1. A computer-implemented method comprising:
receiving, in a clustered storage system, a request to migrate a storage object from a source node servicing the storage object to a destination node;
verifying the destination node is configured to service the storage object, wherein the verifying further comprises attempting to access the storage object and determining the storage object is accessible if the attempted access is successful;
verifying the source node is configured to migrate the storage object, wherein verifying the source node comprises performing a veto check that determines whether active operations on they source node include one or more of fault tolerance, maintenance, and servicing of access requests;
offlining the storage object at the source node to prevent servicing of storage requests on the storage object;
updating ownership information of the storage object to indicate the destination node instead of the source node;
onlining the storage object at the destination node to resume servicing of storage requests on the storage object; and
routing storage requests for the storage object to the destination node instead of the source node as a result of updating the ownership information.
2. A computer-implemented method of claim 1, the step of verifying the destination node comprising determining that the destination node is configured according to predetermined configuration.
3. A computer-implemented method of claim 2, wherein the predetermined configuration is stored as a configuration table at the destination node, the configuration table including an operating characteristic of the destination node for servicing the storage object.
4. A computer-implemented method of claim 2, wherein the predetermined configuration comprises the destination node operating in a cluster quorum.
5. A computer-implemented method of claim 1, wherein performing the veto check comprises determining that a proper operating condition exists at the source node.
6. A computer-implemented method of claim 1, wherein performing the veto check comprises determining migration of the storage object is permitted based on a state of the storage object.
7. A computer-implemented method of claim 1, wherein the ownership information is stored in a metadata location of the storage object and updating ownership information comprises accessing the metadata location of the storage object.
8. A computer-implemented method of claim 1, wherein the step of onlining comprises:
receiving, by the destination node, a notification for new ownership information of the storage object;
reading the new ownership information in a metadata location within the storage object;
updating a list of storage objects serviced by the destination node; and
providing the updated list to nodes in the clustered storage system.
9. A computer-implemented method of claim 1, wherein the step of onlining comprises:
receiving, by the destination node, cached storage requests stored at the source node during the offlining; and
processing, by the destination node, the cached storage requests on the storage object.
10. A computer-implemented method of claim 1, wherein the clustered storage system comprises a plurality of nodes, the plurality of nodes each comprising a D-module, an N-module, and an M-host.
11. A computer-implemented method of claim 10, wherein the step of routing comprises:
receiving a new storage request for the storage object at the N-module of one of the plurality of nodes;
determining, by the N-module, the destination node owns the storage object using the updated ownership information; and
forwarding the new storage request to the D\u2014module of the destination node for processing by the ID-module of the destination node.
12. A computer-implemented method comprising:
determining, by a source node servicing a storage object in a clustered storage system, a destination node is configured to service the storage object in response to a request to migrate the storage object to the destination node, wherein the verifying further comprises attempting to access the storage object and determining the storage object is accessible if the attempted access is successful;
performing a veto check that determines whether active operations on the source node include one or more of fault tolerance, maintenance, and servicing of access requests;
preventing, by the source node, servicing of storage requests on the storage object while ownership information of the storage object is updated to indicated the destination node in accordance with the request;
synchronizing, by the source and destination nodes, updated ownership information to indicate ownership of the storage object by the destination node instead of the source node; and
resuming, by the destination node, servicing of storage requests on the storage object at a second node based on the synchronizing.
13. A computer-implemented method of claim 12, the step of determining comprising the destination node confirming that the destination node is configured according to a predetermined configuration.
14. A computer-implemented method of claim 13, wherein the predetermined configuration is stored as a configuration table at the destination node, the configuration table including an operating characteristic of the destination node for participating in a migration operation.
15. A computer-implemented method of claim 12, wherein the ownership information is stored in a metadata location of the storage object and updating ownership information comprises accessing the metadata location of the storage object.
16. A computer-implemented method of claim 12, further comprising:
storing, by the source node, the storage requests in memory during the preventing;
sending, by the source node, the stored storage requests to the destination after synchronizing the updated ownership information; and
processing, by the destination node, the stored storage requests on the storage object.
17. A computer-implemented method of claim 12, wherein the step of synchronizing comprises:
receiving, by the destination node, a notification from the source node indicating an update to the ownership information;
reading the ownership information in a metadata location of the storage object;
updating a list of storage objects serviced by the destination node; and
providing the updated list to nodes in the clustered storage system.
