KR20080110923A - 아데노신 ａ２ａ 수용체 효능제로서 사용하기 위한 퓨린 유도체 - Google Patents

Info

Publication number

KR20080110923A

KR20080110923A KR1020087028380A KR20087028380A KR20080110923A KR 20080110923 A KR20080110923 A KR 20080110923A KR 1020087028380 A KR1020087028380 A KR 1020087028380A KR 20087028380 A KR20087028380 A KR 20087028380A KR 20080110923 A KR20080110923 A KR 20080110923A

Authority

KR

South Korea

Prior art keywords

optionally substituted

amino

alkyl

purin

ethylamino

Prior art date

2006-04-21

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.)

Withdrawn

Links

• Espacenet
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• 239000002465 adenosine A2a receptor agonist Substances 0.000 title 1
• 229940083251 peripheral vasodilators purine derivative Drugs 0.000 title 1
• 150000003212 purines Chemical class 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 346
• 150000003839 salts Chemical class 0.000 claims abstract description 31
• 238000002360 preparation method Methods 0.000 claims abstract description 26
• 239000003814 drug Substances 0.000 claims abstract description 17
• -1 hydroxy, carboxy, amino Chemical group 0.000 claims description 157
• 238000000034 method Methods 0.000 claims description 124
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 63
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 61
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 57
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 55
• 229910052757 nitrogen Inorganic materials 0.000 claims description 48
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 46
• 229910052760 oxygen Inorganic materials 0.000 claims description 46
• 239000001301 oxygen Chemical group 0.000 claims description 46
• 125000005842 heteroatom Chemical group 0.000 claims description 45
• 229910052717 sulfur Chemical group 0.000 claims description 45
• 239000011593 sulfur Chemical group 0.000 claims description 45
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 44
• 125000005843 halogen group Chemical group 0.000 claims description 39
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 36
• 239000001257 hydrogen Substances 0.000 claims description 30
• 229910052739 hydrogen Inorganic materials 0.000 claims description 30
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 20
• 230000002757 inflammatory effect Effects 0.000 claims description 18
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 17
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
• 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 14
• 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 12
• 150000002431 hydrogen Chemical class 0.000 claims description 12
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 12
• 230000002829 reductive effect Effects 0.000 claims description 11
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
• 125000004043 oxo group Chemical group O=* 0.000 claims description 8
• 239000002126 C01EB10 - Adenosine Substances 0.000 claims description 7
• 229960005305 adenosine Drugs 0.000 claims description 7
• 230000000694 effects Effects 0.000 claims description 7
• 102000005962 receptors Human genes 0.000 claims description 7
• 108020003175 receptors Proteins 0.000 claims description 7
• 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 6
• 230000004913 activation Effects 0.000 claims description 6
• 206010063837 Reperfusion injury Diseases 0.000 claims description 5
• 208000027866 inflammatory disease Diseases 0.000 claims description 5
• 208000011580 syndromic disease Diseases 0.000 claims description 5
• 230000029663 wound healing Effects 0.000 claims description 5
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 4
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
• 208000028867 ischemia Diseases 0.000 claims description 4
• SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 4
• 201000000057 Coronary Stenosis Diseases 0.000 claims description 3
• 201000003883 Cystic fibrosis Diseases 0.000 claims description 3
• 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 3
• 206010061218 Inflammation Diseases 0.000 claims description 3
• 238000009098 adjuvant therapy Methods 0.000 claims description 3
• 238000002399 angioplasty Methods 0.000 claims description 3
• 210000000424 bronchial epithelial cell Anatomy 0.000 claims description 3
• 208000033679 diabetic kidney disease Diseases 0.000 claims description 3
• 230000002526 effect on cardiovascular system Effects 0.000 claims description 3
• 230000004054 inflammatory process Effects 0.000 claims description 3
• 210000000056 organ Anatomy 0.000 claims description 3
• 244000052769 pathogen Species 0.000 claims description 3
• 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 3
• 208000005069 pulmonary fibrosis Diseases 0.000 claims description 3
• 208000002815 pulmonary hypertension Diseases 0.000 claims description 3
• 208000010110 spontaneous platelet aggregation Diseases 0.000 claims description 3
• 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 2
• 125000006730 (C2-C5) alkynyl group Chemical group 0.000 claims description 2
• 208000016192 Demyelinating disease Diseases 0.000 claims description 2
• 229940123038 Integrin antagonist Drugs 0.000 claims description 2
• 125000005099 aryl alkyl carbonyl group Chemical group 0.000 claims description 2
