JP4596913B2 - Ａ１アデノシン受容体の部分および完全アゴニスト - Google Patents
Ａ１アデノシン受容体の部分および完全アゴニスト Download PDFInfo
- Publication number
- JP4596913B2 JP4596913B2 JP2004529472A JP2004529472A JP4596913B2 JP 4596913 B2 JP4596913 B2 JP 4596913B2 JP 2004529472 A JP2004529472 A JP 2004529472A JP 2004529472 A JP2004529472 A JP 2004529472A JP 4596913 B2 JP4596913 B2 JP 4596913B2
- Authority
- JP
- Japan
- Prior art keywords
- purin
- formula
- compound
- dimethyl
- diol
- 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.)
- Expired - Fee Related
Links
- 239000000556 agonist Substances 0.000 title description 26
- 101150007969 ADORA1 gene Proteins 0.000 title description 7
- 230000036961 partial effect Effects 0.000 title description 5
- 239000001257 hydrogen Substances 0.000 claims abstract description 74
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 74
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 58
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 57
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 39
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 33
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 29
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 26
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 18
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims abstract description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 9
- 150000001875 compounds Chemical class 0.000 claims description 305
- -1 2-hydroxycyclopentyl Chemical group 0.000 claims description 133
- 125000004545 purin-9-yl group Chemical group N1=CN=C2N(C=NC2=C1)* 0.000 claims description 72
- 125000003118 aryl group Chemical group 0.000 claims description 48
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 41
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 28
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 27
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 25
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 24
- 125000006312 cyclopentyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 125000001153 fluoro group Chemical group F* 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 230000027455 binding Effects 0.000 claims description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- 150000002009 diols Chemical class 0.000 claims description 8
- ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 3
- SSYDTHANSGMJTP-UHFFFAOYSA-N oxolane-3,4-diol Chemical compound OC1COCC1O SSYDTHANSGMJTP-UHFFFAOYSA-N 0.000 claims description 3
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 3
- 241000282376 Panthera tigris Species 0.000 claims 1
- 125000005549 heteroarylene group Chemical group 0.000 claims 1
- 125000000623 heterocyclic group Chemical group 0.000 abstract description 30
- 239000003379 purinergic P1 receptor agonist Substances 0.000 abstract description 22
- 125000003107 substituted aryl group Chemical group 0.000 abstract description 12
- 125000002252 acyl group Chemical group 0.000 abstract description 11
- 125000001475 halogen functional group Chemical group 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 74
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 58
- 229920002554 vinyl polymer Polymers 0.000 description 58
- 238000006243 chemical reaction Methods 0.000 description 54
- 238000004519 manufacturing process Methods 0.000 description 52
- 238000000034 method Methods 0.000 description 46
- 125000001424 substituent group Chemical group 0.000 description 46
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
- NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 40
- 239000002904 solvent Substances 0.000 description 40
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- 238000002360 preparation method Methods 0.000 description 39
- 239000000243 solution Substances 0.000 description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
- 230000002829 reductive effect Effects 0.000 description 31
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
- 125000003545 alkoxy group Chemical group 0.000 description 27
- 239000004480 active ingredient Substances 0.000 description 26
- 229910052736 halogen Inorganic materials 0.000 description 26
- 150000002367 halogens Chemical class 0.000 description 26
- 239000000126 substance Substances 0.000 description 25
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
- 230000000694 effects Effects 0.000 description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 239000000047 product Substances 0.000 description 21
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 20
- 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 20
- 125000003342 alkenyl group Chemical group 0.000 description 20
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 20
- 239000003826 tablet Substances 0.000 description 20
- 125000004181 carboxyalkyl group Chemical group 0.000 description 19
- 125000000304 alkynyl group Chemical group 0.000 description 17
- 150000001412 amines Chemical class 0.000 description 17
- 125000004432 carbon atom Chemical group C* 0.000 description 17
- 239000004615 ingredient Substances 0.000 description 17
- 125000004542 purin-6-yl group Chemical group N1=CN=C2N=CNC2=C1* 0.000 description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
- 235000021588 free fatty acids Nutrition 0.000 description 16
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- 241000700159 Rattus Species 0.000 description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 14
- 125000000392 cycloalkenyl group Chemical group 0.000 description 14
- 238000012360 testing method Methods 0.000 description 14
- 238000002474 experimental method Methods 0.000 description 13
- 239000012442 inert solvent Substances 0.000 description 13
- 150000005830 nonesterified fatty acids Chemical class 0.000 description 13
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 12
- 150000003839 salts Chemical class 0.000 description 12
- 125000000547 substituted alkyl group Chemical group 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- 206010047700 Vomiting Diseases 0.000 description 11
- 201000010099 disease Diseases 0.000 description 11
- ZKPFRIDJMMOODR-UHFFFAOYSA-N 2-Methyloctanal Chemical compound CCCCCCC(C)C=O ZKPFRIDJMMOODR-UHFFFAOYSA-N 0.000 description 10
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 10
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- 229960005305 adenosine Drugs 0.000 description 10
- 210000001789 adipocyte Anatomy 0.000 description 10
- 125000004414 alkyl thio group Chemical group 0.000 description 10
- 239000002585 base Substances 0.000 description 10
- 238000007796 conventional method Methods 0.000 description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 10
- 239000000843 powder Substances 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 10
- 108050000203 Adenosine receptors Proteins 0.000 description 9
- 102000009346 Adenosine receptors Human genes 0.000 description 9
- FFBDFADSZUINTG-UHFFFAOYSA-N DPCPX Chemical compound N1C=2C(=O)N(CCC)C(=O)N(CCC)C=2N=C1C1CCCC1 FFBDFADSZUINTG-UHFFFAOYSA-N 0.000 description 9
- 229930194542 Keto Natural products 0.000 description 9
- 125000004442 acylamino group Chemical group 0.000 description 9
- 125000004423 acyloxy group Chemical group 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 9
- 125000005110 aryl thio group Chemical group 0.000 description 9
- 125000004104 aryloxy group Chemical group 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- 125000005368 heteroarylthio group Chemical group 0.000 description 9
- 125000000468 ketone group Chemical group 0.000 description 9
- MIPHRQMEIYLZFZ-UHFFFAOYSA-N oxolan-3-amine Chemical compound NC1CCOC1 MIPHRQMEIYLZFZ-UHFFFAOYSA-N 0.000 description 9
- 230000010412 perfusion Effects 0.000 description 9
- 239000000546 pharmaceutical excipient Substances 0.000 description 9
- 102000005962 receptors Human genes 0.000 description 9
- 108020003175 receptors Proteins 0.000 description 9
- 150000003573 thiols Chemical class 0.000 description 9
- 229940122614 Adenosine receptor agonist Drugs 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 8
- 125000004429 atom Chemical group 0.000 description 8
- 150000001540 azides Chemical class 0.000 description 8
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 8
- 230000003197 catalytic effect Effects 0.000 description 8
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 125000005553 heteroaryloxy group Chemical group 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 210000004379 membrane Anatomy 0.000 description 8
- 239000012528 membrane Substances 0.000 description 8
- SQMWSBKSHWARHU-SDBHATRESA-N n6-cyclopentyladenosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(NC3CCCC3)=C2N=C1 SQMWSBKSHWARHU-SDBHATRESA-N 0.000 description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 238000012746 preparative thin layer chromatography Methods 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- 230000008673 vomiting Effects 0.000 description 8
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 7
- 125000006598 aminocarbonylamino group Chemical group 0.000 description 7
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 7
- 230000003243 anti-lipolytic effect Effects 0.000 description 7
- 125000004470 heterocyclooxy group Chemical group 0.000 description 7
- 125000004468 heterocyclylthio group Chemical group 0.000 description 7
- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 7
- 239000008194 pharmaceutical composition Substances 0.000 description 7
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 150000003254 radicals Chemical class 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- LRBPVCVOHOVJOV-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-[2-(2-fluorophenyl)ethynyl]oxolane-3,4-diol Chemical compound C([C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C2=NC=NC(NC3CCCC3)=C2N=C1)#CC1=CC=CC=C1F LRBPVCVOHOVJOV-WGQQHEPDSA-N 0.000 description 6
- CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 6
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 150000001299 aldehydes Chemical class 0.000 description 6
- 125000000033 alkoxyamino group Chemical group 0.000 description 6
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- UBLYEVLMRSPMOG-UHFFFAOYSA-N cyclopentylmethanamine Chemical compound NCC1CCCC1 UBLYEVLMRSPMOG-UHFFFAOYSA-N 0.000 description 6
- 235000014113 dietary fatty acids Nutrition 0.000 description 6
- 239000000194 fatty acid Substances 0.000 description 6
- 229930195729 fatty acid Natural products 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- 230000000638 stimulation Effects 0.000 description 6
- RHTYBXXYBHJICR-XNIJJKJLSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-ethynyloxolane-3,4-diol Chemical compound O1[C@H](C#C)[C@@H](O)[C@@H](O)[C@@H]1N1C2=NC=NC(NC3CCCC3)=C2N=C1 RHTYBXXYBHJICR-XNIJJKJLSA-N 0.000 description 5
- 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 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
- 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
- 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 5
- 241000124008 Mammalia Species 0.000 description 5
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 5
- 229930006000 Sucrose Natural products 0.000 description 5
- 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 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 235000010980 cellulose Nutrition 0.000 description 5
- 229920002678 cellulose Polymers 0.000 description 5
- 239000001913 cellulose Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 206010015037 epilepsy Diseases 0.000 description 5
- 150000004665 fatty acids Chemical class 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 150000002430 hydrocarbons Chemical group 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 235000019359 magnesium stearate Nutrition 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 5
- 239000008108 microcrystalline cellulose Substances 0.000 description 5
- 229940016286 microcrystalline cellulose Drugs 0.000 description 5
- 229960005181 morphine Drugs 0.000 description 5
- 230000009871 nonspecific binding Effects 0.000 description 5
- 150000007524 organic acids Chemical class 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 239000004031 partial agonist Substances 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 125000005017 substituted alkenyl group Chemical group 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 229960004793 sucrose Drugs 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- XOFLBQFBSOEHOG-UUOKFMHZSA-N γS-GTP Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=S)[C@@H](O)[C@H]1O XOFLBQFBSOEHOG-UUOKFMHZSA-N 0.000 description 5
- IGZGUYVVBABKOY-UHFFFAOYSA-N 1-iodo-2-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1I IGZGUYVVBABKOY-UHFFFAOYSA-N 0.000 description 4
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 4
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- 102000055025 Adenosine deaminases Human genes 0.000 description 4
- 206010007559 Cardiac failure congestive Diseases 0.000 description 4
- OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- AQLLBJAXUCIJSR-UHFFFAOYSA-N OC(=O)C[Na] Chemical compound OC(=O)C[Na] AQLLBJAXUCIJSR-UHFFFAOYSA-N 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 208000006011 Stroke Diseases 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 125000003710 aryl alkyl group Chemical group 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 230000001746 atrial effect Effects 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 4
- 239000008121 dextrose Substances 0.000 description 4
- 206010012601 diabetes mellitus Diseases 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 239000003925 fat Substances 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 239000006187 pill Substances 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 239000002287 radioligand Substances 0.000 description 4
- 229930195734 saturated hydrocarbon Natural products 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 229940032147 starch Drugs 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 229910052717 sulfur Inorganic materials 0.000 description 4
- 239000011593 sulfur Substances 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- 235000012222 talc Nutrition 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 4
- JXYRTFGHOYSNBL-ZDXOVATRSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-[3-(2-fluorophenyl)prop-2-ynyl]oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC3CCCC3)=C2N=C1)O)O)C#CC1=CC=CC=C1F JXYRTFGHOYSNBL-ZDXOVATRSA-N 0.000 description 3
- OOFJDDUSXNUSDE-BWZSZYTASA-N (2r,3s,4r,5r)-2-[2-(4-fluorophenyl)ethenyl]-5-[6-(oxolan-3-ylamino)purin-9-yl]oxolane-3,4-diol Chemical group N1=CN=C2N([C@@H]3O[C@@H]([C@H]([C@H]3O)O)C=CC=3C=CC(F)=CC=3)C=NC2=C1NC1CCOC1 OOFJDDUSXNUSDE-BWZSZYTASA-N 0.000 description 3
- JTBQHHBGFPZBCW-TWXIIYJJSA-N (3ar,4r,6s,6ar)-2,2-dimethyl-4-[6-(oxolan-3-ylamino)purin-9-yl]-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxole-6-carbaldehyde Chemical compound N1=CN=C2N([C@@H]3O[C@@H]([C@@H]4OC(O[C@H]43)(C)C)C=O)C=NC2=C1NC1CCOC1 JTBQHHBGFPZBCW-TWXIIYJJSA-N 0.000 description 3
- DAHDOAWPHZYRNB-UHFFFAOYSA-M (4-fluorophenyl)-triphenylphosphanium;bromide Chemical group [Br-].C1=CC(F)=CC=C1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 DAHDOAWPHZYRNB-UHFFFAOYSA-M 0.000 description 3
- IOSAAWHGJUZBOG-UHFFFAOYSA-N 3-(6-amino-9h-purin-9-yl)nonan-2-ol Chemical compound N1=CN=C2N(C(C(C)O)CCCCCC)C=NC2=C1N IOSAAWHGJUZBOG-UHFFFAOYSA-N 0.000 description 3
- XDOIOCJYPKXXMK-UHFFFAOYSA-N 3-(trifluoromethyl)cyclopentan-1-amine Chemical compound NC1CCC(C(F)(F)F)C1 XDOIOCJYPKXXMK-UHFFFAOYSA-N 0.000 description 3
- YEPOLBBUNYSRBS-UHFFFAOYSA-N 3-fluorocyclopentan-1-amine Chemical compound NC1CCC(F)C1 YEPOLBBUNYSRBS-UHFFFAOYSA-N 0.000 description 3
- BVILPGWUKJERFN-UHFFFAOYSA-N 3-methoxycyclopentan-1-amine Chemical compound COC1CCC(N)C1 BVILPGWUKJERFN-UHFFFAOYSA-N 0.000 description 3
- KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 description 3
- ZKBQDFAWXLTYKS-UHFFFAOYSA-N 6-Chloro-1H-purine Chemical group ClC1=NC=NC2=C1NC=N2 ZKBQDFAWXLTYKS-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- SCVHFRLUNIOSGI-UHFFFAOYSA-N 8-cyclopentyl-1,3-dimethyl-7H-purine-2,6-dione Chemical compound N1C=2C(=O)N(C)C(=O)N(C)C=2N=C1C1CCCC1 SCVHFRLUNIOSGI-UHFFFAOYSA-N 0.000 description 3
- ZJZMIZHGAMSAEG-SCFUHWHPSA-N 9-[(3ar,4r,6r,6ar)-6-ethynyl-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-n-cyclopentylpurin-6-amine Chemical compound N1=CN=C2N([C@@H]3O[C@@H]([C@H]4OC(O[C@H]43)(C)C)C#C)C=NC2=C1NC1CCCC1 ZJZMIZHGAMSAEG-SCFUHWHPSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 3
- 206010003658 Atrial Fibrillation Diseases 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000012981 Hank's balanced salt solution Substances 0.000 description 3
- 206010019280 Heart failures Diseases 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 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 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- XTUVJUMINZSXGF-UHFFFAOYSA-N N-methylcyclohexylamine Chemical compound CNC1CCCCC1 XTUVJUMINZSXGF-UHFFFAOYSA-N 0.000 description 3
- 208000008589 Obesity Diseases 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 210000000577 adipose tissue Anatomy 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 206010003119 arrhythmia Diseases 0.000 description 3
- 230000006793 arrhythmia Effects 0.000 description 3
- 235000010323 ascorbic acid Nutrition 0.000 description 3
- 229960005070 ascorbic acid Drugs 0.000 description 3
- 239000011668 ascorbic acid Substances 0.000 description 3
- 210000001992 atrioventricular node Anatomy 0.000 description 3
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- FKDAUYUOARWXGL-UHFFFAOYSA-N bromomethyl(triphenyl)phosphanium Chemical compound C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CBr)C1=CC=CC=C1 FKDAUYUOARWXGL-UHFFFAOYSA-N 0.000 description 3
- YFTMLUSIDVFTKU-UHFFFAOYSA-M bromomethyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CBr)C1=CC=CC=C1 YFTMLUSIDVFTKU-UHFFFAOYSA-M 0.000 description 3
- 210000004375 bundle of his Anatomy 0.000 description 3
- 208000015114 central nervous system disease Diseases 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 3
- 229960004316 cisplatin Drugs 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 201000010063 epididymitis Diseases 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 201000001421 hyperglycemia Diseases 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 239000011630 iodine Chemical group 0.000 description 3
- 229910052740 iodine Chemical group 0.000 description 3
- 208000028867 ischemia Diseases 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 230000004130 lipolysis Effects 0.000 description 3
- 208000030159 metabolic disease Diseases 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 235000020824 obesity Nutrition 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000000638 solvent extraction Methods 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 2
- CHMUHOFITZIING-XNIJJKJLSA-N (2r,3r,4s,5r)-2-(6-aminopurin-9-yl)-2-cyclohexyl-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@]1(C2CCCCC2)O[C@H](CO)[C@@H](O)[C@H]1O CHMUHOFITZIING-XNIJJKJLSA-N 0.000 description 2
- MQSLPHFTXICUDK-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-(2-phenylethyl)oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC3CCCC3)=C2N=C1)O)O)CC1=CC=CC=C1 MQSLPHFTXICUDK-WGQQHEPDSA-N 0.000 description 2
