물리학 및 공학 번역

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Glitazone (2,4-thiazolidinedione) derivatives including substituted pyridine, pyrimidine and purine were synthesized based on the crystal structure of Rosiglitazone binding with PPARγ/RXRα to develop new insulin sensitizing antidiabetic agents. In addition, tyrosine, malonate, and phenyl propionic acid derivatives were synthesized to examine the structure-activity relationship of pharmacophore head groups.

These compounds were evaluated for the effects through the triglyceride accumulation assay using 3T3-L1 cells in vitro. The hypoglycemic and hypolipidemic activities in the diabetic KKAy mice were assessed in vivo. Compared to the reference compounds, substituted pyridine and pyrimidine derivatives in vitro showed generally good activity, while exhibiting a little more toxicity to liver cells. Most of purine derivatives showed less activity and toxicity to liver cells than the reference compounds.

Most of the selected compounds exhibited better hypoglycemic activity than references and the 30g compound (5-[4-(2-{[6-(4-Methocyphenoxy)pyrimidin-4-yl]methylamino}ethoxy)benzyl]thiazolididione) showed excellent hypolipidemic activity in vivo.

Therefore, the 30g compound predicted to have PPARα/γ dual agonistic effect was selected as a candidate substance for clinical studies.

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감수자-부정확한 용어 사용:원문 “글리타존 (2,4-thiazolidinedione)계 화합물들을” 감수자-오역:원문 “이들의 약효 검색은 in vitro 에서는 3T3-L1 cell을 이용한 triglyceride accumulation assay 방법을 사용하였다” 감수자-오역:원문 “대조물질에 비해 전반적으로 우수한 활성을 보였으며” 감수자-유창성:원문 “간세포 독성 면에서는 좀더 독성이 있는 것으로 나타났다” 감수자-오역:원문 “purine 유도체의 경우 전반적으로 대조물질과 비교 시 낮은 활성을 보였고”

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감수자-부정확한 용어 사용:원문 “글리타존 (2,4-thiazolidinedione)계 화합물들을” 원문 “이들의 약효 검색은 in vitro 에서는 3T3-L1 cell을 이용한 triglyceride accumulation assay 방법을 사용하였다” 감수자-오역:원문 “대조물질에 비해 전반적으로 우수한 활성을 보였으며” 감수자-유창성:원문 “간세포 독성 면에서는 좀더 독성이 있는 것으로 나타났다” 원어민 에디터-단어 선택:문장의 개선을 위해 “some more” 대신 “slightly increased”를 사용 감수자-오역:원문 “purine 유도체의 경우 전반적으로 대조물질과 비교 시 낮은 활성을 보였고” 원어민 에디터-절:삽입절로 표시하여 부가적인 정보를 분리함

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Glitazone (2,4-thiazolidinedione) compounds including substituted pyridine, pyrimidine, and purine were synthesized based on the crystal structure of Rosiglitazone binding with PPARγ/RXRα to develop new insulin-sensitizing antidiabetic agents. In addition, tyrosine, malonate, and phenyl propionic acid derivatives were synthesized to examine the structure–activity relationships in pharmacophore head groups.

The effects of these compounds were evaluated via the triglyceride accumulation assay using 3T3-L1 cells in vitro. The hypoglycemic and hypolipidemic activities in diabetic KKAy mice were assessed in vivo. Compared with the reference compounds, the substituted pyridine and pyrimidine derivatives in vitro showed excellent activity in general while exhibiting slightly increased toxicity to liver cells. Purine derivatives generally showed lower activity and toxicity to liver cells than the reference compounds.

Most of the selected compounds exhibited better hypoglycemic activity than the references, and the 30 g compound (5-[4-(2-{[6-(4-Methocyphenoxy)pyrimidin-4-yl]methylamino}ethoxy)benzyl]thiazolididione) showed excellent hypolipidemic activity in vivo.

Therefore, the 30 g compound, which is predicted to exert a PPARα/γ dual agonistic effect, was selected as the candidate substance for clinical studies.