布林佐胺盐酸盐 | 150937-43-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并噻嗪类
• 中文名称: 布林佐胺盐酸盐
• 中文别名: 布林佐胺-D5
• 英文名称: Brinzolamide hydrochloride
• 英文别名: (R)-(+)-4-ethylamino-2-(3-methoxypropyl)-3,4-dihydro-2H-thieno[3,2-e]-1,2-thiazine-6-sulfonamide-1,1-dioxide hydrochloride；(+)-(R)-4-ethylamino-3,4-dihydro-2-(3-methoxypropyl)-2H-thieno-[3,2-e]-1,2-thiazine-6-sulfonamide-1,1-dioxide hydrochloride；(R)-3,4-dihydro-4-ethylamino-2-(3-methoxy)propyl-2H-thieno[3,2-e]-1,2-thiazine-6-sulfonamide-1,1-dioxide hydrochloride；(4R)-4-(ethylamino)-2-(3-methoxypropyl)-1,1-dioxo-3,4-dihydrothieno[3,2-e]thiazine-6-sulfonamide;hydrochloride
• CAS: 150937-43-2
• 化学式: C₁₂H₂₁N₃O₅S₃*ClH
• 分子量: 419.975
• InChiKey: UGAMYTZPFRXCOG-PPHPATTJSA-N

物化性质

• 熔点：
  91-93?C
• 比旋光度：
  D +10.35° (c = 1 in water)
• 溶解度：
  可溶于甲醇（轻微）、水（轻微、超声处理）

计算性质

• 辛醇/水分配系数(LogP)：
  0.51
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  164
• 氢给体数：
  3
• 氢受体数：
  9

制备方法与用途

盐酸布林唑胺（AL-4862）是一种选择性碳酸酐酶II抑制剂，其anIC50值为3.2nM。该药物通过抑制睫状体中的CA-II并减少房水分泌来降低眼内压（IOP），适用于青光眼研究[1][2]。

反应信息

• 作为反应物：
  描述：

  布林佐胺盐酸盐 在 三乙胺 作用下， 以 水 为溶剂， 反应 2.0h， 以500 g的产率得到布林佐胺
  参考文献：
  名称：

  [EN] PHARMACEUTICALLY ACCEPTABLE SALT OF BRINZOLAMIDE AND COMPOSITION THEREOF
  [FR] SEL PHARMACEUTIQUEMENT ACCEPTABLE DE BRINZOLAMIDE ET COMPOSITION DE CELUI-CI

  摘要：

  公开号：

  WO2013114397A3
• 作为产物：
  描述：

  (R)-4-(N-acetyl-N-ethylamino)-3,4-dihydro-2-(3-methoxypropyl)-2H-thieno[3,2-e]-1,2-thiazine-6-sulfonamide-1,1-dioxide 在 硫酸 、 水 、 sodium hydroxide 、 盐酸 作用下， 以 水 、 乙酸乙酯 为溶剂， 以95%的产率得到布林佐胺盐酸盐
  参考文献：
  名称：

  Process for the preparation of brinzolamide and intermediates thereof

  摘要：

  化合物(I)的制备过程包括对其非磺酰胺取代前体的次要胺进行保护；氯磺化和随后用氨进行氨化反应得到中间体；最后，通过酸水解去保护所得的磺酰胺。该过程允许在较温和的反应条件下，以较低成本高产率地工业化生产brinzolamide。该过程中使用了一些新的中间体。

  公开号：

  EP1985618A1

文献信息

• Nitrogen-containing tricyclic compounds
  申请人：Yamada Rintaro

  公开号：US20060247266A1

  公开（公告）日：2006-11-02

  A novel compound represented by the following formula (1) or a salt thereof [wherein R 1 , R 5 , R 6 , R 7 , and R 8 represent hydrogen atom, a halogen atom, hydroxyl group, an alkyl group, an alkenyl group and the like; X 1 . . . X 2 represents —CH(R 2 )—CH(R 3 )—, —CH(R 2 )—CH(R 3 )—CH(R 4 )—, —C(R 2 )═C(R 3 )—, or —C(R 2 )═C(R 3 )—CH(R 4 )—(R 2 , R 3 , and R 4 represent hydrogen atom, or an alkyl group); A 1 , A 11 , A 2 , and A 21 represent hydrogen atom, or an alkyl group; Y represents —CH(A 3 )-, —CH(A 3 )-C(A 4 )(A 41 )-, —CH(A 3 )-C(A 4 )(A 41 )-C(A 5 )(A 51 )-, or a single bond (A 3 , A 4 , A 41 , A 5 , and A 51 represent hydrogen atom, or an alkyl group), and Z represents hydroxyl group, or —N(A 6 )(A 61 )(A 6 represents hydrogen atom, or an alkyl group, and A 61 represents hydrogen atom, an alkyl group, a substituted alkyl group and the like)], having an action of potently inhibiting phosphorylation of myosin regulatory light chain.

