JP2008528665A - ジヌクレオチドポリリン酸誘導体の使用法 - Google Patents
ジヌクレオチドポリリン酸誘導体の使用法 Download PDFInfo
- Publication number
- JP2008528665A JP2008528665A JP2007553689A JP2007553689A JP2008528665A JP 2008528665 A JP2008528665 A JP 2008528665A JP 2007553689 A JP2007553689 A JP 2007553689A JP 2007553689 A JP2007553689 A JP 2007553689A JP 2008528665 A JP2008528665 A JP 2008528665A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- ppa
- formula
- appch
- treatment
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 229920000388 Polyphosphate Polymers 0.000 title abstract description 13
- 239000001205 polyphosphate Substances 0.000 title abstract description 13
- 235000011176 polyphosphates Nutrition 0.000 title abstract description 13
- 238000011282 treatment Methods 0.000 claims abstract description 24
- 208000002193 Pain Diseases 0.000 claims abstract description 21
- 230000036407 pain Effects 0.000 claims abstract description 21
- 208000028867 ischemia Diseases 0.000 claims abstract description 14
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 claims abstract description 12
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 claims abstract description 12
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims abstract description 12
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 claims abstract description 12
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229930024421 Adenine Natural products 0.000 claims abstract description 10
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229960000643 adenine Drugs 0.000 claims abstract description 10
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 claims abstract description 8
- 206010061218 Inflammation Diseases 0.000 claims abstract description 8
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims abstract description 8
- 230000004054 inflammatory process Effects 0.000 claims abstract description 8
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 8
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 claims abstract description 8
- 150000003839 salts Chemical class 0.000 claims abstract description 6
- 229940035893 uracil Drugs 0.000 claims abstract description 6
- ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 claims abstract description 4
- 229930010555 Inosine Natural products 0.000 claims abstract description 4
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 claims abstract description 4
- 229940104302 cytosine Drugs 0.000 claims abstract description 4
- 229960003786 inosine Drugs 0.000 claims abstract description 4
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 4
- 229940113082 thymine Drugs 0.000 claims abstract description 4
- 229940075420 xanthine Drugs 0.000 claims abstract description 4
- 239000004090 neuroprotective agent Substances 0.000 claims abstract description 3
- 230000002669 organ and tissue protective effect Effects 0.000 claims abstract description 3
- 239000003223 protective agent Substances 0.000 claims abstract description 3
- 230000000694 effects Effects 0.000 claims description 51
- 150000001875 compounds Chemical class 0.000 claims description 42
- 101150007969 ADORA1 gene Proteins 0.000 claims description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 150000002009 diols Chemical class 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 7
- CQOQCZLTCMUVMX-UHFFFAOYSA-N 2-[4-(2,3-dihydroxypropoxy)phenyl]acetamide Chemical compound NC(=O)CC1=CC=C(OCC(O)CO)C=C1 CQOQCZLTCMUVMX-UHFFFAOYSA-N 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 230000001419 dependent effect Effects 0.000 claims description 5
- 108091006027 G proteins Proteins 0.000 claims description 2
- 102000030782 GTP binding Human genes 0.000 claims description 2
- 108091000058 GTP-Binding Proteins 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 210000004962 mammalian cell Anatomy 0.000 claims description 2
- 239000008177 pharmaceutical agent Substances 0.000 claims description 2
- 230000003805 potassium influx Effects 0.000 claims description 2
- 230000000302 ischemic effect Effects 0.000 abstract description 6
- 201000006474 Brain Ischemia Diseases 0.000 abstract description 3
- 206010008120 Cerebral ischaemia Diseases 0.000 abstract description 3
- 206010021143 Hypoxia Diseases 0.000 abstract description 3
- 206010008118 cerebral infarction Diseases 0.000 abstract description 3
