1. A method for inhibiting dipeptidyl peptidase-IV comprising contacting dipeptidyl peptidase-IV with an effective amount of a pyrrolidine compound represented by formula I:
or a cyclic isomer thereof, or any pharmaceutically acceptable salt thereof, any prodrug thereof, or any solvate thereof; wherein R2 and R3 independently or together are \u2014OH, \u2014O\u2014M+ wherein M+ is a cation, a hydroxyl bearing a boronic acid protecting group, or a group capable of being hydrolyzed to a hydroxyl group in an aqueous solution at physiological pH or in biological fluids; and the wavy lines at asymmetric carbons Ca and Cb independently indicate for each asymmetric carbon an R configuration, an S configuration, or a mixture of both configurations such that all stereoisomers and all stereomeric mixtures are included.
2. The method of claim 1 wherein the dipeptidyl peptidase-IV is within a mammal in need of treatment for a malcondition that can be regulated or normalized via inhibition of dipeptidyl peptidase-IV and the contacting step comprises administering to the mammal a therapeutically effective amount of a compound of formula I.
3. The method of claim 2, wherein the malcondition is impaired glycemic control.
4. The method of claim 2, wherein the malcondition is diabetes.
5. The method of claim 2, further comprising administering a therapeutically effective amount of a second medicament selected from the group consisting of a known second medicament that increases insulin secretion, increases insulin sensitivity, reduces the uptake of sugar from the gastrointestinal track, enhances the effect of endogenous peptides or proteins that affect glycemic control, or provides a replacement for endogenous peptides, proteins that affect glycemic control, or any combination thereof.
6. The method of claim 1, wherein the pyrrolidine compound selectively inhibits dipeptidyl peptidase-IV over at least one other dipeptidyl peptidase.
7. The method of claim 6, wherein the selective inhibition is by greater than 5-fold.
8. The method of claim 7, wherein the pyrrolidine compound selectively inhibits dipeptidyl peptidase-IV over dipeptidyl peptidase-VII, dipeptidyl peptidase-VIII, dipeptidyl peptidase-IX or fibroblast activation protein.
9. The method of claim 7, wherein the pyrrolidine compound selectively inhibits dipeptidyl peptidase-IV over dipeptidyl peptidase-VIII by greater than 10-fold.
10. The method of claim 7, wherein the pyrrolidine compound selectively inhibits dipeptidyl peptidase-IV over dipeptidyl peptidase-VIII and fibroblast activation protein.
11. The method of claim 7, wherein the pyrrolidine compound selectively inhibits dipeptidyl peptidase-IV over dipeptidyl peptidase-VII, dipeptidyl peptidase-VIII, and fibroblast activation protein.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A method of operating a plasma addressed data storage or display device that comprises a channel structure defining at least first and second channels, first and second plasma electrodes in the first and second channels respectively, a cover sheet over the channel structure, ionizable gas in the channels, a layer of electro-optic material over the cover sheet and an array of data drive electrodes over the layer of electro-optic material, wherein the method includes,
in a first operating cycle, controlling relative potentials of the data drive electrodes and the first and second plasma electrodes to initiate a discharge in the first channel without initiating a discharge in the second channel, and
in a second operating cycle, controlling relative potentials of the data drive electrodes and the first and second plasma electrodes to initiate a discharge in the second channel without initiating a discharge in the first channel.
2. A method of operating a plasma addressed data storage or display device that comprises a channel structure defining at least first and second channels, first and second plasma electrodes in the first and second channels respectively, a cover sheet over the channel structure, ionizable gas in the channels, a layer of electro-optic material over the cover sheet and an array of data drive electrodes over the layer of electro-optic material, wherein the method includes,
in a first operating cycle,
applying data voltages to the data drive electrodes respectively,
driving the first plasma electrode to a sufficient negative potential relative to the data drive electrodes to initiate a discharge in the first channel while maintaining the second plasma electrode at a potential relative to the data drive electrodes such that no discharge is initiated in the second channel, and
changing the potential of the first plasma electrode such as to reduce the potential difference between the first plasma electrode and the data drive electrodes to a level such that the discharge in the first channel is extinguished, and in a second operating cycle,
applying data voltages to the data drive electrodes respectively,
driving the second plasma electrode to a sufficient negative potential relative to the data drive electrodes to initiate a discharge in the second channel while maintaining the first plasma electrode at a potential relative to the data drive electrodes such that no discharge is initiated in the first channel, and
changing the potential of the second plasma electrode such as to reduce the potential difference between the second plasma electrode and the data drive electrodes to a level such that the discharge in the second channel is extinguished.
3. A method of operating a plasma addressed data storage or display device that comprises a channel structure defining at least first and second channels, first and second plasma electrodes in the first and second channels respectively, a cover sheet over the channel structure, ionizable gas in the channels, a layer of electro-optic material over the cover sheet and an array of data drive electrodes over the layer of electro-optic material, wherein the method includes,
in a first operating cycle,
applying data voltages to the data drive electrodes respectively,
driving the first plasma electrode to potentials of alternating polarity and of sufficient magnitude relative to the data drive electrodes to initiate a discharge in the first channel while maintaining the second plasma electrode at a potential relative to the data drive electrodes that no discharge is initiated in the second channel, and
placing the first plasma electrode at a potential relative to the potentials of the data drive electrodes such that the discharge in the first channel is extinguished, and in a second operating cycle,
applying data voltages to the data drive electrodes respectively,
driving the second plasma electrode to potentials of alternating polarity and of sufficient magnitude relative to the data drive electrodes to initiate a discharge in the second channel while maintaining the first plasma electrode at a potential relative to the data drive electrodes that no discharge is initiated in the first channel, and
placing the second plasma electrode at a potential relative to the potentials of the data drive electrodes such that the discharge in the second channel is extinguished.
4. A method of operating a plasma addressed data storage or display device that comprises a channel structure defining at least first and second channels, first and second plasma electrodes in the first and second channels respectively, a cover sheet over the channel structure, ionizable gas in the channels, a layer of electro-optic material over the cover sheet and an array of data drive electrodes over the layer of electro-optic material, wherein the method includes,
placing the first plasma electrode at a first potential level,
placing the second plasma electrode at a second potential level, which is positive relative to the first potential level,
driving the data drive electrodes to a positive potential relative to the second potential level and is such that electric field created in the first channel due to potential difference between the data drive electrodes and the first plasma electrode is sufficient to initiate a discharge in the first channel and electric field created in the second channel due to potential difference between the data drive electrodes and the second plasma electrode is insufficient to initiate a discharge in the second channel,
driving the data drive electrodes to data drive voltages, and
driving the first plasma electrode to a potential that is negative relative to the data drive voltages and is such that the electric field between the data drive electrodes and the first plasma electrode is sufficient to sustain the discharge in the first channel.