Azolidinediones as antihypergylcemic agents
AssigneeAmerican Home Products Corporation
InventorsMichael S. Malamas, Iwan Gunawan
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Abstract
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: X os O or S; n is 0, 1, or 2; ##STR2## A is ##STR3## B is Y is O or S; Z is N or CH when Y is O and Z is CH when Y is S; or a pharmaceutically acceptable salt thereof.
Claims9
A compound according to formula I below ##STR30## wherein:
- R.sup.1 is C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.8 cycloalkyl, thienyl, furyl, pyridyl, ##STR31## where R.sup.10 is hydrogen, C.sub.1 -C.sub.6 alkyl, fluorine, chlorine, bromine, iodine, C.sub.1 -C.sub.6 alkyoxy, trifluoroalkyl or trifluoroalkoxy;
- R.sup.2 is hydrogen or C.sub.1 -C.sub.6 alkyl;
- X is O or S;
- n is 1 or 2;
- A is ##STR32## where R.sup.3 is hydrogen, C.sub.1 -C.sub.6 alkyl, halogen, C.sub.1 -C.sub.6 alkoxy, trifluoroalkyl or trifluoroalkoxy;
- B is ##STR33## where R.sup.4 is hydrogen, C.sub.1 -C.sub.6 alkyl, allyl, C.sub.6 -C.sub.10 aryl, C.sub.6 -C.sub.10 aryl-(CH.sub.2).sub.1-6 --, fluorine, chlorine, bromine, iodine, trimethylsilyl or C.sub.3 -C.sub.8 cycloalkyl;
- R.sup.5 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.6 -C.sub.10 aryl, or C.sub.6 -C.sub.10 aryl-(CH.sub.2).sub.1-6 --;
- m is 0, 1, or 2;
- R.sup.6 is hydrogen or C.sub.1 -C.sub.6 alkyl;
- R.sup.7 is hydrogen or C.sub.1 -C.sub.6 alkyl;
- R.sup.8 and R.sup.9 are selected independently from hydrogen, C.sub.1 -C.sub.6 alkyl, fluorine, chlorine, bromine, or iodine;
- Y is O;
- Z is N;
- or a pharmaceutically acceptable salt thereof.
A method of treating hyperglycemia of non-insulin dependent diabetes mellitus in mammals which comprises administration thereto of a therapeutically effective amound of a compound of formula I ##STR40## wherein:
- R.sup.1 is C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.8 cycloalkyl, thienyl, furyl, pyridyl, ##STR41## where R.sup.10 is hydrogen, C.sub.1 -C.sub.6 alkyl, fluorine, chlorine, bromine, iodine, C.sub.1 -C.sub.6 alkyoxy, trifluoroalkyl or trifluoroalkoxy;
- R.sup.2 is hydrogen or C.sub.1 -C.sub.6 alkyl;
- X is O or S;
- n is 1 or 2;
- A is ##STR42## where R.sup.3 is hydrogen, C.sub.1 -C.sub.6 alkyl, halogen, C.sub.1 -C.sub.6 alkoxy, trifluoroalkyl or trifluoroalkoxy;
- B is ##STR43## where:
- R.sup.4 is hydrogen, C.sub.1 -C.sub.6 alkyl, allyl, C.sub.6 -C.sub.10 aryl, C.sub.6 -C.sub.10 aryl-(CH.sub.2).sub.1-6 --, fluorine, chlorine, bromine, iodine, trimethylsilyl or C.sub.3 -C.sub.8 cycloalkyl;
- R.sup.5 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.6 -C.sub.10 aryl, or C.sub.6 -C.sub.10 aryl-(CH.sub.2).sub.1-6 --;
- m is 0, 1, or 2;
- R.sup.6 is hydrogen or C.sub.1 -C.sub.6 alkyl;
- R.sup.7 is hydrogen or C.sub.1 -C.sub.6 alkyl;
- R.sup.8 and R.sup.9 are selected independently from hydrogen, C.sub.-C.sub.6 alkyl, fluorine, chlorine, bromine, or iodine;
- Y is O;
- Z is N;
- or a pharmaceutically acceptable salt thereof.
A pharmaceutical composition for the treatment of hyperglycemia of non-insulin dependent diabetic mellitus in mammals comprising a pharmaceutical carrier and a therapeutically effective amound of a compound having the formula:
- ##STR49## wherein:
- R.sup.1 is C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.8 cycloalkyl, thienyl, furyl, pyridyl, ##STR50## where R.sup.10 is hydrogen, C.sub.1 -C.sub.6 alkyl, fluorine, chlorine, bromine, iodine, C.sub.1 -C.sub.6 alkyoxy, trifluoroalkyl or trifluoroalkoxy;
- R.sup.2 is hydrogen or C.sub.1 -C.sub.6 alkyl;
- X is O or S;
- n is 1 or 2;
- A is ##STR51## where R.sup.3 is hydrogen, C.sub.1 -C.sub.6 alkyl, halogen, C.sub.1 -C.sub.6 alkoxy, trifluoroalkyl or trifluoroalkoxy;
- B is ##STR52## where R.sup.4 is hydrogen, C.sub.1 -C.sub.6 alkyl, allyl, C.sub.6 -C.sub.10 aryl, C.sub.6 -C.sub.10 aryl-(CH.sub.2).sub.1-6 --, fluorine, chlorine, bromine, iodine, trimethylsilyl or C.sub.3 -C.sub.8 cycloalkyl;
- R.sup.5 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.6 -C.sub.10 aryl, or C.sub.6 -C.sub.10 aryl-(CH.sub.2).sub.1-6 --;
- m is 0, 1, or 2;
- R.sup.6 is hydrogen or C.sub.1 -C.sub.6 alkyl;
- R.sup.7 is hydrogen or C.sub.1 -C.sub.6 alkyl;
- R.sup.8 and R.sup.9 are selected independently from hydrogen, C.sub.1 -C.sub.6 alkyl, fluorine, chlorine, bromine, or iodine;
- Y is O,
- Z is N;
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.