8-(2',6'-dimethoxyphenoxy)octylamine | 251477-84-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 8-(2',6'-dimethoxyphenoxy)octylamine
• 英文别名: 8-(2,6-Dimethoxyphenoxy)octan-1-amine
• CAS: 251477-84-6
• 化学式: C₁₆H₂₇NO₃
• 分子量: 281.395
• InChiKey: VAVGBSDGGYANLA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  53.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-(8-bromo-octyl)phthalimnide 、 2,6-二甲氧基苯酚 生成 8-(2',6'-dimethoxyphenoxy)octylamine
  参考文献：
  名称：

  摘要：

  DOI：

文献信息

• [EN] 2,3,5-SUBSTITUTED BIPHENYLS USEFUL IN THE TREATMENT OF INSULIN RESISTANCE AND HYPERGLYCEMIA<br/>[FR] DIPHENYLES 2,3,5-SUBSTITUES UTILES POUR LE TRAITEMENT DE LA RESISTANCE INSULINIQUE ET DE L'HYPERGLYCEMIE
  申请人：AMERICAN HOME PRODUCTS CORPORATION

  公开号：WO1999061410A1

  公开（公告）日：1999-12-02

  (EN) This invention provides compounds of Formula (I) having structure (I) wherein: B and D are each, independently, hydrogen, halogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, aryl, heteroaryl, aralkyl of 6-12 carbon atoms, or heteroaralkyl of 6-12 carbon atoms except where B and D both are hydrogen; R1 is hydrogen, alkyl of 1-6 carbon atoms, -SO2Ph(OH)(CO2H), -CH(R2)W, -CH2CH2Y, or -CH2CH2CH2Y; R2 is hydrogen, alkyl of 1-6 carbon atoms, aralkyl of 6-12 carbon atoms, -CH2(1H-imidazol-4-yl), -CH2(3-1H-indolyl), -CH2CH2(1,3-dioxo-1,3-dihydro-isoindol-2-yl), -CH2CH2(1-oxo-1,3-dihydro-isoindol-2-yl), or -CH2(3-pyridyl); W is -CO2R3, -CONHOH, -CN, -CONHR3, aryl, heteroaryl, -CHO, -CH=NOR3, or -CH=NHNHR3; Y is -W, -OCH2CO2R3, aryl, heteroaryl, -C(=NOH)NH2, -OR3, -O(C=O)NR4R5, -NR3(C=O)OR3, -NR3(C=O)NR4R5, or -NR4R5; R3 is hydrogen or alkyl of 1-6 carbon atoms; R4 and R5 are each, independently, hydrogen, or alkyl of 1-6 carbon atoms or R4 and R5 are, together, -(CH2)n-, or -CH2CH2XCH2CH2-; X is O, S, SO, SO2, NR3, or CH2; n is 2 to 5; C is alkyl of 1-18 carbon atoms, aryl, heteroaryl, aralkyl of 6-20 carbon atoms, heteroaralkyl of 6-20 carbon atoms, -CONR6R7, -NR3CONR6R7, -NR3COR6, -OR6, -O2CNR6R7, -NR3CO2R6, -O2CR6, -CH2OR6, -NR6R7, -CR3=CR3R8, -CPh3, -CH2NR6R7, or Formula (1); R6 and R7 are each, independently, hydrogen, alkyl of 1-18 carbon atoms, aryl, heteroaryl, aralkyl of 6-20 carbon atoms, heteroaralkyl of 6-20 carbon atoms, cycloalkyl of 3-10 carbon atoms, -(CH2CH2O)nCH3, -(CH2)mA or R6 and R7 are, together, -(CH2)p-, -(CH2)2N(CH3)(CH2)4-, -(CH2)2N(R8)(CH2)2-, or -(CH2)2CH(R8)-(CH2)2-; R8 is hydrogen, alkyl of 1-18 carbon atoms, aryl, heteroaryl, aralkyl of 6-20 carbon atoms, heteroaralkyl of 6-20 carbon atoms, cycloakyl or 3-10 carbon atoms, -(CH2CH2O)nCH3, -(CH2CH2CH2O)nCH3, or -(CH2)mA; A is aryl, heteroaryl, aryloxy, heteroaryloxy, arylthio, heteroarylthio, arylsulfoxy, heteroarylsulfoxy, arylsulfonyl, heteroarylsulfonyl, -CHF2, -CH2F, -CF3, -(CH2CH2O)nCH3, -(CH2CH2CH2O)nCH3, -CO2R3, -O(C=O)NR6R7, aralkyloxy, or heteroaralkyloxy; m is 2 to 16; p is 2 to 12; or a pharmaceutically acceptable salt thereof, which are useful in treating metabolic disorders related to insulin resistance or hyperglycemia.