• 201000009267 bronchiectasis Diseases 0.000 claims description 2
• 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 claims description 2
• 230000001404 mediated effect Effects 0.000 claims description 2
• 239000004090 neuroprotective agent Substances 0.000 claims description 2
• 206010052428 Wound Diseases 0.000 claims 1
• 208000027418 Wounds and injury Diseases 0.000 claims 1
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 133
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 115
• 238000006243 chemical reaction Methods 0.000 description 110
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 81
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 69
• 229940080818 propionamide Drugs 0.000 description 66
• 239000011541 reaction mixture Substances 0.000 description 66
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 61
• 239000002904 solvent Substances 0.000 description 58
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 54
• 239000000203 mixture Substances 0.000 description 51
• 239000000243 solution Substances 0.000 description 49
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 45
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 39
• 239000000543 intermediate Substances 0.000 description 37
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 34
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 34
• 239000003960 organic solvent Substances 0.000 description 34
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
• 239000003795 chemical substances by application Substances 0.000 description 30
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 29
• 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 28
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
• 239000002585 base Substances 0.000 description 26
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 25
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 24
• 239000012298 atmosphere Substances 0.000 description 23
• 239000003054 catalyst Substances 0.000 description 23
• 238000004440 column chromatography Methods 0.000 description 23
• 125000004899 1-ethylpropylamino group Chemical group C(C)C(CC)N* 0.000 description 22
• 239000012300 argon atmosphere Substances 0.000 description 22
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
• 229910052786 argon Inorganic materials 0.000 description 20
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].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.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 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 20
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 19
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 19
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 18
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
• 150000001412 amines Chemical class 0.000 description 18
• 208000006673 asthma Diseases 0.000 description 18
• 230000002441 reversible effect Effects 0.000 description 18
• 235000009518 sodium iodide Nutrition 0.000 description 18
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 16
• MASVPNZBPHOQNL-TYJFDUFHSA-N n-[(1s,2r,3s,4r)-4-[2-chloro-6-(2,2-diphenylethylamino)purin-9-yl]-2,3-dihydroxycyclopentyl]propanamide Chemical compound O[C@@H]1[C@H](O)[C@@H](NC(=O)CC)C[C@H]1N1C2=NC(Cl)=NC(NCC(C=3C=CC=CC=3)C=3C=CC=CC=3)=C2N=C1 MASVPNZBPHOQNL-TYJFDUFHSA-N 0.000 description 16
• 238000000746 purification Methods 0.000 description 15
• 229910052799 carbon Inorganic materials 0.000 description 14
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 13
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 13
• 239000012948 isocyanate Substances 0.000 description 13
• 150000002513 isocyanates Chemical class 0.000 description 13
• 239000000377 silicon dioxide Substances 0.000 description 13
• 239000002253 acid Substances 0.000 description 12
• 239000012044 organic layer Substances 0.000 description 12
• 239000000047 product Substances 0.000 description 12
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 11
• 238000003818 flash chromatography Methods 0.000 description 11
• 230000008569 process Effects 0.000 description 11
• AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 10
• LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 10
• 239000012267 brine Substances 0.000 description 10
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 10
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 10
• QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 10
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 10
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 9
• NRWPBTLQVZIEGO-UHFFFAOYSA-N 2-(1-propan-2-ylimidazol-4-yl)ethanamine Chemical compound CC(C)N1C=NC(CCN)=C1 NRWPBTLQVZIEGO-UHFFFAOYSA-N 0.000 description 9
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
• YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 9
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
• 229940079593 drug Drugs 0.000 description 9
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
• 208000023504 respiratory system disease Diseases 0.000 description 9
• 239000005557 antagonist Substances 0.000 description 8
• TXWOGHSRPAYOML-UHFFFAOYSA-N cyclobutanecarboxylic acid Chemical compound OC(=O)C1CCC1 TXWOGHSRPAYOML-UHFFFAOYSA-N 0.000 description 8