  以下式（1）表示的新化合物或其盐[其中R1、R5、R6、R7和R8代表氢原子、卤素原子、羟基、烷基、烯基等；X1...X2代表—CH(R2)—CH(R3)—、—CH(R2)—CH(R3)—CH(R4)—、—C(R2)=C(R3)—或—C(R2)=C(R3)—CH(R4)—(R2、R3和R4代表氢原子或烷基)；A1、A11、A2和A21代表氢原子或烷基；Y代表—CH(A3)-、—CH(A3)-C(A4)(A41)-、—CH(A3)-C(A4)(A41)-C(A5)(A51)-或单一键（A3、A4、A41、A5和A51代表氢原子或烷基），Z代表羟基或—N(A6)(A61)(A6代表氢原子或烷基，A61代表氢原子、烷基、取代烷基等)]具有强烈抑制肌球蛋白调节轻链磷酸化的作用。
• Sulfonamide compound
  申请人：Matsubara Koki

  公开号：US20090048223A1

  公开（公告）日：2009-02-19

  A compound represented by the formula (1) [A represents a nitrogen-containing saturated ring; m represents an integer of 0 to 2; n represents an integer of 1 to 4; G 1 represents hydrogen atom, chlorine atom, hydroxyl group, an alkoxy group, or amino group; G 2 represents a halogen atom, hydroxyl group, cyano group, carboxy group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, an alkylthio group, an amino group, an alkylsulfinyl group, an alkylsulfonyl group, or an aryl group; G 3 represents hydrogen atom, a halogen atom, hydroxyl group, cyano group, carboxy group, an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, an alkylthio group, an amino group, an alkoxycarbonyl group, an acyl group, an acyloxy group, an alkylsulfinyl group, an alkylsulfonyl group, or an aryl group; Y represents a single bond, or —C(R 3 )(R 4 )— (R 3 and R 4 represent hydrogen atom, or an alkyl group, or alkylene groups which combine together to form a saturated hydrocarbon ring group); G 4 represents hydroxyl group (Y is a single group), or —N(R 1 )(R 2 ) (R 1 and R 2 represent hydrogen atom, an alkyl group, an aralkyl group, an alkenyl group, an alkynyl group, a saturated heterocyclic group, an alkylsulfonyl group, an acyl group, or an amidino group); G 5 is a substituent on a ring-constituting carbon atom of A, and represents hydrogen atom, fluorine atom, or an alkyl group] or a salt thereof, or a derivative thereof that is a prodrug, which potently inhibits Rho kinase.

  由以下化学式表示的化合物：[A代表含氮饱和环；m表示0到2的整数；n表示1到4的整数；G1代表氢原子、氯原子、羟基、烷氧基或氨基；G2代表卤原子、羟基、氰基、羧基、烷基、烯基、炔基、烷氧基、烷硫基、氨基、烷氧羰基、酰基、乙酰氧基、烷基磺基、烷基磺酰基或芳基；G3代表氢原子、卤原子、羟基、氰基、羧基、烷基、烯基、炔基、烷氧基、烷硫基、氨基、烷氧羰基、酰基、乙酰氧基、烷基磺基、烷基磺酰基或芳基；Y代表单键，或-C(R3)(R4)-（R3和R4代表氢原子、烷基或烷烯基，它们结合在一起形成饱和碳氢环基）；G4代表羟基（Y是单个基），或-N(R1)(R2)（R1和R2代表氢原子、烷基、芳基、烯基、炔基、饱和杂环基、烷基磺酰基、酰基或胺基）；G5是A的环构成碳原子上的取代基，代表氢原子、氟原子或烷基]或其盐、或作为前药的衍生物，其强力抑制Rho激酶。
• SULFONAMIDE COMPOUND
  申请人：Yamada Rintaro

