FI116624B - Adenosiini A3 -reseptorin modulaattorit - Google Patents
Adenosiini A3 -reseptorin modulaattorit Download PDFInfo
- Publication number
- FI116624B FI116624B FI20002367A FI20002367A FI116624B FI 116624 B FI116624 B FI 116624B FI 20002367 A FI20002367 A FI 20002367A FI 20002367 A FI20002367 A FI 20002367A FI 116624 B FI116624 B FI 116624B
- Authority
- FI
- Finland
- Prior art keywords
- substituted
- alkyl
- triazolo
- amino
- compound
- Prior art date
Links
- 108010060261 Adenosine A3 Receptor Proteins 0.000 title claims description 13
- 102000008161 Adenosine A3 Receptor Human genes 0.000 title claims description 13
- 229940075993 receptor modulator Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 161
- -1 C 1 -C 10 -alkyl Chemical group 0.000 claims description 60
- 125000003118 aryl group Chemical group 0.000 claims description 39
- 238000002360 preparation method Methods 0.000 claims description 36
- 238000000034 method Methods 0.000 claims description 35
- 210000004027 cell Anatomy 0.000 claims description 34
- 125000000217 alkyl group Chemical group 0.000 claims description 32
- 230000027455 binding Effects 0.000 claims description 29
- 125000001424 substituent group Chemical group 0.000 claims description 21
- 125000001072 heteroaryl group Chemical group 0.000 claims description 19
- 210000004881 tumor cell Anatomy 0.000 claims description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 206010028980 Neoplasm Diseases 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 210000004556 brain Anatomy 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 10
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 10
- 125000005309 thioalkoxy group Chemical group 0.000 claims description 9
- 150000003852 triazoles Chemical class 0.000 claims description 9
- 125000003710 aryl alkyl group Chemical class 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- 206010020772 Hypertension Diseases 0.000 claims description 6
- 150000001408 amides Chemical group 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 125000004442 acylamino group Chemical group 0.000 claims description 5
- 125000004104 aryloxy group Chemical group 0.000 claims description 5
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical group C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 4
- 206010021143 Hypoxia Diseases 0.000 claims description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000004423 acyloxy group Chemical group 0.000 claims description 4
- 125000000266 alpha-aminoacyl group Chemical group 0.000 claims description 4
- 210000003630 histaminocyte Anatomy 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000005296 thioaryloxy group Chemical group 0.000 claims description 4
- 150000003672 ureas Chemical group 0.000 claims description 4
- 235000013877 carbamide Nutrition 0.000 claims description 3
- 125000001589 carboacyl group Chemical group 0.000 claims description 3
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 3
- 230000000747 cardiac effect Effects 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 208000035475 disorder Diseases 0.000 claims description 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
- 229940124530 sulfonamide Drugs 0.000 claims description 3
- 150000003456 sulfonamides Chemical group 0.000 claims description 3
- 125000005404 thioheteroaryloxy group Chemical group 0.000 claims description 3
- 206010061218 Inflammation Diseases 0.000 claims description 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 2
- 208000007502 anemia Diseases 0.000 claims description 2
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims description 2
- 239000006143 cell culture medium Substances 0.000 claims description 2
- 230000002490 cerebral effect Effects 0.000 claims description 2
- 230000004054 inflammatory process Effects 0.000 claims description 2
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 2
- 229930192474 thiophene Natural products 0.000 claims description 2
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims 10
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 6
- 125000005865 C2-C10alkynyl group Chemical group 0.000 claims 4
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 2
- 150000003556 thioamides Chemical group 0.000 claims 2
- 150000003585 thioureas Chemical group 0.000 claims 2
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 1
- 101100516554 Caenorhabditis elegans nhr-5 gene Proteins 0.000 claims 1
- 206010020751 Hypersensitivity Diseases 0.000 claims 1
- 125000005248 alkyl aryloxy group Chemical group 0.000 claims 1
- 230000001605 fetal effect Effects 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 90
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 85
- 238000005481 NMR spectroscopy Methods 0.000 description 61
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 58
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 43
- 239000003208 petroleum Substances 0.000 description 43
- 239000000203 mixture Substances 0.000 description 42
- 102000005962 receptors Human genes 0.000 description 40
- 108020003175 receptors Proteins 0.000 description 40
- 239000007787 solid Substances 0.000 description 40
- 235000019439 ethyl acetate Nutrition 0.000 description 37
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 28
- 239000000243 solution Substances 0.000 description 28
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 25
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 25
- 238000006243 chemical reaction Methods 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 102000004169 proteins and genes Human genes 0.000 description 21
- 108090000623 proteins and genes Proteins 0.000 description 21
- 238000003556 assay Methods 0.000 description 20
- 239000000872 buffer Substances 0.000 description 20
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 17
