1. A compound of formula (1):
wherein:
the (CH2)n\u2014C(\u2550O)Q1 group is substituted at the meta or para position of the phenyl ring to which it is attached;
n is 1 or 2;
Q1 is
*-N(R8)-Q2-A;
* indicates the point of attachment of Q1 to the carbonyl group;
R1, R2, R3 and R4 are the same or different and are H, C1-C4 alkyl, OR6, SR6, halo, CF3, OCF3, COOR6, SO2NR6R7, CONR6R7, NR6R7 or NHCOR6; provided that at least two of R1, R2, R3 and R4 in the definition of Q1 are H;
R8 is H or C1-C4 alkyl;
p is 1 or 2;
Q2 is a single bond or C1-C4 alkylene;
A is pyridyl or a group of formula
R5 is H, C1-C4 alkyl, OR6, SR6, halo, CF3, OCF3, COOR6, SO2NR6R7, CONR6R7, NR6R7 or NHCOR6; provided that at least 2 of R1, R2, R3, R4 and R5 in the definition of A are H;
R6 and R7 are the same or different and are H or C1-C4 alkyl; or an isomer, tautomer or isotope thereof or a pharmaceutically acceptable salt of said compound, isomer, tautomer or isotope.
2. A compound of claim 1 wherein Q1 is *-NH-Q2-A;
Q2 is C1-C4 alkylene;
and A is
3. A compound of claim 2 wherein R1, R2, R3, R4 and R5 are the same or different and are H, C1-C4 alkyl, OR6, Cl, F, CF3, OCF3, COOR6 or SO2NR6R7, provided at least two of R1, R2, R3, R4 and R5 in the definition of A are H; and
R6 and R7 are the same or different and are H or C1-C4 alkyl.
4. A compound of claim 3 wherein R1, R2, R3, R4 and R5 are the same or different and are H, CH3, OH, OCH3, OCH2CH3, Cl, F, CF3, OCF3, COOH or SO2NH2, provided at least two of R1, R2, R3, R4 and R5 in the definition of A are H.
5. A compound of claim 4 wherein at least three of R1, R2, R3, R4 and R5 are H.
6. A compound of claim 1 wherein Q1 is *-NH-Q2-A;
Q2 is C1-C4 alkylene; and
A is pyridin-2-yl.
7. A compound of claim 1 wherein Q2 is \u2014CH2\u2014, \u2014(CH2)2\u2014, \u2014(CH2)3\u2014 or \u2014CH(CH3)\u2014.
8. A compound of claim 1 wherein Q2 is \u2014CH2\u2014.
9. A compound of claim 1 wherein Q1 is
10. A compound of claim 9 wherein R1, R2, R3 and R4 are the same or different and are H or OR7, provided at least 2 of R1 to R4 are equal to H.
