RU2340623C2 - Частичные и полные агонисты аденозиновых рецепторов a1 - Google Patents

Info

Publication number

RU2340623C2

RU2340623C2 RU2005106997/04A RU2005106997A RU2340623C2 RU 2340623 C2 RU2340623 C2 RU 2340623C2 RU 2005106997/04 A RU2005106997/04 A RU 2005106997/04A RU 2005106997 A RU2005106997 A RU 2005106997A RU 2340623 C2 RU2340623 C2 RU 2340623C2

Authority

RU

Russia

Prior art keywords

purin

formula

optionally substituted

oxolan

diol

Prior art date

2002-08-15

Links

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• 239000000556 agonist Substances 0.000 title claims description 28
• 108050000203 Adenosine receptors Proteins 0.000 title claims description 16
• 102000009346 Adenosine receptors Human genes 0.000 title claims description 16
• 230000036961 partial effect Effects 0.000 title description 5
• 150000001875 compounds Chemical class 0.000 claims abstract description 332
• 239000001257 hydrogen Substances 0.000 claims abstract description 82
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 82
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 61
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 47
• 150000002431 hydrogen Chemical group 0.000 claims abstract description 47
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 33
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 30
• 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 29
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 28
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 27
• 230000000694 effects Effects 0.000 claims abstract description 21
• 125000002947 alkylene group Chemical group 0.000 claims abstract description 20
• 125000005843 halogen group Chemical group 0.000 claims abstract description 15
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 15
• 125000005842 heteroatom Chemical group 0.000 claims abstract description 13
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 13
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 12
• 239000001301 oxygen Substances 0.000 claims abstract description 12
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 12
• 230000003243 anti-lipolytic effect Effects 0.000 claims abstract description 10
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 9
• 229910052717 sulfur Inorganic materials 0.000 claims abstract description 9
• 239000011593 sulfur Substances 0.000 claims abstract description 9
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract 2
• -1 C 1-4 -alkyl Chemical group 0.000 claims description 109
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 38
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 34
• 125000003545 alkoxy group Chemical group 0.000 claims description 28
• 238000002360 preparation method Methods 0.000 claims description 28
• 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 claims description 18
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
• 102000005962 receptors Human genes 0.000 claims description 12
• 108020003175 receptors Proteins 0.000 claims description 12
• 201000010099 disease Diseases 0.000 claims description 11
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 11
• 125000003107 substituted aryl group Chemical group 0.000 claims description 11
• 239000002126 C01EB10 - Adenosine Substances 0.000 claims description 9
• 229960005305 adenosine Drugs 0.000 claims description 9
• 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 9
• 239000008194 pharmaceutical composition Substances 0.000 claims 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 claims description 6
• 239000003814 drug Substances 0.000 claims description 6
• 239000002582 adenosine A1 receptor agonist Substances 0.000 claims description 5
• 208000030159 metabolic disease Diseases 0.000 claims description 5
• 208000008589 Obesity Diseases 0.000 claims description 4
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 4
• 235000020824 obesity Nutrition 0.000 claims description 4
• FZOKRCLVLPATSB-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-(2-phenylethenyl)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)C=NC2=C1NC1CCCC1 FZOKRCLVLPATSB-WGQQHEPDSA-N 0.000 claims description 3
• WDASMIRQGXPOGJ-ZDXOVATRSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-[2-(2-methylphenyl)ethenyl]oxolane-3,4-diol Chemical compound CC1=CC=CC=C1C=C[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C3=NC=NC(NC4CCCC4)=C3N=C2)O1 WDASMIRQGXPOGJ-ZDXOVATRSA-N 0.000 claims description 3
• 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 claims description 3
• 229940079593 drug Drugs 0.000 claims description 3
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 3
• 125000001544 thienyl group Chemical group 0.000 claims description 3
• 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 claims description 2
• 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 claims description 2
• JINVIIJODLXFHF-XNIJJKJLSA-N (2r,3r,4s,5r)-2-[6-(cyclopentylamino)purin-9-yl]-5-ethyloxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CC)O[C@H]1N1C2=NC=NC(NC3CCCC3)=C2N=C1 JINVIIJODLXFHF-XNIJJKJLSA-N 0.000 claims 1
• CSAXKCCOTBAQFS-OHYWOBESSA-N (2r,3r,4s,5r)-2-[6-(oxolan-3-ylamino)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(NC3COCC3)=C2N=C1)#CC1=CC=CC=C1C(F)(F)F CSAXKCCOTBAQFS-OHYWOBESSA-N 0.000 claims 1
• QIJPJFOWIOBTIO-OHYWOBESSA-N (2r,3s,4r,5r)-2-[2-(2-fluorophenyl)ethynyl]-5-[6-(oxolan-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(NC3COCC3)=C2N=C1)#CC1=CC=CC=C1F QIJPJFOWIOBTIO-OHYWOBESSA-N 0.000 claims 1
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 1
• 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims 1
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims 1
• 238000004519 manufacturing process Methods 0.000 claims 1
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
• 229910052736 halogen Inorganic materials 0.000 abstract description 31
• 150000002367 halogens Chemical class 0.000 abstract description 31
• 125000004429 atom Chemical group 0.000 abstract description 12
• 239000000126 substance Substances 0.000 abstract description 8
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 2
• 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 1
• 239000000203 mixture Substances 0.000 description 74
• 238000006243 chemical reaction Methods 0.000 description 61
• 238000000034 method Methods 0.000 description 50
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 50
• 229920002554 vinyl polymer Polymers 0.000 description 48
• 125000001424 substituent group Chemical group 0.000 description 46
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 43
• 239000002904 solvent Substances 0.000 description 43
