1. An optical interconnection assembly for optically connecting one or more spine switches to one or more leaf switches in a spine-and-leaf (SF) network, comprising:
an array of duplex fiber optic cables, wherein each of the duplex fiber optic cables has a first end and a second end, and wherein each duplex optical fiber cable forms a parallel channel having a data rate D;
a plurality of ML of leaf multi-fiber (MF) components, wherein each of the leaf MF components optically connects to the first ends of certain ones of the duplex fiber optic cables, and wherein each leaf MF component provides NL parallel channels and a bandwidth BWL;
a plurality of MS of spine MF components, wherein each of the spine MF components optically connects to the second ends of certain ones of the duplex fiber optic cables, and wherein each spine MF component provides NS parallel channels and a bandwidth BWS; and
wherein the array of duplex fiber optic cables connects every leaf MF component to every spine MF component to define the NS and NL parallel channels, and wherein BWS=NS\xb7D and BWL=NL\xb7D so that NSNL=MLMS.
2. The optical interconnection assembly according to claim 1, wherein MS\xb7BWS=ML\xb7BWL.
3. The optical interconnection assembly according to claim 1, further including a housing having an interior that contains the array of duplex fiber optic cables.
4. The optical interconnection assembly according to claim 3, wherein the housing comprises a modular housing having a first side that supports the plurality of spine MF components and a second side that supports the plurality of leaf MF components.
5. The optical interconnection assembly according to claim 1, wherein each of the spine MF components has a first data rate and wherein each of the leaf MF components has a second data rate.
6. The optical interconnection assembly according to claim 5, wherein:
a) the first data rate is 120 GbE and the second data rate is 40 GbE; or
b) the first data rate is 400 GbE and the second data rate is 100 GbE.
7. The optical interconnection assembly according to claim 5, wherein the first and second data rates are each 40 GbE.
8. A spine-and-leaf (SF) network having scale-out capability that maintains multifiber connections, comprising:
one or more spine switches, each having one or more spine MF components;
one or more leaf switches, each having one or more leaf MF components;
at least one optical interconnection assembly having a first plurality of MS spine MF components optically connected to the one or more spine MF components via one or more spine patch cords, and having a second plurality of ML leaf-side MF components optically connected to the one or more leaf MF components via one or more leaf patch cords, the at least one optical interconnection assembly further comprising an array of duplex fiber optic cables that optically connect at least one spine MF component of each spine switch to at least one leaf MF component of each leaf switch so that every spine switch is optically connected to every leaf switch.
9. The SF network according to claim 8, wherein:
each spine-side MF component has NS parallel channels and a bandwidth BWS;
each leaf-side MF component has NL parallel channels and a bandwidth BWL;
each duplex optical fiber has a data rate D; and
BWS=NS\xb7D and BWL=NL\xb7D, so that NSNL=MLMS.
10. The SF network according to claim 9, wherein MS\xb7BWS=ML\xb7BWL.
11. The SF network according to claim 8, further including a housing having an interior that contains the array of duplex fiber optic cables.
12. The SF network according to claim 11, wherein the housing comprises a modular housing having a first side that supports the plurality of spine MF components and a second side that supports the plurality of leaf MF components.
13. The SF network according to claim 8, wherein each of the spine MF components has a first data rate and wherein each of the leaf MF components has a second data rate.
14. The SF network according to claim 8, wherein:
a) the first data rate is 120 GbE and the second data rate is 40 GbE; or
b) the first data rate is 400 GbE and the second data rate is 100 GbE.
15. The SF network according to claim 8, wherein the first and second data rates are each 40 GbE.
16. A method of forming a spine-and-leaf (SF) network using a plurality of spine switches and a plurality of leaf switches, comprising:
providing a least one optical interconnection assembly having a plurality of MS spine MF components and a plurality of ML leaf MF components, wherein each spine MF component is optically connected to each leaf MF component via an array of duplex fiber optic cables; and
optically connecting each of the plurality of spine switches to one or more of the spine MF components of the at least one optical interconnection assembly and optically connecting each of the plurality of leaf switches to one or more of the leaf MF components of the at least one optical interconnection assembly so that each leaf switch is optically connected to each spine switch through the at least one optical interconnection assembly.
