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4-(trans-4-Methylcyclohexyl)-4-Oxobutyric Acid (JTT-608). A New Class of Antidiabetic Agent
- Source :
- Journal of Medicinal Chemistry. 41:5420-5428
- Publication Year :
- 1998
- Publisher :
- American Chemical Society (ACS), 1998.
-
Abstract
- During an investigation of drugs for improving the beta-cell response to glucose, we found that 4-cyclohexyl-4-oxobutyric acid selectively improved glucose-stimulated insulin release and glucose tolerance in both normal and diabetic rats. A series of 4-cycloalkyl-4-oxobutyric acids and related compounds were synthesized and evaluated for their effects on the glucose tolerance test and fasting euglycemia. This study elucidated the structural requirements for drug activity and determined that the optimum compound was 4-(trans-4-methylcyclohexyl)-4-oxobutyric acid 7 (JTT-608). This compound improved glucose tolerance from an oral dose of 3 mg/kg and did not change fasting euglycemia even at an oral dose of 30 mg/kg. Selective improvement of glucose-induced insulin secretion was observed in studies using neonatal streptozotocin rats (nSTZ rats) and perfused pancreases isolated from nSTZ rats.
- Subjects :
- Blood Glucose
Male
medicine.medical_specialty
Carboxylic acid
medicine.medical_treatment
Drug Evaluation, Preclinical
In Vitro Techniques
Diabetes Mellitus, Experimental
Structure-Activity Relationship
Cyclohexanes
Oral administration
In vivo
Internal medicine
Insulin Secretion
Drug Discovery
medicine
Animals
Hypoglycemic Agents
Insulin
Rats, Wistar
Pancreas
chemistry.chemical_classification
Glucose tolerance test
medicine.diagnostic_test
Chemistry
Fasting
Glucose Tolerance Test
Streptozotocin
In vitro
Rats
Butyrates
Endocrinology
Animals, Newborn
Glucose Clamp Technique
Molecular Medicine
Stereoselectivity
medicine.drug
Subjects
Details
- ISSN :
- 15204804 and 00222623
- Volume :
- 41
- Database :
- OpenAIRE
- Journal :
- Journal of Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....a09c9be0ad054a470e6d0636de199a7c