wherein R 1 , R 2 , R 3 and R 4 have the meanings given in claim 1, at least one EP4 receptor antagonist (2), the preparation thereof and the use thereof for the treatment of respiratory complaints.

  本发明涉及新的药物组合物，其包含除了一个或多个PDE4抑制剂（1）之外，至少一个EP4受体拮抗剂（2），以及其用于治疗特别是呼吸系统疾病，如慢性阻塞性肺病（COPD）、慢性鼻窦炎和哮喘的用途。本发明特别涉及那些药物组合物，其除了一个或多个，优选一个，PDE4抑制剂的一般通式1之外，还包含至少一个EP4受体拮抗剂（2），其中X是SO或SO2，但优选SO，并且其中R1、R2、R3和R4具有权利要求1中给出的含义，所述组合物的制备及其用于治疗呼吸系统疾病的用途。
• [EN] N-SUBSTITUTED INDOLE DERIVATIVES<br/>[FR] DÉRIVÉS D'INDOLE N-SUBSTITUÉS
  申请人：IDORSIA PHARMACEUTICALS LTD

  公开号：WO2018210995A1

  公开（公告）日：2018-11-22

  The present invention relates to derivatives of formula (I) Formula (I) wherein R1, and R 2 are as described in the description, to their preparation, to pharmaceutically acceptable salts thereof, and to their use as pharmaceuticals, to pharmaceutical compositions containing one or more compounds of formula (I), and especially to their use as modulators of the prostaglandin 2 receptor EP2.

  本发明涉及公式（I）的衍生物 公式（I）其中R1和R2如描述中所述，以及它们的制备方法，其药用盐，以及它们作为药物的用途，含有一个或多个公式（I）化合物的药物组合物，特别是它们作为前列腺素2受体EP2的调节剂的用途。
• [EN] NOVEL PIPERIDINO-DIHYDROTHIENOPYRIMIDINE SULFOXIDES AND THEIR USE FOR TREATING COPD AND ASTHMA<br/>[FR] NOUVEAUX SULFOXYDES DE PIPÉRIDINO-DIHYDROTHIÉNOPYRIMIDINE ET LEUR UTILISATION POUR LE TRAITEMENT DE LA BPCO ET DE L'ASTHME
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2013026797A1

  公开（公告）日：2013-02-28

  The invention relates to novel piperidino-dihydrothienopyrimidine sulfoxides of formula I, wherein Ring A is a 6-membered aromatic ring which may optionally comprise one or two nitrogen atoms and wherein R is CI and wherein R may be located either in the para-, meta- or ortho-position of Ring A, wherein S* is a sulphur atom that represents a chiral center, and all pharmaceutically acceptable salts, enantiomers and racemates, hydrates and solvates thereof and the use of these compounds for the treatment of inflammatory or allergic diseases of the respiratory tract such as COPD or asthma.

  本发明涉及一种新型的Piperidino-Dihydrothienopyrimidine Sulfoxides化合物，其化学式为I，其中环A是一个6元芳香环，可以选择性地包含一个或两个氮原子，R为CI，且R可以位于环A的对位、间位或邻位，S*为代表手性中心的硫原子，以及其所有药学上可接受的盐、对映体和混合物、水合物和溶剂化合物，以及这些化合物用于治疗呼吸道炎症或过敏性疾病，如慢性阻塞性肺病或哮喘。
• NOVEL PIPERIDINO-DIHYDROTHIENOPYRIMIDINE SULFOXIDES AND THEIR USE FOR TREATING COPD AND ASTHMA
  申请人：POUZET Pascale A.J.

  公开号：US20150045376A1

  公开（公告）日：2015-02-12

  Piperidino-dihydrothienopyrimidine sulfoxides of formula I wherein: Ring A is a 6-membered aromatic ring optionally comprising one or two nitrogen atoms and R is Cl and is located in the para-, meta-, or ortho-position of Ring A, S* is a sulphur atom that represents a chiral center, and all pharmaceutically acceptable salts, enantiomers and racemates, hydrates and solvates thereof and the use of these compounds for the treatment of inflammatory or allergic diseases of the respiratory tract such as COPD or asthma.

  式I中的哌啶基-二氢噻唑嘧啶磺酰氧化物：其中：环A是一种6元芳香环，可选含有一或两个氮原子，R为Cl，位于环A的顺、间或对位，S*是代表一个手性中心的硫原子，以及所有药学上可接受的盐、对映体和外消旋体、水合物和溶剂化物，以及这些化合物用于治疗呼吸道炎症或过敏疾病，如COPD或哮喘。