(FR) L'invention se rapporte à des composés représentés par la formule (I) dans laquelle B et D sont chacun, indépendamment, hydrogène, halogène, alkyle de 1 à 6 atomes de carbone, cycloalkyle de 3 à 8 atomes de carbone, aryle, hétéroaryle, aralkyle de 6 à 12 atomes de carbone, ou hétéroaralkyle de 6 à 12 atomes de carbone sauf lorsque B et D sont tous deux hydrogène; R1 est hydrogène, alkyle de 1 à 6 atomes de carbone, -SO2Ph(OH)(CO2H), -CH(R2)W, -CH2CH2Y ou CH2CH2CH2Y; R2 est hydrogène, alkyle de 1 à 6 atomes de carbone, aralkyle de 6 à 12 atomes de carbone, -CH2(1H-imidazol-4-yle), -CH2(3-1H-indolyle), -CH2CH2(1,3-dioxo-1,3-dihydro-isoindol-2-yle), CH2CH2(1-oxo-1,3-dihydro-isoindol-2-yle) ou CH2(3-pyridyle); W est CO2R3, -CONHOH, -CN, -CONHR3, aryle, hétéroaryle, -CHO, -CH=NOR3 ou CH=NHNHR3; Y est W, -OCH2CO2R3, aryle, hétéroaryle, -C(=NOH)NH2, -OR3, -O(C=O)NR4R5, -NR3(C=O)OR3, -NR3(C=O)NR4R5 ou NR4R5; R3 est hydrogène ou alkyle de 1 à 6 atomes de carbone; R4 et R5 sont chacun, indépendamment, hydrogène ou alkyle de 1 à 6 atomes de carbone ou bien R4 et R5 sont, conjointement, -(CH2)n-, ou CH2CH2XCH2CH2- ; X est O, S, SO, SO2, NR3 ou CH2; n est compris entre 2 et 5; C est alkyle de 1 à 18 atomes de carbone, aryle, hétéroaryle, aralkyle de 6 à 20 atomes de carbone, hétéroaralkyle de 6 à 20 atomes de carbone, -CONR6R7, -NR3CONR6R7, -NR3COR6, -OR6, -O2CNR6R7, -NR3CO2R6, -O2CR6, -CH2OR6, -NR6R7, -CR3=CR3R8, -CPh3, -CH2NR6R7 ou bien le composé représenté par la figure (1); R6 et R7 sont chacun, indépendamment, hydrogène, alkyle de 1 à 18 atomes de carbone, aryle, hétéroaryle, aralkyle de 6 à 20 atomes de carbone, hétéroaralkyle de 6 à 20 atomes de carbone, cycloalkyle de 3 à 10 atomes de carbone, -(CH2CH2O)nCH3, -(CH2)mA ou bien R6 et R7 sont, conjointement, -(CH2)p-, -(CH2)2CH(R8)-(CH2)2-; R8 est hydrogène, alkyle de 1 à 18 atomes de carbone, aryle, hétéroaryle, aralkyle de 6 à 20 atomes de carbone, hétéroaralkyle de 6 à 20 atomes de carbone, cycloalkyle de 3 à 10 atomes de carbone, -(CH2CH2O)nCH3, -(CH2CH2CH2O)nCH3, -(CH2CH2CH2O)nCH3 ou -(CH2)mA ; A est aryle, hétéroaryle, aryloxy, hétéroaryloxy, arylthio, hétéroarylthio, arylsulfoxy, hétéroarylsulfoxy, arylsulfonyle, hétéroarylsulfonyle, -CHF2, -CH2F, -CF3, -(CH2CH2O)nCH3, -(CH2CH2CH2O)nCH3, -CO2R3, -O(C=O)NR6R7, aralkyloxy ou hétéroaralkyloxy; m est compris entre 2 et 16; p est compris entre 2 et 12. L'invention se rapporte également à un sel pharmaceutiquement acceptable de ces composés, qui s'avèrent utiles pour le traitement des troubles métaboliques associés à la résistance insulinique ou l'hyperglycémie.