11. A compound of claim 1 wherein Q1 is
12. A compound of claim 1 wherein n is 1.
13. A compound of claim 1 wherein n is 2.
14. The (R,R)-stereoisomer of a compound of claim 1.
15. A compound of claim 1 wherein the (CH2)n\u2014C(\u2550O)Q1 group is substituted at the meta position.
16. N-(2,6-Dimethoxybenzyl)-2-(3-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino-propyl}-phenyl)-acetamide;
N-(2-ethoxybenzyl)-2-(3-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl)-ethylamino-propyl}-phenyl)-acetamide;
N-(2-hydroxybenzyl)-2-(3-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino-propyl}-phenyl)-acetamide;
2-(3-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino-propyl}-phenyl)-N-indan-2-yl-acetamide;
N-(3,4-dichlorobenzyl)-2-(3-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino-propyl}-phenyl)-acetamide;
N-4-(aminosulfonyl)benzyl-2-(3-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl )-ethylamino-propyl}-phenyl)-acetamide;
2-(3-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino-propyl}-phenyl)-N-(pyridin-2-ylmethyl)-acetamide;
4-{(2-(3-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino-propyl}-phenyl)-acetylamino)-methyl}-benzamide;
N-(3,4-dimethoxybenzyl)-2-(3-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino-propyl}-phenyl)-acetamide;
2-(3-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino-propyl}-phenyl)-N-(4-trifluoromethoxybenzyl)-acetamide;
N-(2-chloro, 6-fluorobenzyl)-2-(3-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino-propyl}-phenyl)-acetamide;
N-(3,4-dimethylbenzyl)-2-(3-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino-propyl}-phenyl)-acetamide;
N2-fluoro-5-(trifluoromethyl)benzyl-2-(3-{(2R)-2-(2R)-2-hydroxy-2(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino-propyl}-phenyl)-acetamide;
N-(2,6-dichlorobenzyl)-2-(3-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino-propyl}-phenyl)-acetamide;
2-(3-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino-propyl}-phenyl)-N-(2-phenylethyl)acetamide;
N-benzyl-2-(3-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino-propyl}-phenyl)-acetamide;
N-(3,5-dichlorobenzyl)-2-(3-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino-propyl}-phenyl)-acetamide;
N-(4-chlorobenzyl )-2-(3-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl)-ethylamino-propyl}-phenyl)-acetamide;
4-{(2-(3-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino-propyl}-phenyl)-acetyl-amino)-methyl}-benzoic acid;
2-{3-(2R)-2-({(2R)-2-hydroxy-2-4-hydroxy-3-(hydroxymethyl)phenylethyl}amino)propylphenyl}-N-(1R)-1-phenylethylacetamide;
4-{(1R)-2-((1R)-2-{3-2-(3,4-dihydroisoquinolin-2(1H)-yl)-2-oxyethylphenyl}-1-methylethyl)amino-1-hydroxyethyl}-2-(hydroxymethyl)phenol;
4-{(1R)-2-((1R)-2-{3-2-(7-ethoxy-6-methoxy-3,4-dihydroisoquinolin-2(1H)-yl)-2-oxyethylphenyl}-1-methylethyl)amino-1-hydroxyethyl}-2-(hydroxymethyl)phenol;
N-2-(4-chlorophenyl)ethyl-2-{3-(2R)-2-({(2R)-2-hydroxy-2-4-hydroxy-3-(hydroxymethyl)phenylethyl}amino)propylphenyl}acetamide;
N2-(4-ethylphenyl)ethyl-2-{3-(2R)-2-({(2R)-2-hydroxy-2-4-hydroxy-3-(hydroxymethyl)phenylethyl}amino)propylphenyl}acetamide;
N-(1,1-dimethyl-2-phenylethyl)-2-{3-(2R)-2-({(2R)-2-hydroxy-2-4-hydroxy-3-(hydroxymethyl)phenylethyl}amino)propylphenyl}acetamide;
