N-t-butoxy-carbonyl-3,4-dihydro-5-methoxy-2H-[1 ]-benzothiopyran-3-amine | 116856-60-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 硫铬烷
• 英文名称: N-t-butoxy-carbonyl-3,4-dihydro-5-methoxy-2H-[1 ]-benzothiopyran-3-amine
• 英文别名: N-t-butoxycarbonyl-3,4-di-hydro-5-methoxy-2H-[1]-benzothiopyran-3-amine；tert-butyl N-(5-methoxy-3,4-dihydro-2H-thiochromen-3-yl)carbamate
• CAS: 116856-60-1
• 化学式: C₁₅H₂₁NO₃S
• 分子量: 295.403
• InChiKey: ZMZFEEBOYDRFCQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  72.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-t-butoxy-carbonyl-3,4-dihydro-5-methoxy-2H-[1 ]-benzothiopyran-3-amine 在 sodium hydroxide 、 乙醚 、 magnesium sulfate 作用下， 以 三氟乙酸 为溶剂， 反应 1.0h， 以to afford 3,4-dihydro-5-methoxy-2H-[1]-benzothiopyran-3-amine as an oil的产率得到5-甲氧基硫代苯并二氢吡喃-3-胺
  参考文献：
  名称：

  3-amino-dihydro-(1)-benzopyrans

  摘要：

  其中Z代表O或S；R代表氢或低碳基；R.sub.1代表氢，低碳基或芳基-低碳基；R.sub.2代表氢，低碳基或芳基-低碳基；或R.sub.1和R.sub.2一起代表4至6个碳原子的烷基；R.sub.3代表氢，羟基，低烷氧基，芳基-低烷氧基，酰氧基或芳氧基，在Z代表S的化合物中；或R.sub.3代表羟基，低烷氧基，芳基-低烷氧基，酰氧基或芳氧基，并且仅在Z代表O的化合物中附着于5-或8-位置；R.sub.4和R.sub.5独立地代表氢，低碳基或卤素；以及其药学上可接受的盐；以及式I化合物的单或双S-氧化物，其中Z代表S及其药学上可接受的盐，其制药组合物；以及作为中枢神经系统活性剂治疗中枢神经系统疾病的用途。

  公开号：

  US04992465A1
• 作为产物：
  描述：

  3,4-dihydro-5-methoxy-2H-[1]-benzothiopyran-3-carboxylic acid 、 叔丁醇 生成 N-t-butoxy-carbonyl-3,4-dihydro-5-methoxy-2H-[1 ]-benzothiopyran-3-amine
  参考文献：
  名称：

  HUTCHISON, ALAN J.

  摘要：

  DOI：

文献信息

• 2-(substituted amino) adenosines as antihypertensives
  申请人：Ciba-Geigy Corporation

  公开号：US05034381A1

  公开（公告）日：1991-07-23

  Disclosed are 2-substituted adenosine derivatives of the formula ##STR1## in which R represents a substituted amino grouping of the formula ##STR2## as defined herein; pharmaceutically acceptable ester derivatives thereof in which free hydroxy groups are esterified in the form of a pharmaceutically acceptable prodrug ester; and pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising said compounds; methods for their preparation; and their use in mammals as therapeutically effective adenosine-2 (A-2) agonists.

  本文披露了公式##STR1##中的2-取代腺苷衍生物，其中R代表定义如下的取代氨基团##STR2##；其药学上可接受的酯衍生物，其中游离羟基以药学上可接受的前药酯的形式酯化；以及其药学上可接受的盐；包括所述化合物的药物组合物；其制备方法；及其在哺乳动物中作为治疗有效的腺苷-2（A-2）激动剂的用途。
• 2-substituted adenosine 5'-carboxamides as antihypertensive agents
  申请人：Ciba-Geigy Corporation