- 238000012986 modification Methods 0.000 abstract description 3
- 230000004048 modification Effects 0.000 abstract description 3
- 230000001146 hypoxic effect Effects 0.000 abstract description 2
- 230000028161 membrane depolarization Effects 0.000 abstract description 2
- 230000001960 triggered effect Effects 0.000 abstract description 2
- 230000006698 induction Effects 0.000 abstract 1
- 238000002474 experimental method Methods 0.000 description 31
- 241000700159 Rattus Species 0.000 description 27
- 102000005962 receptors Human genes 0.000 description 26
- 108020003175 receptors Proteins 0.000 description 26
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 23
- 230000000971 hippocampal effect Effects 0.000 description 22
- 238000000034 method Methods 0.000 description 22
- 230000001404 mediated effect Effects 0.000 description 21
- 230000005764 inhibitory process Effects 0.000 description 18
- 238000012360 testing method Methods 0.000 description 18
- 239000000556 agonist Substances 0.000 description 16
- 239000000126 substance Substances 0.000 description 15
- 239000000243 solution Substances 0.000 description 14
- PNFZSRRRZNXSMF-UHFFFAOYSA-N 5'-phosphopyridoxal-6-azobenzene-2,4-disulfonic acid Chemical compound O=CC1=C(O)C(C)=NC(N=NC=2C(=CC(=CC=2)S(O)(=O)=O)S(O)(=O)=O)=C1COP(O)(O)=O PNFZSRRRZNXSMF-UHFFFAOYSA-N 0.000 description 13
- 210000003414 extremity Anatomy 0.000 description 13
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 12
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 12
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 12
- 239000011780 sodium chloride Substances 0.000 description 12
- 208000004454 Hyperalgesia Diseases 0.000 description 11
- 230000004913 activation Effects 0.000 description 11
- 239000000018 receptor agonist Substances 0.000 description 11
- 229940044601 receptor agonist Drugs 0.000 description 11
- 230000002776 aggregation Effects 0.000 description 9
- 238000004220 aggregation Methods 0.000 description 9
- 230000004044 response Effects 0.000 description 9
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 8
- 230000008859 change Effects 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 230000003040 nociceptive effect Effects 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 7
- 210000003169 central nervous system Anatomy 0.000 description 7
- 230000001537 neural effect Effects 0.000 description 7
- 230000001242 postsynaptic effect Effects 0.000 description 7
- DYUUGILMVYJEHY-UHFFFAOYSA-N 1-$l^{1}-oxidanyl-4,4,5,5-tetramethyl-3-oxido-2-phenylimidazol-3-ium Chemical compound CC1(C)C(C)(C)N([O])C(C=2C=CC=CC=2)=[N+]1[O-] DYUUGILMVYJEHY-UHFFFAOYSA-N 0.000 description 6
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 6
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 6
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 6
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 6
- 229960005305 adenosine Drugs 0.000 description 6
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 230000004770 neurodegeneration Effects 0.000 description 6
- 210000002569 neuron Anatomy 0.000 description 6
- 210000001176 projection neuron Anatomy 0.000 description 6
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 239000005557 antagonist Substances 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 5
- 230000003834 intracellular effect Effects 0.000 description 5
- 229940044551 receptor antagonist Drugs 0.000 description 5
- 239000002464 receptor antagonist Substances 0.000 description 5
- 230000001953 sensory effect Effects 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 208000024827 Alzheimer disease Diseases 0.000 description 4
- 206010010904 Convulsion Diseases 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 208000012902 Nervous system disease Diseases 0.000 description 4
- 208000025966 Neurological disease Diseases 0.000 description 4
- 102100040460 P2X purinoceptor 3 Human genes 0.000 description 4
- 101710189970 P2X purinoceptor 3 Proteins 0.000 description 4
- 208000018737 Parkinson disease Diseases 0.000 description 4
- XCCTYIAWTASOJW-XVFCMESISA-N Uridine-5'-Diphosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 XCCTYIAWTASOJW-XVFCMESISA-N 0.000 description 4
- NLTUCYMLOPLUHL-KQYNXXCUSA-N adenosine 5'-[gamma-thio]triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=S)[C@@H](O)[C@H]1O NLTUCYMLOPLUHL-KQYNXXCUSA-N 0.000 description 4