18. A data processing device comprising:
a processor coupled to a bus;
a memory coupled to the processor through the bus; and
instructions executed by the processor from the memory to cause the processor to:
receive, at a cluster manager, a request to migrate a storage object of a first node to a second node in a clustered storage system;
forward, to the first node, the request to migrate the storage object;
determine, by the cluster manager, the first node is configured to migrate the storage object and the second node is configured to service the storage object, and attempt to access the storage object and determine the storage object is accessible if the attempted access is successful;
perform a veto check that determine; whether active operations on the first node include one or more of fault tolerance, maintenance, and servicing of access requests;
update ownership information of the storage object to indicate the second node instead of the first node; and
prevent servicing of storage request; on the storage object at the first node when the second node is configured to service the storage object and for resuming servicing of storage requests on the storage object at the second node upon updating ownership information of the storage object.
19. A data processing device of claim 18, further configured to update a first data structure of the first node and a second data structure of the second node, the first and second data structures accessed by respective first and second nodes for routing storage requests to the storage object.
20. A data processing device of claim 18, further configured to update a centralized data structure for synchronizing routing information of the storage object at the first and second nodes.
21. A data processing device of claim 18, wherein the determining on the second node by confirming the second node is configured according to a predetermined configuration.
22. A data processing device of claim 21, wherein the predetermined configuration is stored as a configuration table at the second node, the configuration table including an operating characteristic of the second node for participating in a migration operation.
23. A system data processing devise of claim 18, further configured to perform the determining of the first node by performing a veto check on the first node.
24. A data processing device of claim 18, further configured to:
store, at the first node, the storage requests in memory during the preventing;
send the stored storage requests to the second node upon resuming servicing of storage requests at the second node; and
processing the stored storage requests on the storage object at the second node.
25. A data processing device of claim 18, further configured to:
notify the second node of an update to the ownership information of the storage object;
reading the ownership information in a metadata location of the storage object;
updating a list of storage objects serviced by the second node; and
providing the updated list to nodes in the clustered storage system for use in routing a new storage request of the storage object to the second node.
26. A data processing device of claim 18, further configured to:
generate, automatically by the cluster manager, the request to migrate a storage object based on monitoring events in the clustered storage system.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1-20. (canceled)
21. A method of treating a disorder of reduced motility of the gastrointestinal tract in a mammal, the method comprising administering to the mammal a pharmaceutical composition comprising a pharmaceutically-acceptable carrier and a compound of formula (I):
wherein:
R1 is hydrogen, halo, or C1-4alkyl;
R2 is C3-4alkyl or C3-6cycloalkyl;
a is 0 or 1;
Z is a moiety of formula (c):
wherein:
X is carbon and Q is -A-;
or X is nitrogen and Q is selected from \u2014OC(O)\u2014, \u2014S(O)2\u2014, \u2014S(O)2(CH2)2\u2014, and -A(CH2)2\u2014;
b is 1, X is carbon, and W is \u2014S(O)2\u2014;
or b is 2, X is carbon or nitrogen, and W is selected from \u2014S(O)2\u2014, \u2014N{C(O)R9}\u2014, \u2014N{S(O)2R10}\u2014, \u2014N{C(O)NR13R14}\u2014, and \u2014N{R16}\u2014; or
Z is a moiety of formula (d):
wherein:
Q is selected from \u2014OC(O)\u2014, \u2014S(O)2\u2014, \u2014S(O)2(CH2)2\u2014, and -A(CH2)2\u2014;
W\u2032 is selected from \u2014N(R8)C(O)R9, \u2014N(R8)S(O)2R10, \u2014S(R11)(O)2, \u2014N(R8)C(O)NR13R14, \u2014OR15, and \u2014N(R8)R16; provided that when W\u2032 is attached to a carbon atom bonded to the nitrogen atom of the ring, that W\u2032 is \u2014C(O)NR13R14; and
b is 1 or 2;
A is selected from \u2014S(O)2CH2C(O)N(R3)\u2014, \u2014N{C(O)R5}\u2014, \u2014N{C(O)NR6aR6b}\u2014, \u2014N{S(O)2C1-3alkyl}-, \u2014N{S(O)2NR6aR6b}\u2014, \u2014S(O)2N(R7a)\u2014, and \u2014OC(O)N(R7b)\u2014;
R3 is C1-4alkyl;
R5 is hydrogen, C1-3alkyl, or C1-3alkoxy;
R6a and R6b are independently hydrogen or C1-4alkyl;
R7a and R7b are independently hydrogen or C1-4alkyl;
R8 is hydrogen, methyl, or ethyl;
R9 is tetrahydrofuranyl, methyl, or ethyl;
R10 is methyl or ethyl;
R11 is methyl or ethyl;
R13 and R14 are independently hydrogen, methyl or ethyl;
R15 is hydrogen or methyl;
R16 is \u2014(CH2)n\u2014R17, wherein r is 0, 1, or 2; and R17 is selected from hydroxy, cyano, C1-3alkyl, and C1-3alkoxy; provided that when r is O, R17 is C1-3alkyl; and when r is 1, R17 is cyano or C1-3alkyl;
or a pharmaceutically-acceptable salt or stereoisomer thereof.
