(1S)-1,5-anhydro-2,3,4,6-tetra-O-benzyl-1-[2-(benzyloxy)-4-methyl-5-[4-[2-(tritylamino)ethyl]benzyl]phenyl]-D-glucitol | 957774-09-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (1S)-1,5-anhydro-2,3,4,6-tetra-O-benzyl-1-[2-(benzyloxy)-4-methyl-5-[4-[2-(tritylamino)ethyl]benzyl]phenyl]-D-glucitol
• 英文别名: 2-[4-[[2-methyl-4-phenylmethoxy-5-[(2S,3S,4R,5R,6R)-3,4,5-tris(phenylmethoxy)-6-(phenylmethoxymethyl)oxan-2-yl]phenyl]methyl]phenyl]-N-tritylethanamine
• CAS: 957774-09-3
• 化学式: C₇₆H₇₃NO₆
• 分子量: 1096.42
• InChiKey: IBYDYYVMFCWNLD-NHYKEBCOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  15.3
• 重原子数：
  83
• 可旋转键数：
  26
• 环数：
  11.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  67.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (1S)-1,5-anhydro-2,3,4,6-tetra-O-benzyl-1-[2-(benzyloxy)-4-methyl-5-[4-[2-(tritylamino)ethyl]benzyl]phenyl]-D-glucitol 在 三氟乙酸 作用下， 以 甲醇 为溶剂， 反应 3.25h， 生成 (1S)-1-[5-[4-(2-aminoethyl)benzyl]-2-(benzyloxy)-4-methylphenyl]-1,5-anhydro-2,3,4,6-tetra-O-benzyl-D-glucitol benzenesulfonic acid
  参考文献：
  名称：

  WO2007/136116

  摘要：

  公开号：
• 作为产物：
  描述：

  4-(苄氧基)-5-溴-2-甲基苯甲酸 在 盐酸 、 三乙基硅烷 、 正丁基锂 、 草酰氯 、 三氟化硼乙醚 、 对甲苯磺酸 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 氯仿 、 水 、 甲苯 、 乙腈 为溶剂， 生成 (1S)-1,5-anhydro-2,3,4,6-tetra-O-benzyl-1-[2-(benzyloxy)-4-methyl-5-[4-[2-(tritylamino)ethyl]benzyl]phenyl]-D-glucitol
  参考文献：
  名称：

  Discovery of a potent, low-absorbable sodium-dependent glucose cotransporter 1 (SGLT1) inhibitor (TP0438836) for the treatment of type 2 diabetes

  摘要：

  The design and synthesis of a novel class of low-absorbable SGLT1 inhibitors are described. To achieve low absorption in the new series, we performed an optimization study based on a strategy to increase TPSA. Fortunately, the optimization of an aglycon moiety and a side chain of the distal aglycon moiety led to the identification of compound 30b as a potent and low-absorbable SGLT1 inhibitor. Compound 30b showed a desirable PK profile in Sprague-Dawley (SD) rats and a favorable glucose-lowering effect in diabetic rats.

  DOI：

  10.1016/j.bmcl.2018.09.035

文献信息

• C-PHENYL GLYCITOL COMPOUND
  申请人：Kakinuma Hiroyuki

  公开号：US20100022460A1

  公开（公告）日：2010-01-28

  Provided is a novel C-phenyl glycitol compound that may serve as a prophylactic or therapeutic agent for diabetes by inhibiting both SGLT1 activity and SGLT2 activity, thereby exhibiting a glucose absorption suppression action and a urine glucose excretion action. A C-phenyl glycitol compound represented by Formula (I) below or a pharmaceutically acceptable salt thereof or a hydrate thereof wherein R 1 and R 2 are the same or different and represent a hydrogen atom, a hydroxyl group, a C 1-6 alkyl group, a C 1-6 alkoxy group or a halogen atom, R 3 is a hydrogen atom, a C 1-6 alkyl group, a C 1-6 alkoxy group or a halogen atom, Y is a C 1-6 alkylene group, —O—(CH 2 )n— (n is an integer of 1 to 4) or a C 2-6 alkenylene group, provided that when Z is —NHC(═NH)NH 2 or —NHCON(R B )R C , n is not 1, Z is —CONHR A , —NHC(═NH)NH 2 or —NHCON(R B )R C ,

