눈에 묻으면 몇 분간 물로 조심해서 씻으시오. 가능하면 콘택트렌즈를 제거하시오. 계속 씻으시오.
P321
(…) 처치를 하시오.
P332+P313
피부 자극이 생기면 의학적인 조치· 조언을 구하시오.
P362
오염된 의복을 벗고 세척 후에 재사용하기
NFPA 704
0
2
0
Linagliptin C화학적 특성, 용도, 생산
개요
Linagliptin (trade names Tradjenta and Trajetna) is an inhibitor of
dipeptidyl peptidase-4 (DPP-4) that was approved by the U.S. FDA in May
2011 for the treatment of Type 2 diabetes along with diet and exercise.
Linagliptin (BI-1356) has been
described as a potent highly selective, slow-off rate and long acting inhibitor of DPP-4. Linagliptin arose from optimization efforts of xanthine-based
DPP-4 inhibitors with the initial lead identified from an HTS campaign.
After optimizing the activity of the initial micromolar lead, two issues that needed to be addressed were activity for hERG and muscarinic receptor M1.
Introduction of a butynyl group at the N7 position of the xanthine ring gave
much reduced M1 affinity with no measureable hERG activity. Linagliptin
inhibits DPP-4 with an IC50=1 nM and is highly selective (>10,000-fold)
against DPP-8 and DPP-9. Linagliptin shows no interactions with CYPs up
to 50 mM. The described synthesis of linagliptin starts with 8-bromoxanthine,
which is alkylated at the N-7 position to introduce the butyne group,
followed by alkylation of the N-1 group to introduce the methyl-quinazoline
group. Displacement of the bromide with (R)-Boc-3-amino-piperidine
followed by deprotection gives linagliptin. When administered to db/db
mice orally, linagliptin dose dependently reduced glucose excursion from
0.1 mg/kg (15% inhibition) to 1 mg/kg (66% inhibition).
용도
Labeled Linagliptin, intended for use as an internal standard for the quantification of Linagliptin by GC- or LC-mass spectrometry.
정의
ChEBI: A xanthine that is 7H-xanthine bearing (4-methylquinazolin-2-yl)methyl, methyl, but-2-yn-1-yl and 3-aminopiperidin-1-yl substituents at positions 1, 3, 7 and 8 respectively (the R-enantiomer). Used for treatment of type
I diabetes.