17. The method according to claim 16, wherein said optically connecting the plurality of spine switches to the one or more of the spine MF components of the at least one optical interconnection assembly is performed using a first plurality of spine patch cords in a first configuration, and further comprising:
adding one or more spine switches to the SF network by adding a second plurality of spine patch cords and re-arranging the first plurality of patch cords to define a second configuration.
18. The method according to claim 16, wherein:
each spine MF component has NS parallel channels and a bandwidth BWS;
each leaf MF component has NL parallel channels and a bandwidth BWL;
each duplex fiber optic cable has a data rate D; and
wherein BWS=NS\xb7D and BWL=NL\xb7D, so that NSNL=MLMS.
19. The method according to claim 18, wherein MS\xb7BWS=ML\xb7BWL.
20. The method according to claim 16, further comprising scaling out the SF network by operably adding optical interconnection assemblies to the SF network.
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 (I)
wherein
R1 is hydrogen, fluoro, methyl or ethyl,
R2 is methyl, difluoromethyl or trifluoromethyl,
R3 is hydrogen or fluoro,
R4 is hydrogen, methyl or ethyl,
and
R5 is hydrogen or methyl,
or a pharmaceutically acceptable salt, hydrate andor solvate thereof.
2. The compound of formula (I) according to claim 1, wherein
R5 is hydrogen,
or a pharmaceutically acceptable salt, hydrate andor solvate thereof.
3. The compound of formula (I) according to claim 1, wherein
R1 is hydrogen or fluoro,
or a pharmaceutically acceptable salt, hydrate andor solvate thereof.
4. The compound of formula (I) according to claim 1, wherein
R1 is hydrogen or fluoro,
R2 is methyl or difluoromethyl,
R3 is hydrogen or fluoro,
R4 is hydrogen or methyl,
and
R5 is hydrogen,
or a pharmaceutically acceptable salt, hydrate andor solvate thereof.
5. The compound of formula (I) according to claim 1, wherein the compound is selected from the group consisting of
rac-2-Methyl-4-(3-methyl-1H-indazol-5-yl)-6-(trifluoromethyl)-1,4-dihydropyridine-3,5-dicarbonitrile;
(4R)-2-Methyl-4-(3-methyl-1H-indazol-5-yl)-6-(trifluoromethyl)-1,4-dihydropyridine-3,5-dicarbonitrile;
(4S)-2-Methyl-4-(3-methyl-1H-indazol-5-yl)-6-(trifluoromethyl)-1,4-dihydropyridine-3,5-dicarbonitrile;
rac-2-(Difluoromethyl)-4-(6-fluoro-3-methyl-1H-indazol-5-yl)-6-methyl-1,4-dihydro-pyridine-3,5-dicarbonitrile;
(4R)-2-(Difluoromethyl)-4-(6-fluoro-3-methyl-1H-indazol-5-yl)-6-methyl-1,4-dihydro-pyridine-3,5-dicarbonitrile;
(4S)-2-(Difluoromethyl)-4-(6-fluoro-3-methyl-1H-indazol-5-yl)-6-methyl-1,4-dihydro-pyridine-3,5-dicarbonitrile;
2,6-Bis(difluoromethyl)-4-(3-methyl-1H-indazol-5-yl)-1,4-dihydropyridine-3,5-dicarbo-nitrile;
2,6-Bis(difluoromethyl)-4-(6-fluoro-3-methyl-1H-indazol-5-yl)-1,4-dihydropyridine-3,5-dicarbonitrile;
and
rac-4-(6-Fluoro-1H-indazol-5-yl)-2-methyl-6-(trifluoromethyl)-1,4-dihydropyridine-3,5-dicarbonitrile;
or a pharmaceutically acceptable salt, hydrate andor solvate thereof.
6. A salt of a compound of formula (I) according to claim 1, having a formula (I-A)
wherein
R1, R2, R3 and R4 have the meanings defined in claim 1,
and
Q+ is an alkali metal cation or a quaternary ammonium cation,
or a hydrate or solvate thereof.
7. The salt of formula (I-A) according to claim 6, wherein
Q+ is a sodium or potassium cation or a 2-hydroxyethyltrimethyl ammonium (choline) cation,
or a hydrate or solvate thereof.
