4-amino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile | 129462-75-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 4-amino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile
• 英文别名: trans-4-Amino-3,4-dihydro-2,2-dimethyl-6-cyano-2H-benzopyran；4-Amino-6-cyano-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran；6-cyano-4-amino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran；4-amino-2,2-dimethyl-3,4-dihydrochromene-6-carbonitrile
• CAS: 129462-75-5
• 化学式: C₁₂H₁₄N₂O
• 分子量: 202.256
• InChiKey: LMUHXVBASKTZGP-UHFFFAOYSA-N

物化性质

• 沸点：
  306.8±42.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-amino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile 在 diphosphorus pentasulfide 、 碳酸氢钠 作用下， 以 C₁₀H₁₁ClN₂O 为溶剂， 生成 6-cyano-3,4-dihydro-2,2-dimethyl-4-(3-pyridinecarboxamido)-2H-1-benzopyran
  参考文献：
  名称：

  EP536424

  摘要：

  公开号：
• 作为产物：
  描述：

  2,2-二甲基-2H-1-苯并吡喃-6-甲腈 在 palladium on activated charcoal N-溴代丁二酰亚胺(NBS) 、 sodium azide 、 偶氮二异丁腈 、 氢气 作用下， 以 四氯化碳 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 4.5h， 生成 4-amino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile
  参考文献：
  名称：

  Cardioselective Antiischemic ATP-Sensitive Potassium Channel Openers. 2. Structure-Activity Studies on Benzopyranylcyanoguanidines; Modification of the Benzopyran Ring

  摘要：

  The ATP-sensitive potassium channel (K-ATP) openers are of considerable interest as myocardial protecting agents. However, there exists a narrow window of safety for the use of first-generation compounds as antiischemic agents due to their powerful peripheral vasodilating effects, which can result in underperfusion of the area already at risk. We have recently disclosed the discovery of benzopyranylcyanoguanidine type K-ATP openers (BMS-180448) which are more selective for the ischemic myocardium compared to the first-generation compounds. This publication deals with structure-activity relationships for the antiischemic activity of the lead compound 8. The presence of an electron-withdrawing group at C6, an sp(3) center at C4, and a gem-dimethyl group at C2 appears to be essential for antiischemic activity. Cyanoguanidine can be replaced with a urea moiety. The results reported here support the hypothesis that distinct structure-activity relationships exist for antiischemic and vaso:relaxant activities of compounds related to 8 and cromakalim. The trifluoromethyl analog 10 is 550-fold more selective in vitro for the ischemic myocardium compared to the first-generation agent cromakalim. The reasons for the selectivity of these compounds for the ischemic myocardium are not clear at the present time. They may be related to the existence of receptor subtypes in smooth muscle and the myocardium.

  DOI：

  10.1021/jm00011a016

文献信息

• Benzopyran derivatives and heterocyclic analogs thereof as antiischemic
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US05276168A1

  公开（公告）日：1994-01-04

  A new method for the treatment of ischemic conditions and arrhythmia is disclosed. The method uses compounds of the formula ##STR1## wherein A can be --CH.sub.2 --, --O--, --NR.sub.9 --, --S--, --SO--, --SO.sub.2 --; X can be oxygen or sulfur; Y can be --NR.sub.8, --O--, --S--, --CH.sub.2 -- and the R groups are as defined herein. Novel compounds within the definition of formula I are also disclosed.

  揭示了一种用于治疗缺血性疾病和心律失常的新方法。该方法使用公式##STR1##中的化合物，其中A可以是--CH.sub.2 --，--O--，--NR.sub.9 --，--S--，--SO--，--SO.sub.2 --；X可以是氧或硫；Y可以是--NR.sub.8，--O--，--S--，--CH.sub.2--，而R基的定义如本文所述。还披露了符合公式I定义的新化合物。
• Aryl urea (thiourea) and cyanoguanidine derivatives
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US05374643A1

  公开（公告）日：1994-12-20

  Novel compounds useful, for example, in the treatment of ischemic conditions and arrhythmia having the formula I ##STR1## wherein X is oxygen, sulfur or --NCN and the R groups are as defined herein.

  新型化合物具有以下公式I，其中X为氧、硫或--NCN，R基固定如定义。这些化合物可用于治疗缺血症和心律失常等疾病。
• Guanidino-substituted benzopyrans and their use as pharmaceuticals
  申请人：Beecham Group p.l.c.

