174258-41-4Relevant academic research and scientific papers
New azolidinediones as inhibitors of protein tyrosine phosphatase lb with antihyperglycemic properties
Malamas, Michael S.,Sredy, Janet,Gunawan, Iwan,Mihan, Brenda,Sawicki, Diane R.,Seestaller, Laura,Sullivan, Donald,Flam, Brenda R.
, p. 995 - 1010 (2007/10/03)
Insulin resistance in the liver and peripheral tissues together with a pancreatic cell defect are the common causes of type 2 diabetes. It is now appreciated that insulin resistance can result from a defect in the insulin receptor signaling system, at a site post binding of insulin to its receptor. Protein tyrosine phosphatases (PTPases) have been shown to be negative regulators of the insulin receptor. Inhibiton of PTPases may be an effective method in the treatment of type 2 diabetes. A series of azolidinediones has been prepared as protein tyrosine phosphatase 1B (PTP1B) inhibitors. Several compounds were Potent inhibitors against the recombinant rat and human PTP1B enzymes with submicromolar IC50 values. Elongated spacers between the azolidinedione moiety and the central aromatic portion of the molecule as well as hydrophobic groups at the vicinity of this aromatic region were very important to the inhibitory activity. Oxadiazolidinediones 87 and 88 and the corresponding acetic acid analogues 119 and 120 were the best h-PTP1B inhibitors with IC50 values in the range of 0.12-0.3 μM. Several compounds normalized plasma glucose and insulin levels in the ob/ob and db/db diabetic mouse models.
New azolidinediones and thiadiazolidinediones as antihyperglycemic agents
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, (2008/06/13)
This invention relates to novel compounds which have demonstrated oral antihyperglycemic activity in diabetic ob/ob and db/db mice, animal models on non-insulin dependent diabetes mellitus (NIDDM ot Type II diabetes). These compounds have the formula: STR1 wherein: R1 is C1 -C6 alkyl, C3 -C8 cycloalkyl, thienyl, furyl, pyridyl, STR2 where R10 is hydrogen, C1 -C6 alkyl, fluorine, chlorine, bromine, iodine, C1 -C6 alkyoxy, trifluoroalkyl or trifluoroalkoxy; R2 is hydrogen or C1 -C6 alkyl; X is O or S; n is 0, 1, or 2; A is STR3 where R3 is hydrogen, C1 -C6 alkyl, halogen, C1 -C6 alkoxy, trifluoroalkyl or trifluoroalkoxy; B is STR4 where R4 is hydrogen, C1 -C6 alkyl, allyl, C6 -C10 aryl, C6 -C10 aryl-(CH2)1-6 --, fluorine, chlorine, bromine, iodine, trimethylsilyl or C3 -C8 cycloalkyl; R5 is hydrogen, C1 -C6 alkyl, C6 -C10 aryl, or C6 -C10 aryl-(CH2)1-6 --; m is 0, 1, or 2; R6 is hydrogen or C1 -C6 alkyl; R7 is hydrogen or C1 -C6 alkyl; R8 and R9 are selected independently from hydrogen, C1 -C6 alkyl, fluorine, chlorine, bromine, or iodine; Y is S; Z is N or CH; or a pharmaceutically acceptable salt thereof.
