(-)-8-(5,8-Dichloro-1,2,3,4-tetrahydro-2-naphthyl)-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one | 754171-58-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (-)-8-(5,8-Dichloro-1,2,3,4-tetrahydro-2-naphthyl)-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one
• 英文别名: 8-(5,8-Dichloro-1,2,3,4-tetrahydro-2-naphthyl)-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one；8-(5,8-dichloro-1,2,3,4-tetrahydronaphthalen-2-yl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one
• CAS: 754171-58-9
• 化学式: C₂₃H₂₅Cl₂N₃O
• 分子量: 430.377
• InChiKey: GKBLBGBXCLKVGY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  29
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  35.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (-)-8-(5,8-Dichloro-1,2,3,4-tetrahydro-2-naphthyl)-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one 、 3-溴丙烯 在 H+ 作用下， 生成 (RS)-3-allyl-8-(5,8-dichloro-1,2,3,4-tetrahydro-naphthalen-2-yl)-1-phenyl-1,3,8-triazaspiro[4,5]decan-4-one hydrochloride
  参考文献：
  名称：

  1,3,8-triazaspiro[4,5]decan-4-one derivatives

  摘要：

  本发明涉及以下式子的化合物：##STR1## 其中R.sup.1和R.sup.2各自独立地为氢、低烷基、低烷氧基或卤素; R.sup.3为苯，未取代或取代为低烷基、CF.sub.3、低烷氧基或卤素; R.sup.4为氢、低烷基、低烯基、--C（O）-低烷基、--C（O）-苯、低烷基-C（O）-苯、低烷基亚烷基-C（O）O-低烷基、低烷三基-二-C（O）O-低烷基、羟基-低烷基、低烷基-O-低烷基、低烷基-CH（OH）CF.sub.3、苯或苄基，R.sup.5和R.sup.6各自独立地为氢、苯、低烷基或二-低烷基，或R.sup.5和R.sup.6与它们所结合的碳原子形成苯环，或R.sup.5和R.sup.1或R.sup.2中的一个与它们所结合的碳原子形成饱和或不饱和的6元环，A为4-7元饱和环，它们的外消旋体和对映异构体，以及在药学上可接受的酸加盐，它们是OFQ受体的激动剂和/或拮抗剂。

  公开号：

  US06071925A1
• 作为产物：
  描述：

  5,8-二氯-1-四氢萘酮 在 sodium tetrahydroborate 、 四氧化锇 、 4 A molecular sieve 、 对甲苯磺酸 、 N-甲基吗啉氧化物 作用下， 以 乙醇 、 水 、 丙酮 、 甲苯 、 叔丁醇 为溶剂， 反应 39.5h， 生成 (-)-8-(5,8-Dichloro-1,2,3,4-tetrahydro-2-naphthyl)-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one
  参考文献：
  名称：

  High-Affinity, Non-Peptide Agonists for the ORL1 (Orphanin FQ/Nociceptin) Receptor

  摘要：

  The discovery of 8-(5,8-dichloro-1,2,3,4-tetrahydro-naphthalen-2-yl)-1-phenyl-1,3,8-triazaspiro [4.5]decan-4-one, 1a, as a high-affinity ligand for the human ORL1 (orphanin FQ/nociceptin) receptor led to the synthesis of a series of optimized Ligands. These compounds exhibit high affinity for the human ORL1 receptor, exhibit moderate to good selectivity versus opioid receptors, and behave as full agonists in biochemical assays. In this paper we present the synthesis, structure-activity relationship (SAR), and biochemical characterization of substituted 1-phenyl-1,3,8-triazaspiro [4.5]decan-4-ones culminating in the discovery of 8-(5-methyl-1,2,3,4-tetrahydro-naphthalen-1-yl)-1-phenyl-1,3,8-triazaspiro [4.5] decan-4-one, 1p, and 8-acenaphten-1-yl-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one 1q, two high-affinity, potent ORL1 receptor agonists with good to moderate selectivity versus the other opioid receptors.