  公开号：US05053427A1

  公开（公告）日：1991-10-01

  Compounds of formula (I) and pharmaceutically acceptable salts thereof: ##STR1## wherein a and b together form an --O-- or --CH.sub.2 -- linkage or a bond; either Y is N and R.sub.2 is hydrogen; or Y is C-R.sub.1 wherein either one of R.sub.1 and R.sub.2 is hydrogen and the other is nitro, cyano, halo, CF.sub.3, formyl, aldoxime, CF.sub.3 O, NO.sub.2 --CH.dbd.CH--, NC--CH.dbd.CH--; a group R.sub.x X-- wherein R.sub.x and C.sub.1-6 alkyl, aryl or heteroaryl either of which may be optionally substituted by one, two or three of C.sub.1-4 alkyl, C.sub.1-4 alkoxy, nitro, halo, CF.sub.3 and cyano; and X is C.dbd.O, O.C.dbd.O, C.dbd.0.0, CHOH, SO, SO.sub.2, 0.SO, 0.SO.sub.2, CONH, 0.CONH, C.dbd.S, 0.C.dbd.S, C.dbd.S.0, CH.SH, SONH, SO.sub.2 NH, 0.SONH, 0.SO.sub.2 NH, CO--CH.dbd.CH, C.dbd.NHOH, C.dbd.NNH.sub.2 ; or a group R.sub.y R.sub.z NZ-- wherein R.sub.y and R.sub.z are independently hydrogen or C.sub.1-6 alkyl and Z is C.dbd.O, SO or SO.sub.2 ; or R.sub.1 is a C.sub.3-8 cycloalkyl group or a C.sub.1-6 alkyl group optionally substituted by a group which is hydroxy, C.sub.1-6 alkoxy, amino optionally substituted by one or two C.sub.1-6 alkyl groups, C.sub.1-7 alkanoylamino, C.sub.3-8 cycloalkyloxy or C.sub.3-8 cycloalkylamino; and R.sub.2 is hydrogen; or one of R.sub.1 and R.sub.2 is nitro, cyano or C.sub.1-3 alkylcarbonyl and the other is a different group selected from nitro, cyano, halo, C.sub.1-3 alkylcarbonyl, methoxy or amino optionally substituted by one or two C.sub.1-6 alkyl or by C.sub.2-7 alkanoyl; either one of R.sub.3 and R.sub.4 is hydrogen or C.sub.1-4 alkyl and the other is C.sub.1-4 alkyl; or R.sub.3 and R.sub.4 together are C.sub.2-5 polymethylene; either R.sub.5 is hydrogen, hydroxy, C.sub.1-6 alkoxy or C.sub.1-7 acyloxy; and R.sub.6 is hydrogen; or R.sub.5 and R.sub.6 together are a bond; either R.sub.7 is hydrogen, C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, C.sub.2-6 alkenyl or C.sub.2-6 alkynyl; and R.sub.8 is hydrogen or C.sub.1-6 alkyl; or R.sub.7 and R.sub.8 together are C.sub.2-4 polymethylene; R.sub.9 is CN, NO.sub.2, COR.sub.10 or SO.sub.2 R.sub.10 wherein R.sub.10 is C.sub.1-3 alkyl, NH.sub.2, NH(C.sub.1-3 alkyl), CF.sub.3 or phenyl optionally substituted as defined for R.sub.x ; and the R.sub.8 N(NR.sub.9)NHR.sub.7 moiety is trans to the R.sub.5 group when R.sub.5 is hydroxy, C.sub.1-6 alkoxy or C.sub.1-7 acyloxy; having antihypertensive and/or bronchodilator activity, processes for their preparation and their use as pharmaceuticals.