  本发明提供了具有结构式（I）的化合物，其中：B和D各自独立地为氢、卤素、1-6个碳原子的烷基、3-8个碳原子的环烷基、芳基、杂芳基、6-12个碳原子的芳基烷基或6-12个碳原子的杂芳基烷基，但当B和D都为氢时除外；R1为氢、1-6个碳原子的烷基、-SO2Ph(OH)(CO2H)、-CH(R2)W、-CH2CH2Y或-CH2CH2CH2Y；R2为氢、1-6个碳原子的烷基、6-12个碳原子的芳基烷基、-CH2(1H-咪唑-4-基)、-CH2(3-1H-吲哚基)、-CH2CH2(1,3-二氧代-1,3-二氢异吲哚-2-基)、-CH2CH2(1-氧代-1,3-二氢异吲哚-2-基)或-CH2(3-吡啶基)；W为-CO2R3、-CONHOH、-CN、-CONHR3、芳基、杂芳基、-CHO、-CH=NOR3或-CH=NHNHR3；Y为-W、-OCH2CO2R3、芳基、杂芳基、-C(=NOH)NH2、-OR3、-O(C=O)NR4R5、-NR3(C=O)OR3、-NR3(C=O)NR4R5或-NR4R5；R3为氢或1-6个碳原子的烷基；R4和R5各自独立地为氢或1-6个碳原子的烷基，或者R4和R5在一起为-(CH2)n-或-CH2CH2XCH2CH2-；X为O、S、SO、SO2、NR3或CH2；n为2至5；C为1-18个碳原子的烷基、芳基、杂芳基、6-20个碳原子的芳基烷基、6-20个碳原子的杂芳基烷基、-CONR6R7、-NR3CONR6R7、-NR3COR6、-OR6、-O2CNR6R7、-NR3CO2R6、-O2CR6、-CH2OR6、-NR6R7、-CR3=CR3R8、-CPh3、-CH2NR6R7或式（1）；R6和R7各自独立地为氢、1-18个碳原子的烷基、芳基、杂芳基、6-20个碳原子的芳基烷基、6-20个碳原子的杂芳基烷基、3-10个碳原子的环烷基、-(CH2CH2O)nCH3、-(CH2)mA或者R6和R7在一起为-(CH2)p-、-(CH2)2N(CH3)(CH2)4-、-(CH2)2N(R8)(CH2)2-或-(CH2)2CH(R8)-(CH2)2-；R8为氢、1-18个碳原子的烷基、芳基、杂芳基、6-20个碳原子的芳基烷基、6-20个碳原子的杂芳基烷基、3-10个碳原子的环烷基、-(CH2CH2O)nCH3、-(CH2CH2CH2O)nCH3或-(CH2)mA；A为芳基、杂芳基、芳氧基、杂芳氧基、芳硫基、杂芳硫基、芳基磺酸氧基、杂芳基磺酸氧基、芳基磺酰基、杂芳基磺酰基、-CHF2、-CH2F、-CF3、-(CH2CH2O)nCH3、-(CH2CH2CH2O)nCH3、-CO2R3、-O(C=O)NR6R7、芳基烷氧基或杂芳基烷氧基；m为2至16；p为2至12；或其药学上可接受的盐，用于治疗与胰岛素抵抗或高血糖有关的代谢障碍。
• 2, 3, 5-substituted biphenyls useful in the treatment of insulin resistance and hyperglycemia
  申请人：——