22. The method of claim 21, wherein Z is a moiety of formula (c), wherein X is nitrogen and Q is selected from \u2014OC(O)\u2014, \u2014S(O)2\u2014, \u2014S(O)2(CH2)2\u2014, \u2014S(O)2N(R7a)(CH2)2\u2014, \u2014N{C(O)C1-3alkoxy}(CH2)2\u2014, and \u2014N{S(O)2C1-3alkyl}(CH2)2\u2014.
23. The method of claim 21, wherein Z is a moiety of formula (c), wherein X is carbon and Q is selected from \u2014N{C(O)C1-3alkoxy}-, N{C(O)NR6aR6b}\u2014, \u2014N{S(O)2C1-3alkyl}, and \u2014S(O)2N(R7a)\u2014.
24. The method of claim 21, wherein Z is a moiety of formula (d), wherein Q is selected from \u2014OC(O)\u2014 and \u2014S(O)2\u2014.
25. The method of claim 21, wherein the compound of formula (I) is selected from:
1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid {(1S,3R,5R)-8-3-(4-methanesulfonylpiperazine-1-sulfonyl)propyl-8-azabicyclo3.2.1oct-3-yl}amide;
1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid {(1S,3R,5R)-8-3-(3-dimethylaminopyrrolidine-1-sulfonyl)propyl-8-azabicyclo3.2.1oct-3-yl}amide;
1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid ((1S,3R,5R)-8-{3-4-(2-hydroxyethyl)piperazine-1-sulfonylpropyl}-8-azabicyclo3.2.1oct-3-yl)amide;
1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid {(1S,3R,5R)-8-3-(4-methylpiperazine-1-sulfonyl)propyl-8-azabicyclo3.2.1oct-3-yl}amide;
1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid ((1S,3R,5R)-8-{2-methanesulfonyl-(1-propylpiperidin-4-yl)aminoethyl}-8-azabicyclo3.2.1oct-3-yl)-amide;
1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid (1S,3R,5R)-8-(3-{1-(2-methoxyethyl)piperidin-4-ylmethylsulfamoyl}propyl)-8-azabicyclo3.2.1oct-3-ylamide;
1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid ((1S,3R,5R)-8-{3-(1-methanesulfonylpiperidin-4-yl)methylsulfamoylpropyl}-8-azabicyclo3.2.1oct-3-yl)amide;
1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid (1S,3R,5R)-8-(3-{1-(2-cyanoethyl)piperidin-4-ylmethylsulfamoyl}propyl)-8-azabicyclo3.2.1oct-3-ylamide;
1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid ((1S,3R,5R)-8-{2-(1,1-dioxotetrahydro-1\u03bb6-thiophen-3-yl)methanesulfonylaminoethyl}-8-azabicyclo3.2.1oct-3-yl)amide;
1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid ((1S,3R,5R)-8-{2-1-(1,1-dioxotetrahydro-1\u03bb6-thiophen-3-yl)-3,3-dimethylureidoethyl}-8-azabicyclo3.2.1-oct-3-yl)amide;
(1,1-dioxo-tetrahydro-1\u03bb6-thiophen-3-yl)-(2-{(1S,3R,5R)-3-(1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carbonyl)amino-8-azabicyclo3.2.1oct-8-yl}ethyl)-carbamic acid methyl ester;
1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid (1S,3R,5R)-8-(2-{2-(4-dimethylcarbamoylpiperazin-1-yl)ethylmethanesulfonylamino}ethyl)-8-azabicyclo-3.2.1oct-3-ylamide;
1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid ((1S,3R,5R)-8-{2-2-(4-methanesulfonylpiperazin-1-yl)ethanesulfonylethyl}-8-azabicyclo3.2.1oct-3-yl)amide;
1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid (1S,3R,5R)-8-(2-{2-4-(tetrahydrofuran-2-carbonyl)piperazin-1-ylethanesulfonyl}ethyl)-8-azabicyclo3.2.1oct-3-ylamide;
1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid ((1S,3R,5R)-8-{2-2-(4-ethanesulfonylpiperazin-1-yl)ethanesulfonylethyl}-8-azabicyclo3.2.1oct-3-yl)amide;
(1,1-dioxo-hexahydro-1\u03bb6-thiopyran-4-yl)-(2-{(1S,3R,5R)-3-(1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carbonyl)amino-8-azabicyclo3.2.1oct-8-yl}ethyl)-carbamic acid methyl ester;
1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid ((1S,3R,5R)-8-{2-1-(1,1-dioxotetrahydro-1\u03bb6-thiophen-3-yl)-3-methylureidoethyl}-8-azabicyclo3.2.1oct-3-yl)amide;
(2-{(1S,3R,5R)-3-(1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carbonyl)-amino-8-azabicyclo3.2.1oct-8-yl}ethyl)-2-(4-methanesulfonylpiperazin-1-ylethyl-carbamic acid methyl ester;
