(+/-)-SB 221275

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (+/-)-SB 221275
• 英文别名: N-(α-ethylbenzyl)-3-methyl-2-phenylquinoline-4-carboxamide；(R,S)-N-(α-ethylbenzyl)-3-methyl-2-phenylquinoline-4-carboxamide；3-methyl-2-phenyl-N-(1-phenylpropyl)quinoline-4-carboxamide
• 化学式: C₂₆H₂₄N₂O
• 分子量: 380.489
• InChiKey: MQNYRKWJSMQECI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  3-甲基-2-苯基-4-喹啉羧酸 在 草酰氯 、 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 (+/-)-SB 221275
  参考文献：
  名称：

  Discovery of a Novel Class of Selective Non-Peptide Antagonists for the Human Neurokinin-3 Receptor. 2. Identification of (S)-N-(1-Phenylpropyl)-3-hydroxy-2- phenylquinoline-4-carboxamide (SB 223412)

  摘要：

  Optimization of the previously reported 2-phenyl-4-quinolinecarboxamide NK-3 receptor antagonist 14, with regard to potential metabolic instability of the ester moiety and affinity and selectivity for the human neurokinin-3 (hNK-3) receptor, is described. The ester functionality could be successfully replaced by the ketone (31) or by lower alkyl groups (Et, 21, or n-Pr, 24). Investigation of the substitution pattern of the quinoline ring resulted in the identification of position 3 as a key position to enhance hNK-3 binding affinity and selectivity for the hNK-3 versus the hNK-2 receptor. All of the chemical groups introduced at this position, with the exception of halogens, increased the hNK-3 binding affinity, and compounds 53 (3-OH, SE 223412, hNK-3-CHO binding K-i = 1.4 nM) and 55 (3-NHz, hNK-3-CHO binding K-i = 1.2 nM) were the most potent compounds of this series. Selectivity studies versus the other neurokinin receptors (hNK-8-CHO and hNK-1-CHO) revealed that 53 is about 100-fold selective for the hNK-3 versus hNK-2 receptor, with no affinity for the hNK-1 at concentrations up to 100 mu M. In vitro studies demonstrated that 53 is a potent functional antagonist of the hNK-3 receptor (reversal of senktide-induced contractions in rabbit isolated iris sphincter muscles and reversal of NKB-induced Ca2+ mobilization in CHO cells stably expressing the hNK-3 receptor), while in vivo this compound showed oral and intravenous activity in NK-3 receptor-driven models (senktide-induced behavioral responses in mice and senktide-induced miosis in rabbits). Overall, the biological data indicate that (S)-N-(1-phenylpropyl)-3-hydroxy-2-phenylquinoline-4-carboxamide (53, SE 223412) may serve as a pharmacological tool in animal models of disease to assess the functional and pathophysiological role of the NK-3 receptor and to establish therapeutic indications for non-peptide NK-3 receptor antagonists.

  DOI：

  10.1021/jm980633c

文献信息

• [EN] A QUINOLINE AMIDE DERIVATIVE AS AGENT AGAINST DISORDERS OF THE CNS<br/>[FR] DERIVES D'AMIDE QUINOLEIQUE UTILISES COMME AGENTS CONTRE DES TROUBLES DU SNC
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2004050627A1

  公开（公告）日：2004-06-17

  A compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, is provided (Formula I) as is a process for its preparation and methods for its use in therapy, particularly in treating CNS or CNS-mediated disorders.

  提供一种化合物，其化学式为（I），或其药用可接受的盐或溶剂化合物，同时提供其制备方法以及在治疗中的应用方法，特别是用于治疗中枢神经系统或中枢神经系统介导的疾病。
• Use of NK-1 receptor antagonists against benign prostatic hyperplasia
  申请人：——

