1. A ferroelectric recording medium comprising:
a ferroelectric layer which reverses its polarization when receiving a coercive voltage; and
a nonvolatile anisotrophic conduction layer having increased electrical conductivity in a vertical direction and disposed on the ferroelectric layer,
wherein the electrical resistance of the anisotrophic conduction layer decreases when receiving a first voltage lower than the coercive voltage, and the electrical resistance of the anisotrophic conduction layer increases when receiving a second voltage higher than the coercive voltage, and
wherein multi-bit information is stored by a combination of upward and downward polarizations of the ferroelectric layer and high and low electrical resistances of the anisotrophic conduction layer.
2. The ferroelectric recording medium of claim 1, wherein a first state is expressed by the downward polarization of the ferroelectric layer and the low resistance of the anisotrophic conduction layer;
a second state is expressed by the downward polarization of the ferroelectric layer and the high resistance of the anisotrophic conduction layer;
a third state is expressed by the upward polarization of the ferroelectric layer and the low resistance of the anisotrophic conduction layer; and
a fourth state is expressed by the upward polarization of the ferroelectric layer and the high resistance of the anisotrophic conduction layer.
3. The ferroelectric recording medium of claim 1, wherein:
the ferroelectric layer is partitioned into a plurality of domains for recording bit information;
the nonvolatile anisotrophic conduction layer is partitioned into a plurality of domains for recording bit information; and
each of the domains of the ferroelectric layer corresponds to one of the domains of the anisotrophic conduction layer.
4. A ferroelectric recording medium comprising:
a ferroelectric layer which reverses its polarization when receiving a coercive voltage; and
a nonvolatile anisotrophic conduction layer which is disposed on the ferroelectric layer,
wherein the anisotrophic conduction layer is configured to exhibit higher resistance and a nonconductive state, if a received voltage is lower than a first voltage,
wherein the anisotrophic conduction layer is configured to exhibit a lower resistance and a conductive state, if the received voltage is greater than or equal to the first voltage, but less than a second voltage,
wherein the anisotrophic conduction layer is configured to exhibit higher resistance and a nonconductive state if the received voltage is greater than or equal to the second voltage,
wherein the first voltage is less than the second voltage,
wherein the first voltage is less than the coercive voltage,
wherein the coercive voltage is less than the second voltage, and
wherein multi-bit information is stored by a combination of upward and downward polarizations of the ferroelectric layer and higher and lower electrical resistances of the anisotrophic conduction layer.
5. The ferroelectric recording medium of claim 1, wherein the nonvolatile anisotrophic conduction layer has exhibits increased electrical conductivity in the vertical direction relative to electrical conductivity in a horizontal direction.
6. The ferroelectric recording medium of claim 5, wherein the nonvolatile anisotrophic conduction layer exhibits electrical conductivity in the vertical direction but exhibits no electrical conductivity in the horizontal direction.
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 compound of formula (II):
or a pharmaceutically acceptable salt thereof, wherein:
Ar is phenyl, either unsubstituted or substituted with 1 to 5 substituents independently selected from the group consisting of halogen, cyano, hydroxyl, alkyl or alkoxyl, wherein the alkyl or alkoxyl is each independently unsubstituted or substituted with one or more halogens;
R1 is selected from the group consisting of hydrogen, alkyl, trifluoromethyl, cycloalkyl, aryl and heteroaryl, wherein the alkyl, cycloalkyl, aryl or heteroaryl is each independently either unsubstituted or substituted with one or more groups independently selected from the group consisting of halogen, cyano, aryl, hydroxyl and amino;
R2 is selected from the group consisting of hydroxyl, amino, alkyl, alkoxyl, cycloalkyl, heterocyclic alkyl, aryl, heteroaryl and \u2014NR4R5, wherein the alkyl, alkoxyl, cycloalkyl, heterocyclic alkyl, aryl or heteroaryl is each independently either unsubstituted or substituted with one or more groups independently selected from the group consisting of halogen, amino, cyano, hydroxyl, alkyl, cycloalkyl, alkoxyl, aryl, heteroaryl, \u2014NR4R5, \u2014OC(O)OR8, carboxylic acid and carboxylic ester;
R3 is selected from the group consisting of hydrogen and alkyl;
R4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocyclic alkyl, aryl and heteroaryl, wherein the alkyl, cycloalkyl, heterocyclic alkyl, aryl or heteroaryl is each independently either unsubstituted or substituted with one or more groups independently selected from the group consisting of halogen, hydroxyl, amino, alkoxyl, alkyl, cyano, aryl, cycloalkyl, heterocyclic alkyl, heterocyclic aryl, hydroxyalkyl, \u2014SO2R7, \u2014NR4R5, carboxylic acid and carboxylic ester; or
R4 and R5, together with the nitrogen to which they are attached, form a 4 to 8 membered heterocycle, wherein the 4 to 8 membered heterocycle contains one or more N, O, S atoms, and the 4 to 8 membered heterocycle is either unsubstituted or substituted with one or more groups independently selected from the group consisting of halogen, hydroxyl, amino, alkoxyl, alkyl, cyano, aryl, heterocyclic alkyl, heteroaryl, carbonyl, hydroxyalkyl, \u2014SO2R7, \u2014NR4R5, \u2014C(O)NR4R5, \u2014C(O)R7, \u2550O, carboxylic acid and carboxylic ester;
R7 is alkyl; and
R8 is selected from the group consisting of alkyl and cycloalkyl.