- WFZYTXLHKIVLDZ-SYDIUPFYSA-N (2r,3s,4r,5r)-2-[2-(2-methylphenyl)ethyl]-5-[6-(oxolan-3-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound CC1=CC=CC=C1CC[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(NC4COCC4)=C3N=C2)O1 WFZYTXLHKIVLDZ-SYDIUPFYSA-N 0.000 description 2
- MSNCMBUGGFWCBD-ABYLEIOUSA-N (3ar,4r,6s,6ar)-4-[6-(cyclopentylamino)purin-9-yl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxole-6-carbaldehyde Chemical compound N1=CN=C2N([C@@H]3O[C@@H]([C@@H]4OC(O[C@H]43)(C)C)C=O)C=NC2=C1NC1CCCC1 MSNCMBUGGFWCBD-ABYLEIOUSA-N 0.000 description 2
- LHOQCEAXPLQECM-UHFFFAOYSA-N 1,2,3,3a,4,5,6,6a-octahydropentalene-1-carbaldehyde Chemical compound C1CCC2C(C=O)CCC21 LHOQCEAXPLQECM-UHFFFAOYSA-N 0.000 description 2
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 2
- BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 2
- AGGPGYQJSCKFDS-UHFFFAOYSA-N 1-chloroethoxymethylbenzene Chemical compound CC(Cl)OCC1=CC=CC=C1 AGGPGYQJSCKFDS-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 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 2
- LBSLGHRIISXZRN-UHFFFAOYSA-N 5-fluorooxolan-3-amine Chemical compound NC1COC(F)C1 LBSLGHRIISXZRN-UHFFFAOYSA-N 0.000 description 2
- SJXGLMHGVFCANW-ZDXOVATRSA-N 9-[(3ar,4r,6r,6ar)-2,2-dimethyl-6-(2-pyridin-2-ylethynyl)-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-n-cyclopentylpurin-6-amine Chemical compound N1=CN=C2N([C@@H]3O[C@@H]([C@H]4OC(O[C@H]43)(C)C)C#CC=3N=CC=CC=3)C=NC2=C1NC1CCCC1 SJXGLMHGVFCANW-ZDXOVATRSA-N 0.000 description 2
- LBAJEUHVWYAMTB-UMCMBGNQSA-N 9-[(3ar,4r,6r,6ar)-2,2-dimethyl-6-[2-[2-(trifluoromethyl)phenyl]ethynyl]-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-n-cyclopentylpurin-6-amine Chemical compound N1=CN=C2N([C@@H]3O[C@@H]([C@H]4OC(O[C@H]43)(C)C)C#CC=3C(=CC=CC=3)C(F)(F)F)C=NC2=C1NC1CCCC1 LBAJEUHVWYAMTB-UMCMBGNQSA-N 0.000 description 2
- IQWWZPYFIWNKJW-HQLNUNBDSA-N 9-[(4r,6r,6ar)-6-[(e)-3-bromoprop-2-enyl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-n-cyclopentylpurin-6-amine Chemical compound N1=CN=C2N([C@@H]3O[C@H](C\C=C\Br)[C@H]4OC(OC43)(C)C)C=NC2=C1NC1CCCC1 IQWWZPYFIWNKJW-HQLNUNBDSA-N 0.000 description 2
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 2
- 241000700198 Cavia Species 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 241000254173 Coleoptera Species 0.000 description 2
- SUZLHDUTVMZSEV-UHFFFAOYSA-N Deoxycoleonol Natural products C12C(=O)CC(C)(C=C)OC2(C)C(OC(=O)C)C(O)C2C1(C)C(O)CCC2(C)C SUZLHDUTVMZSEV-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 108010001483 Glycogen Synthase Proteins 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 102000018697 Membrane Proteins Human genes 0.000 description 2
- 108010052285 Membrane Proteins Proteins 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 208000008238 Muscle Spasticity Diseases 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- QQONPFPTGQHPMA-UHFFFAOYSA-N Propene Chemical group CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 206010042434 Sudden death Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 229940121359 adenosine receptor antagonist Drugs 0.000 description 2
- 102000030621 adenylate cyclase Human genes 0.000 description 2
- 108060000200 adenylate cyclase Proteins 0.000 description 2
- 150000003973 alkyl amines Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000001773 anti-convulsant effect Effects 0.000 description 2
- 239000001961 anticonvulsive agent Substances 0.000 description 2
- 229960003965 antiepileptics Drugs 0.000 description 2
- 210000000709 aorta Anatomy 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 2
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 2
- 229940043253 butylated hydroxyanisole Drugs 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 150000003943 catecholamines Chemical class 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- OHCQJHSOBUTRHG-UHFFFAOYSA-N colforsin Natural products OC12C(=O)CC(C)(C=C)OC1(C)C(OC(=O)C)C(O)C1C2(C)C(O)CCC1(C)C OHCQJHSOBUTRHG-UHFFFAOYSA-N 0.000 description 2
- 230000009137 competitive binding Effects 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 2
- 239000002285 corn oil Substances 0.000 description 2
- 235000005687 corn oil Nutrition 0.000 description 2
- KZZKOVLJUKWSKX-UHFFFAOYSA-N cyclobutanamine Chemical compound NC1CCC1 KZZKOVLJUKWSKX-UHFFFAOYSA-N 0.000 description 2
- XCIXKGXIYUWCLL-UHFFFAOYSA-N cyclopentanol Chemical compound OC1CCCC1 XCIXKGXIYUWCLL-UHFFFAOYSA-N 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000000586 desensitisation Methods 0.000 description 2
- 235000013681 dietary sucrose Nutrition 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 229940126534 drug product Drugs 0.000 description 2
- 239000012636 effector Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 230000004190 glucose uptake Effects 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- GADIKQPUNWAMEB-UHFFFAOYSA-N methyl 4-ethyl-6,7-dimethoxy-9H-pyrido[5,4-b]indole-3-carboxylate Chemical compound N1C2=CC(OC)=C(OC)C=C2C2=C1C=NC(C(=O)OC)=C2CC GADIKQPUNWAMEB-UHFFFAOYSA-N 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 229960002748 norepinephrine Drugs 0.000 description 2
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000008177 pharmaceutical agent Substances 0.000 description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- RDOWQLZANAYVLL-UHFFFAOYSA-N phenanthridine Chemical compound C1=CC=C2C3=CC=CC=C3C=NC2=C1 RDOWQLZANAYVLL-UHFFFAOYSA-N 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 239000000049 pigment Substances 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 238000004237 preparative chromatography Methods 0.000 description 2
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 239000000296 purinergic P1 receptor antagonist Substances 0.000 description 2
- 229940076788 pyruvate Drugs 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 2
- 239000004299 sodium benzoate Substances 0.000 description 2
- 235000010234 sodium benzoate Nutrition 0.000 description 2
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 2
- 229940080313 sodium starch Drugs 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000008247 solid mixture Substances 0.000 description 2
- 208000018198 spasticity Diseases 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 150000003457 sulfones Chemical class 0.000 description 2
- 150000003462 sulfoxides Chemical class 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 2
- 230000024883 vasodilation Effects 0.000 description 2
- 230000002618 waking effect Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 239000000230 xanthan gum Substances 0.000 description 2
- 235000010493 xanthan gum Nutrition 0.000 description 2
- 229920001285 xanthan gum Polymers 0.000 description 2
- 229940082509 xanthan gum Drugs 0.000 description 2
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
- 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 1
- JFFOUICIRBXFRC-RFZPGFLSSA-N (1r,2r)-2-aminocyclopentan-1-ol Chemical compound N[C@@H]1CCC[C@H]1O JFFOUICIRBXFRC-RFZPGFLSSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- KYOSRONGDTVPDJ-NVQRDWNXSA-N (2r,3r,4s,5r)-2-(6-anilinopurin-9-yl)-5-(hydroxymethyl)-2-propan-2-yloxolane-3,4-diol Chemical compound C1=NC2=C(NC=3C=CC=CC=3)N=CN=C2N1[C@]1(C(C)C)O[C@H](CO)[C@@H](O)[C@H]1O KYOSRONGDTVPDJ-NVQRDWNXSA-N 0.000 description 1
- BHQOMNJHNLXFAL-ZDXOVATRSA-N (2r,3r,4s,5r)-2-(6-anilinopurin-9-yl)-5-[2-(2-fluorophenyl)ethenyl]oxolane-3,4-diol Chemical compound N1=CN=C2N([C@@H]3O[C@@H]([C@H]([C@H]3O)O)C=CC=3C(=CC=CC=3)F)C=NC2=C1NC1=CC=CC=C1 BHQOMNJHNLXFAL-ZDXOVATRSA-N 0.000 description 1
- IGTXBRSVYIKOOO-ZDXOVATRSA-N (2r,3r,4s,5r)-2-(6-anilinopurin-9-yl)-5-[2-(2-fluorophenyl)ethyl]oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC=3C=CC=CC=3)=C2N=C1)O)O)CC1=CC=CC=C1F IGTXBRSVYIKOOO-ZDXOVATRSA-N 0.000 description 1
- UUNUHJXHEOYTSZ-ZDXOVATRSA-N (2r,3r,4s,5r)-2-(6-anilinopurin-9-yl)-5-[2-(2-fluorophenyl)ethynyl]oxolane-3,4-diol Chemical compound C([C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C2=NC=NC(NC=3C=CC=CC=3)=C2N=C1)#CC1=CC=CC=C1F UUNUHJXHEOYTSZ-ZDXOVATRSA-N 0.000 description 1
- HNKUOKOIAZXKRH-UMCMBGNQSA-N (2r,3r,4s,5r)-2-(6-anilinopurin-9-yl)-5-[3-(2-fluorophenyl)prop-2-ynyl]oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC=3C=CC=CC=3)=C2N=C1)O)O)C#CC1=CC=CC=C1F HNKUOKOIAZXKRH-UMCMBGNQSA-N 0.000 description 1
- WTAPMGWQGWCFAT-LSCFUAHRSA-N (2r,3r,4s,5r)-2-(6-anilinopurin-9-yl)-5-ethynyloxolane-3,4-diol Chemical compound O1[C@H](C#C)[C@@H](O)[C@@H](O)[C@@H]1N1C2=NC=NC(NC=3C=CC=CC=3)=C2N=C1 WTAPMGWQGWCFAT-LSCFUAHRSA-N 0.000 description 1
- XSMYYYQVWPZWIZ-IDTAVKCVSA-N (2r,3r,4s,5r)-2-[2-chloro-6-(cyclopentylamino)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(Cl)=NC(NC3CCCC3)=C2N=C1 XSMYYYQVWPZWIZ-IDTAVKCVSA-N 0.000 description 1
- ZVOOVGCUYSAXKF-ZDXOVATRSA-N (2r,3r,4s,5r)-2-[6-(4-fluoroanilino)purin-9-yl]-5-[2-(2-fluorophenyl)ethynyl]oxolane-3,4-diol Chemical compound C([C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C2=NC=NC(NC=3C=CC(F)=CC=3)=C2N=C1)#CC1=CC=CC=C1F ZVOOVGCUYSAXKF-ZDXOVATRSA-N 0.000 description 1
- LHHYWWHLKQAKJQ-UMCMBGNQSA-N (2r,3r,4s,5r)-2-[6-(benzylamino)purin-9-yl]-5-[2-(2-fluorophenyl)ethenyl]oxolane-3,4-diol Chemical compound N1=CN=C2N([C@@H]3O[C@@H]([C@H]([C@H]3O)O)C=CC=3C(=CC=CC=3)F)C=NC2=C1NCC1=CC=CC=C1 LHHYWWHLKQAKJQ-UMCMBGNQSA-N 0.000 description 1
- PLYWRDZPKXJLIY-UMCMBGNQSA-N (2r,3r,4s,5r)-2-[6-(benzylamino)purin-9-yl]-5-[2-(2-fluorophenyl)ethyl]oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NCC=3C=CC=CC=3)=C2N=C1)O)O)CC1=CC=CC=C1F PLYWRDZPKXJLIY-UMCMBGNQSA-N 0.000 description 1
- HNHYWJWYCDUAGF-PTGPVQHPSA-N (2r,3r,4s,5r)-2-[6-(benzylamino)purin-9-yl]-5-[3-(2-fluorophenyl)prop-2-ynyl]oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NCC=3C=CC=CC=3)=C2N=C1)O)O)C#CC1=CC=CC=C1F HNHYWJWYCDUAGF-PTGPVQHPSA-N 0.000 description 1
