Substituted tetrahydropyrrolo[2,1-b]oxazol-5(6H)-ones and tetrahydropyrrolo[2,1-b]thiazol-5(6H)-ones as hypoglycemic agents

Aicher, TD; KUVAKİ BALKAN, BAHAR; Bell, PA; Brand, LJ; Cheon, SH; Deems, RO; Fell, JB; Fillers, WS; Fraser, JD; Gao, JP; Knorr, DC; Kahle, GG; Leone, CL; Nadelson, J; Simpson, R; Smith, HC

doi:10.1021/jm9803121

Substituted tetrahydropyrrolo[2,1-b]oxazol-5(6H)-ones and tetrahydropyrrolo[2,1-b]thiazol-5(6H)-ones as hypoglycemic agents

Aicher T., KUVAKİ BALKAN B., Bell P., Brand L., Cheon S., Deems R., ...Daha Fazla

JOURNAL OF MEDICINAL CHEMISTRY, cilt.41, sa.23, ss.4556-4566, 1998 (SCI-Expanded)

Yayın Türü: Makale / Tam Makale
Cilt numarası: 41 Sayı: 23
Basım Tarihi: 1998
Doi Numarası: 10.1021/jm9803121
Dergi Adı: JOURNAL OF MEDICINAL CHEMISTRY
Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Index Chemicus (IC)
Sayfa Sayıları: ss.4556-4566
Dokuz Eylül Üniversitesi Adresli: Hayır

Özet

A series of substituted tetrahydropyrrolo[2,1-b]oxazol-5(6H)-one and tetrahydropyrrolo[2,1-b]thiazol-5(6H)-ones was synthesized from amino alcohols or amino thiols and keto acids. A pharmacological model based on the results obtained with these compounds led to the synthesis and evaluation of a series of isoxazoles and other monocyclic compounds. These were evaluated for their ability to enhance glucose utilization in cultured L6 myocytes. The in vivo hypoglycemic efficacy and potency of these compounds were evaluated in a model of type 2 diabetes mellitus (non-insulin-dependent diabetes mellitus), the ob/ob mouse. 25a(2S) (SDZ PGU 693) was selected for further pharmacological studies.