  化合物I的公式及其药用可接受的盐：其中a和b共同形成一个-O-或-CH.sub.2-连接或键合; Y为N且R.sub.2为氢; 或Y为C-R.sub.1，其中R.sub.1和R.sub.2中的任意一个为氢，另一个为硝基、氰基、卤素、CF.sub.3、甲酰基、醛肟、CF.sub.3O、NO.sub.2-CH.dbd.CH-、NC-CH.dbd.CH-; 一个R.sub.x X-基团，其中R.sub.x和C.sub.1-6烷基、芳基或杂环芳基，其中任意一个可选地被一个、两个或三个C.sub.1-4烷基、C.sub.1-4烷氧基、硝基、卤素、CF.sub.3和氰基取代; X为C.dbd.O、O.C.dbd.O、C.dbd.0.0、CHOH、SO、SO.sub.2、0.SO、0.SO.sub.2、CONH、0.CONH、C.dbd.S、0.C.dbd.S、C.dbd.S.0、CH.SH、SONH、SO.sub.2NH、0.SONH、0.SO.sub.2NH、CO-CH.dbd.CH、C.dbd.NHOH、C.dbd.NNH.sub.2; 或一个R.sub.yR.sub.zNZ-基团，其中R.sub.y和R.sub.z独立地为氢或C.sub.1-6烷基，Z为C.dbd.O、SO或SO.sub.2; 或R.sub.1为C.sub.3-8环烷基或C.sub.1-6烷基，可选地被一个羟基、C.sub.1-6烷氧基、氨基、C.sub.1-7酰胺基、C.sub.3-8环烷氧基或C.sub.3-8环烷基氨基取代; R.sub.2为氢; 或R.sub.1和R.sub.2中的一个为硝基、氰基或C.sub.1-3烷基羰基，另一个为从硝基、氰基、卤素、C.sub.1-3烷基羰基、甲氧基或氨基中选择的不同基团，该氨基可选地被一个或两个C.sub.1-6烷基或C.sub.2-7酰基取代; R.sub.3和R.sub.4中的任意一个为氢或C.sub.1-4烷基，另一个为C.sub.1-4烷基; 或R.sub.3和R.sub.4共同为C.sub.2-5聚亚甲基; R.sub.5为氢、羟基、C.sub.1-6烷氧基或C.sub.1-7酰氧基; R.sub.6为氢; 或R.sub.5和R.sub.6共同为键合; R.sub.7为氢、C.sub.1-6烷基、C.sub.3-6环烷基、C.sub.2-6烯基或C.sub.2-6炔基; R.sub.8为氢或C.sub.1-6烷基; 或R.sub.7和R.sub.8共同为C.sub.2-4聚亚甲基; R.sub.9为CN、NO.sub.2、COR.sub.10或SO.sub.2R.sub.10，其中R.sub.10为C.sub.1-3烷基、NH.sub.2、NH(C.sub.1-3烷基)、CF.sub.3或苯基，可选地如R.sub.x所定义地取代; 当R.sub.5为羟基、C.sub.1-6烷氧基或C.sub.1-7酰氧基时，R.sub.8N(NR.sub.9)NHR.sub.7基团为与R.sub.5基团相对的构型; 具有降压和/或支气管扩张作用，其制备方法及其作为药物的使用。
• Substituted cyclobutenedione compounds
  申请人：Beecham Group p.l.c.

  公开号：EP0426379A2

  公开（公告）日：1991-05-08

  A compound of formula (I) or a pharmaceutically acceptable salt thereof: wherein a and b together form an -O- or -CH₂- linkage or a bond; either Y is N and R₂ is hydrogen; or Y is C-R₁ wherein either one of R₁ and R₂ is hydrogen and the other is nitro, cyano, halo, -CF₃, C₂F₅, formyl, aldoxime, CF₃O, NO₂-CH=CH-, NC-CH=CH-; a group RxX- wherein Rx is C₁₋₆ alkyl, aryl or heteroaryl either of which may be optionally substituted by one, two or three of C₁₋₄ alkyl, C₁₋₄ alkoxy, nitro, halo, CF₃ and cyano; and X is C=O, O.C=O, C=O.O, CHOH, SO, SO₂, O.SO, O.SO₂, CONH, O.CONH, C=S, O.C=S, C=S.O, CH.SH, SONH, SO₂NH, O.SONH, O.SO₂NH, CO-CH=CH, C=NHOH, C=NNH₂; or a group RyRzNZ- wherein Ry and Rz are independently hydrogen or C₁₋₆ alkyl and Z is C=O, SO or SO₂; or a group (RwO)₂P(O)W wherein Rw is hydrogen or C₁₋₆ alkyl and W is O or a bond; or R₁ is a C₃₋₈ cycloalkyl group or a C₁₋₆ alkyl group optionally substituted by a group R₉ which is hydroxy, C₁₋₆ alkoxy, amino optionally substituted by one or two C₁₋₆ alkyl groups, C₁₋₇ alkanoylamino, C₃₋₈ cycloalkyloxy or C₃₋₈ cycloalkylamino and R₂ is hydrogen; or one of R₁ and R₂ is nitro, cyano or C₁₋₃ alkylcarbonyl and the other is a different group selected from nitro, cyano, halo, C₁₋₃ alkylcarbonyl, methoxy or amino optionally substituted by one or two C₁₋₆ alkyl or by C₂₋₇ alkanoyl; or R₁ and R₂ together with the carbon atoms, to which they are attached form 2,1,3-oxadiazole or triazole; either one of R₃ and R₄ is hydrogen or C₁₋₄ alkyl and the other is C₁₋₄ alkyl; or R₃ and R₄ together are C₂₋₅ polymethylene; R₅ is hydrogen, hydroxy, C₁₋₆ alkoxy or C₁₋₇ acyloxy or ONO₂; R₆ and R₇ are independently hydrogen, C₁₋₆ alkyl; or (when R₆ is hydrogen), then R₇ is allyl, propargyl or C₃₋₆ cycloalkyl; J is O or NR₈ wherein R₈ is hydrogen or C₁₋₆ alkyl.