- 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 16
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 15
- 238000011534 incubation Methods 0.000 description 15
- 125000004432 carbon atom Chemical group C* 0.000 description 14
- 239000012528 membrane Substances 0.000 description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 14
- 238000010992 reflux Methods 0.000 description 14
- 238000003786 synthesis reaction Methods 0.000 description 14
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 14
- 125000003342 alkenyl group Chemical group 0.000 description 13
- 230000015572 biosynthetic process Effects 0.000 description 13
- 239000004615 ingredient Substances 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- 241000700159 Rattus Species 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- 230000009871 nonspecific binding Effects 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 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 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 238000001816 cooling Methods 0.000 description 9
- 230000002285 radioactive effect Effects 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 8
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 8
- 241000124008 Mammalia Species 0.000 description 8
- 229960005305 adenosine Drugs 0.000 description 8
- 125000000304 alkynyl group Chemical group 0.000 description 8
- 239000005557 antagonist Substances 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 150000003230 pyrimidines Chemical class 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 125000000547 substituted alkyl group Chemical group 0.000 description 8
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 8
- 102000009346 Adenosine receptors Human genes 0.000 description 7
- 108050000203 Adenosine receptors Proteins 0.000 description 7
- 150000001412 amines Chemical class 0.000 description 7
- 125000000753 cycloalkyl group Chemical group 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- SKTSVWWOAIAIKI-UHFFFAOYSA-N furan-2-carbohydrazide Chemical compound NNC(=O)C1=CC=CO1 SKTSVWWOAIAIKI-UHFFFAOYSA-N 0.000 description 7
- 239000003446 ligand Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 6
- JADDQZYHOWSFJD-FLNNQWSLSA-N N-ethyl-5'-carboxamidoadenosine Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NCC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 JADDQZYHOWSFJD-FLNNQWSLSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 108060000200 adenylate cyclase Proteins 0.000 description 6
- 102000030621 adenylate cyclase Human genes 0.000 description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
- 150000001735 carboxylic acids Chemical class 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 238000000159 protein binding assay Methods 0.000 description 6
- RIRGCFBBHQEQQH-SSFGXONLSA-N (-)-n6-(2-phenylisopropyl)adenosine Chemical compound C([C@@H](C)NC=1C=2N=CN(C=2N=CN=1)[C@H]1[C@@H]([C@H](O)[C@@H](CO)O1)O)C1=CC=CC=C1 RIRGCFBBHQEQQH-SSFGXONLSA-N 0.000 description 5
- WPWHSFAFEBZWBB-UHFFFAOYSA-N 1-butyl radical Chemical compound [CH2]CCC WPWHSFAFEBZWBB-UHFFFAOYSA-N 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 5
- 101150046889 ADORA3 gene Proteins 0.000 description 5
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 5
- OCBFFGCSTGGPSQ-UHFFFAOYSA-N [CH2]CC Chemical compound [CH2]CC OCBFFGCSTGGPSQ-UHFFFAOYSA-N 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 229910052731 fluorine Inorganic materials 0.000 description 5
- 125000005843 halogen group Chemical group 0.000 description 5
- 239000004005 microsphere Substances 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 238000007911 parenteral administration Methods 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 125000004426 substituted alkynyl group Chemical group 0.000 description 5
- 150000003458 sulfonic acid derivatives Chemical class 0.000 description 5
- XQOLMNXEGDTGML-UHFFFAOYSA-N triazolo[1,5-c]pyrimidine Chemical compound C1=NC=CC2=CN=NN21 XQOLMNXEGDTGML-UHFFFAOYSA-N 0.000 description 5
- 125000004953 trihalomethyl group Chemical group 0.000 description 5
- 229910052722 tritium Inorganic materials 0.000 description 5
- CWGBFIRHYJNILV-UHFFFAOYSA-N (1,4-diphenyl-1,2,4-triazol-4-ium-3-yl)-phenylazanide Chemical compound C=1C=CC=CC=1[N-]C1=NN(C=2C=CC=CC=2)C=[N+]1C1=CC=CC=C1 CWGBFIRHYJNILV-UHFFFAOYSA-N 0.000 description 4
- SZBULDQSDUXAPJ-XNIJJKJLSA-N (2r,3r,4s,5r)-2-[6-(cyclohexylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(NC3CCCCC3)=C2N=C1 SZBULDQSDUXAPJ-XNIJJKJLSA-N 0.000 description 4
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 4
- UVCLVQXCCHSVTH-UHFFFAOYSA-N 3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7,11-pentaene Chemical compound N1=CN2N=CN=C2C2=C1NN=C2 UVCLVQXCCHSVTH-UHFFFAOYSA-N 0.000 description 4
- UJIAOJXCYOPMFR-UHFFFAOYSA-N 3-amino-5-(1-phenylethyl)-1h-pyrazole-4-carbonitrile Chemical compound C=1C=CC=CC=1C(C)C=1NN=C(N)C=1C#N UJIAOJXCYOPMFR-UHFFFAOYSA-N 0.000 description 4
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
- 108010060263 Adenosine A1 Receptor Proteins 0.000 description 4
- 102000030814 Adenosine A1 receptor Human genes 0.000 description 4
- 101150051188 Adora2a gene Proteins 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 4
- UTLPKQYUXOEJIL-UHFFFAOYSA-N LSM-3822 Chemical compound N1=CC=2C3=NC(C=4OC=CC=4)=NN3C(N)=NC=2N1CCC1=CC=CC=C1 UTLPKQYUXOEJIL-UHFFFAOYSA-N 0.000 description 4
- XYSQEJMWZUTVIF-UHFFFAOYSA-N N=1N(CCCC)C=C(C2=N3)C=1N=CN2N=C3C1=CC=CO1 Chemical compound N=1N(CCCC)C=C(C2=N3)C=1N=CN2N=C3C1=CC=CO1 XYSQEJMWZUTVIF-UHFFFAOYSA-N 0.000 description 4
- 239000000556 agonist Substances 0.000 description 4
- 230000000903 blocking effect Effects 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 230000008878 coupling Effects 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000011737 fluorine Substances 0.000 description 4