8. The salt of formula (I-A) according to claim 6, wherein
Q+ is a 2-hydroxyethyltrimethyl ammonium (choline) cation,
or a hydrate or solvate thereof.
9. A process for preparing a compound of formula (I) according to claim 1, wherein an indazolyl aldehyde of formula (II)
wherein R3 and R4 have the meanings indicated in claim 1,
is first reacted with a ketonitrile of formula (III)
or a sodium enolate thereof, wherein R2 has the meaning indicated in claim 1,
in the presence of an acid, acidbase combination andor dehydrating agent to give a compound of formula (IV)
wherein R2, R3 and R4 have the meanings indicated in claim 1,
and the latter is then condensed either with an enaminonitrile of formula (V)
wherein R1 has the meaning indicated in claim 1,
or with a ketonitrile of formula (VI)
wherein R1 has the meaning indicated in claim 1,
in the presence of an ammonia source such as ammonium acetate to give the compound of formula (I-B)
wherein R1, R2, R3 and R4 have the meanings indicated in claim 1,
optionally followed by
A dihydropyridine N-methylation employing a compound of formula (VII)
CH3\u2014X\u2003\u2003(VII),
wherein
X represents a leaving group such as halogen, mesylate, triflate, tosylate or sulfate,
in the presence of a base to give the compound of formula (I-C)
wherein R1, R2, R3 and R4 have the meanings indicated in claim 1,
and optionally followed, by (i) separating compound (I-B) or (I-C) into its respective enantiomers, andor (ii) converting compound (I-B) or (I-C) into its respective hydrates or solvates by treatment with the corresponding solvents.
10. (canceled)
11. (canceled)
12. (canceled)
13. A pharmaceutical composition comprising a compound as defined in claim 1, and a pharmaceutically acceptable excipient.
14. The pharmaceutical composition of claim 13 further comprising one or more additional therapeutic agents.
15. The pharmaceutical composition of claim 14, wherein the additional therapeutic agent is an anti-tumor agent.
16. (canceled)
17. A method of treating or preventing a cell proliferative disorder in a mammal, comprising administering to a mammal in need thereof a therapeutically effective amount of a compound as defined in claim 1.
18. The method of claim 17, wherein the cell proliferative disorder is cancer.
19. The method of claim 18, wherein the cancer is a cancer of the breast, respiratory tract, brain, reproductive organs, digestive tract, urinary tract, eye, liver, skin, head or neck, thyroid, parathyroid, or a distant metastasis of a solid tumor.
20. The method of claim 18, wherein the compound as defined in claim 1 is administered in conjunction with surgery or radiation therapy.
21. A process for preparing a salt of formula (I-A) according to claim 6, wherein an indazolyl aldehyde of formula (II)
wherein R3 and R4 have the meanings indicated in claim 6,
is first reacted with a ketonitrile of formula (III)
or a sodium enolate thereof, wherein R2 has the meaning indicated in claims 6,
in the presence of an acid, acidbase combination andor dehydrating agent to give a compound of formula (IV)
wherein R2, R3 and R4 have the meanings indicated in claims 6,
and the latter is then condensed either with an enaminonitrile of formula (V)
wherein R1 has the meaning indicated in claims 6,
or with a ketonitrile of formula (VI)
wherein R1 has the meaning indicated in claims 6,
in the presence of an ammonia source such as ammonium acetate to give the compound of formula (I-B)
wherein R1, R2, R3 and R4 have the meanings indicated in claims 6,
optionally followed by
A dihydropyridine salt formation by treatment with an agent of formula (VIII)
Q+Z\u2212\u2003\u2003(VIII),
wherein Q+ has the meaning indicated in claim 6,
and
Z\u2212 represents a basic anion such as hydroxide, carbonate or bicarbonate,
to yield the 1,4-dihydropyridinide salt of formula (I-A)
wherein R1, R2, R3, R4, and Q+ have the meanings indicated in claim 6,
and optionally followed by converting the salt (I-A) into a hydrate or solvate thereof by treatment with the corresponding solvents.
22. A pharmaceutical composition comprising a salt as defined in claims 6, and a pharmaceutically acceptable excipient.
23. A method of treating or preventing a cell proliferative disorder in a mammal, comprising administering to a mammal in need thereof a therapeutically effective amount of a salt as defined in claim 6.