2-(2,5-difluoro-phenyl)-chroman-6-ol | 488848-02-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 2-(2,5-difluoro-phenyl)-chroman-6-ol
• 英文别名: 2-(2,5-Difluorophenyl)chroman-6-ol；2-(2,5-difluorophenyl)-3,4-dihydro-2H-chromen-6-ol
• CAS: 488848-02-8
• 化学式: C₁₅H₁₂F₂O₂
• 分子量: 262.256
• InChiKey: BSMNJMSYXGWLBH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(2,5-difluoro-phenyl)-chroman-6-ol 、 1-氯-4-乙氧基-2-硝基苯 在 potassium tert-butylate 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 8.0h， 生成 2-(2,5-difluorophenyl)-6-(4-ethoxy-2-nitrophenoxy)chroman
  参考文献：
  名称：

  JP2005/504738

  摘要：

  公开号：
• 作为产物：
  描述：

  2-(3-fluoro-phenyl)-chroman-6-ol 、 2-(2,5-difluorophenyl)chroman-4,6-diol 生成 2-(2,5-difluoro-phenyl)-chroman-6-ol
  参考文献：
  名称：

  Compounds, which are potent inhibitors of Na+ /Ca2+ exchange mechanism and are useful in the treatment of arrhythmias

  摘要：

  式(I)中所示的治疗活性化合物：其中在式(I)中所示的变量在本文中有定义；以及其药学上可接受的盐和酯。这些化合物是钠/钙交换机制的强效抑制剂。

  公开号：

  US07425568B2

文献信息

• [EN] PYRIDINE DERIVATIVES USEFUL FOR INHIBITING SODIUM/CALCIUM EXCHANGE SYSTEM<br/>[FR] DERIVES PYRIDINE SERVANT A INHIBER LE SYSTEME D'ECHANGE SODIUM/CALCIUM
  申请人：ORION CORP

  公开号：WO2004063191A1

  公开（公告）日：2004-07-29

  Therapeutically active compounds of formula (I) or (II) wherein X is -O-, -CH2- or -C(O)-; Z is -CHR12- or a valence bond; Y is -CH2-, -C(O)-, CH(OR13)-, -O-, -S-; provided that in case Z is a valence bond, Y is not C(O); the dashed line representing an optional double bond in which case Z is -CR12- ­and Y is -CH2-, -C(O)- or -CH(OR10)- (in formula II) or -CH- (in formula I); R2 and R3 are independently H, lower alkyl, lower alkoxy, -NO2, halogen, -CF3, -OH, benzyloxy or a group of formula (IIIa). R1 is H, CN, halogen, -CONH2, -COOR15, CH2NR15R18, NHC(O)R5, NHCH2R5, NHR20, NR21R22, NHC(NH)NHCH3 or, in case the compound is of formula (II) wherein the optional double bond exists or in case R2 or R3 is benzyloxy or a group of formula (IIIa) or in case the pyridine ring of formula (I) or (II) is attached to the oxygen atom in 3-, 4- or 5-position, R1 can also be -NO2 or NR16R17; R4 is H, -NO2, CN, halogen, -CONH2, -COOR15, -CH2NR15R18, -NR16R17, NHC(O)R5 or -NHC(NH)NHCH3; R5 is alkyl substituted with 1-3 substituents selected from the group consisting of halogen, amino and hydroxy, or carboxyalkyl, in which the alkyl portion is optionally substituted with 1-3 substituents selected from the group consisting of halogen, amino and hydroxyl, -CHR6NR,R8 or one of the following groups: formula (IVa), (IVb), (IVc), (IVd), (IVe), and pharmaceutically acceptable salts and esters thereof. The compounds are potent inhibitors of Na+/Ca2+ exchange mechanism.