- 150000004820 halides Chemical class 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 150000002367 halogens Chemical class 0.000 description 4
- 150000002431 hydrogen Chemical class 0.000 description 4
- 238000010348 incorporation Methods 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 239000002502 liposome Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 210000001577 neostriatum Anatomy 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 230000009870 specific binding Effects 0.000 description 4
- 150000003460 sulfonic acids Chemical class 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- PVWUFALGTCRIFZ-ZHAZZZEBSA-N 12-amino-11-(1,2-ditritiopropyl)-4-(furan-2-yl)-N-(4-methoxyphenyl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaene-7-carboxamide Chemical compound COC1=CC=C(C=C1)NC(=O)C1=NC=2C(C=3N1N=C(N=3)C=1OC=CC=1)=C(N(N=2)C(C(C)[3H])[3H])N PVWUFALGTCRIFZ-ZHAZZZEBSA-N 0.000 description 3
- SYOANZBNGDEJFH-UHFFFAOYSA-N 2,5-dihydro-1h-triazole Chemical compound C1NNN=C1 SYOANZBNGDEJFH-UHFFFAOYSA-N 0.000 description 3
- HUJXGQILHAUCCV-MOROJQBDSA-N 3-iodobenzyl-5'-N-methylcarboxamidoadenosine Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NC)O[C@H]1N1C2=NC=NC(NCC=3C=C(I)C=CC=3)=C2N=C1 HUJXGQILHAUCCV-MOROJQBDSA-N 0.000 description 3
- NWEAWDWNMJEULP-UHFFFAOYSA-N 4-(furan-2-yl)-11-(3-methylbutyl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaene Chemical compound N=1N(CCC(C)C)C=C(C2=N3)C=1N=CN2N=C3C1=CC=CO1 NWEAWDWNMJEULP-UHFFFAOYSA-N 0.000 description 3
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 description 3
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 3
- 102000055025 Adenosine deaminases Human genes 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- QLOWGDIISXJREF-UHFFFAOYSA-N [1,2,4]triazolo[1,5-c]pyrimidine Chemical compound C1=CN=CN2N=CN=C21 QLOWGDIISXJREF-UHFFFAOYSA-N 0.000 description 3
- 125000002877 alkyl aryl group Chemical group 0.000 description 3
- 150000001350 alkyl halides Chemical class 0.000 description 3
- 125000002947 alkylene group Chemical group 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 230000036770 blood supply Effects 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- KHXVFMOMODNRAN-UHFFFAOYSA-N chembl137879 Chemical compound N=1N(CC)C=C(C2=N3)C=1N=C(N)N2N=C3C1=CC=CO1 KHXVFMOMODNRAN-UHFFFAOYSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 125000000392 cycloalkenyl group Chemical group 0.000 description 3
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 3
- 125000002541 furyl group Chemical group 0.000 description 3
- 239000003365 glass fiber Substances 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 150000002463 imidates Chemical class 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 239000012948 isocyanate Substances 0.000 description 3
- 150000002513 isocyanates Chemical class 0.000 description 3
- 239000006210 lotion Substances 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 229910001629 magnesium chloride Inorganic materials 0.000 description 3
- 238000003760 magnetic stirring Methods 0.000 description 3
- QYSGYZVSCZSLHT-UHFFFAOYSA-N octafluoropropane Chemical compound FC(F)(F)C(F)(F)C(F)(F)F QYSGYZVSCZSLHT-UHFFFAOYSA-N 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 3
- 238000001525 receptor binding assay Methods 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- 238000004611 spectroscopical analysis Methods 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- YWBFPKPWMSWWEA-UHFFFAOYSA-O triazolopyrimidine Chemical compound BrC1=CC=CC(C=2N=C3N=CN[N+]3=C(NCC=3C=CN=CC=3)C=2)=C1 YWBFPKPWMSWWEA-UHFFFAOYSA-O 0.000 description 3
- 239000008215 water for injection Substances 0.000 description 3
- PBEHSPPPDCLCTM-SCFUHWHPSA-N (2r,3s,4r,5r)-2-(hydroxymethyl)-5-[6-(2-phenylpropan-2-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound C=1C=CC=CC=1C(C)(C)NC(C=1N=C2)=NC=NC=1N2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O PBEHSPPPDCLCTM-SCFUHWHPSA-N 0.000 description 2
- LOGOEBMHHXYBID-WBKNRDRNSA-N (2s,3s,4r,5r)-5-[6-[(4-amino-3-iodanylphenyl)methylamino]purin-9-yl]-3,4-dihydroxy-n-methyloxolane-2-carboxamide Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NC)O[C@H]1N1C2=NC=NC(NCC=3C=C([125I])C(N)=CC=3)=C2N=C1 LOGOEBMHHXYBID-WBKNRDRNSA-N 0.000 description 2
- LDYMCRRFCMRFKB-MOROJQBDSA-N (2s,3s,4r,5r)-5-[6-[(4-aminophenyl)methylamino]purin-9-yl]-3,4-dihydroxy-n-methyloxolane-2-carboxamide Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NC)O[C@H]1N1C2=NC=NC(NCC=3C=CC(N)=CC=3)=C2N=C1 LDYMCRRFCMRFKB-MOROJQBDSA-N 0.000 description 2
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 description 2
- JDEFSGPMHKUDLE-UHFFFAOYSA-N 11-ethyl-4-(furan-2-yl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaene Chemical compound N=1N(CC)C=C(C2=N3)C=1N=CN2N=C3C1=CC=CO1 JDEFSGPMHKUDLE-UHFFFAOYSA-N 0.000 description 2
- JNXNARSUXSJOEK-UHFFFAOYSA-N 12-amino-11-butyl-4-(furan-2-yl)-N-(4-methoxyphenyl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaene-7-carboxamide Chemical compound N12N=C(C=3OC=CC=3)N=C2C2=C(N)N(CCCC)N=C2N=C1C(=O)NC1=CC=C(OC)C=C1 JNXNARSUXSJOEK-UHFFFAOYSA-N 0.000 description 2
- FXLWBLVEXPXQEI-UHFFFAOYSA-N 2-aminopyrazole-3-carbonitrile Chemical class NN1N=CC=C1C#N FXLWBLVEXPXQEI-UHFFFAOYSA-N 0.000 description 2
- 125000004847 2-fluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 125000003853 4-amino-3-iodobenzyl group Chemical group [H]N([H])C1=C(I)C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- CQTHSFXNYBGSTK-UHFFFAOYSA-N 5-amino-1-[(4-fluorophenyl)methyl]triazole-4-carbonitrile Chemical compound NC1=C(C#N)N=NN1CC1=CC=C(F)C=C1 CQTHSFXNYBGSTK-UHFFFAOYSA-N 0.000 description 2
- FFNKBQRKZRMYCL-UHFFFAOYSA-N 5-amino-1h-pyrazole-4-carbonitrile Chemical compound NC1=NNC=C1C#N FFNKBQRKZRMYCL-UHFFFAOYSA-N 0.000 description 2
- RWNZAMWJEFJGJT-UHFFFAOYSA-N 5-amino-2h-triazole-4-carbonitrile Chemical class NC=1N=NNC=1C#N RWNZAMWJEFJGJT-UHFFFAOYSA-N 0.000 description 2
