(1S)-1,5-anhydro-1-{2-hydroxy-5-[4-(4-{[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]amino}-4-oxobutyl)benzyl]-4-methylphenyl}-1-thio-D-glucitol | 1000368-94-4

• 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: (1S)-1,5-anhydro-1-{2-hydroxy-5-[4-(4-{[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]amino}-4-oxobutyl)benzyl]-4-methylphenyl}-1-thio-D-glucitol
• 英文别名: N-[1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl]-4-[4-[[4-hydroxy-2-methyl-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)thian-2-yl]phenyl]methyl]phenyl]butanamide
• CAS: 1000368-94-4
• 化学式: C₂₈H₃₉NO₉S
• 分子量: 565.685
• InChiKey: OXGSVLNDFHQGFL-INFWBLCHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  39
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  216
• 氢给体数：
  9
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2,3,4,6-tetra-O-benzyl-1-C-[2-(benzyloxy)-5-formyl-4-methylphenyl]-5-thio-D-glucopyranose 在 三乙基硅烷 、 正丁基锂 、 三氟化硼乙醚 、 palladium diacetate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三(邻甲基苯基)磷 作用下， 以 四氢呋喃 、 乙醇 、 氯仿 、 乙腈 为溶剂， 生成 (1S)-1,5-anhydro-1-{2-hydroxy-5-[4-(4-{[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]amino}-4-oxobutyl)benzyl]-4-methylphenyl}-1-thio-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 1-THIOGLUCITOL COMPOUND
  申请人：Kakinuma Hiroyuki

  公开号：US20100004465A1

  公开（公告）日：2010-01-07

  C-phenyl 1-thioglucitol compounds of the following formula (I) or pharmaceutically acceptable salts thereof or hydrates thereof: [wherein X represents a hydrogen atom or a C 1-6 alkyl group, Y represents a C 1-6 alkylene group or —O—(CH 2 )n- (wherein n represents an integer of 1 to 5), and Z represents —CONHR A or —NHCONHR B (provided that when Z represents —NHCONHR B , n is not 1), wherein R A represents a C 1-6 alkyl group substituted with 1 to 3 substituents selected from the group consisting of a hydroxyl group and —CONH 2 , and R B represents a hydrogen atom or a C 1-6 alkyl group substituted with 1 to 3 substituents selected from the group consisting of a hydroxyl group and —CONH 2 ] are useful as prophylactic or therapeutic agents for diabetes, because of their suppressive effect on sugar (e.g., glucose) absorption through inhibition of SGLT1 activity, or alternatively, because of their suppressive effect on sugar (e.g., glucose) absorption and excretory effect on urinary sugars through inhibition of both SGLT1 and SGLT2 activities.

  以下公式（I）的C-苯基1-硫代葡萄糖醇化合物或其药学上可接受的盐或水合物是糖尿病的预防或治疗药物，因为它们通过抑制SGLT1活性对糖（例如葡萄糖）吸收具有抑制作用，或者通过抑制SGLT1和SGLT2活性对糖（例如葡萄糖）吸收和尿糖排泄具有抑制作用。其中X代表氢原子或C1-6烷基，Y代表C1-6烷基或-O-（CH2）n-（其中n表示1至5的整数）的烷基，Z代表—CONHRA或—NHCONHRB（但当Z代表—NHCONHRB时，n不为1），其中RA代表C1-6烷基，其被1至3个取自氢氧基和—CONH2的基团取代，而RB代表氢原子或C1-6烷基，其被1至3个取自氢氧基和—CONH2的基团取代。
• US8115017B2
  申请人：——

  公开号：US8115017B2

  公开（公告）日：2012-02-14
• 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.