  公开号：US20010018525A1

  公开（公告）日：2001-08-30

  This invention provides compounds of Formula I having the structure 1 wherein: B and D are each, independently, hydrogen, halogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, aryl, heteroaryl, aralkyl of 6-12 carbon atoms, or heteroaralkyl of 6-12 carbon atoms except where B and D both are hydrogen; R 1 is hydrogen, alkyl of 1-6 carbon atoms, —SO 2 Ph(OH)(CO 2 H), —CH(R 2 )W; —CH 2 CH 2 Y, or —CH 2 CH 2 CH 2 Y; R 2 is hydrogen, alkyl of 1-6 carbon atoms, aralkyl of 6-12 carbon atoms, —CH 2 (1H-imidazol-4-yl), —CH 2 (3-1H-indolyl), —CH 2 CH 2 (1,3-dioxo-1,3-dihydro-isoindol-2-yl), —CH 2 CH 2 (1-oxo-1,3-dihydro-isoindol-2-yl), or —CH 2 (3-pyridyl); W is —CO 2 R 3 , —CONHOH, —CN, —CONHR 3 , aryl, heteroaryl, —CHO, —CH═NOR 3 , or —CH═NHNHR 3 ; Y is —W, —OCH 2 CO 2 R 3 , aryl, heteroaryl, —C(═NOH)NH 2 , —OR 3 , —O(C═O)NR 4 R 5 , —NR 3 (C═O)OR 3 , —NR 3 (C═O)NR 4 R 5 , or —NR 4 R 5 ; R 3 is hydrogen or alkyl of 1-6 carbon atoms; R 4 and R 5 are each, independently, hydrogen, or alkyl of 1-6 carbon atoms or R 4 and R 5 are, together, —(CH 2 ) n —, or —CH 2 CH 2 XCH 2 CH 2 —; X is O, S, SO, SO 2 , NR 3 , or CH 2 ; n is 2 to 5; C is alkyl of 1-18 carbon atoms, aryl, heteroaryl, aralkyl of 6-20 carbon atoms, heteroaralkyl of 6-20 carbon atoms, —CONR 6 R 7 , —NR 3 CONR 6 R 7 , —NR 3 COR 6 , —OR 6 , —O 2 CNR 6 R 7 , —NR 3 CO 2 R 6 , —O 2 CR 6 , —CH 2 OR 6 , —NR 6 R 7 , —CR 3 ═CR 3 R 8 , —CPh 3 , —CH 2 NR 6 R 7 , or 2 R 6 and R 7 are each, independently, hydrogen, alkyl of 1-18 carbon atoms, aryl, heteroaryl, aralkyl of 6-20 carbon atoms, heteroaralkyl of 6-20 carbon atoms, cycloalkyl of 3-10 carbon atoms, —(CH 2 CH 2 O) n CH 3 , —(CH 2 ) m A or R 6 and R 7 are, together, —(CH 2 ) p —, —(CH 2 ) 2 N(CH 3 )(CH 2 ) 4 —, —(CH 2 ) 2 N(R 8 )(CH 2 ) 2 —, or —(CH 2 ) 2 CH(R 8 )—(CH 2 ) 2 —; R 8 is hydrogen, alkyl of 1-18 carbon atoms, aryl, heteroaryl, aralkyl of 6-20 carbon atoms, heteroaralkyl of 6-20 carbon atoms, cycloalkyl of 3-10 carbon atoms, —(CH 2 CH 2 O) n CH 3 , —(CH 2 CH 2 CH 2 O) n CH 3 , or —(CH 2 ) m A; A is aryl, heteroaryl, aryloxy, heteroaryloxy, arylthio, heteroarylthio, arylsulfoxy, heteroarylsulfoxy, arylsulfonyl, heteroarylsulfonyl, —CHF 2 , —CH 2 F, —CF 3 , —(CH 2 CH 2 O) n CH 3 , —(CH 2 CH 2 CH 2 O) n CH 3 , —CO 2 R 3 , —O(C═O)NR 6 R 7 , aralkyloxy, or heteroaralkyloxy; m is 2 to 16 p is 2 to 12 or a pharmaceutically acceptable salt thereof, which are useful in treating metabolic disorders related to insulin resistance or hyperglycemia.