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- FFBDFADSZUINTG-UHFFFAOYSA-N DPCPX Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1C1CCCC1 FFBDFADSZUINTG-UHFFFAOYSA-N 0.000 description 2
- VBMOMCJXZUIGAJ-UHFFFAOYSA-N NC1=NC=2C(C=3N1N=C(N3)C=3OC=CC3)=CN(N2)C(C)C(C)C Chemical compound NC1=NC=2C(C=3N1N=C(N3)C=3OC=CC3)=CN(N2)C(C)C(C)C VBMOMCJXZUIGAJ-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- 241000700157 Rattus norvegicus Species 0.000 description 2
- 206010039085 Rhinitis allergic Diseases 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000008484 agonism Effects 0.000 description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- 201000010105 allergic rhinitis Diseases 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 150000001491 aromatic compounds Chemical class 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 210000001638 cerebellum Anatomy 0.000 description 2
- NSGXVWJIQHDYOE-UHFFFAOYSA-N chembl16894 Chemical compound N=1N(CCCC)C=C(C2=N3)C=1N=C(N)N2N=C3C1=CC=CO1 NSGXVWJIQHDYOE-UHFFFAOYSA-N 0.000 description 2
- SJZFDIQTLVHZRM-UHFFFAOYSA-N chembl344706 Chemical compound N=1N(CCC)C=C(C2=N3)C=1N=C(N)N2N=C3C1=CC=CO1 SJZFDIQTLVHZRM-UHFFFAOYSA-N 0.000 description 2
- KWNNEOHJLFPMKY-UHFFFAOYSA-N chembl423542 Chemical compound C1=C2C3=NC(C=4OC=CC=4)=NN3C(N)=NC2=NN1CCCC1=CC=CC=C1 KWNNEOHJLFPMKY-UHFFFAOYSA-N 0.000 description 2
- 238000012875 competitive assay Methods 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 229940125773 compound 10 Drugs 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- DGJMPUGMZIKDRO-UHFFFAOYSA-N cyanoacetamide Chemical compound NC(=O)CC#N DGJMPUGMZIKDRO-UHFFFAOYSA-N 0.000 description 2
- 125000006165 cyclic alkyl group Chemical group 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 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 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 150000003948 formamides Chemical class 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000011859 microparticle Substances 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- ODUCDPQEXGNKDN-UHFFFAOYSA-N nitroxyl Chemical compound O=N ODUCDPQEXGNKDN-UHFFFAOYSA-N 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 239000004031 partial agonist Substances 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 238000003653 radioligand binding assay Methods 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 125000005017 substituted alkenyl group Chemical group 0.000 description 2
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 150000003566 thiocarboxylic acids Chemical class 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 description 1
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 description 1
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
- UEQMFQIPTDUPPJ-UHFFFAOYSA-N 1-(azidomethyl)-4-fluorobenzene Chemical compound FC1=CC=C(CN=[N+]=[N-])C=C1 UEQMFQIPTDUPPJ-UHFFFAOYSA-N 0.000 description 1
- RVAKYDJLSSJUQI-UHFFFAOYSA-N 10-[(4-fluorophenyl)methyl]-4-(furan-2-yl)-3,4,5,7,9,10,12-heptazatricyclo[7.3.0.02,6]dodeca-1,6,11-trien-8-imine Chemical compound N12C(N)=NC3=NN(C=4OC=CC=4)NC3=C2N=CN1CC1=CC=C(F)C=C1 RVAKYDJLSSJUQI-UHFFFAOYSA-N 0.000 description 1
- XBAVLYPPKOPVEQ-UHFFFAOYSA-N 10-benzyl-4-(furan-2-yl)-3,4,5,7,9,10,12-heptazatricyclo[7.3.0.02,6]dodeca-1,6,11-trien-8-imine Chemical compound N12C(N)=NC3=NN(C=4OC=CC=4)NC3=C2N=CN1CC1=CC=CC=C1 XBAVLYPPKOPVEQ-UHFFFAOYSA-N 0.000 description 1
- JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical compound NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- HMCUJIFYBPSPPS-DFBHQHGXSA-N 2-[(2s,3s,4r,5r)-5-[6-[(4-amino-3-iodophenyl)methylamino]purin-9-yl]-3,4-dihydroxyoxolan-2-yl]-2-hydroxy-n-methylacetamide Chemical compound O[C@@H]1[C@H](O)[C@@H](C(O)C(=O)NC)O[C@H]1N1C2=NC=NC(NCC=3C=C(I)C(N)=CC=3)=C2N=C1 HMCUJIFYBPSPPS-DFBHQHGXSA-N 0.000 description 1
- 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical compound BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
- 238000005084 2D-nuclear magnetic resonance Methods 0.000 description 1
- TUGWYLVATABJHN-UHFFFAOYSA-N 2h-triazol-4-ylcyanamide Chemical compound N#CNC=1C=NNN=1 TUGWYLVATABJHN-UHFFFAOYSA-N 0.000 description 1
- WFOVEDJTASPCIR-UHFFFAOYSA-N 3-[(4-methyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)methylamino]-n-[[2-(trifluoromethyl)phenyl]methyl]benzamide Chemical compound N=1N=C(C=2C=CN=CC=2)N(C)C=1CNC(C=1)=CC=CC=1C(=O)NCC1=CC=CC=C1C(F)(F)F WFOVEDJTASPCIR-UHFFFAOYSA-N 0.000 description 1
- ZSAXYRYNTXXFRN-UHFFFAOYSA-N 3-amino-1-(2-phenylethyl)pyrazole-4-carbonitrile Chemical compound C1=C(C#N)C(N)=NN1CCC1=CC=CC=C1 ZSAXYRYNTXXFRN-UHFFFAOYSA-N 0.000 description 1
- SHEFMZBUSRYFBH-UHFFFAOYSA-N 3-amino-1-(3-methylbutyl)pyrazole-4-carbonitrile Chemical compound CC(C)CCN1C=C(C#N)C(N)=N1 SHEFMZBUSRYFBH-UHFFFAOYSA-N 0.000 description 1
- ROEUPUHYVCLSAD-UHFFFAOYSA-N 3-amino-1-butylpyrazole-4-carbonitrile;3-amino-1-methylpyrazole-4-carbonitrile Chemical compound CN1C=C(C#N)C(N)=N1.CCCCN1C=C(C#N)C(N)=N1 ROEUPUHYVCLSAD-UHFFFAOYSA-N 0.000 description 1
- KQESLKFOEQDJCY-UHFFFAOYSA-N 3-amino-5-(2-phenylethyl)-1h-pyrazole-4-carbonitrile Chemical class NC1=NNC(CCC=2C=CC=CC=2)=C1C#N KQESLKFOEQDJCY-UHFFFAOYSA-N 0.000 description 1
- 125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 description 1
- KNWFSKWYHMIHBO-UHFFFAOYSA-N 4-(furan-2-yl)-10-(3-methylbutyl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7,11-pentaene Chemical compound CC(C)CCN1N=CC(C2=N3)=C1N=CN2N=C3C1=CC=CO1 KNWFSKWYHMIHBO-UHFFFAOYSA-N 0.000 description 1
- LFCWHIUZXFRLCR-UHFFFAOYSA-N 4-(furan-2-yl)-10-methyl-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(9),2,4,7,11-pentaene Chemical compound CN1N=CC(C2=N3)=C1N=CN2N=C3C1=CC=CO1 LFCWHIUZXFRLCR-UHFFFAOYSA-N 0.000 description 1