N2-(3,4-dimethoxyphenyl)ethyl-2-{3-2R)-2-({(2R)-2-hydroxy-2-4-hydroxy-3-(hydroxymethyl)phenylethyl}amino)propylphenyl}acetamide;
N-(3,4-difluorobenzyl)-2-{3-(2R)-2-({(2R)-2-hydroxy-2-4-hydroxy-3-(hydroxymethyl)phenylethyl}amino)propylphenyl}acetamide;
4-{(1R)-2-((1R)-2-{3-2-(1,3-dihydro-2H-isoindol-2-yl)-2-oxyethylphenyl}-1-methylethyl)amino-1 -hydroxyethyl}-2-(hydroxymethyl)phenol;
2-{3-(2R)-2-({(2R)-2-hydroxy-2-4-hydroxy-3-(hydroxymethyl)phenylethyl}amino)propylphenyl}-N-phenylacetamide;
2-{3-(2R)-2-({(2R)-2-hydroxy-2-4-hydroxy-3-(hydroxymethyl)phenylethyl}amino)propylphenyl}-N-(1-naphthylmethyl)acetamide;
N-(3,4-dichlorobenzyl)-2-{3-(2R)-2-({(2R)-2-hydroxy-2-4-hydroxy-3-5 (hydroxymethyl)phenylethyl}amino)propylphenyl}-N-methylacetamide;
2-{3-(2R)-2-({(2R)-2-hydroxy-2-4-hydroxy-3-(hydroxymethyl)phenylethyl}amino)propylphenyl}-N-(2-pyridin-2-ylethyt)acetamide;
2-{3-(2R)-2-({(2R)-2-hydroxy-2-4-hydroxy-3-(hydroxymethyl)phenylethyl}amino)propylphenyl}-N-(2R)-2-phenylpropylacetamide;
N-benzyl-2-{3-(2R)-2-({(2R)-2-hydroxy-2-4-hydroxy-3-(hydroxymethyl)phenylethyl}amino)propylphenyl}-N-methylacetamide;
N-3-(4-fluorophenyl)propyl-2-{3-(2R)-2-({(2R)-2-hydroxy-2-4-hydroxy-3-(hydroxymethyl)phenylethyl}amino)propylphenyl}acetamide;
N-(2,6-dichlorobenzyl)-3-(3-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylamino-propyl}-phenyl)-propanamide;
N-(2,6-dimethoxybenzyl)-3-{3-(2R)-2-({(2R)-2-hydroxy-2-4-hydroxy-3-(hydroxymethyl)phenylethyl}amino)propylphenyl}propanamide;
N-(2-ethoxybenzyl)-3-{3-(2R)-2-({(2R)-2-hydroxy-2-4-hydroxy-3-(hydroxymethyl)phenylethyl}amino)propylphenyl}propanamide;
N-(3,4-dimethylbenzyl)-3-{3-(2R)-2-({(2R)-2-hydroxy-2-4-hydroxy-3-(hydroxymethyl)phenylethyl}amino)propylphenyl}propanamide;
N-(2,3-dihydro-1H-inden-2-yl)-3-{3-(2RI)-2-({(2R)-2-hydroxy-2-4-hydroxy-3-(hydroxymethyl)phenylethyl}amino)propylphenyl}propanamide;
4-{(1R)-2-((1R)-2-{3-3-(3,4-dihydrolsoquinolin-2(1H)-yl)-3-oxopropylphenyl}-1methylethyl)amino-1-hydroxyethyl}-2-(hydroxymethyl)phenol;
N-(2-chloro-6-fluorobenzyl)-3-{3-(2R)-2-({(2R)-2-hydroxy-2-4-hydroxy-3-(hydroxymethyl)phenylethyl}amino)propylphenyl}propanamide;
N-(2-chlorobenzyl)-3-{3-(2R)-2-({(2R)-2-hydroxy-2-4-hydroxy-3-(hydroxymethyl)phenylethyl}amino)propylphenyl}propanamide;
3-{3-(2R)-2-({(2R)-2-hydroxy-2-4-hydroxy-3-(hydroxymethyl)phenylethyl}amino)propylphenyI}-N-(pyridin-2-ylmethyl)propanamide;
N-(2-chlorobenzyl)-3-{3-(2R)-2-({(2R)-2-hyd roxy-2-4-hydroxy-3-(hydroxymethyl)phenylethyl}amino)propylphenyl}propanamide;
3-{3-(2R)-2-({(2R)-2-hydroxy-2-4-hydroxy-3-(hydroxymethyl)phenylethyl}amino)propyphenyl}-N-(pyridin-2-ylmethyl)propanamide;
N-benzyl-3-{3-(2R)-2-({(2R)-2-hydroxy-2-4-hydroxy-3-(hydroxymethyl)phenylethyl}amino)propylphenyl}propanamide;
3-{3-(2R)-2-({(2R)-2-hydroxy-2-4-hydroxy-3-(hydroxymethyl)phenylethyl}amino)propylphenyl}-N-(2-phenylethyl)propanamide;
3-{3-(2R)-2-({(2R)-2-hydroxy-2-4-hydroxy-3-(hydroxymethyl)phenylethyl}amino)propylphenyl}-N-(3-phenylpropyl)propanamide;
4-{(1R)-2-((1R)-2-{3-3-(1,3-dihydro-2H-isoindol-2-yl)-3-oxopropylphenyl}-1-methylethyl)amino-1 -hydroxyethyl}-2-(hydroxymethyl)phenol;
N-2-fluoro-5-(trifluoromethyl)benzyl-3-{3-(2R)-2-({(2R)-2-hydroxy-2-4-hydroxy-3-(hydroxymethyl)phenylethyl}amino)propylphenyl}propanamide;