  提供的是一种新型C-苯基甘露醇化合物，可以作为预防或治疗糖尿病的药物，通过抑制SGLT1活性和SGLT2活性，从而表现出抑制葡萄糖吸收和尿液葡萄糖排泄的作用。该化合物表示为以下式子（I）的C-苯基甘露醇化合物，或其药学上可接受的盐或水合物，其中R1和R2相同或不同，表示氢原子、羟基、C1-6烷基、C1-6烷氧基或卤素原子，R3表示氢原子、C1-6烷基、C1-6烷氧基或卤素原子，Y表示C1-6烷基、-O-(CH2)n-（n为1至4的整数）或C2-6烯基烷基，但当Z为-NHC（=NH）NH2或-NHCON（RB）RC时，n不为1，Z为CONHRA，-NHC（=NH）NH2或-NHCON（RB）RC。
• C-phenyl glycitol compound
  申请人：Taisho Pharmaceutical Co., Ltd

  公开号：US07973012B2

  公开（公告）日：2011-07-05

  Provided is a novel C-phenyl glycitol compound that may serve as a prophylactic or therapeutic agent for diabetes by inhibiting both SGLT1 activity and SGLT2 activity, thereby exhibiting a glucose absorption suppression action and a urine glucose excretion action. A C-phenyl glycitol compound represented by Formula (I) below or a pharmaceutically acceptable salt thereof or a hydrate thereof wherein R1 and R2 are the same or different and represent a hydrogen atom, a hydroxyl group, a C1-6 alkyl group, a C1-6 alkoxy group or a halogen atom, R3 is a hydrogen atom, a C1-6 alkyl group, a C1-6 alkoxy group or a halogen atom, Y is a C1-6 alkylene group, —O—(CH2)n- (n is an integer of 1 to 4) or a C2-6 alkenylene group, provided that when Z is —NHC(═NH)NH2 or —NHCON(RB)RC, n is not 1, Z is —CONHRA, —NHC(═NH)NH2 or —NHCON(RB)RC,

  提供一种新型的C-苯基甘露醇化合物，可以作为预防或治疗糖尿病的药物，通过抑制SGLT1活性和SGLT2活性，从而表现出葡萄糖吸收抑制作用和尿糖排泄作用。所述C-苯基甘露醇化合物如下式（I）所示，或其药学上可接受的盐或水合物，其中R1和R2相同或不同，表示氢原子、羟基、C1-6烷基、C1-6烷氧基或卤素原子，R3表示氢原子、C1-6烷基、C1-6烷氧基或卤素原子，Y表示C1-6烷基、—O—（CH2）n-（n是1到4的整数）或C2-6烯基烷基，但当Z为—NHC（═NH）NH2或—NHCON（RB）RC时，n不为1，Z为—CONHRA、—NHC（═NH）NH2或—NHCON（RB）RC。
• C-PHENYL GLYCITOL COMPOUND FOR THE TREATMENT OF DIABETES
  申请人：TAISHO PHARMACEUTICAL CO., LTD

  公开号：EP2076503B1

  公开（公告）日：2013-07-17
• US7973012B2
  申请人：——

  公开号：US7973012B2

  公开（公告）日：2011-07-05
• Discovery of a potent, low-absorbable sodium-dependent glucose cotransporter 1 (SGLT1) inhibitor (TP0438836) for the treatment of type 2 diabetes
  作者：Shoichi Kuroda、Yohei Kobashi、Takahiro Oi、Hideaki Amada、Lisa Okumura-Kitajima、Fusayo Io、Koji Yamamto、Hiroyuki Kakinuma

  DOI：10.1016/j.bmcl.2018.09.035

  日期：2018.12

  The design and synthesis of a novel class of low-absorbable SGLT1 inhibitors are described. To achieve low absorption in the new series, we performed an optimization study based on a strategy to increase TPSA. Fortunately, the optimization of an aglycon moiety and a side chain of the distal aglycon moiety led to the identification of compound 30b as a potent and low-absorbable SGLT1 inhibitor. Compound 30b showed a desirable PK profile in Sprague-Dawley (SD) rats and a favorable glucose-lowering effect in diabetic rats.