Adenosine analog and its use in regulating the circadian clock
AssigneeNational Institute of Biological Sciences, Beijing
InventorsErquan Zhang, Xiangbing Qi, Dapeng Ju, Zhiqiang Wang, Qingcui Wu, Haijiao Zhao, Long Mei
Life of this patent
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Abstract
The present invention provides a kind of nucleoside analogue compounds, and a composition comprising the compound and pentostatin, their use for modulating circadian rhythm, preferably, for shifting circadian phase, and methods for modulating circadian rhythm, preferably, for shifting circadian phase via the compound or the composition.
Claims14
A composition comprising an adenosine analogue compound of Formula I or a pharmaceutically acceptable salt thereof and pentostatin,
- wherein:
- R1 is H;
- R2 is H, OH, O-Biotin, OAc, OTBS, F, Cl, Br, or I;
- R3 is OH, O-Biotin, OAc, or OTBS;
- or R2 and R3 are independently absent or ═O;
- R4 and R5 are independently H, OH, F, Cl, Br, I, ═O, O-Biotin or N3;
- or R2/R3 and R4/R5 form expoxy ethane together with the carbons they are connected to;
- R6 and R7 are independently H, CH2—OH, CH2—N3, CH2—O-Biotin, CH2—AcO, CH2—OTBS, CO2Me, triphosphorylated methylene, 1,2-bishydroxyethane, tetrabutylammonium monophosphate, 1-hydroxyprop-2-yn-1-yl, or diazacymene;
- R8 is H, NH—CH3, F, Cl, Br, I, —O—CH3, or deuterium;
- R10 is H, —CH3, F, Cl, Br, I, NH2, NH—CH3, NH—NH2, ═O, NHBn, Biotinamide, m-hydroxyaniline, amino-cyclopropane, amino-cyclobutane, amino-cyclopentane, amino-cyclohexane, OMe or octamide;
- and
- R12 is H, NH2, F, Cl, Br, I, OMe, or 4-formamide-substituted pyrazole,
- wherein the adenosine analogue compound does not include adenosine itself.
A composition comprising a compound, or a pharmaceutically acceptable salt thereof and pentostatin, wherein the compound is selected from:
- Name
- Structure
- 1
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- NQZ-067
- 25
- NQZ-068
- 26
- NQZ-069
- 27
- Abacavir NQZ-078
- 28
- Vidaradine NQZ-071
- 29
- NQZ-082
- 30
- NQZ-081
- 31
- NQZ-083
- 32
- NQZ-084
- 33
- NQZ-089
- 34
- NQZ-091
- 35
- NQZ-106
- 36
- NQZ-107
- 37
- NQZ-117
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- NQZ-125
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- +get,574
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- +get,575
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- +get,576
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A method for increasing circadian amplitude, for regulating RUVBL helicase, for treating jet lag, shift-work, age-related sleep disturbances, or circadian clock-related sleep disturbances, which comprises administrating to a subject a therapeutically effective amount of substance, wherein the substance is a compound, or a pharmaceutically acceptable salt thereof, and the subject is a human, wherein the compound is:
Dependencies are inferred from the claim text.