更新于：2023-10-19
Teijin Pharma Ltd.
更新于：2023-10-19
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Comparison of medication persistence, adherence, and glycemic control among different administration frequencies for DPP-4 inhibitor in patients with type 2 diabetes: A retrospective cohort study of real-world data - Comparison of medication persistence, adherence, and glycemic control among different administration frequencies for DPP-4 inhibitor in patients with type 2 diabetes
Maintenance repetitive transcranial magnetic stimulation (rTMS) fortreatment-resistant depression: a multisite, prospective,non-randomized longitudinal study - mTMS-D
Multimorbidity, polypharmacy, and glucose-lowering drugs, and their effects in patients with type 2 diabetes: A longitudinal study of real-world data - Multimorbidity, polypharmacy, and glucose-lowering drugs, and their effects in patients with type 2 diabetes
100 项与 Teijin Pharma Ltd. 相关的临床结果
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2021-01-01Bone (New York, NY, United States)2区 · 医学
Frequent administration of abaloparatide shows greater gains in bone anabolic window and bone mineral density in mice: A comparison with teriparatide
2区 · 医学
Article
作者: Makino, Akito ; Hasegawa, Tomoka ; Takagi, Hideko ; Takahashi, Yoshimasa ; Hase, Naoki ; Amizuka, Norio
Abaloparatide (ABL) is a novel 34-amino acid peptide analog of parathyroid hormone-related protein. In clinical studies, although ABL showed a greater bone mineral density (BMD) increase than teriparatide (TPTD, human parathyroid hormone 1-34), the responses of ABL to bone formation and resorption markers were weaker, making it difficult to understand the relationship between the bone anabolic window (increase in bone formation versus resorption) and bone mass. In the present study, the effects of ABL and TPTD were compared in mice. Given that the rate of bone turnover is higher in rodents than in humans, the comparison was made with several administration regimens providing equivalent daily dosages: once daily (QD, 30 μg/kg every 24 h), twice daily (BID, 15 μg/kg every 12 h), or three times a day (TID, 10 μg/kg every 8 h). Frequent administration of ABL showed higher BMD with enhancement of trabecular and cortical bone mass and structures than that of TPTD, consistent with the clinical results seen with once daily administration. ABL increased bone formation marker levels more than TPTD with more frequent regimens, while bone resorption marker levels were not different between ABL and TPTD in all regimens. Analysis of bone histomorphometry and gene expression also suggested that ABL increased bone formation more than TPTD, while the effect on bone resorption was almost comparable between ABL and TPTD. The bone anabolic windows calculated from bone turnover markers indicated that ABL enhanced the anabolic windows more than TPTD, leading to a robust increase in BMD. The mechanism by which ABL showed a better balance of bone turnover was suggested to be partly due to the enhanced remodeling-based bone formation involved in Ephb4. Taken together, our findings would help elucidate the mechanism by which ABL shows excellent BMD gain and reduction of fractures in patients with osteoporosis.
2020-07-17Organic Process Research & Development
Practical and Scalable Synthesis of a Glucokinase Activator via One-Pot Difluorination and Julia Olefination
作者: Tsuchiya, Hideyoshi ; Iwamoto, Minoru ; Miyamoto, Hidetoshi ; Sakumoto, Chihiro ; Tamamizu, Tokihiko ; Inoshita, Yasuo ; Koyama, Yuzo ; Sato, Yoshinori ; Kumamoto, Takuya
We describe the process research and development of a practical synthesis of glucokinase activator 1 (I ) as a potential drug for treating type 2 diabetes mellitus. The key structure, a 3,4-cis-difluorinated cyclopentane moiety, was constructed via diastereoselective epoxidation, followed by one-pot difluorination with Et3N·3HF and perfluorobutanesulfonyl fluoride (PBSF). Julia olefination of benzothiazol-2-yl sulfone with glyoxylate furnished an E/Z mixture of acrylate, followed by isomerization of the alkene to the desired E configuration during the formation of the acid chloride in the final step. This development achieved a highly practical process route to 1 (15% overall yield, 12 steps). This process route overcomes the drawbacks of the original medicinal chem. synthetic route, which used hazardous and costly reagents (LiAlH4, OsO4, and Deoxo-Fluor) and had low efficiency (<4% overall yield, 20 steps). Safety: Et3N·3HF and perfluorobutanesulfonyl fluoride (PBSF) generate HF - contact with skin must be avoided.
2020-04-09ACS Medicinal Chemistry Letters
Discovery of [1,2,4]Triazolo[1,5-a]pyridine Derivatives as Potent and Orally Bioavailable RORγt Inverse Agonists
作者: Nakajima, Ryota ; Oono, Hiroyuki ; Sugiyama, Sakae ; Matsueda, Yohei ; Ida, Tomohide ; Kakuda, Shinji ; Hirata, Jun ; Baba, Atsushi ; Makino, Akito ; Matsuyama, Ryo ; White, Ryan D. ; Wurz, Ryan Ρ. ; Shin, Youngsook ; Min, Xiaoshan ; Guzman-Perez, Angel ; Wang, Zhulun ; Symons, Antony ; Singh, Sanjay K. ; Mothe, Srinivasa Reddy ; Belyakov, Sergei ; Chakrabarti, Anjan ; Shuto, Satoshi
The retinoic acid receptor-related orphan nuclear receptor γt (RORγt), a promising therapeutic target, is a major transcription factor of genes related to psoriasis pathogenesis such as interleukin (IL)-17A, IL-22, and IL-23R. On the basis of the X-ray cocrystal structure of RORγt with 1a, an analog of the known piperazine RORγt inverse agonist 1, triazolopyridine derivatives of 1 were designed and synthesized, and analog 3a was found to be a potent RORγt inverse agonist. Structure-activity relationship studies on 3a, focusing on the treatment of its metabolically unstable cyclopentyl ring and the central piperazine core, led to a novel analog, namely, 6-methyl-N-(7-methyl-8-(((2S,4S)-2-methyl-1-(4,4,4-trifluoro-3-(trifluoromethyl)butanoyl)piperidin-4-yl)oxy)[1,2,4]triazolo[1,5-a]pyridin-6-yl)nicotinamide (5a), which exhibited strong RORγt inhibitory activity and a favorable pharmacokinetic profile. Moreover, the in vitro and in vivo evaluation of 5a in a human whole-blood assay and a mouse IL-18/23-induced cytokine expression model revealed its robust and dose-dependent inhibitory effect on IL-17A production
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