- 230000003502 anti-nociceptive effect Effects 0.000 description 4
- 230000033228 biological regulation Effects 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 150000001768 cations Chemical class 0.000 description 4
- 230000006353 environmental stress Effects 0.000 description 4
- 230000002964 excitative effect Effects 0.000 description 4
- 239000003257 excitatory amino acid Substances 0.000 description 4
- 230000002461 excitatory amino acid Effects 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- QMGVPVSNSZLJIA-FVWCLLPLSA-N strychnine Chemical compound O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1 QMGVPVSNSZLJIA-FVWCLLPLSA-N 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- CAWZRIXWFRFUQB-IOSLPCCCSA-N α,β Methylene ATP Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)CP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O CAWZRIXWFRFUQB-IOSLPCCCSA-N 0.000 description 4
- QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 description 3
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 102000055025 Adenosine deaminases Human genes 0.000 description 3
- -1 AppCH 2 ppA Chemical compound 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 208000035154 Hyperesthesia Diseases 0.000 description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- 208000006011 Stroke Diseases 0.000 description 3
- 102400000096 Substance P Human genes 0.000 description 3
- 101800003906 Substance P Proteins 0.000 description 3
- YDHWWBZFRZWVHO-UHFFFAOYSA-H [oxido-[oxido(phosphonatooxy)phosphoryl]oxyphosphoryl] phosphate Chemical compound [O-]P([O-])(=O)OP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O YDHWWBZFRZWVHO-UHFFFAOYSA-H 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 235000003704 aspartic acid Nutrition 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 3
- 230000036770 blood supply Effects 0.000 description 3
- 229960003638 dopamine Drugs 0.000 description 3
- 206010015037 epilepsy Diseases 0.000 description 3
- 239000000835 fiber Substances 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 3
- 229940045109 genistein Drugs 0.000 description 3
- TZBJGXHYKVUXJN-UHFFFAOYSA-N genistein Natural products C1=CC(O)=CC=C1C1=COC2=CC(O)=CC(O)=C2C1=O TZBJGXHYKVUXJN-UHFFFAOYSA-N 0.000 description 3
- 235000006539 genistein Nutrition 0.000 description 3
- ZCOLJUOHXJRHDI-CMWLGVBASA-N genistein 7-O-beta-D-glucoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 ZCOLJUOHXJRHDI-CMWLGVBASA-N 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 229930195712 glutamate Natural products 0.000 description 3
- 210000001320 hippocampus Anatomy 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 210000003141 lower extremity Anatomy 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 210000005036 nerve Anatomy 0.000 description 3
- 208000004296 neuralgia Diseases 0.000 description 3
- 208000015122 neurodegenerative disease Diseases 0.000 description 3
- 230000000926 neurological effect Effects 0.000 description 3
- 230000008587 neuronal excitability Effects 0.000 description 3
- 208000021722 neuropathic pain Diseases 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 125000003729 nucleotide group Chemical group 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 230000005855 radiation Effects 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 230000007958 sleep Effects 0.000 description 3
- 230000037322 slow-wave sleep Effects 0.000 description 3
- 210000000278 spinal cord Anatomy 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 230000002459 sustained effect Effects 0.000 description 3
- HWCKGOZZJDHMNC-UHFFFAOYSA-M tetraethylammonium bromide Chemical compound [Br-].CC[N+](CC)(CC)CC HWCKGOZZJDHMNC-UHFFFAOYSA-M 0.000 description 3
- 229960000278 theophylline Drugs 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 206010001497 Agitation Diseases 0.000 description 2
- IYGYMKDQCDOMRE-QRWMCTBCSA-N Bicculine Chemical compound O([C@H]1C2C3=CC=4OCOC=4C=C3CCN2C)C(=O)C2=C1C=CC1=C2OCO1 IYGYMKDQCDOMRE-QRWMCTBCSA-N 0.000 description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 description 2
- 108091006146 Channels Proteins 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 241000206602 Eukaryota Species 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- PHBDHXOBFUBCJD-KQYNXXCUSA-M Nc1nc([O-])c2ncn([C@@H]3O[C@H](COP(O)(=O)OP(O)(=O)C[P+](O)(O)[O-])[C@@H](O)[C@H]3O)c2n1 Chemical compound Nc1nc([O-])c2ncn([C@@H]3O[C@H](COP(O)(=O)OP(O)(=O)C[P+](O)(O)[O-])[C@@H](O)[C@H]3O)c2n1 PHBDHXOBFUBCJD-KQYNXXCUSA-M 0.000 description 2
