N-[5-(2-Amino-1-hydroxy-ethyl)-2-hydroxy-phenyl]-methanesulfonamide | 13698-56-1

• 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: N-[5-(2-Amino-1-hydroxy-ethyl)-2-hydroxy-phenyl]-methanesulfonamide
• 英文别名: N-[5-(2-amino-1-hydroxyethyl)-2-hydroxyphenyl]methanesulphonamide；N-[5-(2-amino-1-hydroxyethyl)-2-hydroxyphenyl]methanesulfonamide
• CAS: 13698-56-1
• 化学式: C₉H₁₄N₂O₄S
• 分子量: 246.287
• InChiKey: PBLGWDFXCCRJAV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  121
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-[5-(2-Amino-1-hydroxy-ethyl)-2-hydroxy-phenyl]-methanesulfonamide 、 4-[4-(3-cyclopentylpropyl)-5-oxo-4,5-dihydrotetrazol-1-yl]-N-[4-(4-oxopiperidin-1-yl)phenyl]benzenesulfonamide 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 以46%的产率得到4-[4-(3-cyclopentylpropyl)-5-oxo-4,5-dihydro-1H-tetraazol-1-yl]-N-(4-{4-[(2-hydroxy-2-{4-hydroxy-3-[(methylsulfonyl)amino]phenyl}ethyl)amino]-1-piperidinyl}phenyl)benzenesulfonamide
  参考文献：
  名称：

  Novel (4-Piperidin-1-yl)-phenyl Sulfonamides as Potent and Selective Human β3 Agonists

  摘要：

  A series of novel (4-piperidin-1-yl)-phenyl sulfonamides was prepared and evaluated for their biological activity on the human beta (3)-adrenergic receptor (AR). Replacement of the 3,4-dihydroxyl group of the catechol moiety with 4-hydroxyl-3-methyl sulfonamide on the left-hand side of the compounds resulted in a number of potent full agonists at the beta (3) receptor. Modification of the right-hand side of the compounds by incorporation of a free carboxylic acid resulted in a few potent human beta (3) agonists with low affinities for beta (1)- and beta (2)-ARs. N-Alkyl substitution on the 4-piperidin-1-yl-phenylamine further increased the beta (3) potency while maintaining the selectivity. For example, sulfonamide 48 is a potent full beta (3) agonist (EC50 = 0.004 muM, IA = 1.0) with > 500-fold selectivity over beta (1)- and beta (2)-ARs. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00114-6
• 作为产物：
  描述：

  N-[2-benzyloxy-5-(2-dibenzylamino-1-hydroxyethyl)phenyl]methanesulfonamide 在 钯 氮气 、 甲醇 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 N-[5-(2-Amino-1-hydroxy-ethyl)-2-hydroxy-phenyl]-methanesulfonamide
  参考文献：
  名称：

  Cyclamine sulfonamides as &bgr;-3 adrenergic receptor agonists

  摘要：

  该发明提供了一种具有公式I结构的化合物，其中R1、R2、R3、W、X和Z如前所定义，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性疾病。

  公开号：

  US06498170B2

文献信息

• Substituted 2- (S) -hydroxy-3- (piperidin-4-yl-methylamino) -propyl ethers and substituted 2-aryl-2- (R) - hydroxy-1- (piperidin-4-yl-methyl) -ethylamine beta-3 adrenergic receptor agonists
  申请人：American Home Products Corporation

  公开号：US20020037907A1

  公开（公告）日：2002-03-28

  This invention provides compounds of Formula I having the structure 1 wherein A, B, Z, R and R 1 are as defined hereinbefore, or a pharmaceutically acceptable salt thereof, which are useful in treating or inhibiting metabolic disorders related to insulin resistance or hyperglycemia (typically associated with obesity or glucose intolerance), atherosclerosis, gastrointestinal disorders, neurogenetic inflammation, glaucoma, ocular hypertension and frequent urination; and are particularly useful in the treatment or inhibition of type II diabetes.

  这项发明提供了具有结构式1的化合物，其中A、B、Z、R和R1如前文所定义，或其药学上可接受的盐，用于治疗或抑制与胰岛素抵抗或高血糖相关的代谢紊乱（通常与肥胖或葡萄糖不耐受有关）、动脉粥样硬化、胃肠道疾病、神经炎症、青光眼、眼压增高和频繁排尿；特别适用于治疗或抑制2型糖尿病。
• Phenethanolamine derivatives
  申请人：Glaxo Group Ltd.

