N-(2-(苄氧基)-5-(2-溴乙酰基)苯基)甲烷磺酰胺 | 14347-25-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: N-(2-(苄氧基)-5-(2-溴乙酰基)苯基)甲烷磺酰胺
• 英文名称: 4-benzyloxy-3-methanesulfonylamino-2'-bromoacetophenone
• 英文别名: 4-Benzyloxy-3-methansulfonamido-α-bromacetophenon；2-Bromo-1-[4-phenylmethoxy-3-[(methylsulfonyl)amino]phenyl]ethanone；4-benzyloxy-3-(methanesulfonylamino)phenacyl bromide；N-(2-(benzyloxy)-5-(2-bromoacetyl)phenyl)methanesulfonamide；N-[5-(bromoacetyl)-2-(phenylmethoxy)phenyl]-methanesulphonamide；2-bromo-1-(4-benzyloxy-3-methylsulfonylamino)phenylethanone；4-benzyloxy-3-methanesulfonamido-α-bromoacetophenone；4-benzyloxy-3-methylsulfonamido-α-bromo-acetophenone；4-benzyloxy-3-methanesulphonamidophenacyl bromide；2-bromo-1-[4-benzyloxy-3-[(methylsulfonyl)amino]phenyl]ethanone(70% purity)；α-bromo-4-benzyloxy-3-methanesulfonamido-acetophenone；N-(2-benzyloxy-5-bromoacetyl-phenyl)-methanesulfonamide；N-[5-(2-bromoacetyl)-2-phenylmethoxyphenyl]methanesulfonamide
• CAS: 14347-25-2
• 化学式: C₁₆H₁₆BrNO₄S
• 分子量: 398.277
• InChiKey: MSZJJGHZRBKVHQ-UHFFFAOYSA-N

物化性质

• 沸点：
  549.5±60.0 °C(Predicted)
• 密度：
  1.535±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  80.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(2-(苄氧基)-5-(2-溴乙酰基)苯基)甲烷磺酰胺 在 sodium azide 作用下， 以 丙酮 为溶剂， 反应 3.5h， 以96.7%的产率得到2-azido-1-(4-benzyloxy-3-methylsulfonylamino)phenylethanone
  参考文献：
  名称：

  METHOD FOR THE PREPARATION OF TRICYCLIC AMINO ALCOHOL DERIVATIVES THROUGH AZIDES

  摘要：

  本发明涉及一种用于治疗和预防糖尿病、肥胖、高脂血症等疾病的三环氨基醇衍生物的制备方法，该化合物由以下式子表示（1）： 其中R1代表较低的烷基或苄基；*1代表一个不对称碳原子；R2代表氢原子、卤素原子或羟基；A代表以下其中一种基团： 其中X代表NH、O或S；R5代表氢原子、羟基、氨基或乙酰氨基；*2代表一个不对称碳原子，当R5不是氢原子时。本发明的方法通过叠氮衍生物进行，是方便、实用、成本低廉的制备方法，包括少量步骤且具有良好的工业工作效率。

  公开号：

  EP1174426A1
• 作为产物：
  描述：

  N-(5-乙酰基-2-(苄氧基)苯基)甲磺酰胺 在 copper(ll) bromide 作用下， 以 正庚烷 、 氯仿 、 乙酸乙酯 为溶剂， 以23.1 g (73%)的产率得到N-(2-(苄氧基)-5-(2-溴乙酰基)苯基)甲烷磺酰胺
  参考文献：
  名称：