- SKWLUVWLCDCWPG-UHFFFAOYSA-N 4-(furan-2-yl)-11-(2-phenylethyl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaene Chemical compound C=1C=CC=CC=1CCN(N=1)C=C(C2=N3)C=1N=CN2N=C3C1=CC=CO1 SKWLUVWLCDCWPG-UHFFFAOYSA-N 0.000 description 1
- FAELKDIIGMFPPA-UHFFFAOYSA-N 4-(furan-2-yl)-11-(3-methylbut-2-enyl)-3,5,6,8,10,11-hexazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,7,9-pentaene Chemical compound N=1N(CC=C(C)C)C=C(C2=N3)C=1N=CN2N=C3C1=CC=CO1 FAELKDIIGMFPPA-UHFFFAOYSA-N 0.000 description 1
- KDXBFLFKAFQDDG-UHFFFAOYSA-N 4-[5-(furan-2-yl)-1h-1,2,4-triazol-3-yl]-1-(2-phenylethyl)pyrazol-3-amine Chemical compound C1=C(C=2N=C(NN=2)C=2OC=CC=2)C(N)=NN1CCC1=CC=CC=C1 KDXBFLFKAFQDDG-UHFFFAOYSA-N 0.000 description 1
- WYFCZWSWFGJODV-MIANJLSGSA-N 4-[[(1s)-2-[(e)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-(4-methyl-2-oxopiperazin-1-yl)-3,4-dihydro-1h-isoquinoline-1-carbonyl]amino]benzoic acid Chemical compound O=C1CN(C)CCN1C1=CC=CC2=C1CCN(C(=O)\C=C\C=1C(=CC=C(Cl)C=1F)N1N=NN=C1)[C@@H]2C(=O)NC1=CC=C(C(O)=O)C=C1 WYFCZWSWFGJODV-MIANJLSGSA-N 0.000 description 1
- SYBADJJDCVDEGD-UHFFFAOYSA-N 5-[5-(furan-2-yl)-1H-1,2,4-triazol-3-yl]-2H-triazol-4-amine Chemical class Nc1[nH]nnc1-c1nc(n[nH]1)-c1ccco1 SYBADJJDCVDEGD-UHFFFAOYSA-N 0.000 description 1
- FAKNEJZRRRHJEU-UHFFFAOYSA-N 5-amino-1-(2-chlorophenyl)pyrazole-4-carbonitrile Chemical compound NC1=C(C#N)C=NN1C1=CC=CC=C1Cl FAKNEJZRRRHJEU-UHFFFAOYSA-N 0.000 description 1
- OAWLDLJXGKITPG-UHFFFAOYSA-N 5-amino-1-[(2-chloro-6-fluorophenyl)methyl]triazole-4-carbonitrile Chemical compound NC1=C(C#N)N=NN1CC1=C(F)C=CC=C1Cl OAWLDLJXGKITPG-UHFFFAOYSA-N 0.000 description 1
- VNQWYAWATIOYNN-UHFFFAOYSA-N 5-amino-1-butylpyrazole-4-carbonitrile Chemical compound CCCCN1N=CC(C#N)=C1N VNQWYAWATIOYNN-UHFFFAOYSA-N 0.000 description 1
- AALDXFFFJTWDIM-UHFFFAOYSA-N 5-amino-2-(3-methylbutyl)triazole-4-carbonitrile Chemical compound CC(C)CCN1N=C(N)C(C#N)=N1 AALDXFFFJTWDIM-UHFFFAOYSA-N 0.000 description 1
- DHOIPXZHIMOIHV-UHFFFAOYSA-N 5-amino-2-[(2-fluorophenyl)methyl]triazole-4-carbonitrile Chemical compound N1=C(C#N)C(N)=NN1CC1=CC=CC=C1F DHOIPXZHIMOIHV-UHFFFAOYSA-N 0.000 description 1
- QIOUOGPOGTZPHF-UHFFFAOYSA-N 5-amino-2-[(4-fluorophenyl)methyl]triazole-4-carbonitrile Chemical compound N1=C(C#N)C(N)=NN1CC1=CC=C(F)C=C1 QIOUOGPOGTZPHF-UHFFFAOYSA-N 0.000 description 1
- ZLVMINWGLLHHFE-UHFFFAOYSA-N 5-amino-2-benzyltriazole-4-carbonitrile Chemical compound N1=C(C#N)C(N)=NN1CC1=CC=CC=C1 ZLVMINWGLLHHFE-UHFFFAOYSA-N 0.000 description 1
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 1
- BVXUKMCTHSFMOS-UHFFFAOYSA-N 8-(furan-2-yl)-3,4,5,7,9,10,12-heptazatricyclo[7.3.0.02,6]dodeca-1(12),2,4,6,10-pentaene Chemical compound C1=COC(C2N3N=CN=C3C3=NN=NC3=N2)=C1 BVXUKMCTHSFMOS-UHFFFAOYSA-N 0.000 description 1
- JRLTTZUODKEYDH-UHFFFAOYSA-N 8-methylquinoline Chemical group C1=CN=C2C(C)=CC=CC2=C1 JRLTTZUODKEYDH-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102000007471 Adenosine A2A receptor Human genes 0.000 description 1
- 108010085277 Adenosine A2A receptor Proteins 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ALDRYCJFTJSORK-UHFFFAOYSA-N C=1C=CC=CC=1CC(=NN1C=NC2=N3)N=C1C2=NN3C1=CC=CO1 Chemical compound C=1C=CC=CC=1CC(=NN1C=NC2=N3)N=C1C2=NN3C1=CC=CO1 ALDRYCJFTJSORK-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 101100397586 Danio rerio jag1a gene Proteins 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 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 1
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Polymers OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 208000001953 Hypotension 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
- 102000004310 Ion Channels Human genes 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- GUXAMEQKVYXFSK-UHFFFAOYSA-N N1=C2N=CN3N=C(CCCCCCC)N=C3C2=NN1C1=CC=CO1 Chemical compound N1=C2N=CN3N=C(CCCCCCC)N=C3C2=NN1C1=CC=CO1 GUXAMEQKVYXFSK-UHFFFAOYSA-N 0.000 description 1
- ZKUQRUMTYGTDAJ-UHFFFAOYSA-N N1=C2N=CN3N=C(CCCCCCCC)N=C3C2=NN1C1=CC=CO1 Chemical compound N1=C2N=CN3N=C(CCCCCCCC)N=C3C2=NN1C1=CC=CO1 ZKUQRUMTYGTDAJ-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000007660 Residual Neoplasm Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 208000000389 T-cell leukemia Diseases 0.000 description 1
- 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 229940121359 adenosine receptor antagonist Drugs 0.000 description 1
- 150000003838 adenosines Chemical class 0.000 description 1
- 125000000033 alkoxyamino group Chemical group 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 230000001088 anti-asthma Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000648 anti-parkinson Effects 0.000 description 1
- 239000000924 antiasthmatic agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000000939 antiparkinson agent Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 230000002763 arrhythmic effect Effects 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- BUZRUIZTMOKRPB-UHFFFAOYSA-N carboxycarbamic acid Chemical compound OC(=O)NC(O)=O BUZRUIZTMOKRPB-UHFFFAOYSA-N 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- CBHWZESTUNVRSU-UHFFFAOYSA-N chembl16508 Chemical compound N=1N2C(N)=NC=3N(CCO)N=CC=3C2=NC=1C1=CC=CO1 CBHWZESTUNVRSU-UHFFFAOYSA-N 0.000 description 1
- KJPNSZSRTOORTA-UHFFFAOYSA-N chembl16509 Chemical compound N=1N2C(N)=NC=3N(C=4C=CC=CC=4)N=CC=3C2=NC=1C1=CC=CO1 KJPNSZSRTOORTA-UHFFFAOYSA-N 0.000 description 1
- YHJRRZYBKBAVDT-UHFFFAOYSA-N chembl17094 Chemical compound CCCCN1N=CC(C2=N3)=C1N=C(N)N2N=C3C1=CC=CO1 YHJRRZYBKBAVDT-UHFFFAOYSA-N 0.000 description 1
- WFWZCXBEKOUWJL-UHFFFAOYSA-N chembl17281 Chemical compound N1=CC=2C3=NC(C=4OC=CC=4)=NN3C(N)=NC=2N1CCOCC1=CC=CC=C1 WFWZCXBEKOUWJL-UHFFFAOYSA-N 0.000 description 1
- DBOSLFUBDMMBMA-UHFFFAOYSA-N chembl277589 Chemical compound CN1N=CC(C2=N3)=C1N=C(N)N2N=C3C1=CC=CO1 DBOSLFUBDMMBMA-UHFFFAOYSA-N 0.000 description 1
- IRAJAJYBBMVTFR-UHFFFAOYSA-N chembl280067 Chemical compound CC(C)(C)N1N=CC(C2=N3)=C1N=C(N)N2N=C3C1=CC=CO1 IRAJAJYBBMVTFR-UHFFFAOYSA-N 0.000 description 1
