- Discovery of remogliflozin etabonate: A potent and highly selective SGLT2 inhibitor
-
We optimized the structure of an active metabolite (1) of WAY-123783, which was obtained from mouse urine after oral administration, to improve selectivity for SGLT2 and oral bioavailability. O-glucoside derivative 24 (remogliflozin etabonate) was subsequently identified as a potent, highly selective, and orally available SGLT2 inhibitor.
- Shimizu, Kazuo,Fujikura, Hideki,Fushimi, Nobuhiko,Nishimura, Toshihiro,Tatani, Kazuya,Katsuno, Kenji,Fujimori, Yoshikazu,Watanabe, Shinjiro,Hiratochi, Masahiro,Nakabayashi, Takeshi,Kamada, Noboru,Arakawa, Koichi,Hikawa, Hidemasa,Azumaya, Isao,Isaji, Masayuki
-
-
- Diazo Activation with Diazonium Salts: Synthesis of Indazole and 1,2,4-Triazole
-
A donor/acceptor diazo activation strategy, processing via condensation using diazonium salts without the addition of any other catalysts or reagents, is reported. The diazenium intermediate was found to undergo cyclization to give indazoles in excellent yields. Alternatively, in the presence of nitriles, substituted 1,2,4-triazoles were obtained in good to excellent yields. This interesting diazenium route provides a new approach to achieve complex heterocycle synthesis under mild conditions.
- Li, Xuming,Ye, Xiaohan,Wei, Chiyu,Shan, Chuan,Wojtas, Lukasz,Wang, Qilin,Shi, Xiaodong
-
supporting information
p. 4151 - 4155
(2020/06/05)
-
- Asymmetric Aza-Wacker-Type Cyclization of N-Ts Hydrazine-Tethered Tetrasubstituted Olefins: Synthesis of Pyrazolines Bearing One Quaternary or Two Vicinal Stereocenters
-
We have developed an asymmetric aza-Wacker-type cyclization of N-Ts hydrazine-tethered tetrasubstituted olefins, affording optically active pyrazolines bearing chiral tetrasubstituted carbon stereocenters. This reaction is tolerant to a broad range of substrates under mild reaction conditions, giving the desired chiral products with high enantioselectivities. Generation of two vicinal stereocenters on the C=C double bonds was also achieved with high selectivities, a process which has been rarely studied for Wacker-type reactions. A mechanistic study revealed that this aza-Wacker-type cyclization undergoes a syn-aminopalladation process. It was also found that for substrates bearing two linear alkyl substituents on the outer carbon atom of the olefin, both of which are larger than a methyl group, the alkyl substituent that is cis to the intranucleophilic group participates more readily in β-hydride elimination. When one of the two alkyl substituents on the outer carbon atom of the olefin is a methyl group, β-hydride elimination proceeds selectively at the methylene side, thus both diastereomers can be prepared via switching the configuration of the olefin. Furthermore, the product can be converted to a pharmaceutical compound in high yields over three steps.
- Kou, Xuezhen,Shao, Qihang,Ye, Chenghao,Yang, Guoqiang,Zhang, Wanbin
-
supporting information
p. 7587 - 7597
(2018/06/04)
-
- 2-AMINO-1,3,4-THIADIAZINE AND 2-AMINO-1,3,4-OXADIAZINE BASED ANTIFUNGAL AGENTS
-
The invention provides a compound which is a diazine of formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt thereof, for use as an antifungal agent: (I) wherein X, N', C', A and E are as defined herein. The invention also provides a compound of Formula (I) as defined herein.
- -
-
Page/Page column 50; 51
(2017/02/09)
-