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| Type |
Poster Presentation |
| Area |
Medicinal Chemistry |
| Room No. |
Grand Ballroom |
| Time |
10월 18일 (목요일) 11:00~12:30 |
| Code |
MEDI.P-310 |
| Subject |
Discovery constipation drug using aminoalkylbenzothiazepine derivative |
| Authors |
Seungin Kim, Jaeho Yoo*
New drug research center, CJ HealthCare, Korea
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| Abstract |
Chronic idiopathic constipation is highly prevalent among adults. Bile acids (BAs) and the enterohepatic BA circulation modulate colonic secretion and motility that affect transit. BAs in the colon have a dual action as osmotic and stimulant agents.
Newer agents, such as CJ-compounds, an inhibitor of the ileal BA transporter, have the potential to improve significantly the management of chronic constipation, with minimal adverse effects. Utilized the strategy adopted in the design of Elobixibat and GSK compound, we prepared several analogs based on core part scaffold of Elobixibat and GSK compound. Primary focus was to increase potency in vitro.The SAR studies described in this project focused side chain, aromatic substitution.
Compound A has non-absorbable properties and it optimized to get efficacy.
Finally, we can found more potent CJ compounds than Elobixibat. CJ compounds, an IBAT inhibitor, modulates the enterohepatic BA circulation, and increases BA synthesis enhancing the delivery of BAs to the colon to increase colonic motility, and secretion and fecal excretion of BAs. CJ compounds has significant effects on the manifestations of chronic constipation with minimal and tolerable adverse effects.
Compound A exhibited potent and selective IBAT inhibition and effectively improved treatment constipation. These results warrant further investigation of compound A as a promising candidate for patient who needs treatment of constipation.
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| E-mail |
seungin1004@gmail.com |
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122nd General Meeting of the KCS