  该发明提供了具有结构1的化合物，其中： B和D分别独立地为氢、卤素、1-6个碳原子的烷基、3-8个碳原子的环烷基、芳基、杂芳基、6-12个碳原子的芳基烷基或6-12个碳原子的杂芳基烷基，但当B和D均为氢时除外。 R1为氢、1-6个碳原子的烷基、-SO2Ph(OH)(CO2H)、-CH(R2)W、-CH2CH2Y或-CH2CH2CH2Y。 R2为氢、1-6个碳原子的烷基、6-12个碳原子的芳基烷基、-CH2(1H-咪唑-4-基)、-CH2(3-1H-吲哚基)、-CH2CH2(1,3-二酮-1,3-二氢异吲哚-2-基)、-CH2CH2(1-酮-1,3-二氢异吲哚-2-基)或-CH2(3-吡啶基)。 W为-CO2R3、-CONHOH、-CN、-CONHR3、芳基、杂芳基、-CHO、-CH═NOR3或-CH═NHNHR3。 Y为-W、-OCH2CO2R3、芳基、杂芳基、-C(═NOH)NH2、-OR3、-O(C═O)NR4R5、-NR3(C═O)OR3、-NR3(C═O)NR4R5或-NR4R5。 R3为氢或1-6个碳原子的烷基。 R4和R5分别独立地为氢或1-6个碳原子的烷基，或者R4和R5在一起为-(CH2)n-或-CH2CH2XCH2CH2-，其中X为O、S、SO、SO2、NR3或CH2，n为2到5。 C为1-18个碳原子的烷基、芳基、杂芳基、6-20个碳原子的芳基烷基、6-20个碳原子的杂芳基烷基、-CONR6R7、-NR3CONR6R7、-NR3COR6、-OR6、-O2CNR6R7、-NR3CO2R6、-O2CR6、-CH2OR6、-NR6R7、-CR3═CR3R8、-CPh3、-CH2NR6R7或2R6和R7分别独立地为氢、1-18个碳原子的烷基、芳基、杂芳基、6-20个碳原子的芳基烷基、6-20个碳原子的杂芳基烷基、3-10个碳原子的环烷基、-(CH2CH2O)nCH3、-(CH2)mA，或者R6和R7在一起为-(CH2)p-、-(CH2)2N(CH3)(CH2)4-、-(CH2)2N(R8)(CH2)2-或-(CH2)2CH(R8)-(CH2)2-，其中R8为氢、1-18个碳原子的烷基、芳基、杂芳基、6-20个碳原子的芳基烷基、6-20个碳原子的杂芳基烷基、3-10个碳原子的环烷基、-(CH2CH2O)nCH3、-(CH2CH2CH2O)nCH3或-(CH2)mA；A为芳基、杂芳基、芳氧基、杂芳氧基、芳硫基、杂芳硫基、芳基亚磺酸基、杂芳基亚磺酸基、芳基磺酰基、杂芳基磺酰基、-CHF2、-CH2F、-CF3、-(CH2CH2O)nCH3、-(CH2CH2CH2O)nCH3、-CO2R3、-O(C═O)NR6R7、芳基烷氧基或杂芳基烷氧基；m为2到16；p为2到12。 或其药学上可接受的盐，适用于治疗与胰岛素抵抗或高血糖有关的代谢障碍。
• 2,3,5-substituted biphenyls useful in the treatment of insulin resistance and hyperglycemia
  申请人：Wyeth

  公开号：US20040214869A1

  公开（公告）日：2004-10-28

  This invention provides compounds of Formula I having the structure 1 wherein: B and D are each, independently, hydrogen, halogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, aryl, heteroaryl, aralkyl of 6-12 carbon atoms, or heteroaralkyl of 6-12 carbon atoms except where B and D both are hydrogen; R 1 is hydrogen, alkyl of 1-6 carbon atoms, —SO 2 Ph(OH)(CO 2 H), —CH(R 2 )W, —CH 2 CH 2 Y, or —CH 2 CH 2 CH 2 Y; R 2 is hydrogen, alkyl of 1-6 carbon atoms, aralkyl of 6-12 carbon atoms, —CH 2 (1H-imidazol-4-yl), —CH 2 (3-1H-indolyl), —CH 2 CH 2 (1,3-dioxo-1,3-dihydro-isoindol-2-yl), —CH 2 CH 2 (1-oxo-1,3-dihydro-isoindol-2-yl), or —CH 2 (3-pyridyl); W is —CO 2 R 3 , —CONHOH, —CN, —CONHR 3 , aryl, heteroaryl, —CHO, —CH═NOR 3 , or —CH═NHNHR 3 ; Y is —W, —OCH 2 CO 2 R 3 , aryl, heteroaryl, —C(═NOH)NH 2 , —OR 3 , —O(C═O)NR 4 R 5 , —NR 3 (C═O)OR 3 , —NR 3 (C═O)NR 4 R 5 , or —NR 4 R 5 ; R 3 is hydrogen or alkyl of 1-6 carbon atoms; R 4 and R 5 are each, independently, hydrogen, or alkyl of 1-6 carbon atoms or R 4 and R 5 are, together, —(CH 2 ) n —, or —CH 2 CH 2 XCH 2 CH 2 —; X is O, S, SO, SO 2 , NR 3 , or CH 2 ; n is 2 to 5; C is alkyl of 1-18 carbon atoms, aryl, heteroaryl, aralkyl of 6-20 carbon atoms, heteroaralkyl of 6-20 carbon atoms, —CONR 6 R 7 , —NR 3 CONR 6 R 7 , —NR 3 COR 6 , —OR 6 , —O 2 CNR 6 R 7 , —NR 3 CO 2 R 6 , —O 2 CR 6 , —CH 2 OR 6 , —NR 6 R 7 , —CR 3 ═CR 3 R 8 , —CPh 3 , —CH 2 NR 5 R 6 , or 2 R 6 and R 7 are each, independently, hydrogen, alkyl of 1-18 carbon atoms, aryl, heteroaryl, aralkyl of 6-20 carbon atoms, heteroaralkyl of 6-20 carbon atoms, cycloalkyl of 3-10 carbon atoms, —(CH 2 CH 2 O) n CH 3 , —(CH 2 ) m A or R 6 and R 7 are, together, —(CH 2 ) p —, —(CH 2 ) 2 N(CH 3 )(CH 2 ) 4 —, —(CH 2 ) 2 N(R 8 )(CH 2 ) 2 —, or —(CH 2 ) 2 CH(R 8 )—(CH 2 ) 2 —; R 8 is hydrogen, alkyl of 1-18 carbon atoms, aryl, heteroaryl, aralkyl of 6-20 carbon atoms, heteroaralkyl of 6-20 carbon atoms, cycloalkyl of 3-10 carbon atoms, —(CH 2 CH 2 O) n CH 3 , —(CH 2 CH 2 CH 2 O) n CH 3 , or —(CH 2 ) m A; A is aryl, heteroaryl, aryloxy, heteroaryloxy, arylthio, heteroarylthio, arylsulfoxy, heteroarylsulfoxy, arylsulfonyl, heteroarylsulfonyl, —CHF 2 , —CH 2 F, —CF 3 , —(CH 2 CH 2 O) n CH 3 , —(CH 2 CH 2 CH 2 O) n CH 3 , —CO 2 R 3 , —O(C═O)NR 6 R 7 , aralkyloxy, or heteroaralkyloxy; m is 2 to 16 p is 2 to 12 or a pharmaceutically acceptable salt thereof, which are useful in treating metabolic disorders related to insulin resistance or hyperglycemia.