- NVEIHOOJTMSUIK-SCFUHWHPSA-N (2r,3r,4s,5r)-2-[6-(benzylamino)purin-9-yl]-5-ethynyloxolane-3,4-diol Chemical compound O1[C@H](C#C)[C@@H](O)[C@@H](O)[C@@H]1N1C2=NC=NC(NCC=3C=CC=CC=3)=C2N=C1 NVEIHOOJTMSUIK-SCFUHWHPSA-N 0.000 description 1
- OSZVXLYAZDQZCE-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-(cyclobutylmethylamino)purin-9-yl]-5-[2-(2-fluorophenyl)ethenyl]oxolane-3,4-diol Chemical compound C([C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C2=NC=NC(NCC3CCC3)=C2N=C1)=CC1=CC=CC=C1F OSZVXLYAZDQZCE-WGQQHEPDSA-N 0.000 description 1
- OTDLGXCGLIJCNA-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-(cyclobutylmethylamino)purin-9-yl]-5-[2-(2-fluorophenyl)ethyl]oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NCC3CCC3)=C2N=C1)O)O)CC1=CC=CC=C1F OTDLGXCGLIJCNA-WGQQHEPDSA-N 0.000 description 1
- KTXFTCOBUPOKAX-XNIJJKJLSA-N (2r,3r,4s,5r)-2-[6-(cyclohexylamino)-2-fluoropurin-9-yl]-5-ethynyloxolane-3,4-diol Chemical compound O1[C@H](C#C)[C@@H](O)[C@@H](O)[C@@H]1N1C2=NC(F)=NC(NC3CCCCC3)=C2N=C1 KTXFTCOBUPOKAX-XNIJJKJLSA-N 0.000 description 1
- JIRKYAOSLZOYJH-ZDXOVATRSA-N (2r,3r,4s,5r)-2-[6-(cyclohexylamino)purin-9-yl]-5-[2-(2-fluorophenyl)ethenyl]oxolane-3,4-diol Chemical compound N1=CN=C2N([C@@H]3O[C@@H]([C@H]([C@H]3O)O)C=CC=3C(=CC=CC=3)F)C=NC2=C1NC1CCCCC1 JIRKYAOSLZOYJH-ZDXOVATRSA-N 0.000 description 1
- FWHCEWYYTITSLT-ZDXOVATRSA-N (2r,3r,4s,5r)-2-[6-(cyclohexylamino)purin-9-yl]-5-[2-(2-fluorophenyl)ethyl]oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC3CCCCC3)=C2N=C1)O)O)CC1=CC=CC=C1F FWHCEWYYTITSLT-ZDXOVATRSA-N 0.000 description 1
- IJDAPRXZRGDFIT-ZDXOVATRSA-N (2r,3r,4s,5r)-2-[6-(cyclohexylamino)purin-9-yl]-5-[2-(2-fluorophenyl)ethynyl]oxolane-3,4-diol Chemical compound C([C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C2=NC=NC(NC3CCCCC3)=C2N=C1)#CC1=CC=CC=C1F IJDAPRXZRGDFIT-ZDXOVATRSA-N 0.000 description 1
- YWWNCLQWONTCFQ-UMCMBGNQSA-N (2r,3r,4s,5r)-2-[6-(cyclohexylamino)purin-9-yl]-5-[3-(2-fluorophenyl)prop-2-ynyl]oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC3CCCCC3)=C2N=C1)O)O)C#CC1=CC=CC=C1F YWWNCLQWONTCFQ-UMCMBGNQSA-N 0.000 description 1
- PQLVQTHSNLWFLK-UMCMBGNQSA-N (2r,3r,4s,5r)-2-[6-(cyclohexylmethylamino)purin-9-yl]-5-[2-(2-fluorophenyl)ethynyl]oxolane-3,4-diol Chemical compound C([C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C2=NC=NC(NCC3CCCCC3)=C2N=C1)#CC1=CC=CC=C1F PQLVQTHSNLWFLK-UMCMBGNQSA-N 0.000 description 1
- FNKHDANNNOYCTO-SCFUHWHPSA-N (2r,3r,4s,5r)-2-[6-(cyclohexylmethylamino)purin-9-yl]-5-ethynyloxolane-3,4-diol Chemical compound O1[C@H](C#C)[C@@H](O)[C@@H](O)[C@@H]1N1C2=NC=NC(NCC3CCCCC3)=C2N=C1 FNKHDANNNOYCTO-SCFUHWHPSA-N 0.000 description 1
- KEPLHHWWJWXZQX-SDBHATRESA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)-2-(trifluoromethyl)purin-9-yl]-5-ethynyloxolane-3,4-diol Chemical compound O1[C@H](C#C)[C@@H](O)[C@@H](O)[C@@H]1N1C2=NC(C(F)(F)F)=NC(NC3CCCC3)=C2N=C1 KEPLHHWWJWXZQX-SDBHATRESA-N 0.000 description 1
- CZCWAEASNRQEQE-QTQZEZTPSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-(2-cyclopentylethyl)oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC3CCCC3)=C2N=C1)O)O)CC1CCCC1 CZCWAEASNRQEQE-QTQZEZTPSA-N 0.000 description 1
- RDIXTNDOIMGRLZ-AEVYOOLXSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-(2-pyrimidin-2-ylethyl)oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC3CCCC3)=C2N=C1)O)O)CC1=NC=CC=N1 RDIXTNDOIMGRLZ-AEVYOOLXSA-N 0.000 description 1
- MXXPIRBLJREVAV-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-(3-cyclopentylprop-2-ynyl)oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC3CCCC3)=C2N=C1)O)O)C#CC1CCCC1 MXXPIRBLJREVAV-WGQQHEPDSA-N 0.000 description 1
- CMELKYRPHNUVAZ-ZDXOVATRSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-(3-phenylprop-2-ynyl)oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC3CCCC3)=C2N=C1)O)O)C#CC1=CC=CC=C1 CMELKYRPHNUVAZ-ZDXOVATRSA-N 0.000 description 1
- IDVFSPNZOMMFOE-SEQHXNGFSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-(3-piperidin-2-ylprop-2-ynyl)oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC3CCCC3)=C2N=C1)O)O)C#CC1CCCCN1 IDVFSPNZOMMFOE-SEQHXNGFSA-N 0.000 description 1
- APELOSCWGXNBMA-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-(3-pyridin-2-ylprop-2-ynyl)oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC3CCCC3)=C2N=C1)O)O)C#CC1=CC=CC=N1 APELOSCWGXNBMA-WGQQHEPDSA-N 0.000 description 1
- VTROMWGGWSDTTP-HAXDFEGKSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-(3-pyrimidin-2-ylprop-2-ynyl)oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC3CCCC3)=C2N=C1)O)O)C#CC1=NC=CC=N1 VTROMWGGWSDTTP-HAXDFEGKSA-N 0.000 description 1
- KVUDKTSXYVORFG-GVPALMIXSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-[2-(2-fluorocyclohexyl)ethyl]oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC3CCCC3)=C2N=C1)O)O)CC1CCCCC1F KVUDKTSXYVORFG-GVPALMIXSA-N 0.000 description 1
- MFHZBCLOTIIHOQ-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-[2-(2-fluorophenyl)ethyl]oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC3CCCC3)=C2N=C1)O)O)CC1=CC=CC=C1F MFHZBCLOTIIHOQ-WGQQHEPDSA-N 0.000 description 1
- VOKNEXUCXAFUMO-ZDXOVATRSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-[2-(2-methylphenyl)ethyl]oxolane-3,4-diol Chemical compound CC1=CC=CC=C1CC[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(NC4CCCC4)=C3N=C2)O1 VOKNEXUCXAFUMO-ZDXOVATRSA-N 0.000 description 1
- GPWYHDOWLXBWSP-QTQZEZTPSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-[2-(3,5-dimethyl-1,2-oxazol-4-yl)ethyl]oxolane-3,4-diol Chemical compound CC1=NOC(C)=C1CC[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(NC4CCCC4)=C3N=C2)O1 GPWYHDOWLXBWSP-QTQZEZTPSA-N 0.000 description 1
- WIAYXXLJDUUIPJ-QTQZEZTPSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-[2-(4-methylpiperazin-1-yl)ethenyl]oxolane-3,4-diol Chemical compound C1CN(C)CCN1C=C[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(NC4CCCC4)=C3N=C2)O1 WIAYXXLJDUUIPJ-QTQZEZTPSA-N 0.000 description 1
- KXULCIYWIBANBZ-QTQZEZTPSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-[2-(4-methylpiperazin-1-yl)ethyl]oxolane-3,4-diol Chemical compound C1CN(C)CCN1CC[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(NC4CCCC4)=C3N=C2)O1 KXULCIYWIBANBZ-QTQZEZTPSA-N 0.000 description 1
- XAIZACUBJZTLFF-HAXDFEGKSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-[2-(6-fluoropyridin-2-yl)ethenyl]oxolane-3,4-diol Chemical compound N1=CN=C2N([C@@H]3O[C@@H]([C@H]([C@H]3O)O)C=CC=3N=C(F)C=CC=3)C=NC2=C1NC1CCCC1 XAIZACUBJZTLFF-HAXDFEGKSA-N 0.000 description 1
- QIXZTJDGYFWBKI-HAXDFEGKSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-[2-(6-fluoropyridin-2-yl)ethyl]oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC3CCCC3)=C2N=C1)O)O)CC1=CC=CC(F)=N1 QIXZTJDGYFWBKI-HAXDFEGKSA-N 0.000 description 1
- KZAFGTJSARYXDI-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-[2-[2-(trifluoromethyl)phenyl]ethynyl]oxolane-3,4-diol Chemical compound C([C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C2=NC=NC(NC3CCCC3)=C2N=C1)#CC1=CC=CC=C1C(F)(F)F KZAFGTJSARYXDI-WGQQHEPDSA-N 0.000 description 1
- IYLQODSXLHNYAY-DNEBCRIASA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-[3-(2-fluorocyclohexyl)prop-2-ynyl]oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC3CCCC3)=C2N=C1)O)O)C#CC1CCCCC1F IYLQODSXLHNYAY-DNEBCRIASA-N 0.000 description 1
- RBCYVCWDJSYGBH-UMCMBGNQSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-[3-(2-methylphenyl)prop-2-ynyl]oxolane-3,4-diol Chemical compound CC1=CC=CC=C1C#CC[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(NC4CCCC4)=C3N=C2)O1 RBCYVCWDJSYGBH-UMCMBGNQSA-N 0.000 description 1
- QHWJJFSPWYWTCS-QTQZEZTPSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-[3-(4-methyl-1,2-oxazol-3-yl)prop-2-ynyl]oxolane-3,4-diol Chemical compound CC1=CON=C1C#CC[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(NC4CCCC4)=C3N=C2)O1 QHWJJFSPWYWTCS-QTQZEZTPSA-N 0.000 description 1
- DNFMTZHOLYUZDF-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-[3-(4-methylpiperazin-1-yl)prop-2-ynyl]oxolane-3,4-diol Chemical compound C1CN(C)CCN1C#CC[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(NC4CCCC4)=C3N=C2)O1 DNFMTZHOLYUZDF-WGQQHEPDSA-N 0.000 description 1
- TYDXHFZSTVJGSC-CIVUBGFFSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-[3-(6-fluoropyridin-2-yl)prop-2-ynyl]oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC3CCCC3)=C2N=C1)O)O)C#CC1=CC=CC(F)=N1 TYDXHFZSTVJGSC-CIVUBGFFSA-N 0.000 description 1
- ROGRMSYJFDBLQQ-ZDXOVATRSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-[3-[2-(trifluoromethyl)phenyl]prop-2-ynyl]oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC3CCCC3)=C2N=C1)O)O)C#CC1=CC=CC=C1C(F)(F)F ROGRMSYJFDBLQQ-ZDXOVATRSA-N 0.000 description 1
- BJNRFGTUCXWMPA-ZDXOVATRSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylmethylamino)purin-9-yl]-5-[2-(2-fluorophenyl)ethyl]oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NCC3CCCC3)=C2N=C1)O)O)CC1=CC=CC=C1F BJNRFGTUCXWMPA-ZDXOVATRSA-N 0.000 description 1
- CJKDAOLERIJGAF-ZDXOVATRSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylmethylamino)purin-9-yl]-5-[2-(2-fluorophenyl)ethynyl]oxolane-3,4-diol Chemical compound C([C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C2=NC=NC(NCC3CCCC3)=C2N=C1)#CC1=CC=CC=C1F CJKDAOLERIJGAF-ZDXOVATRSA-N 0.000 description 1
- ZWZBROVMHKXOED-UMCMBGNQSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylmethylamino)purin-9-yl]-5-[3-(2-fluorophenyl)prop-2-ynyl]oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NCC3CCCC3)=C2N=C1)O)O)C#CC1=CC=CC=C1F ZWZBROVMHKXOED-UMCMBGNQSA-N 0.000 description 1
- RVEPUGRKEMXANC-LSCFUAHRSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylmethylamino)purin-9-yl]-5-ethynyloxolane-3,4-diol Chemical compound O1[C@H](C#C)[C@@H](O)[C@@H](O)[C@@H]1N1C2=NC=NC(NCC3CCCC3)=C2N=C1 RVEPUGRKEMXANC-LSCFUAHRSA-N 0.000 description 1