N-(2-hydroxybenzyl)-3-{3-(2R)-2-({(2R)-2-hydroxy-2-4-hydroxy-3-(hydroxymethyl)phenylethyl}amino)propylphenyl}propanamide;
3-{3-(2R)-2-({(2R)-2-hydroxy-2-4-hydroxy-3-(hydroxymethyl)phenylethyl}amino)propylphenyl}-N-phenylpropanamide;
N-benzyl-2-(4-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl)ethyl-aminopropyl}phenyl)acetamide;
2-(4-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl)ethylaminopropyl}phenyl)-N-(3-phenyl-propyl)acetamide;
2-(4-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl)ethylaminopropyl}phenyl)-N-indan-2-yl-acetamide;
1-(3,4-dihydro-1H-isoquinolin-2-yl)-2-(4-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl)-ethylaminopropyl}phenyl)ethanone;
N-(2-hydroxybenzyl)-2-(4-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethyl-phenyl)-ethylaminopropyl}phenyl)-acetamide;
N-(3-chlorobenzyl)-2-(4-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl)-ethylaminopropyl}phenyl)-acetamide;
N-(4-chlorobenzyl)-2-(4-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl)-ethylaminopropyl}phenyl)-acetamide;
2-(4-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl)-ethylamino-propyl}phenyl)-N-(2-methoxybenzyl)-acetamide;
2-(4-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl)-ethylamino-propyl}phenyl)-N-(3-methoxybenzyl)acetamide;
2-(4-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl)-ethylamino-propyl}phenyl)-N-(4-methoxybenzyl)-acetamide;
N-(2,6-dimethoxybenzyl)-2-(4-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl)-ethylaminopropyl}phenyl)-acetamide;
2-(4-{(2R)-2-(2R)-2-hydroxy-2-(4-hydroxy-3-hydroxymethylphenyl) -ethylaminopropyl}phenyl)-N-(pyridin-2-ylmethyl)acetamide;
N-2-fluoro-5-(trifluoromethyl)benzyl-2-{4-(2R)-2-({(2R)-2-hydroxy-2-4-hydroxy-3-(hydroxymethyl)phenylethyl}amino)propylphenyl}acetamide; or
2-{4-(2R)-2-({(2R)-2-hydroxy-2-4-hydroxy-3-(hydroxymethyl)phenylethyl}amino)propylphenyl}-N-(2-phenylethyl)acetamide.
17. A process for preparing a compound of claim 1 or a pharmaceutically acceptable salt thereof comprising the step of coupling an acid of formula (2):
with an amine of formula (3), (3\u2032) or (3\u2033):
NH2-Q2-A (3),
18. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient or additive.
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 hydrogen fuel cell cartridge comprising a plurality of cartridge segments, each of the plurality of cartridge segments comprising:
at least one insulation layer;
at least one heater layer;
at least one fuel source layer comprising a hydrogen fuel source compound; and
at least one waste heat exchange layer,
wherein the at least one fuel source layer is adjacent to the heater layer and the waste heat exchange layer, and
wherein the at least one waste heat exchange layer contains a coolant fluid.
2. The hydrogen fuel cell cartridge according to claim 1, wherein the at least one insulation layer comprises an insulation material having a thermal conductivity of no greater than 0.04 WmK.
3. The hydrogen fuel cell cartridge according to claim 1, wherein the at least one insulation layer comprises an insulation material selected from the group consisting of aerogels, pyrogels, perlite, and mineral wool.