  公开号：US04968697A1

  公开（公告）日：1990-11-06

  The compounds of the formula I ##STR1## wherein R represents hydrogen or lower alkyl; R.sub.1 represents C.sub.3 -C.sub.6 -cycloalkyl optionally substituted by lower alkyl, C.sub.3 -C.sub.6 -cycloalkyl-lower alkyl optionally substituted by lower alkyl, bicycloalkyl, bicycloalkyl-lower alkyl, aryl, aryl-lower alkyl, aryl-C.sub.3 -C.sub.6 -cycloalkyl, 9-fluorenyl, diaryl-lower alkyl, 9-fluorenyl-lower alkyl, cycloalkenyl-lower alkyl, bicycloalkenyl-lower alkyl, tetrahydropyranyl-lower alkyl, tetrahydrothiopyranyl-lower alkyl or adamantyl-lower alkyl; or R.sub.1 represents a bicyclic benzo-fused 5- or 6-membered saturated carbocyclic radical or a benzo-fused 5- or 6-membered saturated heterocyclic radical containing a heteroatom selected from oxygen and sulfur which is directly attached to the fused benzene ring, any said bicyclic radical being unsubstituted or substituted on the benzo portion by lower alkyl, lower alkoxy, hydroxy, halogen or trifluoromethyl, or by a substituent -W-Z in which W represents a direct bond, lower alkylene, lower alkenylene, thio-lower alkylene or oxy-lower alkylene and Z represents cyano, carboxy or carboxy derivatized in the form of a pharmaceutically acceptable ester or amide, or R.sub.1 represents any said bicyclic radical substituted-lower alkyl; or R.sub.1 represents aryl-hydroxy-lower alkyl; R.sub.2 represents hydrogen, lower alkyl or aryl-lower alkyl; R.sub.3 represents hydrogen or hydroxy; R.sub.4 represents hydrogen, lower alkyl, aryl-lower alkyl, C.sub.3 -C.sub.6 -cycloalkyl or hydroxy-lower alkyl; aryl represents an optionally substituted carbocyclic aromatic radical, being preferably 1- or 2-naphthyl, phenyl, or naphthyl or phenyl substituted by one to three of lower alkyl, lower alkoxy, hydroxy, halogen or trifluoromethyl, or naphthyl or phenyl substituted by a substitutent -W-Z in which W represents a direct bond, lower alkylene, lower alkenylene, thio-lower alkylene or oxy-lower alkylene and Z represents cyano, carboxy or carboxy derivatized in the form of a pharmaceutically acceptable ester or amide; or aryl represents a heterocyclic aromatic radical, being preferably pyridyl or thienyl, each optionally substituted as described above for phenyl; pharmaceutically acceptable ester derivatives thereof in which free hydroxy groups are esterified in the form of a pharmaceutically acceptable ester; and pharmaceutically acceptable salts thereof; their preparation; and their use as adenosine-2 receptor agonists are disclosed.

  公式I的化合物如下：其中R代表氢或低碳基；R1代表C3-C6-环烷基，可选地被低碳基取代，C3-C6-环烷基-低碳基，可选地被低碳基取代，双环烷基，双环烷基-低碳基，芳基，芳基-低碳基，芳基-C3-C6-环烷基，9-芴基，双芳基-低碳基，9-芴基-低碳基，环烯基-低碳基，双环烯基-低碳基，四氢吡喃基-低碳基，四氢硫吡喃基-低碳基或金刚烷基-低碳基；或R1代表一个双环苯并5-或6-成员饱和碳环基或一个苯并5-或6-成员饱和杂环基，其中所述的杂原子从氧和硫中选择，直接连接到融合的苯环上，任何所述的双环基在苯基部分上未取代或被低碳基，低烷氧基，羟基，卤素或三氟甲基取代，或被取代基-W-Z取代，其中W代表直接键，低碳基，低烯基，硫代低碳基或氧代低碳基，Z代表氰基，羧基或以药学上可接受的酯或酰胺形式衍生的羧基；或R1代表任何所述的双环基取代的低碳基；或R1代表芳基-羟基-低碳基；R2代表氢，低碳基或芳基-低碳基；R3代表氢或羟基；R4代表氢，低碳基，芳基-低碳基，C3-C6-环烷基或羟基-低碳基；芳基代表选择性取代的碳环芳基基团，最好是1-或2-萘基，苯基，或被1到3个低碳基，低烷氧基，羟基，卤素或三氟甲基取代的萘基或苯基，或萘基或苯基被取代基-W-Z取代，其中W代表直接键，低碳基，低烯基，硫代低碳基或氧代低碳基，Z代表氰基，羧基或以药学上可接受的酯或酰胺形式衍生的羧基；或芳基代表选择性取代的杂环芳基基团，最好是吡啶基或噻吩基，每个基团可选择性地被上述描述的基团取代；其药学上可接受的酯衍生物，其中游离的羟基被酯化为药学上可接受的酯；以及其药学上可接受的盐；其制备方法；以及其作为腺苷-2受体激动剂的用途。
• Diagnostic uses of 2-substituted adenosine carboxamides
  申请人：King Pharmaceuticals Research and Development, Inc.

  公开号：US06368573B1

  公开（公告）日：2002-04-09

  The present invention discloses a method for measuring myocardial function in a mammal in need of such measurement by: a) administering 2-substituted adenosine carboxamide derivatives at a dosage rate of less than 1 &mgr;g/kg/min, preferably between about 0.01 and 1 &mgr;g/kg/min; and then: b) performing a technique on the mammal to detect myocardial function. The method can be used to diagnose myocardial dysfunction by electrophysiologic analysis or by imaging the vasculature of the heart, especially under conditions that simulate stress.