- YCQSMALYWCESJF-BHCULOIHSA-N (2r,3r,4s,5r)-2-[6-[(2-fluorocyclohexyl)amino]purin-9-yl]-5-[2-(2-fluorophenyl)ethenyl]oxolane-3,4-diol Chemical compound N1=CN=C2N([C@@H]3O[C@@H]([C@H]([C@H]3O)O)C=CC=3C(=CC=CC=3)F)C=NC2=C1NC1CCCCC1F YCQSMALYWCESJF-BHCULOIHSA-N 0.000 description 1
- BFTAKDQCVNROAS-BHCULOIHSA-N (2r,3r,4s,5r)-2-[6-[(2-fluorocyclohexyl)amino]purin-9-yl]-5-[2-(2-fluorophenyl)ethyl]oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC3C(CCCC3)F)=C2N=C1)O)O)CC1=CC=CC=C1F BFTAKDQCVNROAS-BHCULOIHSA-N 0.000 description 1
- SLOBFBKFMPBGEF-BHCULOIHSA-N (2r,3r,4s,5r)-2-[6-[(2-fluorocyclohexyl)amino]purin-9-yl]-5-[2-(2-fluorophenyl)ethynyl]oxolane-3,4-diol Chemical compound C([C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C2=NC=NC(NC3C(CCCC3)F)=C2N=C1)#CC1=CC=CC=C1F SLOBFBKFMPBGEF-BHCULOIHSA-N 0.000 description 1
- SFPFVYLICSOGSF-MAJGUDNFSA-N (2r,3r,4s,5r)-2-[6-[(2-fluorocyclohexyl)amino]purin-9-yl]-5-[3-(2-fluorophenyl)prop-2-ynyl]oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC3C(CCCC3)F)=C2N=C1)O)O)C#CC1=CC=CC=C1F SFPFVYLICSOGSF-MAJGUDNFSA-N 0.000 description 1
- SPXZTXVXCLNIFW-JNDNADJNSA-N (2r,3r,4s,5r)-2-[6-[(2-fluorocyclohexyl)methylamino]purin-9-yl]-5-[2-(2-fluorophenyl)ethenyl]oxolane-3,4-diol Chemical compound C([C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C2=NC=NC(NCC3C(CCCC3)F)=C2N=C1)=CC1=CC=CC=C1F SPXZTXVXCLNIFW-JNDNADJNSA-N 0.000 description 1
- RMDOKDARRAMVSH-JNDNADJNSA-N (2r,3r,4s,5r)-2-[6-[(2-fluorocyclohexyl)methylamino]purin-9-yl]-5-[2-(2-fluorophenyl)ethyl]oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NCC3C(CCCC3)F)=C2N=C1)O)O)CC1=CC=CC=C1F RMDOKDARRAMVSH-JNDNADJNSA-N 0.000 description 1
- IGVYICGTOISBAF-RJYJEMIWSA-N (2r,3r,4s,5r)-2-[6-[(2-fluorocyclohexyl)methylamino]purin-9-yl]-5-[3-(2-fluorophenyl)prop-2-ynyl]oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NCC3C(CCCC3)F)=C2N=C1)O)O)C#CC1=CC=CC=C1F IGVYICGTOISBAF-RJYJEMIWSA-N 0.000 description 1
- BLCDQFGGRHVOME-AFPYFSFUSA-N (2r,3r,4s,5r)-2-[6-[(3-fluorocyclopentyl)amino]purin-9-yl]-5-[2-(2-fluorophenyl)ethenyl]oxolane-3,4-diol Chemical compound N1=CN=C2N([C@@H]3O[C@@H]([C@H]([C@H]3O)O)C=CC=3C(=CC=CC=3)F)C=NC2=C1NC1CCC(F)C1 BLCDQFGGRHVOME-AFPYFSFUSA-N 0.000 description 1
- APMNEHKPJHCYFW-AFPYFSFUSA-N (2r,3r,4s,5r)-2-[6-[(3-fluorocyclopentyl)amino]purin-9-yl]-5-[2-(2-fluorophenyl)ethyl]oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC3CC(F)CC3)=C2N=C1)O)O)CC1=CC=CC=C1F APMNEHKPJHCYFW-AFPYFSFUSA-N 0.000 description 1
- RUUAFLSNKYWUIN-AFPYFSFUSA-N (2r,3r,4s,5r)-2-[6-[(3-fluorocyclopentyl)amino]purin-9-yl]-5-[2-(2-fluorophenyl)ethynyl]oxolane-3,4-diol Chemical compound C([C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C2=NC=NC(NC3CC(F)CC3)=C2N=C1)#CC1=CC=CC=C1F RUUAFLSNKYWUIN-AFPYFSFUSA-N 0.000 description 1
- UIYIKETUIMJZRK-QXXFMFGFSA-N (2r,3r,4s,5r)-2-[6-[(3-fluorocyclopentyl)amino]purin-9-yl]-5-[3-(2-fluorophenyl)prop-2-ynyl]oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC3CC(F)CC3)=C2N=C1)O)O)C#CC1=CC=CC=C1F UIYIKETUIMJZRK-QXXFMFGFSA-N 0.000 description 1
- BVXPHUTYSKUPNV-DNXMWZIASA-N (2r,3r,4s,5r)-2-[6-[(5-fluorooxolan-3-yl)amino]purin-9-yl]-5-[2-(2-fluorophenyl)ethynyl]oxolane-3,4-diol Chemical compound C([C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C2=NC=NC(NC3CC(F)OC3)=C2N=C1)#CC1=CC=CC=C1F BVXPHUTYSKUPNV-DNXMWZIASA-N 0.000 description 1
- BGRSHMRPLLNWOG-GCPJYRIMSA-N (2r,3r,4s,5r)-2-[6-[(5-fluorooxolan-3-yl)amino]purin-9-yl]-5-[3-(2-fluorophenyl)prop-2-ynyl]oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC3CC(F)OC3)=C2N=C1)O)O)C#CC1=CC=CC=C1F BGRSHMRPLLNWOG-GCPJYRIMSA-N 0.000 description 1
- UHJRJLPSYJUCPF-SDBHATRESA-N (2r,3r,4s,5r)-2-[6-amino-2-(cyclohexylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound N=1C=2N([C@H]3[C@@H]([C@H](O)[C@@H](CO)O3)O)C=NC=2C(N)=NC=1NC1CCCCC1 UHJRJLPSYJUCPF-SDBHATRESA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- OESBDSFYJMDRJY-BAYCTPFLSA-N (2r,3s,4r,5r)-2-(hydroxymethyl)-5-[6-[[(3r)-oxolan-3-yl]amino]purin-9-yl]oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(N[C@H]3COCC3)=C2N=C1 OESBDSFYJMDRJY-BAYCTPFLSA-N 0.000 description 1
- OELAXFSUTIFNCA-NVQRDWNXSA-N (2r,3s,4r,5r)-2-[2-(2-fluorophenyl)ethenyl]-5-[6-(1,3-thiazol-2-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound N1=CN=C2N([C@@H]3O[C@@H]([C@H]([C@H]3O)O)C=CC=3C(=CC=CC=3)F)C=NC2=C1NC1=NC=CS1 OELAXFSUTIFNCA-NVQRDWNXSA-N 0.000 description 1
- FIBKHIGWICEUSA-WGQQHEPDSA-N (2r,3s,4r,5r)-2-[2-(2-fluorophenyl)ethenyl]-5-[6-(pyridin-3-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound N1=CN=C2N([C@@H]3O[C@@H]([C@H]([C@H]3O)O)C=CC=3C(=CC=CC=3)F)C=NC2=C1NC1=CC=CN=C1 FIBKHIGWICEUSA-WGQQHEPDSA-N 0.000 description 1
- DVMSBXKSMJOZOT-QXXFMFGFSA-N (2r,3s,4r,5r)-2-[2-(2-fluorophenyl)ethenyl]-5-[6-[(3-methoxycyclopentyl)amino]purin-9-yl]oxolane-3,4-diol Chemical compound C1C(OC)CCC1NC1=NC=NC2=C1N=CN2[C@H]1[C@H](O)[C@H](O)[C@@H](C=CC=2C(=CC=CC=2)F)O1 DVMSBXKSMJOZOT-QXXFMFGFSA-N 0.000 description 1
- ARCKUERYPJSIQI-AFPYFSFUSA-N (2r,3s,4r,5r)-2-[2-(2-fluorophenyl)ethenyl]-5-[6-[[3-(trifluoromethyl)cyclopentyl]amino]purin-9-yl]oxolane-3,4-diol Chemical compound N1=CN=C2N([C@@H]3O[C@@H]([C@H]([C@H]3O)O)C=CC=3C(=CC=CC=3)F)C=NC2=C1NC1CCC(C(F)(F)F)C1 ARCKUERYPJSIQI-AFPYFSFUSA-N 0.000 description 1
- ZOIGJLXIBXBWSM-NVQRDWNXSA-N (2r,3s,4r,5r)-2-[2-(2-fluorophenyl)ethyl]-5-[6-(1,3-thiazol-2-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC=3SC=CN=3)=C2N=C1)O)O)CC1=CC=CC=C1F ZOIGJLXIBXBWSM-NVQRDWNXSA-N 0.000 description 1
- TUKXHJXQRMDOSC-WGQQHEPDSA-N (2r,3s,4r,5r)-2-[2-(2-fluorophenyl)ethyl]-5-[6-(pyridin-3-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC=3C=NC=CC=3)=C2N=C1)O)O)CC1=CC=CC=C1F TUKXHJXQRMDOSC-WGQQHEPDSA-N 0.000 description 1
- RLOFTJYOGVMJSJ-QXXFMFGFSA-N (2r,3s,4r,5r)-2-[2-(2-fluorophenyl)ethyl]-5-[6-[(3-methoxycyclopentyl)amino]purin-9-yl]oxolane-3,4-diol Chemical compound C1C(OC)CCC1NC1=NC=NC2=C1N=CN2[C@H]1[C@H](O)[C@H](O)[C@@H](CCC=2C(=CC=CC=2)F)O1 RLOFTJYOGVMJSJ-QXXFMFGFSA-N 0.000 description 1
- OPACOJMDSQWDPA-NVQRDWNXSA-N (2r,3s,4r,5r)-2-[2-(2-fluorophenyl)ethynyl]-5-[6-(1,3-thiazol-2-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound C([C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C2=NC=NC(NC=3SC=CN=3)=C2N=C1)#CC1=CC=CC=C1F OPACOJMDSQWDPA-NVQRDWNXSA-N 0.000 description 1
- OYERBLUIOMOYMS-QIKISSGUSA-N (2r,3s,4r,5r)-2-[2-(2-fluorophenyl)ethynyl]-5-[6-(oxolan-3-ylmethylamino)purin-9-yl]oxolane-3,4-diol Chemical compound C([C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C2=NC=NC(NCC3COCC3)=C2N=C1)#CC1=CC=CC=C1F OYERBLUIOMOYMS-QIKISSGUSA-N 0.000 description 1
- OWKRLNDECHRWQW-WGQQHEPDSA-N (2r,3s,4r,5r)-2-[2-(2-fluorophenyl)ethynyl]-5-[6-(pyridin-3-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound C([C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C2=NC=NC(NC=3C=NC=CC=3)=C2N=C1)#CC1=CC=CC=C1F OWKRLNDECHRWQW-WGQQHEPDSA-N 0.000 description 1
- GPRMNXGHKNWILB-QXXFMFGFSA-N (2r,3s,4r,5r)-2-[2-(2-fluorophenyl)ethynyl]-5-[6-[(3-methoxycyclopentyl)amino]purin-9-yl]oxolane-3,4-diol Chemical compound C1C(OC)CCC1NC1=NC=NC2=C1N=CN2[C@H]1[C@H](O)[C@H](O)[C@@H](C#CC=2C(=CC=CC=2)F)O1 GPRMNXGHKNWILB-QXXFMFGFSA-N 0.000 description 1
- FWQFFXMQFNEAKE-AFPYFSFUSA-N (2r,3s,4r,5r)-2-[2-(2-fluorophenyl)ethynyl]-5-[6-[[3-(trifluoromethyl)cyclopentyl]amino]purin-9-yl]oxolane-3,4-diol Chemical compound C([C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C2=NC=NC(NC3CC(CC3)C(F)(F)F)=C2N=C1)#CC1=CC=CC=C1F FWQFFXMQFNEAKE-AFPYFSFUSA-N 0.000 description 1
- UZRITEQLAAXYQH-AEVYOOLXSA-N (2r,3s,4r,5r)-2-[2-(5-chlorothiophen-2-yl)ethyl]-5-[6-(cyclopentylamino)purin-9-yl]oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC3CCCC3)=C2N=C1)O)O)CC1=CC=C(Cl)S1 UZRITEQLAAXYQH-AEVYOOLXSA-N 0.000 description 1
- NLRANBISGWQFHU-WVSUBDOOSA-N (2r,3s,4r,5r)-2-[3-(2-fluorophenyl)prop-2-ynyl]-5-[6-(1,3-thiazol-2-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC=3SC=CN=3)=C2N=C1)O)O)C#CC1=CC=CC=C1F NLRANBISGWQFHU-WVSUBDOOSA-N 0.000 description 1
- MHLINOZMDNOBOA-SEQHXNGFSA-N (2r,3s,4r,5r)-2-[3-(2-fluorophenyl)prop-2-ynyl]-5-[6-(oxolan-3-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC3COCC3)=C2N=C1)O)O)C#CC1=CC=CC=C1F MHLINOZMDNOBOA-SEQHXNGFSA-N 0.000 description 1
- KXNSMQXILYBZAP-ZDXOVATRSA-N (2r,3s,4r,5r)-2-[3-(2-fluorophenyl)prop-2-ynyl]-5-[6-(pyridin-3-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC=3C=NC=CC=3)=C2N=C1)O)O)C#CC1=CC=CC=C1F KXNSMQXILYBZAP-ZDXOVATRSA-N 0.000 description 1
- YBJFZHNZBUGVBS-QXXFMFGFSA-N (2r,3s,4r,5r)-2-[3-(2-fluorophenyl)prop-2-ynyl]-5-[6-[[3-(trifluoromethyl)cyclopentyl]amino]purin-9-yl]oxolane-3,4-diol Chemical compound C([C@@H]1[C@H]([C@H]([C@@H](O1)N1C2=NC=NC(NC3CC(CC3)C(F)(F)F)=C2N=C1)O)O)C#CC1=CC=CC=C1F YBJFZHNZBUGVBS-QXXFMFGFSA-N 0.000 description 1
- XPKXCZDHHBIDOM-QYVSTXNMSA-N (2r,3s,4r,5r)-2-ethynyl-5-[6-(1,3-thiazol-2-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound O1[C@H](C#C)[C@@H](O)[C@@H](O)[C@@H]1N1C2=NC=NC(NC=3SC=CN=3)=C2N=C1 XPKXCZDHHBIDOM-QYVSTXNMSA-N 0.000 description 1
- MZIBYEBNWFCEAR-LSCFUAHRSA-N (2r,3s,4r,5r)-2-ethynyl-5-[6-(4-fluoroanilino)purin-9-yl]oxolane-3,4-diol Chemical compound O1[C@H](C#C)[C@@H](O)[C@@H](O)[C@@H]1N1C2=NC=NC(NC=3C=CC(F)=CC=3)=C2N=C1 MZIBYEBNWFCEAR-LSCFUAHRSA-N 0.000 description 1
- DUJLUZNRHFAJIE-CALCHNCGSA-N (2r,3s,4r,5r)-2-ethynyl-5-[6-(oxan-3-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound O1[C@H](C#C)[C@@H](O)[C@@H](O)[C@@H]1N1C2=NC=NC(NC3COCCC3)=C2N=C1 DUJLUZNRHFAJIE-CALCHNCGSA-N 0.000 description 1
- DPIXLDHSEYHJGL-QIFOKDCASA-N (2r,3s,4r,5r)-2-ethynyl-5-[6-(oxan-3-ylmethylamino)purin-9-yl]oxolane-3,4-diol Chemical compound O1[C@H](C#C)[C@@H](O)[C@@H](O)[C@@H]1N1C2=NC=NC(NCC3COCCC3)=C2N=C1 DPIXLDHSEYHJGL-QIFOKDCASA-N 0.000 description 1