  式 (I) 的化合物或其药学上可接受的盐： 其中 a和b共同形成-O-或-CH₂-连接或键； Y 是 N 且 R₂ 是氢；或 Y 是 C-R₁ 其中 R₁ 和 R₂ 中的一个是氢，另一个是硝基、氰基、卤素、-CF₃、 C₂F₅、甲酰基、醛肟、CF₃O、NO₂-CH=CH-、NC-CH=CH-；基团 RxX-，其中 Rx 是 C₁₋₆烷基、芳基或杂芳基，其中任一个可被一个、两个或三个 C₁₋₄烷基、C₁₋₄烷氧基、硝基、卤代、CF₃ 和氰基任选取代；且 X 是 C=O、O.c=o、c=o.o、choh、so、so₂、o.so、o.so₂、conh、o.conh、c=s、o.c=s、c=s.o、ch.sh、sonh、so₂nh、o.sonh、o.SO₂NH、CO-CH=CH、C=NHOH、C=NNH₂；或基团 RyRzNZ-，其中 Ry 和 Rz 独立地为氢或 C₁₋₆烷基，Z 为 C=O、SO 或 SO₂；或基团 (RwO)₂P(O)W，其中 Rw 为氢或 C₁₋₆ 烷基，W 为 O 或键；或 R₁ 是 C₃₋₈环烷基或任选被羟基、C₁₋₆ 烷氧基的基团 R₉ 取代的 C₁₋₆ 烷基、被一个或两个 C₁₋₆烷基、C₁₋₇烷酰氨基、C₃₋₈ 环烷氧基或 C₃₋₈ 环烷基氨基任选取代的氨基，且 R₂ 为氢；或 R₁ 和 R₂ 中的一个是硝基、氰基或 C₁₋₃烷基羰基，另一个是选自硝基、氰基、卤素、C₁₋₃烷基羰基的不同基团、卤代、C₁₋₃烷基羰基、甲氧基或被一个或两个 C₁₋₆ 烷基或 C₂₋₇ 烷酰基任选取代的氨基；或 R₁ 和 R₂ 与它们所连接的碳原子一起形成 2,1,3-噁二唑或三唑； R₃ 和 R₄ 中的一个是氢或 C₁₋₄ 烷基，另一个是 C₁₋₄ 烷基；或 R₃ 和 R₄ 合在一起是 C₂₋₅ 聚亚甲基； R₅ 是氢、羟基、C₁₋₆ 烷氧基或 C₁₋₇酰氧基或 ONO₂； R₆ 和 R₇ 独立地为氢、C₁₋₆ 烷基；或（当 R₆ 为氢时），则 R₇ 为烯丙基、丙炔基或 C₃₋₆ 环烷基； J 是 O 或 NR₈，其中 R₈ 是氢或 C₁₋₆ 烷基。
• Benzopyran derivatives and heterocyclic analogs thereof as antiischemic agents
  申请人：E.R. SQUIBB & SONS, INC.

  公开号：EP0462761A2

  公开（公告）日：1991-12-27

  A new method for the treatment of ischemic conditions and arrhythmia is disclosed. The method uses compounds of the formula wherein A can be -CH₂-, -O-, -NR₉-, -S-, -SO-, -SO₂-; X can be oxygen or sulfur; Y can be -NR₈, -O-, -S-, -CH₂- and the R groups are as defined herein. Novel compounds within the definition of formula I are also disclosed.

  本研究公开了一种治疗缺血性疾病和心律失常的新方法。该方法使用式 其中 A 可以是-CH₂-、-O-、-NR₉-、-S-、-SO-、-SO₂-；X 可以是氧或硫；Y 可以是-NR₈、-O-、-S-、-CH₂-，R 基团如本文所定义。还公开了符合式 I 定义的新型化合物。