- NXSARBYAOXIQJA-UHFFFAOYSA-N chembl315150 Chemical compound N=1N(CCC(C)C)C=C(C2=N3)C=1N=C(N)N2N=C3C1=CC=CO1 NXSARBYAOXIQJA-UHFFFAOYSA-N 0.000 description 1
- PKVBGKUACUZPER-UHFFFAOYSA-N chembl342059 Chemical compound N=1N(C)C=C(C2=N3)C=1N=C(N)N2N=C3C1=CC=CO1 PKVBGKUACUZPER-UHFFFAOYSA-N 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- 125000004986 diarylamino group Chemical group 0.000 description 1
- 125000005240 diheteroarylamino group Chemical group 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- MLEDMGQDCYYSAH-UHFFFAOYSA-N ethyl n-(2-butyl-4-cyanopyrazol-3-yl)methanimidate Chemical compound CCCCN1N=CC(C#N)=C1N=COCC MLEDMGQDCYYSAH-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000012025 fluorinating agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 210000002418 meninge Anatomy 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000007932 molded tablet Substances 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- IOMMMLWIABWRKL-WUTDNEBXSA-N nazartinib Chemical compound C1N(C(=O)/C=C/CN(C)C)CCCC[C@H]1N1C2=C(Cl)C=CC=C2N=C1NC(=O)C1=CC=NC(C)=C1 IOMMMLWIABWRKL-WUTDNEBXSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 229940096978 oral tablet Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000003379 purinergic P1 receptor agonist Substances 0.000 description 1
- 239000000296 purinergic P1 receptor antagonist Substances 0.000 description 1
- 230000001696 purinergic effect Effects 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- XVIAPHVAGFEFFN-UHFFFAOYSA-N pyrimidine-5-carbonitrile Chemical compound N#CC1=CN=CN=C1 XVIAPHVAGFEFFN-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000007423 screening assay Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000012421 spiking Methods 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 150000003461 sulfonyl halides Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 230000002381 testicular Effects 0.000 description 1
- 125000005207 tetraalkylammonium group Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
- C07D513/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/14—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0459—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/0491—Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers
-
- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- 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
-
- 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
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
-
- 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
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
- G01N2333/72—Assays involving receptors, cell surface antigens or cell surface determinants for hormones
- G01N2333/726—G protein coupled receptor, e.g. TSHR-thyrotropin-receptor, LH/hCG receptor, FSH
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Optics & Photonics (AREA)
- Physics & Mathematics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Saccharide Compounds (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US15443598 | 1998-09-16 | ||
US09/154,435 US6448253B1 (en) | 1998-09-16 | 1998-09-16 | Adenosine A3 receptor modulators |
US09/379,300 US6407236B1 (en) | 1998-09-16 | 1999-08-23 | Adenosine A3 receptor modulators |
US37930099 | 1999-08-23 | ||
US9921103 | 1999-09-15 | ||
PCT/US1999/021103 WO2000015231A1 (en) | 1998-09-16 | 1999-09-15 | Adenosine a3 receptor modulators |
Publications (2)
Publication Number | Publication Date |
---|---|
FI20002367A FI20002367A (fi) | 2001-01-19 |
FI116624B true FI116624B (fi) | 2006-01-13 |
Family
ID=22551355
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
FI20002367A FI116624B (fi) | 1998-09-16 | 2000-10-27 | Adenosiini A3 -reseptorin modulaattorit |
Country Status (28)
Country | Link |
---|---|
US (2) | US6448253B1 (ru) |
JP (1) | JP2002524519A (ru) |
KR (1) | KR100448555B1 (ru) |
CN (1) | CN1154494C (ru) |
AT (2) | AT414240B (ru) |
AU (1) | AU749211B2 (ru) |
BR (1) | BR9913766A (ru) |
CA (1) | CA2332007C (ru) |
CH (1) | CH692132A5 (ru) |
DE (1) | DE19983530T1 (ru) |
DK (1) | DK200100432A (ru) |
ES (1) | ES2204262B1 (ru) |
FI (1) | FI116624B (ru) |
GB (1) | GB2353527B (ru) |
HK (1) | HK1035671A1 (ru) |
HU (1) | HUP0102589A3 (ru) |
ID (1) | ID28100A (ru) |
IL (1) | IL156851A (ru) |
LU (1) | LU90687B1 (ru) |
NO (1) | NO318078B1 (ru) |
NZ (1) | NZ509149A (ru) |
RO (1) | RO121030B1 (ru) |
RU (1) | RU2250904C2 (ru) |
SE (1) | SE522578C2 (ru) |
TR (1) | TR200003461T2 (ru) |
WO (1) | WO2000015231A1 (ru) |
YU (1) | YU83600A (ru) |
ZA (1) | ZA200101626B (ru) |
Families Citing this family (51)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6921825B2 (en) * | 1998-09-16 | 2005-07-26 | King Pharmaceuticuals Research & Development, Inc. | Adenosine A3 receptor modulators |
IL133680A0 (en) | 1999-09-10 | 2001-04-30 | Can Fite Technologies Ltd | Pharmaceutical compositions comprising an adenosine receptor agonist or antagonist |
JPWO2002062801A1 (ja) * | 2001-02-05 | 2004-06-10 | 株式会社大塚製薬工場 | トリアゾロキナゾリン及びピラゾロトリアゾロピリミジン誘導体、医薬組成物、アデノシンa3受容体親和剤、眼圧低下剤、緑内障の予防及び治療のための製剤、並びに眼圧低下方法 |
CN1692116A (zh) * | 2001-11-30 | 2005-11-02 | 先灵公司 | 腺苷A2a受体拮抗剂 |
HUP0105407A3 (en) * | 2001-12-21 | 2004-04-28 | Sanofi Aventis | Triazolo[1,5-a]quinolin derivatives, process for their preparation, pharmaceutical compositions thereof and intermediates |
EP1549319A2 (en) * | 2002-05-30 | 2005-07-06 | King Pharmaceuticals Research and Development Inc. | Pharmaceutically active compounds having a tricyclic pyrazolotriazolopyrimidine ring structure and methods of use |
AU2003277044A1 (en) * | 2002-09-30 | 2004-04-23 | The Trustees Of Boston University | Method of treating cancer using adenosine and its analogs |
WO2004032864A2 (en) * | 2002-10-07 | 2004-04-22 | Radiorx, Inc. | X-nitro compounds, pharmaceutical compositions thereof and uses therof |