- CCIINHOVOBWPKX-YXYADJKSSA-N (2r,3s,4r,5r)-2-ethynyl-5-[6-(oxolan-3-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound O1[C@H](C#C)[C@@H](O)[C@@H](O)[C@@H]1N1C2=NC=NC(NC3COCC3)=C2N=C1 CCIINHOVOBWPKX-YXYADJKSSA-N 0.000 description 1
- FXIDKUWSVACUKS-XNIJJKJLSA-N (2r,3s,4r,5r)-2-ethynyl-5-[6-(pyridin-3-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound O1[C@H](C#C)[C@@H](O)[C@@H](O)[C@@H]1N1C2=NC=NC(NC=3C=NC=CC=3)=C2N=C1 FXIDKUWSVACUKS-XNIJJKJLSA-N 0.000 description 1
- PDMYHOOOMMFRJI-FDEMZPBOSA-N (2r,3s,4r,5r)-2-ethynyl-5-[6-[(2-hydroxycyclopentyl)amino]purin-9-yl]oxolane-3,4-diol Chemical compound OC1CCCC1NC1=NC=NC2=C1N=CN2[C@H]1[C@H](O)[C@H](O)[C@@H](C#C)O1 PDMYHOOOMMFRJI-FDEMZPBOSA-N 0.000 description 1
- MVPHBFQIFJQPMH-FDEMZPBOSA-N (2r,3s,4r,5r)-2-ethynyl-5-[6-[(3-fluorocyclopentyl)amino]purin-9-yl]oxolane-3,4-diol Chemical compound O1[C@H](C#C)[C@@H](O)[C@@H](O)[C@@H]1N1C2=NC=NC(NC3CC(F)CC3)=C2N=C1 MVPHBFQIFJQPMH-FDEMZPBOSA-N 0.000 description 1
- WLWKHSZIMHQWHG-WJDBLMMSSA-N (2r,3s,4r,5r)-2-ethynyl-5-[6-[(3-methoxycyclopentyl)amino]purin-9-yl]oxolane-3,4-diol Chemical compound C1C(OC)CCC1NC1=NC=NC2=C1N=CN2[C@H]1[C@H](O)[C@H](O)[C@@H](C#C)O1 WLWKHSZIMHQWHG-WJDBLMMSSA-N 0.000 description 1
- HHQHBQHVGMOQTC-FDEMZPBOSA-N (2r,3s,4r,5r)-2-ethynyl-5-[6-[(5-fluorooxan-3-yl)amino]purin-9-yl]oxolane-3,4-diol Chemical compound O1[C@H](C#C)[C@@H](O)[C@@H](O)[C@@H]1N1C2=NC=NC(NC3CC(F)COC3)=C2N=C1 HHQHBQHVGMOQTC-FDEMZPBOSA-N 0.000 description 1
- AODORIUMTYRPKE-FDEMZPBOSA-N (2r,3s,4r,5r)-2-ethynyl-5-[6-[[3-(trifluoromethyl)cyclopentyl]amino]purin-9-yl]oxolane-3,4-diol Chemical compound O1[C@H](C#C)[C@@H](O)[C@@H](O)[C@@H]1N1C2=NC=NC(NC3CC(CC3)C(F)(F)F)=C2N=C1 AODORIUMTYRPKE-FDEMZPBOSA-N 0.000 description 1
- MHTCZUAVNUVCMF-CDJAJGPJSA-N (2r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-prop-2-ynyloxolane-3,4-diol Chemical compound OC1[C@H](O)[C@@H](CC#C)O[C@H]1N1C2=NC=NC(NC3CCCC3)=C2N=C1 MHTCZUAVNUVCMF-CDJAJGPJSA-N 0.000 description 1
- QWPLCHDPESWJRN-UHFFFAOYSA-N (4-fluorophenyl)-triphenylphosphanium Chemical compound C1=CC(F)=CC=C1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 QWPLCHDPESWJRN-UHFFFAOYSA-N 0.000 description 1
- MSNCMBUGGFWCBD-NUKIEUHSSA-N (4r,6s,6ar)-4-[6-(cyclopentylamino)purin-9-yl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxole-6-carbaldehyde Chemical compound N1=CN=C2N([C@@H]3O[C@@H]([C@@H]4OC(OC43)(C)C)C=O)C=NC2=C1NC1CCCC1 MSNCMBUGGFWCBD-NUKIEUHSSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- ZNRPLBYPKAMVTM-UHFFFAOYSA-N 1,3-dichloro-1-hexylurea Chemical compound CCCCCCN(Cl)C(=O)NCl ZNRPLBYPKAMVTM-UHFFFAOYSA-N 0.000 description 1
- 150000000190 1,4-diols Chemical class 0.000 description 1
- RRQYJINTUHWNHW-UHFFFAOYSA-N 1-ethoxy-2-(2-ethoxyethoxy)ethane Chemical compound CCOCCOCCOCC RRQYJINTUHWNHW-UHFFFAOYSA-N 0.000 description 1
- TYHUGKGZNOULKD-UHFFFAOYSA-N 1-fluoro-2-iodobenzene Chemical compound FC1=CC=CC=C1I TYHUGKGZNOULKD-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
- TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical compound C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 description 1
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
- VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical compound OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-N 0.000 description 1
- WEEMDRWIKYCTQM-UHFFFAOYSA-N 2,6-dimethoxybenzenecarbothioamide Chemical compound COC1=CC=CC(OC)=C1C(N)=S WEEMDRWIKYCTQM-UHFFFAOYSA-N 0.000 description 1
- JKNCOURZONDCGV-UHFFFAOYSA-N 2-(dimethylamino)ethyl 2-methylprop-2-enoate Chemical compound CN(C)CCOC(=O)C(C)=C JKNCOURZONDCGV-UHFFFAOYSA-N 0.000 description 1
- UVXAUKWRMQFPIJ-WSIGBLOUSA-N 2-[(4r,6r,6ar)-4-[6-(cyclopentylamino)purin-9-yl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]acetaldehyde Chemical compound N1=CN=C2N([C@@H]3O[C@H](CC=O)[C@H]4OC(OC43)(C)C)C=NC2=C1NC1CCCC1 UVXAUKWRMQFPIJ-WSIGBLOUSA-N 0.000 description 1
- OOFJDDUSXNUSDE-UHFFFAOYSA-N 2-[2-(4-fluorophenyl)ethenyl]-5-[6-(oxolan-3-ylamino)purin-9-yl]oxolane-3,4-diol Chemical compound OC1C(O)C(C=CC=2C=CC(F)=CC=2)OC1N(C1=NC=N2)C=NC1=C2NC1CCOC1 OOFJDDUSXNUSDE-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- ZFZUTWAYBJFSIL-UHFFFAOYSA-N 2-fluorocyclohexan-1-amine Chemical compound NC1CCCCC1F ZFZUTWAYBJFSIL-UHFFFAOYSA-N 0.000 description 1
- AUVALWUPUHHNQV-UHFFFAOYSA-N 2-hydroxy-3-propylbenzoic acid Chemical compound CCCC1=CC=CC(C(O)=O)=C1O AUVALWUPUHHNQV-UHFFFAOYSA-N 0.000 description 1
- OXCGHDNCMSOEBZ-UHFFFAOYSA-N 2-methoxyfuran Chemical compound COC1=CC=CO1 OXCGHDNCMSOEBZ-UHFFFAOYSA-N 0.000 description 1
- VLRSADZEDXVUPG-UHFFFAOYSA-N 2-naphthalen-1-ylpyridine Chemical compound N1=CC=CC=C1C1=CC=CC2=CC=CC=C12 VLRSADZEDXVUPG-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- ZPZKJQKFLQCCMD-UHFFFAOYSA-N 3-fluorocyclohexan-1-amine Chemical compound NC1CCCC(F)C1 ZPZKJQKFLQCCMD-UHFFFAOYSA-N 0.000 description 1
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- YJXMUHPIQWNBSX-UHFFFAOYSA-N 5-fluorooxan-3-amine Chemical compound NC1COCC(F)C1 YJXMUHPIQWNBSX-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- QMUSXTGQLQHEAT-PNODFLSHSA-N 9-[(3ar,4r,6r,6ar)-2,2-dimethyl-6-(2-piperidin-2-ylethynyl)-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-n-cyclopentylpurin-6-amine Chemical compound N1=CN=C2N([C@@H]3O[C@@H]([C@H]4OC(O[C@H]43)(C)C)C#CC3NCCCC3)C=NC2=C1NC1CCCC1 QMUSXTGQLQHEAT-PNODFLSHSA-N 0.000 description 1
- AYKVGFWDCCQNPT-OHYWOBESSA-N 9-[(3ar,4r,6r,6ar)-2,2-dimethyl-6-(2-thiophen-2-ylethynyl)-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-n-(oxolan-3-yl)purin-6-amine Chemical compound N1=CN=C2N([C@@H]3O[C@@H]([C@H]4OC(O[C@H]43)(C)C)C#CC=3SC=CC=3)C=NC2=C1NC1CCOC1 AYKVGFWDCCQNPT-OHYWOBESSA-N 0.000 description 1
- NTKYTVGTOPVEPK-WGQQHEPDSA-N 9-[(3ar,4r,6r,6ar)-2,2-dimethyl-6-(2-thiophen-2-ylethynyl)-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-n-cyclopentylpurin-6-amine Chemical compound N1=CN=C2N([C@@H]3O[C@@H]([C@H]4OC(O[C@H]43)(C)C)C#CC=3SC=CC=3)C=NC2=C1NC1CCCC1 NTKYTVGTOPVEPK-WGQQHEPDSA-N 0.000 description 1
- VGSWSOQWLVHAFX-HAXDFEGKSA-N 9-[(3ar,4r,6r,6ar)-2,2-dimethyl-6-[2-(1,3-thiazol-2-yl)ethynyl]-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-n-cyclopentylpurin-6-amine Chemical compound N1=CN=C2N([C@@H]3O[C@@H]([C@H]4OC(O[C@H]43)(C)C)C#CC=3SC=CN=3)C=NC2=C1NC1CCCC1 VGSWSOQWLVHAFX-HAXDFEGKSA-N 0.000 description 1
- VGBXAXDRHWQEEW-WGQQHEPDSA-N 9-[(3ar,4r,6r,6ar)-2,2-dimethyl-6-[2-(4-methyl-1,2-oxazol-3-yl)ethynyl]-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-n-cyclopentylpurin-6-amine Chemical compound CC1=CON=C1C#C[C@@H]1[C@H]2OC(C)(C)O[C@H]2[C@H](N2C3=NC=NC(NC4CCCC4)=C3N=C2)O1 VGBXAXDRHWQEEW-WGQQHEPDSA-N 0.000 description 1
- OYGHXIZPAWDCIM-ZDXOVATRSA-N 9-[(3ar,4r,6r,6ar)-6-(2-cyclopentylethynyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-n-cyclopentylpurin-6-amine Chemical compound N1=CN=C2N([C@@H]3O[C@@H]([C@H]4OC(O[C@H]43)(C)C)C#CC3CCCC3)C=NC2=C1NC1CCCC1 OYGHXIZPAWDCIM-ZDXOVATRSA-N 0.000 description 1
- CNPSJNRJGUQKFG-UMCMBGNQSA-N 9-[(3ar,4r,6r,6ar)-6-[2-(2-chlorophenyl)ethynyl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-n-cyclopentylpurin-6-amine Chemical compound N1=CN=C2N([C@@H]3O[C@@H]([C@H]4OC(O[C@H]43)(C)C)C#CC=3C(=CC=CC=3)Cl)C=NC2=C1NC1CCCC1 CNPSJNRJGUQKFG-UMCMBGNQSA-N 0.000 description 1
- OEZQJMLBCFJDDM-ZDXOVATRSA-N 9-[(3ar,4r,6r,6ar)-6-[2-(3,5-dimethyl-1,2-oxazol-4-yl)ethynyl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-n-cyclopentylpurin-6-amine Chemical compound CC1=NOC(C)=C1C#C[C@@H]1[C@H]2OC(C)(C)O[C@H]2[C@H](N2C3=NC=NC(NC4CCCC4)=C3N=C2)O1 OEZQJMLBCFJDDM-ZDXOVATRSA-N 0.000 description 1
- ASTVHHZOVHVHHO-CIVUBGFFSA-N 9-[(3ar,4r,6r,6ar)-6-[2-(5-chlorothiophen-2-yl)ethynyl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-n-cyclopentylpurin-6-amine Chemical compound N1=CN=C2N([C@@H]3O[C@@H]([C@H]4OC(O[C@H]43)(C)C)C#CC=3SC(Cl)=CC=3)C=NC2=C1NC1CCCC1 ASTVHHZOVHVHHO-CIVUBGFFSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 102100036664 Adenosine deaminase Human genes 0.000 description 1
- 229940080778 Adenosine deaminase inhibitor Drugs 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 206010002388 Angina unstable Diseases 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 241000512259 Ascophyllum nodosum Species 0.000 description 1
- 206010003662 Atrial flutter Diseases 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical group C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- WWVUZFUWOAHUBO-ZBZASNMZSA-N C1(CCCCC1)NC1=C2N=CN(C2=NC=N1)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)C#C.C1(CCC1)NC1=C2N=CN(C2=NC=N1)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)C#C Chemical compound C1(CCCCC1)NC1=C2N=CN(C2=NC=N1)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)C#C.C1(CCC1)NC1=C2N=CN(C2=NC=N1)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)C#C WWVUZFUWOAHUBO-ZBZASNMZSA-N 0.000 description 1
- 238000009641 CAMP test Methods 0.000 description 1
- OBDVJSHYRAKJEP-UXRYMUROSA-N CC(C)(OC12)OC1=C(/C=C/OCc1ccccc1)O[C@H]2[n]1c(ncnc2NC3CCCC3)c2nc1 Chemical compound CC(C)(OC12)OC1=C(/C=C/OCc1ccccc1)O[C@H]2[n]1c(ncnc2NC3CCCC3)c2nc1 OBDVJSHYRAKJEP-UXRYMUROSA-N 0.000 description 1
- VVADJZAGLAVTRC-OPEAARRCSA-N CC([C@H]([n]1c(ncnc2NC3CCCC3)c2nc1)OC)OC(C)(C)/[O]=C/COCc1ccccc1 Chemical compound CC([C@H]([n]1c(ncnc2NC3CCCC3)c2nc1)OC)OC(C)(C)/[O]=C/COCc1ccccc1 VVADJZAGLAVTRC-OPEAARRCSA-N 0.000 description 1
- QWOJMRHUQHTCJG-UHFFFAOYSA-N CC([CH2-])=O Chemical group CC([CH2-])=O QWOJMRHUQHTCJG-UHFFFAOYSA-N 0.000 description 1
- 0 CCCI1=C(*C2CCCC2)C(*=C*2[C@@]3O[C@](CC(*)=O)C4OC(C)(C)OC34)=C2*=C1 Chemical compound CCCI1=C(*C2CCCC2)C(*=C*2[C@@]3O[C@](CC(*)=O)C4OC(C)(C)OC34)=C2*=C1 0.000 description 1