  这项发明提供了具有结构1的化合物，其中：B和D各自独立地为氢、卤素、1-6个碳原子的烷基、3-8个碳原子的环烷基、芳基、杂芳基、6-12个碳原子的芳基烷基或6-12个碳原子的杂芳基烷基，但当B和D都为氢时除外；R1为氢、1-6个碳原子的烷基、-SO2Ph(OH)(CO2H)、-CH(R2)W、-CH2CH2Y或-CH2CH2CH2Y；R2为氢、1-6个碳原子的烷基、6-12个碳原子的芳基烷基、-CH2(1H-咪唑-4-基)、-CH2(3-1H-吲哚基)、-CH2CH2(1,3-二酮-1,3-二氢-异吲哚-2-基)、-CH2CH2(1-酮-1,3-二氢-异吲哚-2-基)或-CH2(3-吡啶基)；W为-CO2R3、-CONHOH、-CN、-CONHR3、芳基、杂芳基、-CHO、-CH═NOR3或-CH═NHNHR3；Y为-W、-OCH2CO2R3、芳基、杂芳基、-C(═NOH)NH2、-OR3、-O(C═O)NR4R5、-NR3(C═O)OR3、-NR3(C═O)NR4R5或-NR4R5；R3为氢或1-6个碳原子的烷基；R4和R5各自独立地为氢或1-6个碳原子的烷基，或R4和R5在一起为-(CH2)n-或-CH2CH2XCH2CH2-；X为O、S、SO、SO2、NR3或CH2；n为2至5；C为1-18个碳原子的烷基、芳基、杂芳基、6-20个碳原子的芳基烷基、6-20个碳原子的杂芳基烷基、-CONR6R7、-NR3CONR6R7、-NR3COR6、-OR6、-O2CNR6R7、-NR3CO2R6、-O2CR6、-CH2OR6、-NR6R7、-CR3═CR3R8、-CPh3、-CH2NR5R6或2R6和R7各自独立地为氢、1-18个碳原子的烷基、芳基、杂芳基、6-20个碳原子的芳基烷基、6-20个碳原子的杂芳基烷基、3-10个碳原子的环烷基、-(CH2CH2O)nCH3、-(CH2)mA或R6和R7在一起为-(CH2)p-、-(CH2)2N(CH3)(CH2)4-、-(CH2)2N(R8)(CH2)2-或-(CH2)2CH(R8)-(CH2)2-；R8为氢、1-18个碳原子的烷基、芳基、杂芳基、6-20个碳原子的芳基烷基、6-20个碳原子的杂芳基烷基、3-10个碳原子的环烷基、-(CH2CH2O)nCH3、-(CH2CH2CH2O)nCH3或-(CH2)mA；A为芳基、杂芳基、芳氧基、杂芳氧基、芳硫基、杂芳硫基、芳基磺酸氧基、杂芳基磺酸氧基、芳基磺酰基、杂芳基磺酰基、-CHF2、-CH2F、-CF3、-(CH2CH2O)nCH3、-(CH2CH2CH2O)nCH3、-CO2R3、-O(C═O)NR6R7、芳基烷氧基或杂芳基烷氧基；m为2至16；p为2至12；或其药学上可接受的盐，其可用于治疗与胰岛素抵抗或高血糖相关的代谢紊乱。
• 2,3,5-Substituted biphenyls useful in the treatment of insulin resistance and hyperglycemia
  申请人：Wyeth