  本发明公开了一种测量需要进行心肌功能测量的哺乳动物的方法，包括：a)以小于1 &mgr;g/kg/min的剂量率给予2-取代腺苷酸甲酰衍生物，最好在大约0.01和1 &mgr;g/kg/min之间；然后：b)对哺乳动物进行技术操作以检测心肌功能。该方法可用于通过电生理分析或通过成像心脏血管特别是在模拟应激条件下来诊断心肌功能异常。
• N.sub.9 -cyclopentyl-substituted adenine derivatives having adenosine-2
  申请人：Ciba-Geigy Corporation

  公开号：US04954504A1

  公开（公告）日：1990-09-04

  The compound of the formula I ##STR1## wherein R, R.sub.3 and R.sub.5 independently represent hydrogen or hydroxy provided that at least one of R, R.sub.3 and R.sub.5 represents hydroxy; R.sub.1 represents hydrogen, lower alkyl, C.sub.3 -C.sub.7 -alkenyl, hydroxy-lower alkyl, optionally substituted cycloalkyl or optionally substituted cycloalkyl-lower alkyl, bicycloalkyl, bicycloalkyl-lower alkyl, adamantyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydropyranyl-lower alkyl, tetrahydrothiopyranyl-lower alkyl, adamantyl-lower alkyl, aryl-hydroxy-lower alkyl, aryl, aryl-lower alkyl, aryl-C.sub.3 -C.sub.6 -cycloalkyl, 9-fluorenyl, 9-fluorenyl-lower alkyl or cycloalkenyl-lower alkyl; or R.sub.1 represents a bicyclic benzo-fused 5 or 6-membered saturated cyabocyclic radical or a benzo-fused 5 or 6-membered saturated heterocyclic radical containing a heteroatom selected from oxygen and sulfur directly attached to the fused benzene ring, any said bicyclic radicals being optionally substituted on the benzo portion by lower alkyl, lower alkoxy or halogen, or R.sub.1 represents any said bicyclic radical substituted-lower alkyl; R.sub.2 represents hydrogen, halogen, --S--R.sub.1 ', --NR.sub.b --R.sub.1 ', or --NH--R.sub.1 ' in each of which R.sub.1 ' has meaning as defined for R.sub.1 provided that R.sub.1 ' in --SR.sub.1 ' does not represent hydrogen; R.sub.b represents lower alkyl; R.sub.4 represents hydroxymethyl provided that R.sub.2 does not represent either hydrogen or --NHR.sub.1 ' in which R.sub.1 ' represents either hydrogen or lower alkyl; or R.sub.4 represents lower alkoxymethyl or lower alkylthiomethyl; or R.sub.4 represents --CONHR.sub.6 in which R.sub.6 represents lower alkyl; aryl-lower alkyl, C.sub.3 -C.sub.6 -cycloalkyl or hydroxy-lower alkyl; pharmaceutically acceptable ester derivatives thereof in which free hydroxy groups are esterified in form of a pharmaceutically acceptable ester; and pharmaceutically acceptable salts thereof; methods for their preparation; and their use as adenosine receptor agonists are disclosed.

  公式I的化合物如下：其中R、R.sub.3和R.sub.5独立地表示氢或羟基，但至少其中一个表示羟基；R.sub.1表示氢、较低的烷基、C.sub.3-C.sub.7-烯基、羟基-较低的烷基、可选地取代的环烷基或可选地取代的环烷基-较低的烷基、双环烷基、双环烷基-较低的烷基、金刚烷基、四氢吡喃基、四氢硫吡喃基、四氢吡喃基-较低的烷基、四氢硫吡喃基-较低的烷基、金刚烷基-较低的烷基、芳基-羟基-较低的烷基、芳基、芳基-较低的烷基、芳基-C.sub.3-C.sub.6-环烷基、9-芴基、9-芴基-较低的烷基或环烯基-较低的烷基；或R.sub.1表示一个双环苯并5或6-成员饱和环的腈状环基或一个苯并5或6-成员饱和杂环基，其中所述杂原子从氧和硫直接连接到融合苯环，任何所述双环基在苯部分上可选地被较低的烷基、较低的烷氧基或卤素取代，或R.sub.1表示任何所述双环基取代的较低烷基；R.sub.2表示氢、卤素、--S--R.sub.1 '、--NR.sub.b--R.sub.1 '或--NH--R.sub.1'，其中在每个中R.sub.1'的含义如R.sub.1所定义，但在--SR.sub.1'中，R.sub.1'不表示氢；R.sub.b表示较低的烷基；R.sub.4表示羟甲基，但当R.sub.2不表示氢或--NHR.sub.1'时，其中R.sub.1'表示氢或较低的烷基；或R.sub.4表示较低的烷氧甲基或较低的烷硫甲基；或R.sub.4表示--CONHR.sub.6，其中R.sub.6表示芳基-较低的烷基、C.sub.3-C.sub.6-环烷基或羟基-较低的烷基；还公开了其药学上可接受的酯衍生物，其中游离羟基以药学上可接受的酯形式酯化，以及其药学上可接受的盐；公开了其制备方法；以及其作为腺苷受体激动剂的用途。
• N.sub.9 -cyclopentyl-substituted adenine derivatives useful as adenosine
  申请人：Ciba-Geigy Corporation