- QMGVPVSNSZLJIA-UHFFFAOYSA-N Nux Vomica Natural products C1C2C3C4N(C=5C6=CC=CC=5)C(=O)CC3OCC=C2CN2C1C46CC2 QMGVPVSNSZLJIA-UHFFFAOYSA-N 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
- 241000700157 Rattus norvegicus Species 0.000 description 2
- 241001279009 Strychnos toxifera Species 0.000 description 2
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N Theophylline Natural products O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
- DLHMKHREUTXMCH-UHFFFAOYSA-N [2-(2,6-dimethylanilino)-2-oxoethyl]-triethylazanium;bromide Chemical compound [Br-].CC[N+](CC)(CC)CC(=O)NC1=C(C)C=CC=C1C DLHMKHREUTXMCH-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- 206010053552 allodynia Diseases 0.000 description 2
- AACMFFIUYXGCOC-UHFFFAOYSA-N bicuculline Natural products CN1CCc2cc3OCOc3cc2C1C4OCc5c6OCOc6ccc45 AACMFFIUYXGCOC-UHFFFAOYSA-N 0.000 description 2
- 239000013060 biological fluid Substances 0.000 description 2
- 230000008827 biological function Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- IYGYMKDQCDOMRE-UHFFFAOYSA-N d-Bicucullin Natural products CN1CCC2=CC=3OCOC=3C=C2C1C1OC(=O)C2=C1C=CC1=C2OCO1 IYGYMKDQCDOMRE-UHFFFAOYSA-N 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 210000001787 dendrite Anatomy 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 230000003291 dopaminomimetic effect Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 229950002932 hexamethonium Drugs 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000016273 neuron death Effects 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 210000001428 peripheral nervous system Anatomy 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 238000011533 pre-incubation Methods 0.000 description 2
- 210000000063 presynaptic terminal Anatomy 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000036385 rapid eye movement (rem) sleep Effects 0.000 description 2
- 238000011552 rat model Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 210000002460 smooth muscle Anatomy 0.000 description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- 229960005453 strychnine Drugs 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 210000000225 synapse Anatomy 0.000 description 2
- PYIHTIJNCRKDBV-UHFFFAOYSA-L trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;dichloride Chemical compound [Cl-].[Cl-].C[N+](C)(C)CCCCCC[N+](C)(C)C PYIHTIJNCRKDBV-UHFFFAOYSA-L 0.000 description 2
- 230000009278 visceral effect Effects 0.000 description 2
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
- DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- WWMWAMFHUSTZTA-UHFFFAOYSA-N Adenosine tetraphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O WWMWAMFHUSTZTA-UHFFFAOYSA-N 0.000 description 1
- 206010049589 Afterbirth pain Diseases 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 206010002388 Angina unstable Diseases 0.000 description 1
- CKLJMWTZIZZHCS-UHFFFAOYSA-N Aspartic acid Chemical compound OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 1
- 240000006439 Aspergillus oryzae Species 0.000 description 1
- 235000002247 Aspergillus oryzae Nutrition 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010048994 Bladder spasm Diseases 0.000 description 1
- 208000020084 Bone disease Diseases 0.000 description 1
- QWUACGXLPZRCMH-MPXCPUAZSA-N C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](C(=C)OP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](C(=C)OP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O QWUACGXLPZRCMH-MPXCPUAZSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- ZNZYKNKBJPZETN-WELNAUFTSA-N Dialdehyde 11678 Chemical compound N1C2=CC=CC=C2C2=C1[C@H](C[C@H](/C(=C/O)C(=O)OC)[C@@H](C=C)C=O)NCC2 ZNZYKNKBJPZETN-WELNAUFTSA-N 0.000 description 1
- 102100039104 Dolichyl-diphosphooligosaccharide-protein glycosyltransferase subunit DAD1 Human genes 0.000 description 1
- 206010052804 Drug tolerance Diseases 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 102000011714 Glycine Receptors Human genes 0.000 description 1
- 108010076533 Glycine Receptors Proteins 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 101000884921 Homo sapiens Dolichyl-diphosphooligosaccharide-protein glycosyltransferase subunit DAD1 Proteins 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 208000037147 Hypercalcaemia Diseases 0.000 description 1