ATE371191T1 (de) * | 2002-10-22 | 2007-09-15 | Can Fite Biopharma Ltd | Die verwendung von dem a3 adenosin rezeptor als marker eines krankheitszustandes |
HUP0203976A3 (en) * | 2002-11-15 | 2004-08-30 | Sanofi Aventis | Adenozine a3 receptors, process for their preparation and pharmaceutical compositions containing them |
US7402625B2 (en) * | 2003-06-11 | 2008-07-22 | 3M Innovative Properties Company | Compositions and method for improving the processing of polymer composites |
US8236874B2 (en) * | 2003-06-11 | 2012-08-07 | 3M Innovative Properties Company | Compositions and method for improving the processing of polymer composites |
EP1678182B1 (en) * | 2003-10-28 | 2007-02-07 | Schering Corporation | Process for preparing substituted 5-amino-pyrazolo- [4,3-e]-1,2,4-triazolo [1,5-c]pyrimidines |
KR20060111581A (ko) * | 2003-12-19 | 2006-10-27 | 쉐링 코포레이션 | 약제학적 조성물 |
EP1766060A4 (en) * | 2004-05-14 | 2007-11-28 | King Pharmaceuticals Res & Dev | METHODS FOR DIAGNOSIS AND PROGNOSIS OF SOLID TUMORS AND MELANOMAS |
US20060194756A1 (en) * | 2004-11-22 | 2006-08-31 | Borea Pier A | Enhancing treatment of HIF-1 mediated disorders with adenosine A3 receptor agonists |
CA2586420A1 (en) * | 2004-11-22 | 2007-04-12 | King Pharmaceuticals Research & Development, Inc. | Enhancing treatment of cancer and hif-1 mediated disoders with adenosine a3 receptor antagonists |
US7507842B2 (en) * | 2005-08-12 | 2009-03-24 | Radiorx, Inc. | Cyclic nitro compounds, pharmaceutical compositions thereof and uses thereof |
US20070135380A1 (en) | 2005-08-12 | 2007-06-14 | Radiorx, Inc. | O-nitro compounds, pharmaceutical compositions thereof and uses thereof |
US20090088403A1 (en) * | 2007-05-07 | 2009-04-02 | Randy Blakely | A3 adenosine receptors as targets for the modulation of central serotonergic signaling |
JP2011528363A (ja) * | 2008-07-16 | 2011-11-17 | キング・ファーマシューティカルズ・リサーチ・アンド・デベロプメント・インコーポレイティッド | アテローム性動脈硬化症の治療 |
TWI404931B (zh) * | 2009-02-20 | 2013-08-11 | Nat Synchrotron Radiation Res Ct | 癌化生物樣本之檢測方法及其使用之檢驗試劑 |
WO2011010306A1 (en) | 2009-07-21 | 2011-01-27 | Ramot At Tel-Aviv University Ltd. | A3 adenosine receptor ligands for modulation of pigmentation |
PL2506716T3 (pl) * | 2009-12-01 | 2017-10-31 | Abbvie Inc | Nowe związki tricykliczne |
US8471041B2 (en) * | 2010-02-09 | 2013-06-25 | Alliant Techsystems Inc. | Methods of synthesizing and isolating N-(bromoacetyl)-3,3-dinitroazetidine and a composition including the same |
US8664247B2 (en) | 2011-08-26 | 2014-03-04 | Radiorx, Inc. | Acyclic organonitro compounds for use in treating cancer |
WO2013052803A2 (en) | 2011-10-07 | 2013-04-11 | Radiorx, Inc. | Methods and compositions comprising a nitrite-reductase promoter for treatment of medical disorders and preservation of blood products |
US9139519B2 (en) | 2011-10-07 | 2015-09-22 | Epicentrx, Inc. | Organonitro thioether compounds and medical uses thereof |
US9227979B2 (en) * | 2012-01-25 | 2016-01-05 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Fluorescent antagonists of the A3 adenosine receptor |
ES2578363B1 (es) | 2015-01-22 | 2017-01-31 | Palobiofarma, S.L. | Moduladores de los receptores A3 de adenosina |
WO2016202935A1 (en) * | 2015-06-19 | 2016-12-22 | Bayer Pharma Aktiengesellschaft | Glucose transport inhibitors |
US11780848B2 (en) | 2015-10-16 | 2023-10-10 | Abbvie Inc. | Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]-pyrazin-8-yl)-n-(2,2,2-trifluoroethyl)pyrrolidine-1- carboxamide and solid state forms thereof |
US11512092B2 (en) | 2015-10-16 | 2022-11-29 | Abbvie Inc. | Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]-pyrazin-8-yl)-n-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof |
SG10201913999PA (en) | 2015-10-16 | 2020-03-30 | Abbvie Inc | PROCESSES FOR THE PREPARATION OF (3S,4R)-3-ETHYL-4-(3H-IMIDAZO[1,2-a]PYRROLO[2,3-e]-PYRAZIN-8-YL)-N-(2,2,2-TRIFLUOROETHYL)PYRROLIDINE-1-CARBOXAMIDE AND SOLID STATE FORMS THEREOF |
US11365198B2 (en) | 2015-10-16 | 2022-06-21 | Abbvie Inc. | Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]-pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof |
US10550126B2 (en) | 2015-10-16 | 2020-02-04 | Abbvie Inc. | Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-A]pyrrolo[2,3-e]-pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof |
US11524964B2 (en) | 2015-10-16 | 2022-12-13 | Abbvie Inc. | Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]-pyrazin-8-yl)-n-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof |
US10342778B1 (en) | 2015-10-20 | 2019-07-09 | Epicentrx, Inc. | Treatment of brain metastases using organonitro compound combination therapy |
US9987270B1 (en) | 2015-10-29 | 2018-06-05 | Epicentrix, Inc. | Treatment of gliomas using organonitro compound combination therapy |
PL3402480T3 (pl) | 2016-01-11 | 2021-11-22 | Epicentrx, Inc. | Kompozycje i sposoby dożylnego podawania 2-bromo-1-(3,3-dinitroazetydyn-1-ylo)etanonu |
AU2017342436C1 (en) | 2016-10-14 | 2022-11-03 | Epicentrx, Inc. | Sulfoxyalkyl organonitro and related compounds and pharmaceutical compositions for use in medicine |
ES2676535B1 (es) | 2017-01-20 | 2019-04-29 | Palobiofarma Sl | Moduladores de los receptores a3 de adenosina |
EP3592353A1 (en) | 2017-03-09 | 2020-01-15 | AbbVie Inc. | Methods of treating crohn's disease and ulcerative colitis |
US11564922B2 (en) | 2017-03-09 | 2023-01-31 | Abbvie Inc. | Methods of treating crohn's disease and ulcerative colitis |
LT3601296T (lt) | 2017-03-30 | 2022-09-26 | iTeos Belgium SA | 2-okso-tiazolo derivatai kaip a2a inhibitoriai ir junginiai, skirti naudoti gydant vėžį |
CN111511350B (zh) | 2017-07-07 | 2023-10-13 | 埃皮辛特瑞柯斯公司 | 用于治疗剂的肠胃外施用的组合物 |
US11510901B2 (en) | 2018-01-08 | 2022-11-29 | Epicentrx, Inc. | Methods and compositions utilizing RRx-001 combination therapy for radioprotection |
CN108864114B (zh) | 2018-06-04 | 2020-11-06 | 应世生物科技(南京)有限公司 | 选择性a2a受体拮抗剂 |