• 229940043279 diisopropylamine Drugs 0.000 description 8
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
• CJNRGSHEMCMUOE-UHFFFAOYSA-N 2-piperidin-1-ylethanamine Chemical compound NCCN1CCCCC1 CJNRGSHEMCMUOE-UHFFFAOYSA-N 0.000 description 7
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 7
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 7
• 125000004432 carbon atom Chemical group C* 0.000 description 7
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
• 230000000414 obstructive effect Effects 0.000 description 7
• 229910000489 osmium tetroxide Inorganic materials 0.000 description 7
• 125000003386 piperidinyl group Chemical group 0.000 description 7
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 6
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
• 239000004202 carbamide Substances 0.000 description 6
• 150000001721 carbon Chemical group 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
• 210000003979 eosinophil Anatomy 0.000 description 6
• 238000009472 formulation Methods 0.000 description 6
• 230000005445 isotope effect Effects 0.000 description 6
• 125000004076 pyridyl group Chemical group 0.000 description 6
• 239000012312 sodium hydride Substances 0.000 description 6
• 229910000104 sodium hydride Inorganic materials 0.000 description 6
• 239000007787 solid Substances 0.000 description 6
• 238000004809 thin layer chromatography Methods 0.000 description 6
• NGXSWUFDCSEIOO-SCSAIBSYSA-N (3r)-pyrrolidin-3-amine Chemical compound N[C@@H]1CCNC1 NGXSWUFDCSEIOO-SCSAIBSYSA-N 0.000 description 5
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
• 230000003110 anti-inflammatory effect Effects 0.000 description 5
• 229940124630 bronchodilator Drugs 0.000 description 5
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 5
• 230000003197 catalytic effect Effects 0.000 description 5
• 238000004587 chromatography analysis Methods 0.000 description 5
• 150000004820 halides Chemical class 0.000 description 5
• 125000000623 heterocyclic group Chemical group 0.000 description 5
• 125000002883 imidazolyl group Chemical group 0.000 description 5
• 229960004592 isopropanol Drugs 0.000 description 5
• BNGCBNFCYFRFLY-FSNRGTNLSA-N n-[(1s,2r,3s,4r)-4-[2-[(3r)-3-aminopyrrolidin-1-yl]-6-(2,2-diphenylethylamino)purin-9-yl]-2,3-dihydroxycyclopentyl]propanamide Chemical compound O[C@@H]1[C@H](O)[C@@H](NC(=O)CC)C[C@H]1N1C2=NC(N3C[C@H](N)CC3)=NC(NCC(C=3C=CC=CC=3)C=3C=CC=CC=3)=C2N=C1 BNGCBNFCYFRFLY-FSNRGTNLSA-N 0.000 description 5
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 5
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
• 125000006239 protecting group Chemical group 0.000 description 5
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 5
• JEFSRSDIVFQOAH-AXDNMTBYSA-N (1s,2r,3s,5r)-3-amino-5-(6-amino-2-chloropurin-9-yl)cyclopentane-1,2-diol;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.O[C@@H]1[C@H](O)[C@@H](N)C[C@H]1N1C2=NC(Cl)=NC(N)=C2N=C1 JEFSRSDIVFQOAH-AXDNMTBYSA-N 0.000 description 4
• IJDYOKVVRXZCFD-UHFFFAOYSA-N (4-hydroxycyclopent-2-en-1-yl) acetate Chemical compound CC(=O)OC1CC(O)C=C1 IJDYOKVVRXZCFD-UHFFFAOYSA-N 0.000 description 4
• DKCWQRKXTQSULZ-UHFFFAOYSA-N 1h-imidazole;urea Chemical compound NC(N)=O.C1=CNC=N1 DKCWQRKXTQSULZ-UHFFFAOYSA-N 0.000 description 4
• LIXGKSRWGHVUHT-UHFFFAOYSA-N 2-(1-ethylimidazol-4-yl)ethanamine Chemical compound CCN1C=NC(CCN)=C1 LIXGKSRWGHVUHT-UHFFFAOYSA-N 0.000 description 4
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• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
• APDVABVEGFBHBA-UHFFFAOYSA-N Cl.C(C(CCC)O)O Chemical compound Cl.C(C(CCC)O)O APDVABVEGFBHBA-UHFFFAOYSA-N 0.000 description 4
• 206010010904 Convulsion Diseases 0.000 description 4
• KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 4
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
• 125000000217 alkyl group Chemical group 0.000 description 4
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• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
• 239000013058 crude material Substances 0.000 description 4
• 125000000753 cycloalkyl group Chemical group 0.000 description 4
• 201000010099 disease Diseases 0.000 description 4
• 208000035475 disorder Diseases 0.000 description 4
• 239000000706 filtrate Substances 0.000 description 4
• GTGCBQSIGWTVFC-UHFFFAOYSA-N n-(1-pyridin-2-ylpiperidin-4-yl)imidazole-1-carboxamide Chemical compound C1=CN=CN1C(=O)NC(CC1)CCN1C1=CC=CC=N1 GTGCBQSIGWTVFC-UHFFFAOYSA-N 0.000 description 4
• KZRQKFCINIDKCM-QEJHQWKJSA-N n-[(1s,2r,3s,4r)-4-[2-chloro-6-(2,2-diphenylethylamino)purin-9-yl]-2,3-dihydroxycyclopentyl]-2-phenylacetamide Chemical compound N1=C(Cl)N=C2N([C@@H]3C[C@@H]([C@H]([C@H]3O)O)NC(=O)CC=3C=CC=CC=3)C=NC2=C1NCC(C=1C=CC=CC=1)C1=CC=CC=C1 KZRQKFCINIDKCM-QEJHQWKJSA-N 0.000 description 4
• WTBFFQADNOOTDX-JMLJLYKJSA-N n-[(1s,2r,3s,4r)-4-[2-chloro-6-(2,2-diphenylethylamino)purin-9-yl]-2,3-dihydroxycyclopentyl]butanamide Chemical compound O[C@@H]1[C@H](O)[C@@H](NC(=O)CCC)C[C@H]1N1C2=NC(Cl)=NC(NCC(C=3C=CC=CC=3)C=3C=CC=CC=3)=C2N=C1 WTBFFQADNOOTDX-JMLJLYKJSA-N 0.000 description 4
• 125000001624 naphthyl group Chemical group 0.000 description 4
• 150000007524 organic acids Chemical class 0.000 description 4
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