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
• 125000003118 aryl group Chemical group 0.000 description 42
• 125000004545 purin-9-yl group Chemical group N1=CN=C2N(C=NC2=C1)* 0.000 description 41
• 239000000243 solution Substances 0.000 description 40
• 230000002829 reductive effect Effects 0.000 description 32
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
• NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 30
• 239000004480 active ingredient Substances 0.000 description 27
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
• 125000004093 cyano group Chemical group *C#N 0.000 description 24
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
• 239000000047 product Substances 0.000 description 22
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 21
• 125000004181 carboxyalkyl group Chemical group 0.000 description 20
• 125000003342 alkenyl group Chemical group 0.000 description 19
• 239000004615 ingredient Substances 0.000 description 19
• 239000003826 tablet Substances 0.000 description 19
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 17
• 150000001412 amines Chemical class 0.000 description 17
• 125000004432 carbon atom Chemical group C* 0.000 description 17
• 125000000392 cycloalkenyl group Chemical group 0.000 description 17
• 238000012360 testing method Methods 0.000 description 17
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
• 125000000304 alkynyl group Chemical group 0.000 description 16
• 235000021588 free fatty acids Nutrition 0.000 description 16
• 235000019439 ethyl acetate Nutrition 0.000 description 15
• 239000003379 purinergic P1 receptor agonist Substances 0.000 description 15
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
• 241000700159 Rattus Species 0.000 description 14
• 210000004027 cell Anatomy 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
• 239000000725 suspension Substances 0.000 description 13
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 12
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
• 150000003839 salts Chemical class 0.000 description 12
• 239000000843 powder Substances 0.000 description 11
• 125000000547 substituted alkyl group Chemical group 0.000 description 11
• 210000001519 tissue Anatomy 0.000 description 11
• 230000008673 vomiting Effects 0.000 description 11
• 239000002253 acid Substances 0.000 description 10
• 125000002252 acyl group Chemical group 0.000 description 10
• 210000001789 adipocyte Anatomy 0.000 description 10
• 239000000872 buffer Substances 0.000 description 10
• 239000003795 chemical substances by application Substances 0.000 description 10
• 229910052740 iodine Inorganic materials 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
• 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 Chemical group 0.000 description 9
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
• 206010047700 Vomiting Diseases 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
• 239000002585 base Substances 0.000 description 9
• 125000000468 ketone group Chemical group 0.000 description 9
• 230000010412 perfusion Effects 0.000 description 9
• 230000000638 stimulation Effects 0.000 description 9
• 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 9
• 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 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 8
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 8
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
• 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 8
• 125000000852 azido group Chemical group *N=[N+]=[N-] 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
• 238000007796 conventional method Methods 0.000 description 8
• HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 8
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 8
• 239000000706 filtrate Substances 0.000 description 8
• 239000007788 liquid Substances 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
• 239000012044 organic layer Substances 0.000 description 8
• 238000012746 preparative thin layer chromatography Methods 0.000 description 8
• 239000011734 sodium Substances 0.000 description 8
• 241000282339 Mustela Species 0.000 description 7
• 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 7
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 7
• 230000027455 binding Effects 0.000 description 7
• 230000003197 catalytic effect Effects 0.000 description 7
• 125000005368 heteroarylthio group Chemical group 0.000 description 7
• 238000002347 injection Methods 0.000 description 7
• 239000007924 injection Substances 0.000 description 7
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 7
• MIPHRQMEIYLZFZ-UHFFFAOYSA-N oxolan-3-amine Chemical compound NC1CCOC1 MIPHRQMEIYLZFZ-UHFFFAOYSA-N 0.000 description 7
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 7
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 7
• 238000000746 purification Methods 0.000 description 7
• 239000011541 reaction mixture Substances 0.000 description 7
• 210000002966 serum Anatomy 0.000 description 7
• CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 6
• 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 6
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-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
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 6
• 241001465754 Metazoa Species 0.000 description 6
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 6
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• 150000001299 aldehydes Chemical class 0.000 description 6
• 125000000033 alkoxyamino group Chemical group 0.000 description 6
• 125000004414 alkyl thio group Chemical group 0.000 description 6
• 210000001992 atrioventricular node Anatomy 0.000 description 6
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 6
• 210000004369 blood Anatomy 0.000 description 6
• 239000008280 blood Substances 0.000 description 6
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• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
• PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
• 125000004470 heterocyclooxy group Chemical group 0.000 description 6
• 125000004468 heterocyclylthio group Chemical group 0.000 description 6
• 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 6
• 235000019359 magnesium stearate Nutrition 0.000 description 6
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• 235000019698 starch Nutrition 0.000 description 6
• 150000003573 thiols Chemical group 0.000 description 6
• 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 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
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