η-Phenyl-caprylsaeurenitril | 17734-25-7

• 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: η-Phenyl-caprylsaeurenitril
• 英文别名: 7-phenyl-1-cyanoheptane；8-Phenyloctanenitrile
• CAS: 17734-25-7
• 化学式: C₁₄H₁₉N
• 分子量: 201.312
• InChiKey: NKSCZSRQOWGPGG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  15
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  23.8
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  η-Phenyl-caprylsaeurenitril 在 氯(甲基)铝酰胺 作用下， 以 甲苯 为溶剂， 以93%的产率得到8-Phenyl-octanamidine
  参考文献：
  名称：

  腈到am的有效转化

  摘要：

  已经开发了一种方便的方法，用于以高收率将腈直接转化为am。该方法还可用于由N-烷基氰酰胺制备胍。

  DOI：

  10.1016/s0040-4039(00)88891-7
• 作为产物：
  描述：

  7-苯基-1-庚醇 在 氢溴酸 作用下， 以 乙醇 为溶剂， 生成 η-Phenyl-caprylsaeurenitril
  参考文献：
  名称：

  Shklyaev,V.S.; Chekryshkin,Yu.S., Journal of Organic Chemistry USSR (English Translation), 1968, vol. 4, p. 74 - 76

  摘要：

  DOI：

文献信息

• Nickel‐Catalyzed Migratory Hydrocyanation of Internal Alkenes: Unexpected Diastereomeric‐Ligand‐Controlled Regiodivergence
  作者：Jihui Gao、Mingdong Jiao、Jie Ni、Rongrong Yu、Gui‐Juan Cheng、Xianjie Fang

  DOI：10.1002/anie.202011231

  日期：2021.1.25

  A regiodivergent nickel‐catalyzed hydrocyanation of a broad range of internal alkenes involving a chain‐walking process is reported. When appropriate diastereomeric biaryl diphosphite ligands are applied, the same starting materials can be converted to either linear or branched nitriles with good yields and high regioselectivities. DFT calculations suggested that the catalyst architecture determines

  据报道，涉及区域内链烯的区域发散性镍催化氢氰化涉及链行走过程。当使用合适的非对映体联芳基二亚磷酸酯配体时，相同的原料可以良好的收率和高的区域选择性转化为线性或支化的腈。DFT计算表明，催化剂结构通过调节电子和空间相互作用来确定区域选择性。另外，当产生支链腈时，观察到中等的对映选择性。
• [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。