  式（I）或（II）的治疗活性化合物，其中X为-O-，-CH2-或-C（O）-；Z为-CHR12-或一个价键；Y为-CH2-，-C（O）-，CH（OR13）-，-O-，-S-；条件是如果Z为一个价键，则Y不是C（O）；虚线表示可选的双键，此时Z为-CR12-，Y为-CH2-，-C（O）-或-CH（OR10）-（在式（II）中）或-CH-（在式（I）中）；R2和R3独立地为H，较低的烷基，较低的烷氧基，-NO2，卤素，-CF3，-OH，苄氧基或式（IIIa）的基团。R1为H，CN，卤素，-CONH2，-COOR15，CH2NR15R18，NHC（O）R5，NHCH2R5，NHR20，NR21R22，NHC（NH）NHCH3的基团，或者，如果化合物为式（II），其中存在可选的双键，或者如果R2或R3为苄氧基或式（IIIa）的基团，或者如果式（I）或（II）的吡啶环附着在3-，4-或5-位置的氧原子上，则R1也可以是-NO2或NR16R17；R4为H，-NO2，CN，卤素，-CONH2，-COOR15，-CH2NR15R18，-NR16R17，NHC（O）R5或-NHC（NH）NHCH3；R5为烷基，其上取代有1-3个取自卤素、氨基和羟基或羧基的取代基，其中烷基部分可选地取代有1-3个取自卤素、氨基和羟基的取代基，-CHR6NR,R8或以下所示的一个基团之一：式（IVa），（IVb），（IVc），（IVd），（IVe），以及其药用可接受的盐和酯。这些化合物是Na+/Ca2+交换机制的有效抑制剂。
• SUBSTITUTED 2-(CHROMAN-6-YLOXY)-THIAZOLES AND THEIR USE AS PHARMACEUTICALS
  申请人：CZECHTIZKY Werngard

  公开号：US20130065859A1

  公开（公告）日：2013-03-14

  The present invention relates to substituted 2-(chroman-6-yloxy)-thiazoles of the formula I, in which Ar, R2, R3 and R4 are as defined in the claims. The compounds of the formula I are inhibitors of the sodium-calcium exchanger (NCX), especially of the sodium-calcium exchanger of subtype 1 (NCX1), and are suitable for the treatment of diverse disorders in which intracellular calcium homeostasis is disturbed, such as arrhythmias, heart failure and stroke. The invention furthermore relates to processes for the preparation of the compounds of the formula I, their use as pharmaceuticals, and pharmaceutical compositions comprising them.

  本发明涉及式I的取代2-(色甘醇-6-氧基)-噻唑衍生物，其中Ar、R2、R3和R4如权利要求中所定义。式I的化合物是钠-钙交换蛋白（NCX）的抑制剂，特别是亚型1的钠-钙交换蛋白（NCX1），适用于处理细胞内钙离子稳态受扰的各种疾病，如心律失常、心力衰竭和中风。本发明还涉及制备式I的化合物的方法，它们作为药物的用途，以及包含它们的药物组合物。
• [EN] SUBSTITUTED 2-(CHROMAN-6-YLOXY)-THIAZOLES AND THEIR USE AS PHARMACEUTICALS<br/>[FR] 2-(CHROMAN-6-YLOXY)-THIAZOLES SUBSTITUÉS ET LEUR UTILISATION EN TANT QUE PRODUITS PHARMACEUTIQUES
  申请人：SANOFI SA

  公开号：WO2013037724A1

  公开（公告）日：2013-03-21

  The present invention relates to substituted 2-(chroman-6-yloxy)-thiazoles of the formula I in which Ar, R2, R3 and R4 are as defined in the claims. The compounds of the formula I are inhibitors of the sodium-calcium exchanger (NCX), especially of the sodium-calcium exchanger of subtype 1 (NCX1 ), and are suitable for the treatment of diverse disorders in which intracellular calcium homeostasis is disturbed, such as arrhythmias, heart failure and stroke. The invention furthermore relates to processes for the preparation of the compounds of the formula I, their use as pharmaceuticals, and pharmaceutical compositions comprising them.

  本发明涉及公式I中Ar、R2、R3和R4所定义的取代的2-(色甘醇-6-氧基)-噻唑。公式I的化合物是钠钙交换蛋白(NCX)的抑制剂，特别是亚型1的钠钙交换蛋白(NCX1)，适用于治疗细胞内钙稳态紊乱的各种疾病，如心律失常、心力衰竭和中风。此外，该发明还涉及制备公式I化合物的方法，它们作为药物的用途，以及包含它们的药物组合物。
• [EN] SUBSTITUTED 2-(CHROMAN-6-YLOXY)-THIAZOLES AND THEIR USE AS PHARMACEUTICALS<br/>[FR] THIAZOLES À SUBSTITUTION 2-(CHROMAN-6-YLOXY) ET LEUR UTILISATION COMME PRODUITS PHARMACEUTIQUES
  申请人：SANOFI SA

  公开号：WO2013037388A1

  公开（公告）日：2013-03-21

  The present invention relates to substituted 2-(chroman-6-yloxy)-thiazoles of the formula (I), in which Ar, R2, R3 and R4 are as defined in the claims. The compounds of the formula (I) are inhibitors of the sodium-calcium exchanger (NCX), especially of the sodium-calcium exchanger of subtype 1 (NCX1), and are suitable for the treatment of diverse disorders in which intracellular calcium homeostasis is disturbed, such as arrhythmias, heart failure and stroke. The invention furthermore relates to processes for the preparation of the compounds of the formula (I), their use as pharmaceuticals, and pharmaceutical compositions comprising them.