  Catecholamine surrogates useful as .beta..sub.3 agonists

  摘要：

  公式为##STR1##的化合物或其药学上可接受的盐，其中：A是键，--(CH.sub.2).sub.n --或--CH(B)--，其中n是1到3的整数，B是--CN，--CON(R.sup.9)R.sup.9'或--CO.sub.2 R.sup.7；R.sup.1是较低的烷基，芳基或芳基烷基；R.sup.2是氢，羟基，烷氧基，--CH.sub.2 OH，氰基，--C(O)OR.sup.7，--CO.sub.2 H，--CONH.sub.2，四唑基，--CH.sub.2 NH.sub.2或卤素；##STR2## R.sup.3是氢，烷基，杂环或R.sup.4是氢，烷基或B；R.sup.5，R.sup.5'，R.sup.8，R.sup.8'或R.sup.8"独立地是氢，烷氧基，较低烷基，卤素，--OH，--CN，--(CH.sub.2).sub.n NR.sup.6 COR.sup.7，--CON(R.sup.6)R.sup.6'，--CON(R.sup.6)OR.sup.6'，--CO.sub.2 R.sup.6，--SR.sup.7，--SOR.sup.7，--SO.sub.2 R.sup.7，--N(R.sup.6)SO.sub.2 R.sup.1，--N(R.sup.6)R.sup.6'，--NR.sup.6 COR.sup.7，--OCH.sub.2 CON(R.sup.6)R.sup.6'，--OCH.sub.2 CO.sub.2 R.sup.7或芳基；或R.sup.5和R.sup.5'或R.sup.8和R.sup.8'可以与它们连接的碳原子一起形成芳基或杂环；R.sup.6和R.sup.6'独立地是氢或较低烷基；R.sup.7是较低烷基；R.sup.9是氢，较低烷基，烷基，环烷基，芳基烷基，芳基，杂芳基；或R.sup.9和R.sup.9'可以与它们连接的氮原子一起形成杂环；但是当A是键或--(CH.sub.2).sub.n且R.sup.3是氢或未取代烷基时，R.sup.4是B或取代烷基。这些化合物是β.sub.3肾上腺素受体激动剂，因此在糖尿病、肥胖症和胃肠疾病的治疗中很有用。

  公开号：

  US05776983A1

文献信息

• INDOLE, INDAZOLE, AND BENZAZOLE DERIVATIVE
  申请人：Sumitomo Pharmaceuticals Company, Limited

  公开号：EP1514869A1

  公开（公告）日：2005-03-16

  The compound of the formula (I): wherein W is a group of the following formula (VIII) binding to any possible position on the Q: Q is, together with W, a group of the formula: -C(M=C(R3A)-N(R3)-, etc.; R3A is H or optionally substituted lower alkyl; R4, R5, R6, and R7 are independently H or optionally substituted lower alkyl; R1 is optionally substituted lower alkyl, etc.; R2 is H, etc.; R3 is H, etc.; Ar is phenyl, etc., or a pharmaceutically acceptable salt thereof, where these compounds exhibiting β3-adrenoceptor-stimulating activity and being useful as a medicament for treatment of obesity, etc.

  公式(I)的化合物： 其中W是以下公式(VIII)的基团，可以与Q的任何可能位置结合： Q与W一起是以下公式的基团：-C(M=C(R3A)-N(R3)-等； R3A是H或可选地取代的低级烷基；R4、R5、R6和R7独立的是H或可选地取代的低级烷基；R1是可选地取代的低级烷基等；R2是H等；R3是H等；Ar是苯基等，或其药物可接受的盐，其中这些化合物具有β3-肾上腺素受体刺激活性，并作为治疗肥胖等的药物有用。
• 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。
• Chemical compounds
  申请人：Glaxo Group Limited

  公开号：US04937268A1

  公开（公告）日：1990-06-26

  This invention relates to compounds of the general formula (I) and physiologically acceptable salts and solvates thereof wherein Ar represents ##STR1## where R.sup.3 is a bond or a straight or branched C.sub.1-2 alkylene group, R.sup.4 is a hydroxy group or a group R.sup.5 NH-- where R.sup.5 represents a group CH.sub.3 SO.sub.2 --, HCO-- or NH.sub.2 CO--, ##STR2## where R.sup.6 is a chlorine atom or the group F.sub.3 C--, ##STR3## k represents an integer from 1 to 8, m represents zero or an integer from 2 to 7 and n represents an integer from 2 to 7 with the proviso that the sum total of k, m and n is 4 to 12; R.sup.1 and R.sup.2 each represents a hydrogen atom or a methyl or ethyl group with the proviso that the sum total of carbon atoms in R.sup.1 and R.sup.2 is not more than 2; R.sup.30 represents hydrogen or C.sub.1-2 alkyl; X represents an oxygen or sulphur atom; and Y and Q may each represent a bond or an oxygen or sulphur atom with the provisos that at least one of Y and Q represents an oxygen or sulphur atom and when Y is a bond m is zero, or when Y represents an oxygen or sulphur atom m is an integer from 2 to 7; P represents a phenyl group optionally substituted by one or more substituents selected from halogen atoms, or the groups C.sub.1-3 alkyl, C.sub.1-3 alkoxy, hydroxy, --CH.sub.2 OH--, --(CH.sub.2).sub.2 OH, --CO.sub.2 H, --CO.sub.2 CH.sub.3, --CO.sub.2 (CH.sub.2).sub.2 CH.sub.3, --R.sup.7, COR.sup.7, --NHCOR.sup.8 and --NR.sup.9 SO.sub.2 R.sup.10 ; where R.sup.7 represents an amino, aminoC.sub.1-3 alkyl, aminoC.sub.1-3 dialkyl, pyrrolidino, piperidino, hexamethyleneimino, piperazino, N-methylpiperazino or morpholino group; R.sup.8 represents a hydrogen atom or a C.sub.1-4 alkyl, C.sub.1-4 alkoxy, phenyl or amino group; R.sup.9 represents a hydrogen atom or a methyl group; R.sup.10 represents a methyl, phenyl, amino or dimethylamino group; or P represents a pyridyl group optionally substituted by one or two substitutents selected from halogen atoms or hydroxy, C.sub.1-3 alkyl and C.sub.1-3 alkoxy groups. The compounds have a stimulant action at .beta..sub.2 -adrenoreceptors and are useful, in particular, in the treatment of diseases associated with reversible airways obstruction such as asthma and chronic bronchitis.