- 206010020843 Hyperthermia Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 206010022562 Intermittent claudication Diseases 0.000 description 1
- 241000581650 Ivesia Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 1
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 208000009525 Myocarditis Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000010191 Osteitis Deformans Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 102100040479 P2X purinoceptor 2 Human genes 0.000 description 1
- 101710189968 P2X purinoceptor 2 Proteins 0.000 description 1
- 208000027868 Paget disease Diseases 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- LHNKBXRFNPMIBR-UHFFFAOYSA-N Picrotoxin Natural products CC(C)(O)C1(O)C2OC(=O)C1C3(O)C4OC4C5C(=O)OC2C35C LHNKBXRFNPMIBR-UHFFFAOYSA-N 0.000 description 1
- 208000004550 Postoperative Pain Diseases 0.000 description 1
- 201000001068 Prinzmetal angina Diseases 0.000 description 1
- 206010062886 Procedural hypertension Diseases 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102000002294 Purinergic P2X Receptors Human genes 0.000 description 1
- 108010000836 Purinergic P2X Receptors Proteins 0.000 description 1
- 102000002298 Purinergic P2Y Receptors Human genes 0.000 description 1
- 108010000818 Purinergic P2Y Receptors Proteins 0.000 description 1
- 102000000033 Purinergic Receptors Human genes 0.000 description 1
- 108010080192 Purinergic Receptors Proteins 0.000 description 1
- 102000009609 Pyrophosphatases Human genes 0.000 description 1
- 108010009413 Pyrophosphatases Proteins 0.000 description 1
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 1
- QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 208000007718 Stable Angina Diseases 0.000 description 1
- 206010042496 Sunburn Diseases 0.000 description 1
- 229940100514 Syk tyrosine kinase inhibitor Drugs 0.000 description 1
- 206010057040 Temperature intolerance Diseases 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 208000030886 Traumatic Brain injury Diseases 0.000 description 1
- 208000007814 Unstable Angina Diseases 0.000 description 1
- 206010051958 Ureteral spasm Diseases 0.000 description 1
- 208000009325 Variant Angina Pectoris Diseases 0.000 description 1
- 206010047163 Vasospasm Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- WWMWAMFHUSTZTA-KQYNXXCUSA-N adenosine 5'-(pentahydrogen tetraphosphate) Chemical class C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O WWMWAMFHUSTZTA-KQYNXXCUSA-N 0.000 description 1
- UFZTZBNSLXELAL-IOSLPCCCSA-N adenosine 5'-[beta,gamma-methylene]triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)CP(O)(O)=O)[C@@H](O)[C@H]1O UFZTZBNSLXELAL-IOSLPCCCSA-N 0.000 description 1
- 229940121359 adenosine receptor antagonist Drugs 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000002583 angiography Methods 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 239000000164 antipsychotic agent Substances 0.000 description 1
- 229940005529 antipsychotics Drugs 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 230000000949 anxiolytic effect Effects 0.000 description 1
- 229940005530 anxiolytics Drugs 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 239000005388 borosilicate glass Substances 0.000 description 1
- HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Inorganic materials [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 description 1
- 230000004094 calcium homeostasis Effects 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000005056 cell body Anatomy 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000002475 cognitive enhancer Substances 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 230000009519 contusion Effects 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 208000002925 dental caries Diseases 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- MWEQTWJABOLLOS-UHFFFAOYSA-L disodium;[[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-oxidophosphoryl] hydrogen phosphate;trihydrate Chemical compound O.O.O.[Na+].[Na+].C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP([O-])(=O)OP(O)([O-])=O)C(O)C1O MWEQTWJABOLLOS-UHFFFAOYSA-L 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 208000028329 epileptic seizure Diseases 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 239000000928 excitatory amino acid agonist Substances 0.000 description 1