- PAOANWZGLPPROA-RQXXJAGISA-N CGS-21680 Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NCC)O[C@H]1N1C2=NC(NCCC=3C=CC(CCC(O)=O)=CC=3)=NC(N)=C2N=C1 PAOANWZGLPPROA-RQXXJAGISA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 241000238586 Cirripedia Species 0.000 description 1
- 102000012422 Collagen Type I Human genes 0.000 description 1
- 108010022452 Collagen Type I Proteins 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 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
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 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
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 206010015719 Exsanguination Diseases 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-N Gluconic acid Natural products OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical group CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- 241001024304 Mino Species 0.000 description 1
- 241001504654 Mustela nivalis Species 0.000 description 1
- 235000009421 Myristica fragrans Nutrition 0.000 description 1
- UIAYVIIHMORPSJ-UHFFFAOYSA-N N-cyclohexyl-N-methyl-4-[(2-oxo-1H-quinolin-6-yl)oxy]butanamide Chemical compound C=1C=C2NC(=O)C=CC2=CC=1OCCCC(=O)N(C)C1CCCCC1 UIAYVIIHMORPSJ-UHFFFAOYSA-N 0.000 description 1
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 102100035591 POU domain, class 2, transcription factor 2 Human genes 0.000 description 1
- 101710084411 POU domain, class 2, transcription factor 2 Proteins 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241000237503 Pectinidae Species 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- DYAHQFWOVKZOOW-UHFFFAOYSA-N Sarin Chemical compound CC(C)OP(C)(F)=O DYAHQFWOVKZOOW-UHFFFAOYSA-N 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
- 208000007718 Stable Angina Diseases 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 208000003734 Supraventricular Tachycardia Diseases 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 239000007984 Tris EDTA buffer Substances 0.000 description 1
- 208000007814 Unstable Angina Diseases 0.000 description 1
- 208000008131 Ventricular Flutter Diseases 0.000 description 1
- 238000007239 Wittig reaction Methods 0.000 description 1
- OBAAIGREYDUOHX-ZGOQAQPGSA-N [(2r,3s,4r,5r)-3,4-dihydroxy-5-[6-[[(3r)-oxolan-3-yl]amino]purin-9-yl]oxolan-2-yl]methyl n-ethylcarbamate Chemical compound O[C@@H]1[C@H](O)[C@@H](COC(=O)NCC)O[C@H]1N1C2=NC=NC(N[C@H]3COCC3)=C2N=C1 OBAAIGREYDUOHX-ZGOQAQPGSA-N 0.000 description 1
- AVJAINSHNSCCJY-JJPFLPBXSA-N [(3ar,4r,6r,6ar)-2,2-dimethyl-4-[6-(oxan-3-ylmethylamino)purin-9-yl]-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methanol Chemical compound N1=CN=C2N([C@@H]3O[C@H](CO)[C@H]4OC(O[C@H]43)(C)C)C=NC2=C1NCC1CCCOC1 AVJAINSHNSCCJY-JJPFLPBXSA-N 0.000 description 1
- ASENTPNZMQSPKQ-SCFUHWHPSA-N [(3ar,4r,6r,6ar)-4-(6-anilinopurin-9-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methanol Chemical compound N1=CN=C2N([C@@H]3O[C@H](CO)[C@H]4OC(O[C@H]43)(C)C)C=NC2=C1NC1=CC=CC=C1 ASENTPNZMQSPKQ-SCFUHWHPSA-N 0.000 description 1
- JNQFYSBBKJODPY-NVQRDWNXSA-N [(3ar,4r,6r,6ar)-4-[6-(benzylamino)purin-9-yl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methanol Chemical compound N1=CN=C2N([C@@H]3O[C@H](CO)[C@H]4OC(O[C@H]43)(C)C)C=NC2=C1NCC1=CC=CC=C1 JNQFYSBBKJODPY-NVQRDWNXSA-N 0.000 description 1
- NBWSVYXKNNNRKW-XNIJJKJLSA-N [(3ar,4r,6r,6ar)-4-[6-(cyclopentylamino)-2-(trifluoromethyl)purin-9-yl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methanol Chemical compound N1=C(C(F)(F)F)N=C2N([C@@H]3O[C@H](CO)[C@H]4OC(O[C@H]43)(C)C)C=NC2=C1NC1CCCC1 NBWSVYXKNNNRKW-XNIJJKJLSA-N 0.000 description 1
- NGWPRNQVDRXJAE-LSCFUAHRSA-N [(3ar,4r,6r,6ar)-4-[6-(cyclopentylamino)purin-9-yl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methanol Chemical compound N1=CN=C2N([C@@H]3O[C@H](CO)[C@H]4OC(O[C@H]43)(C)C)C=NC2=C1NC1CCCC1 NGWPRNQVDRXJAE-LSCFUAHRSA-N 0.000 description 1
- TXQASMANOARPSW-WJDBLMMSSA-N [(3ar,4r,6r,6ar)-4-[6-[(5-fluorooxan-3-yl)amino]purin-9-yl]-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methanol Chemical compound N1=CN=C2N([C@@H]3O[C@H](CO)[C@H]4OC(O[C@H]43)(C)C)C=NC2=C1NC1COCC(F)C1 TXQASMANOARPSW-WJDBLMMSSA-N 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- PEHFQTGKICLBSA-UHFFFAOYSA-N [Cl-].[PH4+].C(C1=CC=CC=C1)OC[P](C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 Chemical compound [Cl-].[PH4+].C(C1=CC=CC=C1)OC[P](C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 PEHFQTGKICLBSA-UHFFFAOYSA-N 0.000 description 1
- 210000003815 abdominal wall Anatomy 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 229940081735 acetylcellulose Drugs 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 description 1
- 239000002582 adenosine A1 receptor agonist Substances 0.000 description 1
- 239000002487 adenosine deaminase inhibitor Substances 0.000 description 1
- 239000003121 adenosine kinase inhibitor Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000008485 antagonism Effects 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
- 230000003457 anti-vomiting effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 239000000305 astragalus gummifer gum Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 210000003157 atrial septum Anatomy 0.000 description 1
- 239000000759 benzodiazepine receptor stimulating agent Substances 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 1
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 229960001714 calcium phosphate Drugs 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 230000025938 carbohydrate utilization Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 210000001168 carotid artery common Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- LADPCMZCENPFGV-UHFFFAOYSA-N chloromethoxymethylbenzene Chemical compound ClCOCC1=CC=CC=C1 LADPCMZCENPFGV-UHFFFAOYSA-N 0.000 description 1
- 125000000068 chlorophenyl group Chemical group 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229950002934 cilostamide Drugs 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000006165 cyclic alkyl group Chemical group 0.000 description 1
- 150000001925 cycloalkenes Chemical class 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- LQNHRNOPWKZUSN-UHFFFAOYSA-N cyclobutylmethanamine Chemical compound NCC1CCC1 LQNHRNOPWKZUSN-UHFFFAOYSA-N 0.000 description 1
- 150000003946 cyclohexylamines Chemical class 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
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 125000005265 dialkylamine group Chemical group 0.000 description 1
- 125000005266 diarylamine group Chemical group 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 229940112141 dry powder inhaler Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 239000002662 enteric coated tablet Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- 229940012017 ethylenediamine Drugs 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229940029575 guanosine Drugs 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000005003 heart tissue Anatomy 0.000 description 1
- 125000005241 heteroarylamino group Chemical group 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 229960002885 histidine Drugs 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 1
- 230000003871 intestinal function Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- IQPQWNKOIGAROB-UHFFFAOYSA-N isocyanate Chemical compound [N-]=C=O IQPQWNKOIGAROB-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 229940039009 isoproterenol Drugs 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 239000001115 mace Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 238000012423 maintenance Methods 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
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229940117841 methacrylic acid copolymer Drugs 0.000 description 1
- 229920003145 methacrylic acid copolymer Polymers 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- KHOPQCKQZYSGIG-LQLSJNDNSA-N methyl 3-[(2r,3s,4r,5r)-3,4-dihydroxy-5-[6-(oxolan-3-ylamino)purin-9-yl]oxolan-2-yl]propanoate Chemical compound O[C@@H]1[C@H](O)[C@@H](CCC(=O)OC)O[C@H]1N1C2=NC=NC(NC3COCC3)=C2N=C1 KHOPQCKQZYSGIG-LQLSJNDNSA-N 0.000 description 1
- XMSZANIMCDLNKA-UHFFFAOYSA-N methyl hypofluorite Chemical compound COF XMSZANIMCDLNKA-UHFFFAOYSA-N 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 239000013081 microcrystal Substances 0.000 description 1
- 210000004115 mitral valve Anatomy 0.000 description 1
- 239000011812 mixed powder Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- ATHHXGZTWNVVOU-UHFFFAOYSA-N monomethyl-formamide Natural products CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- TTYMURDBXAIXQT-UHFFFAOYSA-N n'-(1,3-dichlorohexyl)methanediimine Chemical compound CCCC(Cl)CC(Cl)N=C=N TTYMURDBXAIXQT-UHFFFAOYSA-N 0.000 description 1
- SMBBZHGTZJNSRQ-UHFFFAOYSA-N n'-(6,6-dichlorohexyl)methanediimine Chemical compound ClC(Cl)CCCCCN=C=N SMBBZHGTZJNSRQ-UHFFFAOYSA-N 0.000 description 1
- HGUZQMQXAHVIQC-UHFFFAOYSA-N n-methylethenamine Chemical group CNC=C HGUZQMQXAHVIQC-UHFFFAOYSA-N 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000004112 neuroprotection Effects 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical group C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000009377 nuclear transmutation Methods 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- WUUOEJJGRCQGBQ-UHFFFAOYSA-N oxan-3-amine Chemical compound NC1CCCOC1 WUUOEJJGRCQGBQ-UHFFFAOYSA-N 0.000 description 1
- ZTCHEOLGUZDPAN-UHFFFAOYSA-N oxan-3-ylmethanamine Chemical compound NCC1CCCOC1 ZTCHEOLGUZDPAN-UHFFFAOYSA-N 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 229940056360 penicillin g Drugs 0.000 description 1
- QSYOAKOOQMVVTO-UHFFFAOYSA-N pentan-2-yl 2-methylprop-2-enoate Chemical compound CCCC(C)OC(=O)C(C)=C QSYOAKOOQMVVTO-UHFFFAOYSA-N 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000003200 peritoneal cavity Anatomy 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 229950000688 phenothiazine Drugs 0.000 description 1
