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

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

  • Bioorg Med Chem Lett. 2018 Dec 1;28(22):3534-3539. doi: 10.1016/j.bmcl.2018.09.035.
Shoichi Kuroda 1,  Yohei Kobashi 2,  Takahiro Oi 3,  Hideaki Amada 4,  Lisa Okumura-Kitajima 5,  Fusayo Io 6,  Koji Yamamto 5,  Hiroyuki Kakinuma 7
Affiliations

Affiliations

  • 1 Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan. Electronic address: s-kuroda@taisho.co.jp.
  • 2 Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan.
  • 3 Pharmaceutical Science Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan.
  • 4 Development Management, Taisho Pharmaceutical Co., Ltd., 3-24-1, Takada, Toshima-ku, Tokyo 170-8633, Japan.
  • 5 Pharmacology Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan.
  • 6 Medical Affairs Group, Taisho Toyama Pharmaceutical Co., 3-25-1, Takada, Toshima-ku, Tokyo 170-8635, Japan.
  • 7 Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd., 1-403 Yoshino-cho, Kita-ku, Saitama 331-9530, Japan. Electronic address: h-kakinuma@taisho.co.jp.
PMID: 30297284 DOI: 10.1016/j.bmcl.2018.09.035
Abstract

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.

Keywords

Diabetes; Low-absorbable; SGLT1; SGLT1 inhibitor; TPSA.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z