  公开号：US20030083341A1

  公开（公告）日：2003-05-01

  This invention provides compounds of Formula I having the structure 1 wherein: B and D are each, independently, hydrogen, halogen, alkyl of 1-6 carbon atoms, cycloalkyl of 3-8 carbon atoms, aryl, heteroaryl, aralkyl of 6-12 carbon atoms, or heteroaralkyl of 6-12 carbon atoms except where B and D both are hydrogen; R 1 is hydrogen, alkyl of 1-6 carbon atoms, —SO 2 Ph(OH)(CO 2 H), —CH(R 2 )W, —CH 2 CH 2 Y, or —CH 2 CH 2 CH 2 Y; R 2 is hydrogen, alkyl of 1-6 carbon atoms, aralkyl of 6-12 carbon atoms, —CH 2 (1H-imidazol-4-yl), —CH 2 (3-1H-indolyl), —CH 2 CH 2 (1,3-dioxo-1,3-dihydro-isoindol-2-yl), —CH 2 CH 2 (1-oxo-1,3-dihydro-isoindol-2-yl), or —CH 2 (3-pyridyl); W is —CO 2 R 3 , —CONHOH, —CN, —CONHR 3 , aryl, heteroaryl, —CHO, —CH═NOR 3 , or —CH═NHNHR 3 ; Y is —W, —OCH 2 CO 2 R 3 , aryl, heteroaryl, —C(═NOH)NH 2 , —OR 3 , —O(C═O)NR 4 R 5 , —NR 3 (C═O)OR 3 , —NR 3 (C═O)NR 4 R 5 , or —NR 4 R 5 ; R 3 is hydrogen or alkyl of 1-6 carbon atoms; R 4 and R 5 are each, independently, hydrogen, or alkyl of 1-6 carbon atoms or R 4 and R 5 are, together, —(CH 2 ) n —, or —CH 2 CH 2 XCH 2 CH 2 —; X is O, S, SO, SO 2 , NR 3 , or CH 2 ; n is 2 to 5; C is alkyl of 1-18 carbon atoms, aryl, heteroaryl, aralkyl of 6-20 carbon atoms, heteroaralkyl of 6-20 carbon atoms, —CONR 6 R 7 , —NR 3 CONR 6 R 7 , —NR 3 COR 6 , —OR 6 , —O 2 CNR 6 R 7 , —NR 3 CO 2 R 6 , —O 2 CR 6 , —CH 2 OR 6 , —NR 6 R 7 , —CR 3 ═CR 3 R 8 , —CPh 3 , —CH 2 NR 6 R 7 , or 2 R 6 and R 7 are each, independently, hydrogen, alkyl of 1-18 carbon atoms, aryl, heteroaryl, aralkyl of 6-20 carbon atoms, heteroaralkyl of 6-20 carbon atoms, cycloalkyl of 3-10 carbon atoms, —(CH 2 CH 2 O) n CH 3 , —(CH 2 ) m A or R 6 and R 7 are, together, —(CH 2 ) p —, —(CH 2 ) 2 N(CH 3 )(CH 2 ) 4 —, —(CH 2 ) 2 N(R 8 )(CH 2 ) 2 —, or —(CH 2 ) 2 CH(R 8 )—(CH 2 ) 2 —; R 8 is hydrogen, alkyl of 1-18 carbon atoms, aryl, heteroaryl, aralkyl of 6-20 carbon atoms, heteroaralkyl of 6-20 carbon atoms, cycloalkyl of 3-10 carbon atoms, —(CH 2 CH 2 O) n CH 3 , —(CH 2 CH 2 CH 2 O) n CH 3 , or —(CH 2 ) m A; A is aryl, heteroaryl, aryloxy, heteroaryloxy, arylthio, heteroarylthio, arylsulfoxy, heteroarylsulfoxy, arylsulfonyl, heteroarylsulfonyl, —CHF 2 , —CH 2 F, —CF 3 , —(CH 2 CH 2 O) n CH 3 , —(CH 2 CH 2 CH 2 O) n CH 3 , —CO 2 R 3 , —O(C═O)NR 6 R 7 , aralkyloxy, or heteroaralkyloxy; m is 2 to 16 p is 2 to 12 or a pharmaceutically acceptable salt thereof, which are useful in treating metabolic disorders related to insulin resistance or hyperglycemia.