- 239000011574 phosphorus Chemical group 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 125000004574 piperidin-2-yl group Chemical group N1C(CCCC1)* 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000003334 potential effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
- 230000001696 purinergic effect Effects 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000036279 refractory period Effects 0.000 description 1
- 230000025053 regulation of cell proliferation Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- HJORMJIFDVBMOB-UHFFFAOYSA-N rolipram Chemical compound COC1=CC=C(C2CC(=O)NC2)C=C1OC1CCCC1 HJORMJIFDVBMOB-UHFFFAOYSA-N 0.000 description 1
- 229950005741 rolipram Drugs 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 235000020637 scallop Nutrition 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical class O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 201000002932 second-degree atrioventricular block Diseases 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 238000009958 sewing Methods 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 210000001013 sinoatrial node Anatomy 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
- 229910001948 sodium oxide Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000012058 sterile packaged powder Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229960002385 streptomycin sulfate Drugs 0.000 description 1
- 125000005156 substituted alkylene group Chemical group 0.000 description 1
- 125000004426 substituted alkynyl group Chemical group 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229960004559 theobromine Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 125000005259 triarylamine group Chemical group 0.000 description 1
- BDJWKDVEYUXIRO-UHFFFAOYSA-N triazol-2-amine Chemical compound NN1N=CC=N1 BDJWKDVEYUXIRO-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- GJPGLLAXZTYTFW-UHFFFAOYSA-M triphenyl(phenylmethoxymethyl)phosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1COC[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 GJPGLLAXZTYTFW-UHFFFAOYSA-M 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
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000009777 vacuum freeze-drying Methods 0.000 description 1
- 210000001177 vas deferen Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 206010047302 ventricular tachycardia Diseases 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229940075420 xanthine Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
- C07H19/167—Purine radicals with ribosyl as the saccharide radical
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- A61P9/06—Antiarrhythmics
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Diabetes (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Vascular Medicine (AREA)
- Transplantation (AREA)
- Endocrinology (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US40371202P | 2002-08-15 | 2002-08-15 | |
| US45009403P | 2003-02-25 | 2003-02-25 | |
| PCT/US2003/025629 WO2004016635A2 (en) | 2002-08-15 | 2003-08-15 | Partial and full agonists of a1 adenosine receptors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2006505525A JP2006505525A (ja) | 2006-02-16 |
| JP2006505525A5 JP2006505525A5 (https=) | 2006-08-17 |
| JP4596913B2 true JP4596913B2 (ja) | 2010-12-15 |
Family
ID=31891396
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004529472A Expired - Fee Related JP4596913B2 (ja) | 2002-08-15 | 2003-08-15 | Ａ１アデノシン受容体の部分および完全アゴニスト |
Country Status (15)
| Country | Link |
|---|---|
| US (2) | US7022681B2 (https=) |
| EP (1) | EP1537133B1 (https=) |
| JP (1) | JP4596913B2 (https=) |
| KR (1) | KR20050067384A (https=) |
| CN (1) | CN100480255C (https=) |
| AT (1) | ATE368048T1 (https=) |
| AU (1) | AU2003263846B2 (https=) |
| CA (1) | CA2495370A1 (https=) |
| DE (1) | DE60315164T2 (https=) |
| ES (1) | ES2288632T3 (https=) |
| MX (1) | MXPA05001844A (https=) |
| NO (1) | NO20051296L (https=) |
| NZ (1) | NZ538590A (https=) |
| RU (1) | RU2340623C2 (https=) |
| WO (1) | WO2004016635A2 (https=) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2528385C (en) | 2003-06-06 | 2011-03-15 | Endacea, Inc. | A1 adenosine receptor antogonists |
| WO2008143667A1 (en) * | 2007-05-17 | 2008-11-27 | Cv Therapeutics, Inc. | Process for preparing an a2a-adenosine receptor agonist and its polymorphs |
| JP2014530910A (ja) * | 2011-10-24 | 2014-11-20 | グラクソスミスクライン、インテレクチュアル、プロパティー、ナンバー２、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ Ｎｏ．２ Ｌｉｍｉｔｅｄ | 新規化合物 |
| JP6584521B2 (ja) * | 2015-02-24 | 2019-10-02 | ファイザー・インク | 抗がん剤として有用な置換ヌクレオシド誘導体 |
| JP6643719B2 (ja) * | 2016-05-31 | 2020-02-12 | セントラル硝子株式会社 | ３，３，３−トリフルオロプロパノールの製造方法 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1254888A (en) * | 1984-10-26 | 1989-05-30 | Bharat Trivedi | N.sup.6-bicycloadenosines |
| USRE36494E (en) * | 1990-02-20 | 2000-01-11 | Discovery Therapeutics, Inc. | 2-aralkoxy and 2-alkoxy adenosine derivatives as coronary vasodilators and antihypertensive agents |
| US5140015A (en) * | 1990-02-20 | 1992-08-18 | Whitby Research, Inc. | 2-aralkoxy and 2-alkoxy adenosine derivatives as coronary vasodilators and antihypertensive agents |
| US5278150A (en) * | 1992-04-24 | 1994-01-11 | Whitby Research, Inc. | 2-hydrazoadenosines and their utility for the treatmeat of vascular conditions |
| GB9301000D0 (en) * | 1993-01-20 | 1993-03-10 | Glaxo Group Ltd | Chemical compounds |
| US5589467A (en) * | 1993-09-17 | 1996-12-31 | Novo Nordisk A/S | 2,5',N6-trisubstituted adenosine derivatives |
| WO1997033591A1 (en) * | 1996-03-13 | 1997-09-18 | Novo Nordisk A/S | A method of treating disorders related to cytokines in mammals |
| WO1998016539A1 (en) * | 1996-10-14 | 1998-04-23 | Novo Nordisk A/S | Novel therapeutically active adenosine derivatives |
| GB9723589D0 (en) * | 1997-11-08 | 1998-01-07 | Glaxo Group Ltd | Chemical compounds |
| GB9813554D0 (en) * | 1998-06-23 | 1998-08-19 | Glaxo Group Ltd | Chemical compounds |
| US20040162422A1 (en) * | 2001-03-20 | 2004-08-19 | Adrian Hall | Chemical compounds |
-
2003
- 2003-08-15 JP JP2004529472A patent/JP4596913B2/ja not_active Expired - Fee Related
- 2003-08-15 US US10/641,930 patent/US7022681B2/en not_active Expired - Fee Related
- 2003-08-15 AU AU2003263846A patent/AU2003263846B2/en not_active Ceased
- 2003-08-15 WO PCT/US2003/025629 patent/WO2004016635A2/en not_active Ceased
- 2003-08-15 RU RU2005106997/04A patent/RU2340623C2/ru not_active IP Right Cessation
- 2003-08-15 NZ NZ538590A patent/NZ538590A/en not_active IP Right Cessation
- 2003-08-15 MX MXPA05001844A patent/MXPA05001844A/es active IP Right Grant
- 2003-08-15 EP EP03788541A patent/EP1537133B1/en not_active Expired - Lifetime
- 2003-08-15 CA CA002495370A patent/CA2495370A1/en not_active Abandoned
- 2003-08-15 KR KR1020057002587A patent/KR20050067384A/ko not_active Ceased
- 2003-08-15 DE DE60315164T patent/DE60315164T2/de not_active Expired - Lifetime
- 2003-08-15 CN CNB038193612A patent/CN100480255C/zh not_active Expired - Fee Related
- 2003-08-15 ES ES03788541T patent/ES2288632T3/es not_active Expired - Lifetime
- 2003-08-15 AT AT03788541T patent/ATE368048T1/de not_active IP Right Cessation
-
2005
- 2005-03-14 NO NO20051296A patent/NO20051296L/no not_active Application Discontinuation
-
2006
- 2006-02-15 US US11/355,656 patent/US20060135467A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| NZ538590A (en) | 2006-10-27 |
| CN1675235A (zh) | 2005-09-28 |
| US7022681B2 (en) | 2006-04-04 |
| JP2006505525A (ja) | 2006-02-16 |
| US20060135467A1 (en) | 2006-06-22 |
| EP1537133A2 (en) | 2005-06-08 |
| CA2495370A1 (en) | 2004-02-26 |
| ES2288632T3 (es) | 2008-01-16 |
| RU2340623C2 (ru) | 2008-12-10 |
| NO20051296L (no) | 2005-05-13 |
| AU2003263846B2 (en) | 2009-12-17 |
| KR20050067384A (ko) | 2005-07-01 |
| US20040043960A1 (en) | 2004-03-04 |
| MXPA05001844A (es) | 2005-04-19 |
| DE60315164T2 (de) | 2008-04-30 |
| RU2005106997A (ru) | 2005-11-10 |
| ATE368048T1 (de) | 2007-08-15 |
| DE60315164D1 (de) | 2007-09-06 |
| CN100480255C (zh) | 2009-04-22 |
| WO2004016635A3 (en) | 2004-04-08 |
| EP1537133B1 (en) | 2007-07-25 |
| AU2003263846A1 (en) | 2004-03-03 |
| WO2004016635A2 (en) | 2004-02-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2008249143B2 (en) | Partial and full agonists of A1 adenosine receptors | |
| JP4021196B2 (ja) | Ｎ６複素環複素環式８−修飾アデノシン誘導体 | |
| EP0992510B1 (en) | N6 heterocyclic substituted adenosine derivatives | |
| JP2010513565A (ja) | Ａ１アデノシン受容体の部分アゴニストまたは完全アゴニストとしてのアデノシン誘導体 | |
| JP5042996B2 (ja) | Ａ１アデノシンレセプターアゴニスト | |
| JP4596913B2 (ja) | Ａ１アデノシン受容体の部分および完全アゴニスト | |
| JP2008505967A (ja) | Ａ１アデノシンレセプターアゴニストの製造方法 | |
| JP2008540685A (ja) | Ａ１アデノシンレセプターアゴニスト | |
| US7488720B2 (en) | A1 adenosine receptor agonists | |
| HK1130805A (en) | Partial and full agonists of a1 adenosine receptors | |
| MXPA99001509A (en) | N6 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20060627 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20060627 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20090917 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20100119 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20100419 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20100426 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20100518 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100525 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20100525 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20100824 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20100921 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20131001 Year of fee payment: 3 |
|
| LAPS | Cancellation because of no payment of annual fees |