- A preparation method of the compounds
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The invention discloses a preparation method of a compound. The preparation method comprises the steps: carrying out chemical resolution on a compound 3 namely 5-amino-6-(2,5-difluorophenyl)-tetrahydro-2H-pyran-3-ol, to obtain a salt formed from the compound 3 and a resolving agent; carrying out chemical combination of the salt formed from the compound 3 and the resolving agent with di-tert-butyl dicarbonate in an alkali liquid to obtain a compound 4; and oxidizing hydroxyl of the compound 4 to obtain a compound N-[(2R,3S)-2-(2,5-difluorophenyl)tetrahydro-5-oxo-2H-pyran-3-yl]-carbamic acid 1,1-dimethylethyl ester represented by the formula I. According to the preparation method, by selecting the low-price raw materials, the synthetic route is shortened, asymmetric hydrogenation reaction steps are omitted, and thus the production cost is greatly reduced, and the yield is significantly improved.
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Paragraph 0029-0031
(2017/07/13)
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- Omarigliptin (MK-3102): A novel long-acting DPP-4 inhibitor for once-weekly treatment of type 2 diabetes
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In our effort to discover DPP-4 inhibitors with added benefits over currently commercially available DPP-4 inhibitors, MK-3102 (omarigliptin), was identified as a potent and selective dipeptidyl peptidase 4 (DPP-4) inhibitor with an excellent pharmacokinetic profile amenable for once-weekly human dosing and selected as a clinical development candidate. This manuscript summarizes the mechanism of action, scientific rationale, medicinal chemistry, pharmacokinetic properties, and human efficacy data for omarigliptin, which is currently in phase 3 clinical development.
- Biftu, Tesfaye,Sinha-Roy, Ranabir,Chen, Ping,Qian, Xiaoxia,Feng, Dennis,Kuethe, Jeffrey T.,Scapin, Giovanna,Gao, Ying Duo,Yan, Youwei,Krueger, Davida,Bak, Annette,Eiermann, George,He, Jiafang,Cox, Jason,Hicks, Jacqueline,Lyons, Kathy,He, Huaibing,Salituro, Gino,Tong, Sharon,Patel, Sangita,Doss, George,Petrov, Aleksandr,Wu, Joseph,Xu, Shiyao Sherrie,Sewall, Charles,Zhang, Xiaoping,Zhang, Bei,Thornberry, Nancy A.,Weber, Ann E.
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p. 3205 - 3212
(2014/05/20)
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- Novel tetrahydropyran analogs as dipeptidyl peptidase IV inhibitors: Profile of clinical candidate (2R,3S,5R)-2-(2,5-difluorophenyl)-5-[2- (methylsulfonyl)-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]tetrahydro-2H-pyran- 3-amine (23)
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A series of novel tri-2,3,5-substituted tetrahydropyran analogs were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4) for the treatment of type 2 diabetes. Optimization of the series provided inhibitors with good DPP-4 potency and selectivity over other peptidases (QPP, DPP8, and FAP). Compound 23, which is very potent, selective, efficacious in the diabetes PD model, and has an excellent pharmacokinetic profile, is selected as a clinical candidate.
- Biftu, Tesfaye,Qian, Xiaoxia,Chen, Ping,Feng, Dennis,Scapin, Giovanna,Gao, Ying-Duo,Cox, Jason,Sinha Roy, Ranabir,Eiermann, George,He, Huabing,Lyons, Kathy,Salituro, Gino,Patel, Sangita,Petrov, Alexander,Xu, Feng,Xu, Shiyao Sherrie,Zhang, Bei,Caldwell, Charles,Wu, Joseph K.,Weber, Ann E.
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p. 5361 - 5366
(2013/09/23)
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