  公开号：US05063233A1

  公开（公告）日：1991-11-05

  The compound of the formula I ##STR1## wherein R, R.sub.3 and R.sub.5 independently represent hydrogen or hydroxy provided that at least one of R, R.sub.3 and R.sub.5 represents hydroxy; R.sub.1 represents hydrogen, lower alkyl, C.sub.3 -C.sub.7 -alkenyl, hydroxy-lower alkyl, optionally substituted cycloalkyl or optionally substituted cycloalkyl-lower alkyl, bicycloalkyl, bicycloalkyl-lower alkyl, adamantyl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydropyranyl-lower alkyl, tetrahydrothiopyranyl-lower alkyl, adamantyl-lower alkyl, aryl-hydroxy-lower alkyl, aryl, aryl-lower alkyl, aryl-C.sub.3 -C.sub.6 -cycloalkyl, 9-fluorenyl, 9-fluorenyl-lower alkyl or cycloalkenyl-lower alkyl; or R.sub.1 represents a bicyclic benzo-fused 5 or 6-membered saturated carbocyclic radical or a benz-fused 5 or 6-membered saturated heterocyclic radical containing a heteroatom selected from oxygen and sulfur directly attached to the fused benzene ring, any said bicyclic radicals being optionally substituted on the benzo portion by lower alkyl, lower alkoxy or halogen, or R.sub.1 represents any said bicyclic radical substituted-lower alkyl; R.sub.2 represents hydrogen, halogen, --S--R.sub.1 ', --NR.sub.b --R.sub.1 ', or --NH--R.sub.1 ' in each of which R.sub.1 ' has meaning as defined for R.sub.1 provided that R.sub.1 ' in --SR.sub.1 ' does not represent hydrogen; R.sub.b represents lower alkyl; R.sub.4 represents hydroxymethyl provided that R.sub.2 does not represent either hydrogen or --NHR.sub.1 ' in which R.sub.1 ' represents either hydrogen or lower alkyl; or R.sub.4 represents lower alkoxymethyl or lower alkylthiomethyl; or R.sub.4 represents --CONHR.sub.6 in which R.sub.6 represents lower alkyl, aryl-lower alkyl, C.sub.3 -C.sub.6 -cycloalkyl or hydroxy-lower alkyl; pharmaceutically acceptable ester derivatives thereof in which free hydroxy groups are esterified in form of a pharmaceutically acceptable ester; and pharmaceutically acceptable salts thereof; methods for their preparation; and their use as adenosine receptor agonists are disclosed.

  该化合物的化学式为I，其中R、R.sub.3和R.sub.5分别独立地表示氢或羟基，但至少其中一个表示羟基；R.sub.1表示氢、低碳基、C.sub.3-C.sub.7-烯基、羟基-低碳基、可选取代的环烷基或可选取代的环烷基-低碳基、双环烷基、双环烷基-低碳基、金刚烷基、四氢吡喃基、四氢硫吡喃基、四氢吡喃基-低碳基、四氢硫吡喃基-低碳基、金刚烷基-低碳基、芳基-羟基-低碳基、芳基、芳基-低碳基、芳基-C.sub.3-C.sub.6-环烷基、9-芴基、9-芴基-低碳基或环烷烯基-低碳基；或R.sub.1表示一个双环苯并5或6-成员饱和碳环基或一个苯并5或6-成员饱和杂环基，所述杂原子选择性地从直接连接到融合苯环上的氧和硫中选择，任何所述双环基在苯基部分上可选择地被低碳基、低烷氧基或卤素取代，或R.sub.1表示任何所述双环基取代-低碳基；R.sub.2表示氢、卤素、--S--R.sub.1 '、--NR.sub.b--R.sub.1 '或--NH--R.sub.1'，其中R.sub.1'具有如R.sub.1所定义的含义，但在--SR.sub.1'中，R.sub.1'不表示氢；R.sub.b表示低碳基；R.sub.4表示羟甲基，但当R.sub.2不表示氢或--NHR.sub.1'时，其中R.sub.1'表示氢或低碳基；或R.sub.4表示低烷氧甲基或低硫代甲基；或R.sub.4表示--CONHR.sub.6，其中R.sub.6表示低碳基、芳基-低碳基、C.sub.3-C.sub.6-环烷基或羟基-低碳基；公认的药物可接受的酯衍生物，其中自由羟基以药物可接受的酯形式酯化；以及其药物可接受的盐；公开了其制备方法；以及其作为腺苷受体激动剂的用途。