  DOI：

  10.1021/jm991129q

文献信息

• [EN] NOCICEPTIN RECEPTOR ORL-1 AGONISTS FOR USE IN TREATING COUGH<br/>[FR] AGONISTES DU RECEPTEUR ORL-1 DE LA NOCICEPTINE UTILISES POUR LE TRAITEMENT DE LA TOUX
  申请人：SCHERING CORP

  公开号：WO2001007050A1

  公开（公告）日：2001-02-01

  The present invention relates to the use of ORL-1 receptor agonists for the treatment of cough, alone or in combination with one or more agents for the treatment of cough, allergy or asthma symptoms, in particular to the use of ORL-1 agonists of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein: the dotted line represents and optional double bond; X1 is optionally substituted alkyl, cycloalkyl, aryl, heteroaryl or heterocycloalkyl; X2 is-CHO, -CN, optionally substituted amino, alkyl, or aryl; or X1 is optionally substituted benzofused heterocyclyl and X2 is hydrogen; or X?1 and X2¿ together form an optionally benzofused spiro heterocyclyl group R?1, R2, R3 and R4¿ are independently H and alkyl, or (R?1 and R4) or (R2 and R3) or (R1 and R3) or (R2 and R4¿) together can form an alkylene bridge of 1 to 3 carbon atoms; Z1 is optionally substituted alkyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, or -CO¿2?(alkyl or substituted amino) or CN; Z?2¿ is H or Z1; Z3 is H or alkyl; or Z?1, Z2 and Z3¿, together with the carbon to which they are attached, form bicyclic saturated or unsaturated rings.

  本发明涉及使用ORL-1受体激动剂治疗咳嗽，单独或与一种或多种用于治疗咳嗽、过敏或哮喘症状的药物组合使用，特别是使用式（I）的ORL-1激动剂或其药学上可接受的盐或溶剂，其中：虚线代表可选的双键；X1是可选的取代基的烷基、环烷基、芳基、杂芳基或杂环烷基；X2是-CHO、-CN、可选的取代氨基、烷基或芳基；或X1是可选的取代苯并杂环基，X2是氢；或X1和X2一起形成可选的苯并螺杂环基团；R1、R2、R3和R4独立地为H和烷基，或（R1和R4）或（R2和R3）或（R1和R3）或（R2和R4）一起形成1至3个碳原子的烷基桥；Z1是可选的取代基的烷基、芳基、杂芳基、环烷基或杂环烷基，或-CO2（烷基或取代氨基）或-CN；Z2是H或Z1；Z3是H或烷基；或Z1、Z2和Z3，与它们连接的碳一起，形成二环饱和或不饱和环。
• 8-substituted-1,3,8-triazaspiro[4.5]decan-4-on derivatives
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0856514B1

  公开（公告）日：2001-06-13
• NOCICEPTIN RECEPTOR ORL-1 AGONISTS FOR USE IN TREATING COUGH
  申请人：SCHERING CORPORATION

  公开号：EP1200087A1

  公开（公告）日：2002-05-02
• High affinity ligands for nociceptin receptor ORL-1
  申请人：Schering-Plough Corporation

  公开号：US20040067950A1

  公开（公告）日：2004-04-08

  The present invention relates to the method of treating cough with ORL-1 agonists, alone or in combination with additional agents for treating symptoms of cough, allergy or asthma, pharmaceutical compositions comprising the combinations, and to compounds of the formula 1 or a pharmaceutically acceptable salt or solvate thereof, wherein: the dotted line represents an optional double bond; X 1 is optionally substituted alkyl, cycloalkyl, aryl, heteroaryl or heterocycloalkyl; X 2 is —CHO, —CN, optionally substituted amino, alkyl, or aryl; or X 1 is optionally substituted benzofused heterocyclyl and X 2 is hydrogen; or X 1 and X 2 together form an optionally benzofused spiro heterocyclyl group R 1 , R 2 , R 3 and R 4 are independently H and alkyl, or (R 1 and R 4 ) or (R 2 and R 3 ) or (R 1 and R 3 ) or (R 2 and R 4 ) together can form an alkylene bridge of 1 to 3 carbon atoms; Z 1 is optionally substituted alkyl, aryl, heteroaryl, cycloalkyl or heterocycloalkyl, or —CO 2 (alkyl or substituted amino) or CN ; Z 2 is H or Z 1 ; Z 3 is H or alkyl; or Z 1 , Z 2 and Z 3 , together with the carbon to which they are attached, form bicyclic saturated or unsaturated rings; pharmaceutical compositions therefore, and the use of said compounds as nociceptin receptor inhibitors useful in the treatment of pain, anxiety, cough, asthma, depression and alcohol abuse.
• US6071925A
  申请人：——

  公开号：US6071925A

  公开（公告）日：2000-06-06