4. The hydrogen fuel cell cartridge according to claim 1, wherein the at least one heater layer comprises a resistive film heater selected from the group consisting of polyimide heaters, silicone rubber heaters, mica heaters, metal heaters, ceramic heaters, semiconductor heaters, and carbon heaters.
5. The hydrogen fuel cell cartridge according to claim 1, wherein the hydrogen fuel source compound is a compound selected from a group consisting of alane, ammonia borane, and ethylene diaminoborane, lithium hydride, and lithium aluminum hydride.
6. The hydrogen fuel cell cartridge according to claim 1, further comprising a temperature sensor.
7. The hydrogen fuel cell cartridge according to claim 1, wherein the coolant fluid has a vaporization point ranging from 180\xb0 C.
8. A non-transitory computer-readable storage medium configured to store a program for controlling a hydrogen fuel cell cartridge of a fuel cell, the program comprising instructions for:
selecting a cartridge segment of the hydrogen fuel cell cartridge with the hydrogen fuel source that has not been depleted,
determining a required hydrogen demand of the hydrogen fuel cell cartridge,
controlling a heater layer of the selected cartridge segment,
measuring hydrogen production of the selected cartridge segment, and
determining whether the required hydrogen demand has been met.
9. The non-transitory computer-readable storage medium according to claim 8, the program further comprising instructions for controlling waste heat produced by the fuel cell by controlling wattage of the fuel cell, depending on a load required by the fuel cell.
10. The non-transitory computer-readable storage medium according to claim 8, the program further comprising instructions for controlling a flow rate of a coolant fluid in a waste heat exchange layer of the selected cartridge segment.
11. The non-transitory computer-readable storage medium according to claim 8, the program further comprising instructions for controlling a flow rate of a coolant fluid in a waste heat exchange layer of the selected cartridge segment, depending upon a power demand of the fuel cell.
12. The non-transitory computer-readable storage medium according to claim 8, the program further comprising instructions for controlling a flow rate of a waste heat exchange layer of an unused cartridge segment, based on a temperature of the unused cartridge segment determined by a temperature sensor.
13. The non-transitory computer-readable storage medium according to claim 8, the program further comprising instructions for controlling the heat applied to the selected cartridge segment by the heater layer, based on a temperature of an unused cartridge segment determined by a temperature sensor.
14. A hydrogen fuel cell system comprising:
a plurality of cartridge segments, each of the plurality of cartridge segments comprising:
at least one insulation layer, at least one heater layer, at least one waste heat exchange layer, and at least one fuel source layer; and
a control unit configured to:
select a cartridge segment of the hydrogen fuel cell cartridge with the hydrogen fuel source that has not been depleted,
determine a required hydrogen demand of the hydrogen fuel cell cartridge,
control a heater layer of the selected cartridge segment,
measure hydrogen production of the selected cartridge segment, and
determine whether the required hydrogen demand has been met.
15. The hydrogen fuel cell system according to claim 14, wherein the at least one fuel source layer comprises a hydrogen fuel source compound selected from a group consisting of alane, ammonia borane, and ethylene diaminoborane, lithium hydride, and lithium aluminum hydride.
16. The hydrogen fuel cell system according to claim 14, wherein the control unit is further configured to control waste heat produced by the fuel cell by controlling wattage of the fuel cell, depending on a load required by the fuel cell.
17. The hydrogen fuel cell system according to claim 14, wherein the control unit is further configured to control a flow rate of a coolant fluid in a waste heat exchange layer of the selected cartridge segment.
18. The hydrogen fuel cell system according to claim 14, wherein the control unit is further configured to control a flow rate of a coolant fluid in a waste heat exchange layer of the selected cartridge segment, depending upon a power demand of the fuel cell.
19. The hydrogen fuel cell system according to claim 14, wherein the control unit is further configured to control a flow rate of a waste heat exchange layer of an unused cartridge segment, based on a temperature of the unused cartridge segment determined by a temperature sensor.
20. The hydrogen fuel cell system according to claim 14, wherein the control unit is further configured to control the heat applied to the selected cartridge segment by the heater layer, based on a temperature of an unused cartridge segment determined by a temperature sensor.