- 230000008622 extracellular signaling Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000003371 gabaergic effect Effects 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 208000007565 gingivitis Diseases 0.000 description 1
- 208000035474 group of disease Diseases 0.000 description 1
- 230000026781 habituation Effects 0.000 description 1
- 230000008543 heat sensitivity Effects 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 210000004295 hippocampal neuron Anatomy 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000000148 hypercalcaemia Effects 0.000 description 1
- 208000030915 hypercalcemia disease Diseases 0.000 description 1
- 230000036031 hyperthermia Effects 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003983 inhalation anesthetic agent Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 1
- 208000021156 intermittent vascular claudication Diseases 0.000 description 1
- 210000001153 interneuron Anatomy 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000001535 kindling effect Effects 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 208000027202 mammary Paget disease Diseases 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000001259 mesencephalon Anatomy 0.000 description 1
- 230000037023 motor activity Effects 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- NCGWKCHAJOUDHQ-UHFFFAOYSA-N n,n-diethylethanamine;formic acid Chemical compound OC=O.OC=O.CCN(CC)CC NCGWKCHAJOUDHQ-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 239000002664 nootropic agent Substances 0.000 description 1
- 230000001777 nootropic effect Effects 0.000 description 1
- 230000001473 noxious effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000000014 opioid analgesic Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000000082 organ preservation Substances 0.000 description 1
- 230000003534 oscillatory effect Effects 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000037324 pain perception Effects 0.000 description 1
- 230000000803 paradoxical effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- VJKUPQSHOVKBCO-AHMKVGDJSA-N picrotoxin Chemical compound O=C([C@@]12O[C@@H]1C[C@]1(O)[C@@]32C)O[C@@H]3[C@H]2[C@@H](C(=C)C)[C@@H]1C(=O)O2.O=C([C@@]12O[C@@H]1C[C@]1(O)[C@@]32C)O[C@@H]3[C@H]2[C@@H](C(C)(O)C)[C@@H]1C(=O)O2 VJKUPQSHOVKBCO-AHMKVGDJSA-N 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 210000004044 posterior horn cell Anatomy 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000000296 purinergic P1 receptor antagonist Substances 0.000 description 1
- 230000001696 purinergic effect Effects 0.000 description 1
- 210000002763 pyramidal cell Anatomy 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 1
- 229960003147 reserpine Drugs 0.000 description 1
- 230000006965 reversible inhibition Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000004065 semiconductor Substances 0.000 description 1
- 230000021317 sensory perception Effects 0.000 description 1
- 230000020341 sensory perception of pain Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- ZNJHFNUEQDVFCJ-UHFFFAOYSA-M sodium;2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid;hydroxide Chemical compound [OH-].[Na+].OCCN1CCN(CCS(O)(=O)=O)CC1 ZNJHFNUEQDVFCJ-UHFFFAOYSA-M 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 208000023516 stroke disease Diseases 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229920003002 synthetic resin Polymers 0.000 description 1
- 239000000057 synthetic resin Substances 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- YMBCJWGVCUEGHA-UHFFFAOYSA-M tetraethylammonium chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC YMBCJWGVCUEGHA-UHFFFAOYSA-M 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 206010043778 thyroiditis Diseases 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7084—Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07H21/02—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biochemistry (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pain & Pain Management (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Epidemiology (AREA)
- Psychology (AREA)
- Gastroenterology & Hepatology (AREA)
- Cardiology (AREA)
- Psychiatry (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Immunology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0502250.4A GB0502250D0 (en) | 2005-02-03 | 2005-02-03 | Use |