  公开号：US04963564A1

  公开（公告）日：1990-10-16

  The invention provides compounds of the general formula (I) ##STR1## and physiologically acceptable salts and solvates thereof, wherein Z represents the group ##STR2## (wherein Q.sup.1 represents a straight or branched C.sub.1-3 alkylene group), ##STR3## (where Q.sup.2 represents a group R.sup.5 CO--, R.sup.5 NHCO--, R.sup.5 R.sup.6 NSO.sub.2 -- or R.sup.7 SO.sub.2 --, where R.sup.5 and R.sup.6 each represent a hydrogen atom or a C.sub.1-3 alkyl group, and R.sup.7 represents a C.sub.1-3 alkyl group), or ##STR4## X represents a bond, or a C.sub.1-7 alkylene, C.sub.2-7 alkenylene or C.sub.2-7 alkynylene chain, and Y represents a bond, or a C.sub.1-6 alkylene, C.sub.2-6 alkenylene or C.sub.2-6 alkynylene chain with the proviso that the sum total of carbon atoms in the chains X and Y is not more than 10; R represents a hydrogen atom or C.sub.1-3 alkyl group; R.sup.1 and R.sup.2 each represent a hydrogen atom or a C.sub.1-3 alkyl group; with the proviso that the sum total of carbon atoms in R.sup.1 and R.sup.2 is not more than 4; and Het represents a benzoheteroaryl or a monocyclic heteroaryl group wherein the heteroaryl group is 5 or 6 membered and contains 1, 2 or 3 hetero atoms, one of which is a nitrogen atom and the other(s) is (are) nitrogen, oxygen or sulphur atom(s), and the group Het may optionally be substituted by one or two groups selected from C.sub.1-4 alkyl, C.sub.1-4 alkoxy, hydroxy, halogen, --NR.sup.3 R.sup.4 and --COR.sup.8 ; where R.sup.3 and R.sup.4 each represent a hydrogen atom or a C.sub.1-4 alkyl group or --NR.sup.3 R.sup.4 forms a saturated heterocyclic amino group which has 5-7 ring members and optionally contains in the ring one or more atoms selected from --O-- or --S-- or a group --NH-- or --N(CH.sub.3)--; and R.sup.8 represents hydroxy, C.sub.1-4 alkoxy or --NR.sup.3 R.sup.4. The compounds have a stimulant action at .beta.2-adrenoreceptors and may be used in the treatment of diseases associated with reversible airways obstruction such as asthma and chronic bronchitis.

  该发明提供了一般式（I）的化合物及其生理上可接受的盐和溶剂化合物，其中Z代表该基团（其中Q.sup.1代表直链或支链C.sub.1-3烷基链），##STR3##（其中Q.sup.2代表一个基团R.sup.5 CO--，R.sup.5 NHCO--，R.sup.5 R.sup.6 NSO.sub.2 --或R.sup.7 SO.sub.2 --，其中R.sup.5和R.sup.6分别代表氢原子或C.sub.1-3烷基链，R.sup.7代表C.sub.1-3烷基链），或##STR4##X代表键，或C.sub.1-7烷基，C.sub.2-7烯基或C.sub.2-7炔基链，Y代表键，或C.sub.1-6烷基，C.sub.2-6烯基或C.sub.2-6炔基链，但要求链X和Y中碳原子的总数不超过10；R代表氢原子或C.sub.1-3烷基链；R.sup.1和R.sup.2分别代表氢原子或C.sub.1-3烷基链，但要求R.sup.1和R.sup.2中碳原子的总数不超过4；Het代表苯基杂芳基或单环杂芳基，其中杂芳基是5或6元杂环，含有1、2或3个杂原子，其中一个是氮原子，其他是氮、氧或硫原子，Het基团可以选择性地由C.sub.1-4烷基、C.sub.1-4烷氧基、羟基、卤素、--NR.sup.3R.sup.4和--COR.sup.8中的一个或两个基团取代；其中R.sup.3和R.sup.4分别代表氢原子或C.sub.1-4烷基链，或--NR.sup.3R.sup.4形成饱和杂环氨基基团，具有5-7环成员，环中可能含有一个或多个选自--O--或--S--的原子，或一个基团--NH--或--N(CH.sub.3)--，R.sup.8代表羟基、C.sub.1-4烷氧基或--NR.sup.3R.sup.4。这些化合物在β2-肾上腺素受体上具有兴奋作用，并可用于治疗与可逆气道阻塞相关的疾病，如哮喘和慢性支气管炎。
• N-(4-sulfonylaryl)Cyclylamine 2-hydroxyethylamines as beta-3 adrenergic receptor agonists
  申请人：American Home Products Corporation

  公开号：US20020028797A1

  公开（公告）日：2002-03-07

  This invention provides compounds of Formula I having the structure 1 wherein R 1 , R 2 , R 3 , R 4 , W, X, and Y are as defined hereinbefore 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R1、R2、R3、R4、W、X和Y如前文所定义，或其药用盐，这些化合物可用于治疗与胰岛素抵抗或高血糖相关的代谢紊乱。
• Ethanolamine derivatives
  申请人：Glaxo Group Limited