2. The compound, or a pharmaceutically acceptable salt thereof, of claim 1, which is of formula (I):
3. The compound, or a pharmaceutically acceptable salt thereof, of claim 1, wherein Ar is halogen-substituted phenyl.
4. The compound, or a pharmaceutically acceptable salt thereof, of claim 3, wherein Ar is trifluoro-phenyl.
5. The compound, or a pharmaceutically acceptable salt thereof, of claim 1, wherein R1 is halogen-substituted alkyl.
6. The compound, or a pharmaceutically acceptable salt thereof, of claim 1, wherein R1 is trifluoromethyl.
7. The compound, or a pharmaceutically acceptable salt thereof, of claim 1, wherein R2 is selected from the group consisting of \u2014OH, \u2014OCH3, \u2014NHCH3, \u2014NHCH2CH3, \u2014NHCH2CN, and \u2014NHCH2CH2SO2CH3.
8. The compound, or a pharmaceutically acceptable salt thereof, of claim 1, wherein R3 is hydrogen or methyl.
9. The compound, or a pharmaceutically acceptable salt thereof, of claim 1, which is selected from the group consisting of:
10. The compound, or a pharmaceutically acceptable salt thereof, of claim 1, which is selected from the group consisting of:
11. The compound, or a pharmaceutically acceptable salt thereof, of claim 1, which is
12. The compound, or a pharmaceutically acceptable salt thereof, of claim 1, wherein the pharmaceutically acceptable salt is an addition salt of an acid selected from the group consisting of malic acid, lactic acid, maleic acid, hydrochloric acid, methanesulfonic acid, sulfuric acid, phosphoric acid, citric acid, tartaric acid, acetic acid, and trifluoroacetic acid.
13. The compound, or a pharmaceutically acceptable salt thereof, of claim 12, wherein the acid is hydrochloric acid.
14. A compound of formula (IA):
wherein:
Ar is phenyl, either unsubstituted or substituted with 1 to 5 substituents independently selected from the group consisting of halogen, cyano, hydroxyl, alkyl or alkoxyl, wherein the alkyl or alkoxyl is each independently unsubstituted or substituted with one or more halogens;
R1 is selected from the group consisting of hydrogen, alkyl, trifluoromethyl, cycloalkyl, aryl and heteroaryl, wherein the alkyl, cycloalkyl, aryl or heteroaryl is each independently either unsubstituted or substituted with one or more groups independently selected from the group consisting of halogen, cyano, aryl, hydroxyl and amino;
R3 is selected from the group consisting of hydrogen and alkyl;
X is halogen; and
D is an amino protected group.
15. The compound of claim 14, wherein Ar is trifluoro-phenyl.
16. The compound of claim 14, wherein R1 istrifluoromethyl.
17. A process comprising:
reacting an acid anhydride with pyrazine 2-methylamine (IA_I) to obtain an amide (IA\u20142), wherein R1 is selected from the group consisting of hydrogen, alkyl, trifluoromethyl, cycloalkyl, aryl and heteroaryl, wherein the alkyl, cycloalkyl, aryl or heteroaryl is each independently either unsubstituted or substituted with one or more groups independently selected from the group consisting of halogen, cyano, aryl, hydroxyl and amino; and R3 is selected from the group consisting of hydrogen and
condensing the amide (IA2) to obtain the imidazole1,5-\u03b1pyrazine derivative (IA\u20143);
reducing the imidazole1,5-apyrazine derivative (IA\u20143) to obtain the R1 and R3 substituted tetrahydro-imidazo1,5-apyrazine derivative (IA\u20144);
reacting the R1 and R3 substituted tetrahydro-imidazo1,5-\u03b1pyrazine derivative (IA\u20144) with a carboxylic acid (IA\u20145), in the presence of a condensation reagent, to obtain the condensation product (IA\u20146), wherein Ar is phenyl, either unsubstituted or substituted with 1 to 5 substituents independently selected from the group consisting of halogen, cyano, hydroxyl, alkyl or alkoxyl, wherein the alkyl or alkoxyl is each independently unsubstituted or substituted with one or more halogens; D is an amino protecting group;
halogenating the condensation product (IA\u20146) to obtain the compound of formula (IA), wherein X is halogen.