  本发明涉及一般式（I）的化合物以及其生理上可接受的盐和溶剂化合物，其中Ar代表##STR1##其中R.sup.3是键或直链或支链C.sub.1-2烷基基团，R.sup.4是一个羟基或一个基团R.sup.5 NH--，其中R.sup.5代表一个基团CH.sub.3 SO.sub.2 --，HCO--或NH.sub.2 CO--，##STR2##其中R.sup.6是氯原子或基团F.sub.3 C--，##STR3##k代表一个从1到8的整数，m代表零或一个从2到7的整数，n代表一个从2到7的整数，但k、m和n的总和为4到12；R.sup.1和R.sup.2分别代表氢原子或甲基或乙基基团，但R.sup.1和R.sup.2中碳原子的总和不超过2；R.sup.30代表氢或C.sub.1-2烷基；X代表氧或硫原子；Y和Q可以分别表示键或氧或硫原子，但至少一个Y和Q代表氧或硫原子，当Y是键时，m为零，或当Y代表氧或硫原子时，m为一个从2到7的整数；P代表一个苯基，可选择地被一个或多个卤原子或基团C.sub.1-3烷基，C.sub.1-3烷氧基，羟基，--CH.sub.2 OH--，--(CH.sub.2).sub.2 OH，--CO.sub.2 H，--CO.sub.2 CH.sub.3，--CO.sub.2 (CH.sub.2).sub.2 CH.sub.3，--R.sup.7，COR.sup.7，--NHCOR.sup.8和--NR.sup.9 SO.sub.2 R.sup.10取代；其中R.sup.7代表氨基，氨基C.sub.1-3烷基，氨基C.sub.1-3二烷基，吡咯烷基，哌啶基，己亚甲基氨基，哌嗪基，N-甲基哌嗪基或吗啉基；R.sup.8代表氢原子或C.sub.1-4烷基，C.sub.1-4烷氧基，苯基或氨基；R.sup.9代表氢原子或甲基基团；R.sup.10代表甲基，苯基，氨基或二甲基氨基；或P代表一个吡啶基，可选择地被一个或两个卤原子或羟基，C.sub.1-3烷基和C.sub.1-3烷氧基取代。这些化合物在β.sub.2 -肾上腺素受体上具有兴奋作用，特别适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。
• Phenethandamine derivatives and pharmaceutical use thereof
  申请人：Glaxo Group Limited