  公开号：US04990664A1

  公开（公告）日：1991-02-05

  The invention provides compounds of the general formula ##STR1## and physiologically acceptable salts and solvates thereof, wherein Z represents the group ##STR2## where A represents a group selected from HOR.sup.3 --, R.sup.6 NH(CH.sub.2)p--, R.sup.10 R.sup.11 N--, R.sup.12 OCH.sub.2 --, CH.sub.3 SO.sub.2 CH.sub.2 -- or NCCH.sub.2 --; where R.sup.3 is a C.sub.1-3 alkylene group, R.sup.6 is a group selected from R.sup.7 CO--, R.sup.7 NHCO--, R.sup.7 R.sup.8 NSO.sub.2 -- or R.sup.9 SO.sub.2 --, and p is zero or 1, R.sup.7 and R.sup.8 each represent a hydrogen atom or a C.sub.1-3 alkyl group, R.sup.9 is a C.sub.1-3 alkyl group, R.sup.10 and R.sup.11 each represent a hydrogen atom or a C.sub.1-4 alkyl group or, when R.sup.10 is a hydrogen atom, R.sup.11 may also be a C.sub.1-4 alkoxycarbonyl group, and R.sup.12 is a C.sub.1-3 alkyl group; ##STR3## where one of R.sup.4 and R.sup.5 is a hydroxy group and the other is a hydrogen or halogen atom or a hydroxy group; ##STR4## where A.sup.1 is either a chlorine atom or a --CF.sub.3 group; ##STR5## X represents a bond or a C.sub.1-7 alkenylene or C.sub.2-7 alkynylene chain, and Y represents a bond, or a C.sub.1-6 alkylene, C.sub.2-6 alkenylene or C.sub.2-6 alkynylene chain, with the proviso that the sum total of carbon atoms in X and Y is 2 to 10; R represents a hydrogen atom or a C.sub.1-3 alkyl group; R.sup.1 and R.sup.2 each represents a hydrogen atom or a C.sub.1-3 alkyl group; with the proviso that the sum total of carbon atoms in R.sup.1 and R.sup.2 is not more than 4; Q represents a pyridyl group optionally substituted by one or two substituents selected from halogen atoms or hydroxy, C.sub.1-3 alkyl or C.sub.1-3 alkoxy groups, or Q represents a phenyl group optionally substituted by one or more substituents selected from halogen atoms or the groups C.sub.1-6 alkyl, nitro, --(CH.sub.2).sub.q R.sup.13 or --O(CH.sub.2).sub.r R.sup.14, or Q represents a phenyl group substituted by an alkylenedioxy group of formula --O(CH.sub.2).sub.t O--; where R.sup.13 represents hydroxy, C.sub.1-6 alkoxy, cyano, --NR.sup.15 R.sup.16, --NR.sup.17 COR.sup.18, --NR.sup.17 SO.sub.2 R.sup.19, --COR.sup.20, --SR.sup.21, --SOR.sup.22 or --SO.sub.2 R.sup.22 ; R.sup.14 represents hydroxy or C.sub.1-4 alkoxy; R.sup.15 and R.sup.16 each represent a hydrogen atom or a C.sub.1-4 alkyl group or --NR.sup.15 R.sup.16 forms a saturated heterocyclic amino group which has 5-7 ring members and optionally contains in the ring one or more atoms selected from --O-- or --S-- or a group --NH-- or --N(CH.sub.3)--; R.sup.17 represents a hydrogen atom or a C.sub.1-4 alkyl group; R.sup.18 represents a hydrogen atom or a C.sub.1-4 alkyl, C.sub.1-4 alkoxy, phenyl or --NR.sup.15 R.sup.16 group; R.sup.19 represents C.sub.1-4 alkyl, phenyl or --NR.sup.15 R.sup.16 ; R.sup.20 represents hydroxy, C.sub.1-4 alkoxy or --NR.sup.15 R.sup.16 ; R.sup.21 represents a hydrogen atom or a C.sub.1-4 alkyl or phenyl group; R.sup.22 represents a C.sub.1-4 alkyl or phenyl group; q represents an integer from 0 to 3; r represents 2 or 3; and t represents 1 or 2. The compounds have a stimulant action at .beta..sub.2 -adrenoreceptors and may be used in the treatment of diseases associated with reversible airways obstruction such as asthma and chronic bronchitis.