18. The process of claim 17, further comprising:
converting the compound of formula (IA) to the corresponding carboxylic acid (IA\u20147);
reacting the carboxylic acid (IA\u20147) with an amine or an alcohol in the presence of a condensation reagent, or with 1-halogenated carbonate, wherein R2 is selected from the group consisting of hydroxyl, amino, alkyl, alkoxyl, cycloalkyl, heterocyclic alkyl, aryl, heteroaryl and \u2014NR4R5, wherein the alkyl, alkoxyl, cycloalkyl, heterocyclic alkyl, aryl or heteroaryl is each independently either unsubstituted or substituted with one or more groups independently selected from the group consisting of halogen, amino, cyano, hydroxyl, alkyl, cycloalkyl, alkoxyl, aryl, heteroaryl, \u2014NR4R5, \u2014OC(O)OR8, carboxylic acid and carboxylic ester; D is an amino protecting group and deprotecting the amino protecting group to obtain the compound of formula (I).
19. A process, comprising:
reducing the R1 substituted imidazole1,5-\u03b1pyrazine derivative (IB_I) and protecting the amino group in the resulting reduced product to obtain the amino protected R1 substituted imidazole1,5-\u03b1pyrazine derivative (IB\u20142), wherein R1 is selected from the group consisting of hydrogen, alkyl, trifluoromethyl, cycloalkyl, aryl and heteroaryl, wherein the alkyl, cycloalkyl, aryl or heteroaryl is each independently either unsubstituted or substituted with one or more groups independently selected from the group consisting of halogen, cyano, aryl, hydroxyl and amino; D is an amino protecting group;
halogenating the amino protected R1 substituted imidazole1,5-\u03b1pyrazine derivative (IB\u20142) to obtain the halogenated compound (IB\u20143), wherein X is halogen;
converting the halogenated compound (IB\u20143) to the ester substituted tetrahydro-imidazo1,5-\u03b1pyrazine derivative (IB\u20144);
hydrolyzing the ester substituted tetrahydro-imidazo1,5-apyrazine derivative (IB4) to obtain the carboxylic acid compound (IB\u20145);
converting the carboxylic acid compound (IB\u20145) to obtain the compound (IB\u20146) when R3 is alkyl, wherein R3 is selected from the group consisting of hydrogen and alkyl;
converting the compound (IB\u20146) to obtain the tetrahydro-imidazo1,5-apyrazine derivative (IB\u20147), wherein R2 is selected from the group consisting of hydroxyl, amino, alkyl, alkoxyl, cycloalkyl, heterocyclic alkyl, aryl, heteroaryl and \u2014NR4R5, wherein the alkyl, alkoxyl, cycloalkyl, heterocyclic alkyl, aryl or heteroaryl is each independently either unsubstituted or substituted with one or more groups independently selected from the group consisting of halogen, amino, cyano, hydroxyl, alkyl, cycloalkyl, alkoxyl, aryl, heteroaryl, \u2014NR4R5, \u2014OC(O)OR8, carboxylic acid and carboxylic ester;
deprotecting the ketone substituted tetrahydro-imidazo1,5-a\u2032lpyrazine derivative (IB7) to obtain the compound of formula (IB); and
reacting the compound of formula (IB) with a carboxylic acid in the presence of a condensation reagent to obtain the condensation product; and deprotectinq the amino protecting group to obtain the compound of formula (I).
20. A pharmaceutical composition comprising the compound, or a pharmaceutically acceptable salt thereof, of claim 1, and a pharmaceutically acceptable carrier or excipient.
21. A method for treating type 2 diabetes, hyperglycemia, or insulin resistance, comprising administering the pharmaceutical composition of claim 20 to a patient in need of the treatment.
22. A method for treating type 2 diabetes, hyperglycemia, or insulin resistance, comprising administering a therapeutically effective amount of the compound, or a pharmaceutically acceptable salt thereof, of claim 1, to a patient in need of the treatment.
23. A method for inhibiting the catalytic activity of dipeptidyl peptidase IV, comprising contacting dipeptidyl peptidase IV with the compound, or a pharmaceutically acceptable salt thereof, of claim 1.