US11376255B2 (en) | 2018-09-11 | 2022-07-05 | iTeos Belgium SA | Thiocarbamate derivatives as A2A inhibitors, pharmaceutical composition thereof and combinations with anticancer agents |
CN111205291B (zh) * | 2018-11-22 | 2022-08-23 | 上海科技大学 | 三唑并环类化合物、其制备方法、中间体和应用 |
CN111004245B (zh) * | 2019-12-11 | 2022-01-07 | 徐州医科大学 | 吡唑-嘧啶并咪唑类化合物、制备方法及其应用 |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3625214A (en) | 1970-05-18 | 1971-12-07 | Alza Corp | Drug-delivery device |
US4906474A (en) | 1983-03-22 | 1990-03-06 | Massachusetts Institute Of Technology | Bioerodible polyanhydrides for controlled drug delivery |
US4789734A (en) | 1985-08-06 | 1988-12-06 | La Jolla Cancer Research Foundation | Vitronectin specific cell receptor derived from mammalian mesenchymal tissue |
JP2876058B2 (ja) | 1986-08-18 | 1999-03-31 | エミスフィア・テクノロジーズ・インコーポレイテッド | 薬物送達システム |
DE3781080T2 (de) * | 1986-09-30 | 1992-12-24 | Ciba Geigy Ag | 2-substituierte-e-kondensierte(1,2,4)triazolo-(1,5-c)pyrimidine, pharmazeutische zubereitungen und ihre verwendung. |
IT1264901B1 (it) | 1993-06-29 | 1996-10-17 | Schering Plough S P A | Analoghi eterociclici di 1,2,4-triazolo(15-c)pirimidine ad attivita' antagonista per il recettore a2 dell'adenosina |
US5688774A (en) | 1993-07-13 | 1997-11-18 | The United States Of America As Represented By The Department Of Health And Human Services | A3 adenosine receptor agonists |
US5565460A (en) * | 1993-07-27 | 1996-10-15 | Kyowa Hakko Koygo Co., Ltd. | Therapeutic purine agents for parkinson's disease |
IT1275420B (it) | 1995-06-02 | 1997-08-05 | Schering Plough S P A | Metodo per misurare l'affinita' di legame al recettore a2a dell'adenosina di componenti di interesse farmacologico mediante l'uso del ligando triziato (3h)-sch 58261 |
IT1277392B1 (it) | 1995-07-28 | 1997-11-10 | Schering Plough S P A | Analoghi eterociclici di 1,2,4-triazolo(1,5-c]pirimidine ad attivita' antagonista per il recettore a2a dell'adenosina |
ATE548351T1 (de) * | 1996-01-29 | 2012-03-15 | Us Of America Represented By The Secretary Dept Of Health And Human Services | Dihydropyridin-pyridin-, benzopyranon- und triazolochinazolin-derivate, deren herstellung und verwendung als adenosinrezeptor-antagonisten |
US6326390B1 (en) * | 1998-08-25 | 2001-12-04 | King Pharmaceuticals Reseach And Development, Inc. | Use of adenosine A3 receptor antagonists to inhibit tumor growth |
-
1998
- 1998-09-16 US US09/154,435 patent/US6448253B1/en not_active Expired - Lifetime
-
1999
- 1999-08-23 US US09/379,300 patent/US6407236B1/en not_active Expired - Lifetime
- 1999-09-15 HU HU0102589A patent/HUP0102589A3/hu unknown
- 1999-09-15 RU RU2000127721/15A patent/RU2250904C2/ru not_active IP Right Cessation
- 1999-09-15 ES ES200150007A patent/ES2204262B1/es not_active Expired - Fee Related
- 1999-09-15 NZ NZ509149A patent/NZ509149A/en unknown
- 1999-09-15 AU AU62482/99A patent/AU749211B2/en not_active Ceased
- 1999-09-15 ID IDW20002336A patent/ID28100A/id unknown
- 1999-09-15 YU YU83600A patent/YU83600A/sh unknown
- 1999-09-15 KR KR10-2001-7001542A patent/KR100448555B1/ko not_active IP Right Cessation
- 1999-09-15 CN CNB998065943A patent/CN1154494C/zh not_active Expired - Fee Related
- 1999-09-15 AT AT0904399A patent/AT414240B/de not_active IP Right Cessation
- 1999-09-15 RO ROA200001172A patent/RO121030B1/ro unknown
- 1999-09-15 TR TR2000/03461T patent/TR200003461T2/xx unknown
- 1999-09-15 JP JP2000569815A patent/JP2002524519A/ja not_active Abandoned
- 1999-09-15 CA CA002332007A patent/CA2332007C/en not_active Expired - Fee Related
- 1999-09-15 DE DE19983530T patent/DE19983530T1/de not_active Withdrawn
- 1999-09-15 WO PCT/US1999/021103 patent/WO2000015231A1/en not_active IP Right Cessation
- 1999-09-15 GB GB0027879A patent/GB2353527B/en not_active Expired - Fee Related
- 1999-09-15 BR BR9913766-6A patent/BR9913766A/pt not_active Application Discontinuation
- 1999-09-15 CH CH00012/01A patent/CH692132A5/de not_active IP Right Cessation
-
2000
- 2000-10-27 FI FI20002367A patent/FI116624B/fi not_active IP Right Cessation
- 2000-11-01 SE SE0003984A patent/SE522578C2/sv unknown
- 2000-11-01 NO NO20005508A patent/NO318078B1/no unknown
- 2000-12-06 LU LU90687A patent/LU90687B1/en active
-
2001
- 2001-02-27 ZA ZA200101626A patent/ZA200101626B/en unknown
- 2001-03-14 DK DK200100432A patent/DK200100432A/da not_active Application Discontinuation
- 2001-09-07 HK HK01106364A patent/HK1035671A1/xx not_active IP Right Cessation
-
2003
- 2003-07-09 IL IL156851A patent/IL156851A/en not_active IP Right Cessation
-
2006
- 2006-06-29 AT AT0800107A patent/AT503591A2/de not_active Application Discontinuation
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
FI116624B (fi) | Adenosiini A3 -reseptorin modulaattorit | |
US7470698B2 (en) | Adenosine A3 receptor modulators | |
Gatta et al. | Synthesis of imidazo [1, 2-c] pyrazolo [4, 3-e] pyrimidines, pyrazolo [4, 3-e] 1, 2, 4-triazolo [1, 5-c] pyrimidines and 1, 2, 4-triazolo [5, 1-i] purines: new potent adenosine A2 receptor antagonists | |
US20080096903A1 (en) | Sulfamoyl-containing derivatives and uses thereof | |
KR20150036239A (ko) | 바이러스 감염증의 치료를 위한 거대환식 푸린 | |
US20130324565A1 (en) | Organic compounds | |
US6358964B1 (en) | Adenosine, A3 receptor modulators | |
US7435740B2 (en) | Adenosine A3 receptor modulators | |
CN116568675A (zh) | 作为cxcr4调节剂的环状异硫脲衍生物 | |
MXPA00012385A (en) | Adenosine a3 | |
CZ20004240A3 (cs) | Modulátory adenosinového receptorů A3 | |
KR20050015956A (ko) | 아데노신 에이3 수용체 조절제 | |
EP3988100A1 (en) | Adenosine compound, pharmaceutically acceptable salt or stereoisomeride thereof, and use | |
MXPA00009575A (en) | Aminoalkyl substituted pyrrolo[2,3-b]pyridine and pyrrolo[2,3-d]pyrimidine derivatives:modulators of crf1 receptors |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
FG | Patent granted |
Ref document number: 116624 Country of ref document: FI |
|
MA | Patent expired |