  公开号：US20100093789A1

  公开（公告）日：2010-04-15

  A compound represented by the formula (1) [A represents a nitrogen-containing saturated ring; m represents an integer of 0 to 2; n represents an integer of 1 to 4; G 1 represents hydrogen atom, chlorine atom, hydroxyl group, an alkoxy group, or amino group; G 2 represents a halogen atom, hydroxyl group, cyano group, carboxy group, an alkyl group, an alkenyl group, and the like; G 3 represents hydrogen atom, a halogen atom, hydroxyl group, cyano group, carboxy group, an alkyl group, an alkenyl group, and the like; G 4 represents hydroxyl group, or —N(R 1 )(R 2 ) (R 1 and R 2 represent hydrogen atom, an alkyl group, an aralkyl group, an alkenyl group, an alkynyl group, or a saturated heterocyclic group); G 5 is a substituent on a ring-constituting carbon atom of A, and represents hydrogen atom, fluorine atom, or an alkyl group] or a salt thereof, or a derivative thereof that is a prodrug, which potently inhibits Rho kinase.

  化合物由以下公式表示(1) [A代表含氮饱和环；m表示0到2的整数；n表示1到4的整数；G1代表氢原子、氯原子、羟基、烷氧基或氨基；G2代表卤原子、羟基、氰基、羧基、烷基、烯基等；G3代表氢原子、卤原子、羟基、氰基、羧基、烷基、烯基等；G4代表羟基，或-N(R1)(R2) (R1和R2代表氢原子、烷基、芳基烷基、烯基、炔基或饱和杂环基)；G5是A的环构成碳原子上的取代基，代表氢原子、氟原子或烷基]或其盐，或其作为前药的衍生物，强力抑制Rho激酶。
• Thiophene sulfonamides useful as carbonic anhydrase inhibitors
  申请人：Alcon Laboratories, Inc.

  公开号：US05646142A1

  公开（公告）日：1997-07-08

  New thiophene sulfonamides useful as carbonic anhydrase inhibitors are disclosed. Methods for using the compounds to control IOP are also disclosed.

  本发明揭示了作为碳酸酐酶抑制剂有用的新噻吩磺酰胺。还揭示了使用这些化合物控制眼压的方法。
• NITROGENEOUS TRICYCLIC COMPOUND
  申请人：Asahi Kasei Pharma Corporation

  公开号：EP1829876A1

  公开（公告）日：2007-09-05

  A novel compound represented by the following formula (1) or a salt thereof [wherein R1, R5, R6, R7, and R8 represent hydrogen atom, a halogen atom, hydroxyl group, an alkyl group, an alkenyl group and the like; X1···X2 represents -CH(R2)-CH(R3)-, -CH(R2)-CH(R3)-CH(R4)-, -C(R2)=C(R3)-, or -C(R2)=C(R3)-CH(R4)- (R2, R3, and R4 represent hydrogen atom, or an alkyl group); A1, A11, A2, and A21 represent hydrogen atom, or an alkyl group; Y represents -CH(A3)-, -CH(A3)-C(A4)(A41)-, -CH(A3)-C(A4)(A41)-C(A5)(A51)-, or a single bond (A3, A4, A41, A5, and A51 represent hydrogen atom, or an alkyl group), and Z represents hydroxyl group, or -N(A6)(A61) (As represents hydrogen atom, or an alkyl group, and A61 represents hydrogen atom, an alkyl group, a substituted alkyl group and the like)], having an action of potently inhibiting phosphorylation of myosin regulatory light chain.

  由下式(1)代表的新型化合物或其盐[其中R1、R5、R6、R7和R8代表氢原子、卤素原子、羟基、烷基、烯基等；X1---X2代表-CH(R2)-CH(R3)-、-CH(R2)-CH(R3)-CH(R4)-、-C(R2)=C(R3)-或-C(R2)=C(R3)-CH(R4)-（R2、R3和R4代表氢原子或烷基）；A1、A11、A2和A21代表氢原子或烷基；Y 代表 -CH(A3)-、-CH(A3)-C(A4)(A41)-、-CH(A3)-C(A4)(A41)-C(A5)(A51)- 或单键（A3、A4、A41、A5 和 A51 代表氢原子或烷基），Z 代表羟基或 -N(A6)(A61) （As 代表氢原子、或烷基，A61 代表氢原子、烷基、取代的烷基等）]，具有有效抑制肌球蛋白调节轻链磷酸化的作用。