2-(4-dimethylcarbamoylpiperazin-1-yl)ethyl-(2-{(1S,3R,5R)-3-(1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carbonyl)amino-8-azabicyclo3.2.1oct-8-yl}-ethyl)-carbamic acid methyl ester;
2-(4-acetyl-piperazin-1-yl)ethyl-(2-{(1S,3R,5R)-3-(1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carbonyl)amino-8-azabicyclo3.2.1oct-8-yl}ethyl)-carbamic acid methyl ester;
2-(1,1-dioxo-1\u03bb6-thiomorpholin-4-yl)ethyl-(2-{(1S,3R,5R)-3-(1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carbonyl)amino-8-azabicyclo3.2.1oct-8-yl}ethyl)-carbamic acid methyl ester;
(1,1-dioxo-tetrahydro-1\u03bb6-thiophen-3-yl)-(3-{(1S,3R,5R)-3-(1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carbonyl)amino-8-azabicyclo3.2.1oct-8-yl}propyl)-carbamic acid methyl ester;
((S)-1,1-dioxo-tetrahydro-1\u03bb6-thiophen-3-yl)-(2-{(1S,3R,5R)-3-(1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carbonyl)amino-8-azabicyclo3.2.1oct-8-yl}ethyl)-carbamic acid methyl ester;
1-isopropyl-2-oxo-1,2-dihydro-quinoline-3-carboxylic acid {(1S,3R,5R)-8-3-(methyl-{2-4-(tetrahydrofuran-2-carbonyl)piperazin-1-ylethyl}sulfamoyl)propyl-8-azabicyclo3.2.1oct-3-yl}amide;
1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid ((1S,3R,5R)-8-{3-4-(tetrahydrofuran-2-carbonyl)piperazine-1-sulfonylpropyl}-8-azabicyclo-3.2.1oct-3-yl)amide;
1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid {(1S,3R,5R)-8-3-(4-acetylpiperazine-1-sulfonyl)propyl-8-azabicyclo3.2.1oct-3-yl}amide;
4-methanesulfonyl-piperazine-1-carboxylic acid 3-{(1S,3R,5R)-3-(1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carbonyl)amino-8-azabicyclo3.2.1oct-8-yl}propyl ester;
4-(tetrahydrofuran-2-carbonyl)piperazine-1-carboxylic acid 3-{(1S,3R,5R)-3-(1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carbonyl)amino-8-azabicyclo3.2.1oct-8-yl}propyl ester;
4-acetyl-piperazine-1-carboxylic acid 3-{(1S,3R,5R)-3-(1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carbonyl)amino-8-azabicyclo3.2.1oct-8-yl}propyl ester; and
4-hydroxypiperidine-1-carboxylic acid 3-{(1S,3R,5R)-3-(1-isopropyl-2-oxo-1,2-dihydroquinoline-3-carbonyl)amino-8-azabicyclo3.2.1oct-8-yl}-propyl ester;
and pharmaceutically-acceptable salts thereof.
26. The method of claim 21, wherein the disorder of reduced motility is chronic constipation, irritable bowel syndrome, gastroparesis, post-operative ileus, intestinal pseudo-obstruction, drug-induced delayed transit, or functional dyspepsia.
27. The method of claim 26, wherein the disorder of reduced motility is chronic constipation, constipation-predominant irritable bowel syndrome, diabetic and idiopathic gastroparesis, or functional dyspepsia.
28. The method of claim 25, wherein the disorder of reduced motility is chronic constipation, irritable bowel syndrome, gastroparesis, post-operative ileus, intestinal pseudo-obstruction, drug-induced delayed transit, or functional dyspepsia.
29. The method of claim 28, wherein the disorder of reduced motility is chronic constipation, constipation-predominant irritable bowel syndrome, diabetic and idiopathic gastroparesis, or functional dyspepsia.
30. A method of treating a mammal having a medical condition ameliorated by treatment with a 5-HT4 receptor agonist, the method comprising administering to the mammal, a therapeutically effective amount of a pharmaceutical composition comprising a pharmaceutically-acceptable carrier and a compound of formula (I) as defined in claim 21 or a pharmaceutically-acceptable salt or stereoisomer thereof.
31. The method of claim 30 wherein the medical condition is irritable bowel syndrome, chronic constipation, functional dyspepsia, delayed gastric emptying, gastroesophageal reflux disease, gastroparesis, post-operative ileus, intestinal pseudo-obstruction, or drug-induced delayed transit.