  本发明涉及式(I)的取代2-(色苷-6-氧基)-噻唑，其中Ar、R2、R3和R4如权利要求中所定义。式(I)的化合物是钠钙交换蛋白(NCX)的抑制剂，特别是钠钙交换蛋白的亚型1(NCX1)的抑制剂，并适用于治疗细胞内钙离子稳态紊乱的各种疾病，如心律失常、心力衰竭和中风。此外，该发明还涉及制备式(I)化合物的方法，它们作为药物的用途，以及包含它们的药物组合物。
• Compounds, which are potent inhibitors of na+ / ca2+ exchange mechanism and are useful in the treatment of arrhythmias
  申请人：——

  公开号：US20040235905A1

  公开（公告）日：2004-11-25

  Therapeutically active compounds of formula (I): wherein X is —O—, —CH 2 — or —C(O)—; Z is —CHR 9 — or valence bond; Y is —CH 2 —, —C(O)—, CH(OR 10 )—, —CH(NR 11 R 12 )—, —O—, —S—, —S(O)— or —S(O 2 )—, provided that in case Z is a valence bond, Y is not C(O); the dashed line represents an optional double bond in which case Z is —CR 9 — and Y is —CH—, C(OR 10 )— or —C(NR 11 R 12 )—; R 1 is —(CH 2 ) n NR 4 R 7 or one of the following groups: n is 1-4; R 2 and R 3 are independently H, lower alkyl, lower alkoxy, —NO 2 , halogen, —CF 3 , —OH, —NHR 8 or —COOH, R 4 and R 7 are independently H, lower alkyl or lower hydroxyalkyl; R 5 is H, lower alkoxy, —CF 3 , —NH 2 or —CN; R 6 is —NO 2 , —NR 14 R 19 , —CF 3 or R 8 and R 16 are independently H or acyl; R 9 is H or lower alkyl; R 10 is H, alkylsulfonyl or acyl; R 11 and R 12 are independently H, lower alkyl or acyl; R 13 and R 18 are independently H or —OR 20 ; R 14 and R 19 are independently H, acyl, alkylsulfonyl, C(S)NHR 17 or C(O)NHR 17 ; R 15 is H or NH 2 ; R 17 is H or lower alkyl; R 20 is H or acyl; and pharmaceutically acceptable salts and esters thereof are disclosed. The compounds are potent inhibitors of Na + /Ca 2+ exchange mechanism. 1

  公式（I）中的治疗活性化合物：其中X是—O—，—CH2—或—C（O）—; Z是—CHR9—或价键; Y是—CH2—，—C（O）—，CH（OR10）—，—CH（NR11R12）—，—O—，—S—，—S（O）—或—S（O2）—，前提是如果Z是价键，则Y不是C（O）; 虚线表示可选的双键，在这种情况下Z是—CR9—，Y是—CH—，C（OR10）—或—C（NR11R12）—; R1是—（CH2）nNR4R7或以下组之一：n为1-4; R2和R3独立地为H，较低的烷基，较低的烷氧基，—NO2，卤素，—CF3，—OH，—NHR8或—COOH，R4和R7独立地为H，较低的烷基或较低的羟基烷基; R5为H，较低的烷氧基，—CF3，—NH2或—CN; R6为—NO2，—NR14R19，—CF3或R8和R16独立地为H或酰基; R9为H或较低的烷基; R10为H，烷基磺酰基或酰基; R11和R12独立地为H，较低的烷基或酰基; R13和R18独立地为H或—OR20; R14和R19独立地为H，酰基，烷基磺酰基，C（S）NHR17或C（O）NHR17; R15为H或NH2; R17为H或较低的烷基; R20为H或酰基; 其药学上可接受的盐和酯被披露。这些化合物是钠/钙交换机制的有效抑制剂。