  该发明提供了公式I的化合物，其结构为1其中：B和D各自独立地为氢、卤素、1-6碳原子的烷基、3-8碳原子的环烷基、芳基、杂芳基、6-12碳原子的芳基烷基或除B和D均为氢外的6-12碳原子的杂芳基烷基；R1为氢、1-6碳原子的烷基、—SO2Ph(OH)(CO2H)、—CH(R2)W、—CH2CH2Y或—CH2CH2CH2Y；R2为氢、1-6碳原子的烷基、6-12碳原子的芳基烷基、—CH2(1H-咪唑-4-基)、—CH2(3-1H-吲哚基)、—CH2CH2(1,3-二酮-1,3-二氢-异吲哚-2-基)、—CH2CH2(1-氧代-1,3-二氢-异吲哚-2-基)或—CH2(3-吡啶基)；W为—CO2R3、—CONHOH、—CN、—CONHR3、芳基、杂芳基、—CHO、—CH═NOR3或—CH═NHNHR3；Y为—W、—OCH2CO2R3、芳基、杂芳基、—C(═NOH)NH2、—OR3、—O(C═O)NR4R5、—NR3(C═O)OR3、—NR3(C═O)NR4R5或—NR4R5；R3为氢或1-6碳原子的烷基；R4和R5各自独立地为氢、1-6碳原子的烷基或R4和R5在一起为—(CH2)n—或—CH2CH2XCH2CH2—；X为O、S、SO、SO2、NR3或CH2；n为2至5；C为1-18碳原子的烷基、芳基、杂芳基、6-20碳原子的芳基烷基、6-20碳原子的杂芳基烷基、—CONR6R7、—NR3CONR6R7、—NR3COR6、—OR6、—O2CNR6R7、—NR3CO2R6、—O2CR6、—CH2OR6、—NR6R7、—CR3═CR3R8、—CPh3、—CH2NR6R7或2R6和R7各自独立地为氢、1-18碳原子的烷基、芳基、杂芳基、6-20碳原子的芳基烷基、6-20碳原子的杂芳基烷基、3-10碳原子的环烷基、—(CH2CH2O)nCH3、—(CH2)mA或R6和R7在一起为—(CH2)p—、—(CH2)2N(CH3)(CH2)4—、—(CH2)2N(R8)(CH2)2—或—(CH2)2CH(R8)—(CH2)2—；R8为氢、1-18碳原子的烷基、芳基、杂芳基、6-20碳原子的芳基烷基、6-20碳原子的杂芳基烷基、3-10碳原子的环烷基、—(CH2CH2O)nCH3、—(CH2CH2CH2O)nCH3或—(CH2)mA；A为芳基、杂芳基、芳氧基、杂芳氧基、芳硫基、杂芳硫基、芳基磺酸氧基、杂芳基磺酸氧基、芳基磺酰基、杂芳基磺酰基、—CHF2、—CH2F、—CF3、—(CH2CH2O)nCH3、—(CH2CH2CH2O)nCH3、—CO2R3、—O(C═O)NR6R7、芳基烷氧基或杂芳基烷氧基；m为2至16；p为2至12；或其药学上可接受的盐，用于治疗与胰岛素抵抗或高血糖相关的代谢紊乱。
• 2,3,5-SUBSTITUTED BIPHENYLS USEFUL IN THE TREATMENT OF INSULIN RESISTANCE AND HYPERGLYCEMIA
  申请人：AMERICAN HOME PRODUCTS CORPORATION

  公开号：EP1077929A1

  公开（公告）日：2001-02-28