| PCT/GB2006/000343 WO2006082397A1 (en) | 2005-02-03 | 2006-02-01 | New uses of dinucleotide polyphosphate derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2008528665A true JP2008528665A (ja) | 2008-07-31 |
| JP2008528665A5 JP2008528665A5 (enExample) | 2009-03-19 |
Family
ID=34307930
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2007553689A Pending JP2008528665A (ja) | 2005-02-03 | 2006-02-01 | ジヌクレオチドポリリン酸誘導体の使用法 |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US20080319184A1 (enExample) |
| EP (1) | EP1846004A1 (enExample) |
| JP (1) | JP2008528665A (enExample) |
| CN (1) | CN101180066A (enExample) |
| AU (1) | AU2006210715A1 (enExample) |
| CA (1) | CA2596959A1 (enExample) |
| GB (1) | GB0502250D0 (enExample) |
| WO (1) | WO2006082397A1 (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015517565A (ja) * | 2012-05-25 | 2015-06-22 | グローバラコーン リミテッド | 疼痛の治療のためのジヌクレオシドポリリン酸 |
| CN109096346A (zh) * | 2017-06-21 | 2018-12-28 | 株式会社钟根堂 | 制备二核苷多磷酸化合物的方法 |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB201320962D0 (en) * | 2013-11-27 | 2014-01-08 | Globalacorn Ltd | Compositions |
| GB201320959D0 (en) * | 2013-11-27 | 2014-01-08 | Globalacorn Ltd | Compositions |
| WO2021123388A1 (en) * | 2019-12-20 | 2021-06-24 | Nuvamid Sa | Novel nicotinamide di-nucleotide derivatives and use thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998055494A1 (en) * | 1997-06-06 | 1998-12-10 | William Harvey Research Limited | Treatmemt and prophylaxis of infarction by dinucleotides |
| WO1999003480A1 (en) * | 1997-07-17 | 1999-01-28 | William Harvey Research Limited | Use of adenosine tri- or tetra-phosphates and their analogues for the treatment of cerebral infarction |
| WO2003039473A2 (en) * | 2001-11-06 | 2003-05-15 | Inspire Pharmaceuticals, Inc. | Method for treating or preventing inflammatory diseases |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5837861A (en) * | 1997-02-10 | 1998-11-17 | Inspire Pharmaceuticals, Inc. | Dinucleotides and their use as modulators of mucociliary clearance and ciliary beat frequency |
| US5681823A (en) * | 1996-05-02 | 1997-10-28 | Prp Inc. | P1, P4 -dithio-P2 -P3 -monochloromethylene 5', 5'"-diadenosine P1, P4 -tetraphosphate as antithrombotic agent |
| US6696425B2 (en) * | 1997-02-06 | 2004-02-24 | Inspire Pharmaceuticals, Inc. | Method of treating dry eye disease with purinergic receptor agonists |
| ES2264197T3 (es) * | 1997-02-06 | 2006-12-16 | Inspire Pharmaceuticals, Inc. | Dinucleotidos y sus usos. |
| US6596725B2 (en) * | 1997-02-10 | 2003-07-22 | Inspire Pharmaceuticals, Inc. | Use of certain dinucleotides to stimulate removal of fluid in retinal detachment and retinal edema |
| US7084126B1 (en) * | 2000-05-01 | 2006-08-01 | Healthpartners Research Foundation | Methods and compositions for enhancing cellular function through protection of tissue components |
| US6555675B2 (en) * | 2000-08-21 | 2003-04-29 | Inspire Pharmaceuticals, Inc. | Dinucleoside polyphosphate compositions and their therapuetic use as purinergic receptor agonists |
| GB2394419B (en) * | 2001-06-25 | 2005-09-07 | Inspire Pharmaceuticals Inc | Joint lubrication with p2y purinergic receptor agonists |
| US7203743B2 (en) * | 2001-12-28 | 2007-04-10 | Nortel Networks Limited | Hierarchical tree-based protection scheme for mesh networks |
-
2005
- 2005-02-03 GB GBGB0502250.4A patent/GB0502250D0/en not_active Ceased
-
2006
- 2006-02-01 WO PCT/GB2006/000343 patent/WO2006082397A1/en not_active Ceased
- 2006-02-01 JP JP2007553689A patent/JP2008528665A/ja active Pending
- 2006-02-01 AU AU2006210715A patent/AU2006210715A1/en not_active Abandoned
- 2006-02-01 US US11/883,661 patent/US20080319184A1/en not_active Abandoned
- 2006-02-01 CN CNA2006800090694A patent/CN101180066A/zh active Pending
- 2006-02-01 EP EP06704231A patent/EP1846004A1/en not_active Withdrawn
- 2006-02-01 CA CA002596959A patent/CA2596959A1/en not_active Abandoned
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998055494A1 (en) * | 1997-06-06 | 1998-12-10 | William Harvey Research Limited | Treatmemt and prophylaxis of infarction by dinucleotides |
| WO1999003480A1 (en) * | 1997-07-17 | 1999-01-28 | William Harvey Research Limited | Use of adenosine tri- or tetra-phosphates and their analogues for the treatment of cerebral infarction |