  公开号：US20030004157A1

  公开（公告）日：2003-01-02

  The invention relates to the use of an NK-1 receptor antagonist for the treatment or prevention of benign prostatic hyperplasia (BPH). The preferred NK-1 receptor antagonists are compounds of the general formula 1 wherein the meanings of R, R 1 , R 2 , R 2′ , R 3 , R 4 are explained in the specification and the pharmaceutically acceptable acid addition salts and the prodrugs thereof Preferred compounds are 2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-N-(6-morpholin-4-yl-4-o-tolyl-pyridin-3-yl)-isobutyramide, 2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-N-[6-(4-methyl-piperazin-1-yl)-4-o-tolyl-pyridin-3-yl]-isobutyramide, 2-(3,5-bis-trifluoromethyl-phenyl)-N-[6-(1,1-dioxo-1&lgr; 6 -thiomorpholin-4-yl)-4-o-tolyl-pyridin-3-yl]-N-methyl-isobutyramide and 2-(3,5-bis-trifluoromethyl-phenyl)-N-[6-(1,1-dioxo-1&lgr; 6 -thiomorpholin-4-yl)-4-(4-fluoro-2-methyl-phenyl)-pyridin-3-yl]-N-methyl-isobutyramide. The invention also relates to pharmaceutical composition comprising one or more such NK-1 receptor antagonists and a pharmaceutically acceptable excipient for the treatment and/or prevention of benign prostatic hyperplasia.

  本发明涉及使用NK-1受体拮抗剂治疗或预防良性前列腺增生（BPH）。首选的NK-1受体拮抗剂是一般式1中R，R1，R2，R2'，R3，R4的含义在规范中解释的化合物，以及其药学上可接受的酸盐和前药。首选化合物是2-(3,5-双三氟甲基苯基)-N-甲基-N-(6-吗啉-4-基-4-o-甲苯基-吡啶-3-基)-异丁酰胺，2-(3,5-双三氟甲基苯基)-N-甲基-N-[6-(4-甲基哌嗪-1-基)-4-o-甲苯基-吡啶-3-基]-异丁酰胺，2-(3,5-双三氟甲基苯基)-N-[6-(1,1-二氧-1&lgr;6-硫代吗啉-4-基)-4-o-甲苯基-吡啶-3-基]-N-甲基异丁酰胺和2-(3,5-双三氟甲基苯基)-N-[6-(1,1-二氧-1&lgr;6-硫代吗啉-4-基)-4-(4-氟-2-甲基苯基)-吡啶-3-基]-N-甲基异丁酰胺。本发明还涉及包含一种或多种此类NK-1受体拮抗剂和药学上可接受的载体的制药组合物，用于治疗和/或预防良性前列腺增生。
• [EN] A QUINOLINE AMIDE DERIVATIVE AS AGENT AGAINST DISORDERS OF THE CNS<br/>[FR] DERIVE D'AMIDE QUINOLEIQUE UTILISE COMME AGENT CONTRE DES TROUBLES DU SNC
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2004050626A1

  公开（公告）日：2004-06-17

  A compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, is provided, as is a process for its preparation and methods for its use in therapy, particularly in treating CNS or CNS-mediated disorders.

  提供一种化合物(I)的公式，或其药学上可接受的盐或溶剂，以及其制备方法和在治疗中使用的方法，特别是在治疗中枢神经系统或中枢神经系统介导的疾病方面。
• [EN] QUINOLINE DERIVATIVES AS TACHYKININ NK3 RECEPTOR ANTAGONISTS<br/>[FR] DERIVES DE QUINOLINE UTILISES COMME ANTAGONISTES DU RECEPTEUR NK3 DE LA TACHYKININE
  申请人：SMITHKLINE BEECHAM FARMACEUTICI S.P.A.

  公开号：WO1995032948A1

  公开（公告）日：1995-12-07

  (EN) NK3 receptor antagonists of formula (I) are useful in treating $i(inter alia) pulmonary disorders, CNS disorders and neurodegenerative disorders.(FR) L'invention se rapporte à des antagonistes du récepteur NK3 de la formule (I) qui sont utiles dans le traitement, entre autres, des maladies pulmonaires, des troubles du SNC et des troubles neurodégénératifs.

  NK3受体拮抗剂(I)的公式在治疗肺部疾病、中枢神经系统疾病和神经退行性疾病等方面非常有用。
• Quinoline derivatives(2)
  申请人：——

  公开号：US20030236281A1

  公开（公告）日：2003-12-25

  NK 3 receptor antagonists of formula (I): 1 are useful in treating inter alia pulmonary disorders, CNS disorders and neurodegenerative disorders.

  公式（I）的NK3受体拮抗剂1在治疗肺部疾病、中枢神经系统疾病和神经退行性疾病等方面是有用的。