  该发明提供了一般式为##STR1##的化合物及其生理上可接受的盐和溶剂化合物，其中Z代表##STR2##中的基团，其中A代表从HOR.sup.3 --、R.sup.6 NH(CH.sub.2)p--、R.sup.10 R.sup.11 N--、R.sup.12 OCH.sub.2 --、CH.sub.3 SO.sub.2 CH.sub.2 --或NCCH.sub.2 --中选择的基团；其中R.sup.3是一个C.sub.1-3烷基基团，R.sup.6是从R.sup.7 CO--、R.sup.7 NHCO--、R.sup.7 R.sup.8 NSO.sub.2 --或R.sup.9 SO.sub.2 --中选择的基团，p为零或1，R.sup.7和R.sup.8分别代表氢原子或C.sub.1-3烷基基团，R.sup.9是一个C.sub.1-3烷基基团，R.sup.10和R.sup.11分别代表氢原子或C.sub.1-4烷基基团或者当R.sup.10是氢原子时，R.sup.11也可以是C.sub.1-4烷氧羰基基团，R.sup.12是一个C.sub.1-3烷基基团；##STR3##其中R.sup.4和R.sup.5中的一个是羟基，另一个是氢原子或卤素原子或羟基；##STR4##其中A.sup.1是氯原子或--CF.sub.3基团；##STR5##X代表键或C.sub.1-7烯基或C.sub.2-7炔基链，Y代表键或C.sub.1-6烷基、C.sub.2-6烯基或C.sub.2-6炔基链，但X和Y中碳原子的总和为2到10；R代表氢原子或C.sub.1-3烷基基团；R.sup.1和R.sup.2分别代表氢原子或C.sub.1-3烷基基团；但R.sup.1和R.sup.2中碳原子的总和不超过4；Q代表通过卤素原子或羟基、C.sub.1-3烷基或C.sub.1-3烷氧基团中选择的一个或两个取代基可选地取代的吡啶基团，或者Q代表通过卤素原子或基团C.sub.1-6烷基、硝基、--(CH.sub.2).sub.q R.sup.13或--O(CH.sub.2).sub.r R.sup.14中选择的一个或多个取代基可选地取代的苯基团，或者Q代表通过式--O(CH.sub.2).sub.t O--的烷二氧基基团取代的苯基团；其中R.sup.13代表羟基、C.sub.1-6烷氧基、氰基、--NR.sup.15 R.sup.16、--NR.sup.17 COR.sup.18、--NR.sup.17 SO.sub.2 R.sup.19、--COR.sup.20、--SR.sup.21、--SOR.sup.22或--SO.sub.2 R.sup.22；R.sup.14代表羟基或C.sub.1-4烷氧基；R.sup.15和R.sup.16分别代表氢原子或C.sub.1-4烷基基团或--NR.sup.15 R.sup.16形成一个有5-7个环成员的饱和杂环氨基基团，环中可选地含有一个或多个从--O--或--S--中选择的原子或一个羟基团--NH--或--N(CH.sub.3)--；R.sup.17代表氢原子或C.sub.1-4烷基基团；R.sup.18代表氢原子或C.sub.1-4烷基、C.sub.1-4烷氧基、苯基或--NR.sup.15 R.sup.16基团；R.sup.19代表C.sub.1-4烷基、苯基或--NR.sup.15 R.sup.16；R.sup.20代表羟基、C.sub.1-4烷氧基或--NR.sup.15 R.sup.16；R.sup.21代表氢原子或C.sub.1-4烷基或苯基；R.sup.22代表C.sub.1-4烷基或苯基；q代表0到3之间的整数；r代表2或3；t代表1或2。这些化合物在β2-肾上腺素受体上具有刺激作用，可用于治疗与可逆气道阻塞有关的疾病，如哮喘和慢性支气管炎。
• 2-substituted thiazolidinones as beta-3 adrenergic receptor agonists
  申请人：Wyeth

  公开号：US06410734B1

  公开（公告）日：2002-06-25

  This invention provides compounds of Formula I having the structure wherein: A, X, Y, Z, R1, R2, R3, R4, R5, and R6 are as defined hereinbefore or a pharmaceutically acceptable salt thereof, which are useful in treating or inhibiting metabolic disorders related to insulin resistance or hyperglycemia (typically associated with obesity or glucose intolerance), atherosclerosis, gastrointestinal disorders, neurogenetic inflammation, and frequent urination; and are particularly useful in the treatment or inhibition of type II diabetes.

  该发明提供了具有以下结构的I型化合物，其中：A、X、Y、Z、R1、R2、R3、R4、R5和R6如前所定义或其药学上可接受的盐，可用于治疗或抑制与胰岛素抵抗或高血糖相关的代谢障碍（通常与肥胖或葡萄糖不耐受有关）、动脉粥样硬化、胃肠道障碍、神经遗传性炎症和频繁排尿；并且特别适用于治疗或抑制2型糖尿病。