| WO2003039473A2 (en) * | 2001-11-06 | 2003-05-15 | Inspire Pharmaceuticals, Inc. | Method for treating or preventing inflammatory diseases |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015517565A (ja) * | 2012-05-25 | 2015-06-22 | グローバラコーン リミテッド | 疼痛の治療のためのジヌクレオシドポリリン酸 |
| CN109096346A (zh) * | 2017-06-21 | 2018-12-28 | 株式会社钟根堂 | 制备二核苷多磷酸化合物的方法 |
| JP2019006771A (ja) * | 2017-06-21 | 2019-01-17 | チョン クン ダン ファーマシューティカル コーポレーション | ジヌクレオシドポリリン酸化合物の製造方法｛Ｍｅｔｈｏｄ ｆｏｒ Ｐｒｅｐａｒｉｎｇ ａ Ｄｉｎｕｃｌｅｏｓｉｄｅ Ｐｏｌｙｐｈｏｓｐｈａｔｅ Ｃｏｍｐｏｕｎｄ｝ |
| JP7028727B2 (ja) | 2017-06-21 | 2022-03-02 | チョン クン ダン ファーマシューティカル コーポレーション | ジヌクレオシドポリリン酸化合物の製造方法｛Ｍｅｔｈｏｄ ｆｏｒ Ｐｒｅｐａｒｉｎｇ ａ Ｄｉｎｕｃｌｅｏｓｉｄｅ Ｐｏｌｙｐｈｏｓｐｈａｔｅ Ｃｏｍｐｏｕｎｄ｝ |
| JP7028727B6 (ja) | 2017-06-21 | 2022-03-14 | チョン クン ダン ファーマシューティカル コーポレーション | ジヌクレオシドポリリン酸化合物の製造方法｛Ｍｅｔｈｏｄ ｆｏｒ Ｐｒｅｐａｒｉｎｇ ａ Ｄｉｎｕｃｌｅｏｓｉｄｅ Ｐｏｌｙｐｈｏｓｐｈａｔｅ Ｃｏｍｐｏｕｎｄ｝ |
| JP2022065110A (ja) * | 2017-06-21 | 2022-04-26 | チョン クン ダン ファーマシューティカル コーポレーション | ジヌクレオシドポリリン酸化合物の製造方法 |
| CN109096346B (zh) * | 2017-06-21 | 2023-08-01 | 株式会社钟根堂 | 制备二核苷多磷酸化合物的方法 |
| JP7373598B2 (ja) | 2017-06-21 | 2023-11-02 | チョン クン ダン ファーマシューティカル コーポレーション | ジヌクレオシドポリリン酸化合物の製造方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| GB0502250D0 (en) | 2005-03-09 |
| WO2006082397A1 (en) | 2006-08-10 |
| AU2006210715A1 (en) | 2006-08-10 |
| CN101180066A (zh) | 2008-05-14 |
| EP1846004A1 (en) | 2007-10-24 |
| CA2596959A1 (en) | 2006-08-10 |
| US20080319184A1 (en) | 2008-12-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Boison | The adenosine kinase hypothesis of epileptogenesis | |
| Fields et al. | Purinergic signalling in neuron–glia interactions | |
| Burnstock | The journey to establish purinergic signalling in the gut | |
| Battaglia et al. | Selective blockade of type-1 metabotropic glutamate receptors induces neuroprotection by enhancing gabaergic transmission | |
| Kennedy | P2X receptors: targets for novel analgesics? | |
| BRPI0918868B1 (pt) | compostos moduladores do receptor de nmda e composições compreendendo os mesmos | |
| KR20180075630A (ko) | [1,2,4]트리아졸로[1,5-a]피리미딘-7-일 화합물 | |
| Wada et al. | Role of serotonin receptor subtype in seizures kindled from the feline hippocampus | |
| US20100284984A1 (en) | Adenosine and its mimetics. modulators, transport inhibitors, and receptor agonists as a therapeutic tool to replace or improve the efficacy of deep brain stimulation | |
| JP2015517565A (ja) | 疼痛の治療のためのジヌクレオシドポリリン酸 | |
| JP2008528665A (ja) | ジヌクレオチドポリリン酸誘導体の使用法 | |
| Natale et al. | Genetic up-regulation or pharmacological activation of the Na+/Ca2+ Exchanger 1 (NCX1) enhances hippocampal-dependent contextual and spatial learning and memory | |
| Rathbone et al. | AIT-082 as a potential neuroprotective and regenerative agent in stroke and central nervous system injury | |
| Darstein et al. | Strychnine-sensitive glycine receptors inducing [3H]-acetylcholine release in rat caudatoputamen: a new site of action of ethanol? | |
| Hasegawa¹ et al. | p75 neurotrophin receptor signaling in the nervous system | |
| Yamazaki et al. | Stimulatory and inhibitory effects of serotonergic hallucinogens on spinal mono-and polysynaptic reflex pathways in the rat | |
| Isaak et al. | Unveiling the Structure–Activity Relationships at the Orthosteric Binding Site of P2X Ion Channels: The Route to Selectivity | |
| RU2614759C1 (ru) | Анальгетический пептид из морской анемоны | |
| KR102237590B1 (ko) | 퓨린성 수용체의 펩티드 조절자 | |
| Yoon et al. | Sanjoinine A isolated from Semen Zizyphi Spinosi protects against kainic acid-induced convulsions | |
| Cho et al. | P2X and P2Y receptors mediate contraction induced by electrical field stimulation in feline esophageal smooth muscle | |
| Zubrzycka et al. | Inhibition of tongue reflex in rats by tooth pulp stimulation during cerebral ventricle perfusion with (6–11) substance P analogs | |
| Jung et al. | Group I mGluR regulates the polarity of spike-timing dependent plasticity in substantia gelatinosa neurons | |
| Verkhratsky et al. | Adenosine triphosphate (ATP) as a neurotransmitter | |
| Sala et al. | Polydeoxyribonucleotide (defibrotide) protects against post-ischemic behavioral, electroencephalographic and neuronal damage in the gerbil |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090127 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20090127 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120220 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20120709 |