  公开号：US05066678A1

  公开（公告）日：1991-11-19

  The invention relates to compounds of the general formula (I) ##STR1## and physiologically acceptable salts and solvates thereof; wherein; R.sup.1 and R.sup.2 each independently represent a hydrogen atom or a C.sub.1-3 -alkyl group with the proviso that the sum total of carbon atom in R.sup.1 and R.sup.2 is not more than 4; X represents a direct bond or a C.sub.1-7 alkylene, C.sub.2-7 alkenylene or C.sub.2-7 alkynylene group and Y represents a direct bond or a C.sub.1-6 alkylene C.sub.2-6 alkenylene or C.sub.2-6 alknylene group with the proviso that the sum total of carbon atoms in X and Y is not more than 10; W represents a group ##STR2## wherein Z represents a group R.sup.3 (CH.sub.2).sub.q where q is 0, 1 or 2 and R.sup.3 is a group R.sup.4 CONH--, R.sup.4 NHCONH--, R.sup.4 R.sup.5 NSO.sub.2 NH--, R.sup.6 SO.sub.2 NH-- or --OH; R.sup.4 and R.sup.5 each represent a hydrogen atom or a C.sub.1-3 alkyl group; R.sup.6 represents a C.sub.1-3 alkyl group; R.sup.7 represents a chlorine atom or the group --CF.sub.3 ; A represents a straight or branched C.sub.1-6 alkyl group, a C.sub.3-8 cycloalkyl group, either of which may be saturated or unsaturated, or a C.sub.1-6 alkoxy group, with the proviso that the sum total of carbon atoms in A and Y is not less than 5; having a stimulant action at .beta..sub.2 -adrenoreceptors and are useful in the treatment of diseases associated with reversible airways obstruction such as asthma and chronic bronchitis.

  该发明涉及通式（I）的化合物及其生理上可接受的盐和溶剂化合物；其中；R.sup.1和R.sup.2分别独立地代表氢原子或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；X代表直接键或C.sub.1-7烷基、C.sub.2-7烯基或C.sub.2-7炔基团，Y代表直接键或C.sub.1-6烷基、C.sub.2-6烯基或C.sub.2-6炔基团，但X和Y中碳原子的总和不超过10；W代表一个基团##STR2##其中Z代表一个基团R.sup.3(CH.sub.2).sub.q，其中q为0、1或2，R.sup.3是一个基团R.sup.4 CONH--、R.sup.4 NHCONH--、R.sup.4 R.sup.5 NSO.sub.2 NH--、R.sup.6 SO.sub.2 NH--或--OH；R.sup.4和R.sup.5分别代表氢原子或C.sub.1-3烷基基团；R.sup.6代表一个C.sub.1-3烷基基团；R.sup.7代表氯原子或基团--CF.sub.3；A代表直链或支链C.sub.1-6烷基基团、C.sub.3-8环烷基基团，二者可以饱和或不饱和，或C.sub.1-6烷氧基团，但A和Y中碳原子的总和不少于5；具有在β.sub.2-肾上腺素受体上的兴奋作用，并且在治疗与可逆气道阻塞相关的疾病，如哮喘和慢性支气管炎中有用。
• Synthesis and Evaluation of Novel Phenylethanolamine Derivatives containing Acetanilides as Potent and Selective .BETA.3-Adrenergic Receptor Agonists
  作者：Tatsuya Maruyama、Kenichi Onda、Masahiko Hayakawa、Takayuki Suzuki、Tetsuya Kimizuka、Tetsuo Matsui、Toshiyuki Takasu、Itsuro Nagase、Noritaka Hamada、Mitsuaki Ohta

  DOI：10.1248/cpb.58.533

  日期：——

  In the search for potent and selective human β3-adrenergic receptor (AR) agonists as potential pharmacotherapies for the treatment of obesity and non-insulin dependent (type II) diabetes, we prepared a novel series of phenylethanolamine derivatives containing acetanilides and evaluated their biological activities at the human β3-, β2-, and β1-ARs. Among these compounds, the 6-amino-2-pyridylacetanilide (36b), 2-amino-5-methylthiazol-4-ylacetanilide (36g), and 5-amino-1,2,4-thiadiazol-3-ylacetanilide (36h) derivatives showed potent agonistic activity at the β3-AR with functional selectivity over the β1- and β2-ARs. In addition, these compounds exhibited significant hypoglycemic activity in a rodent diabetic model.

  在寻找有效且选择性的人类β3-肾上腺素受体（AR）激动剂作为治疗肥胖和非胰岛素依赖型（2型）糖尿病的潜在药物治疗时，我们准备了一系列新颖的含有醋酸酰胺的苯乙醇胺衍生物，并评估了它们在人体β3-、β2-和β1-AR上的生物活性。在这些化合物中，6-氨基-2-吡啶基醋酸酰胺（36b）、2-氨基-5-甲基噻唑-4-基醋酸酰胺（36g）和5-氨基-1,2,4-噻二唑-3-基醋酸酰胺（36h）衍生物在β3-AR上显示出强烈的激动活性，并且对β1-和β2-AR具有功能选择性。此外，这些化合物在啮齿动物糖尿病模型中还表现出显著的降血糖活性。