MX2008013418A

MX2008013418A - Derivados de purina para utilizarse como agonistas del receptor de adenosina a2a.

Derivados de purina para utilizarse como agonistas del receptor de adenosina a2a.

Info

Publication number: MX2008013418A
Authority: MX; Mexico
Prior art keywords: carbon atoms; amino; alkyl; optionally substituted; ethyl
Prior art date: 2006-04-21

Application number

MX2008013418A

Other languages

English (en)

Spanish (es)

Inventor

Robin Alec Fairhurst

Roger John Taylor

Original Assignee

Novartis Ag

Priority date

2006-04-21

Filing date

2007-04-19

Publication date

2008-11-04

2007-04-19 Application filed by Novartis Ag filed Critical Novartis Ag

2008-11-04 Publication of MX2008013418A publication Critical patent/MX2008013418A/es

Links

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 title description 4
229940083251 peripheral vasodilators purine derivative Drugs 0.000 title description 2
150000003212 purines Chemical class 0.000 title description 2
101150051188 Adora2a gene Proteins 0.000 title 1
239000000018 receptor agonist Substances 0.000 title 1
229940044601 receptor agonist Drugs 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 360
238000002360 preparation method Methods 0.000 claims abstract description 67
150000003839 salts Chemical class 0.000 claims abstract description 37
239000003814 drug Substances 0.000 claims abstract description 17
125000004432 carbon atom Chemical group C* 0.000 claims description 238
-1 substituted Chemical class 0.000 claims description 200
125000000217 alkyl group Chemical group 0.000 claims description 169
229910052799 carbon Inorganic materials 0.000 claims description 128
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 119
125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 62
125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 62
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 56
125000000753 cycloalkyl group Chemical group 0.000 claims description 52
229910052757 nitrogen Inorganic materials 0.000 claims description 48
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 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
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 45
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
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 43
229910052736 halogen Inorganic materials 0.000 claims description 40
125000003118 aryl group Chemical group 0.000 claims description 34
239000003795 chemical substances by application Substances 0.000 claims description 33
150000002367 halogens Chemical group 0.000 claims description 32
229910052739 hydrogen Inorganic materials 0.000 claims description 31
239000001257 hydrogen Substances 0.000 claims description 30
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 24
125000003710 aryl alkyl group Chemical group 0.000 claims description 22
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
230000002757 inflammatory effect Effects 0.000 claims description 17
125000003545 alkoxy group Chemical group 0.000 claims description 16
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 16
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 16
230000000694 effects Effects 0.000 claims description 11
125000003342 alkenyl group Chemical group 0.000 claims description 10
125000000304 alkynyl group Chemical group 0.000 claims description 10
102000007471 Adenosine A2A receptor Human genes 0.000 claims description 9
108010085277 Adenosine A2A receptor Proteins 0.000 claims description 9
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
125000005843 halogen group Chemical group 0.000 claims description 9
230000004913 activation Effects 0.000 claims description 8
125000004093 cyano group Chemical group *C#N 0.000 claims description 8
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
125000004043 oxo group Chemical group O=* 0.000 claims description 8
125000004429 atom Chemical group 0.000 claims description 7
125000000623 heterocyclic group Chemical group 0.000 claims description 7
238000002560 therapeutic procedure Methods 0.000 claims description 7
125000001309 chloro group Chemical group Cl* 0.000 claims description 6
208000027866 inflammatory disease Diseases 0.000 claims description 6
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
208000011580 syndromic disease Diseases 0.000 claims description 6
206010061218 Inflammation Diseases 0.000 claims description 5
230000004054 inflammatory process Effects 0.000 claims description 5
206010063837 Reperfusion injury Diseases 0.000 claims description 4
208000028867 ischemia Diseases 0.000 claims description 4
230000001404 mediated effect Effects 0.000 claims description 4
230000009467 reduction Effects 0.000 claims description 4
201000000057 Coronary Stenosis Diseases 0.000 claims description 3
206010011089 Coronary artery 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
229940123038 Integrin antagonist Drugs 0.000 claims description 3
229940124158 Protease/peptidase inhibitor Drugs 0.000 claims description 3
206010052428 Wound Diseases 0.000 claims description 3
208000027418 Wounds and injury Diseases 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
239000012216 imaging agent Substances 0.000 claims description 3
238000003384 imaging method Methods 0.000 claims description 3
238000004519 manufacturing process Methods 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
230000009805 platelet accumulation Effects 0.000 claims description 3
208000005069 pulmonary fibrosis Diseases 0.000 claims description 3
208000002815 pulmonary hypertension Diseases 0.000 claims description 3
230000002285 radioactive effect Effects 0.000 claims description 3
230000029663 wound healing Effects 0.000 claims description 3
208000016192 Demyelinating disease Diseases 0.000 claims description 2
201000009267 bronchiectasis Diseases 0.000 claims description 2
230000000295 complement effect Effects 0.000 claims description 2
239000004090 neuroprotective agent Substances 0.000 claims description 2
238000011156 evaluation Methods 0.000 claims 1
238000006243 chemical reaction Methods 0.000 description 135
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 130
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 120
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 113
238000000034 method Methods 0.000 description 99
229940080818 propionamide Drugs 0.000 description 91
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 85
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 81
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 79
239000011541 reaction mixture Substances 0.000 description 66
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 60
239000002904 solvent Substances 0.000 description 58
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 58
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 57
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 54
239000000203 mixture Substances 0.000 description 53
239000000243 solution Substances 0.000 description 52
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 50
239000002253 acid Substances 0.000 description 48
238000005481 NMR spectroscopy Methods 0.000 description 39
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
239000000543 intermediate Substances 0.000 description 38
239000003960 organic solvent Substances 0.000 description 35
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
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 32
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 29
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 28
239000002585 base Substances 0.000 description 28
230000008569 process Effects 0.000 description 28
238000000746 purification Methods 0.000 description 28
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 27
229910052786 argon Inorganic materials 0.000 description 25
238000004440 column chromatography Methods 0.000 description 23
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 22
URIQBJVSUFSHGF-NDLZIURDSA-N 2-[(1S,2R,3S,4R)-4-[2-chloro-6-(2,2-diphenylethylamino)purin-9-yl]-2,3-dihydroxycyclopentyl]propanamide Chemical compound ClC1=NC(=C2N=CN(C2=N1)[C@H]1[C@@H]([C@@H]([C@@H](C1)C(C(=O)N)C)O)O)NCC(C1=CC=CC=C1)C1=CC=CC=C1 URIQBJVSUFSHGF-NDLZIURDSA-N 0.000 description 21
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
230000002441 reversible effect Effects 0.000 description 21
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 20
208000006673 asthma Diseases 0.000 description 20
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 19
150000004702 methyl esters Chemical class 0.000 description 19
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 18
239000012300 argon atmosphere Substances 0.000 description 18
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 18
235000009518 sodium iodide Nutrition 0.000 description 18
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 17
150000001412 amines Chemical class 0.000 description 17
OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 17
125000004899 1-ethylpropylamino group Chemical group C(C)C(CC)N* 0.000 description 16
239000003054 catalyst Substances 0.000 description 15
239000012298 atmosphere Substances 0.000 description 14
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 14
239000012948 isocyanate Substances 0.000 description 14
239000000047 product Substances 0.000 description 14
WOWFIILXWFHMGC-ZSXPUABSSA-N (1s,2r,3s,5r)-3-amino-5-[2-chloro-6-(2,2-diphenylethylamino)purin-9-yl]cyclopentane-1,2-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](N)C[C@H]1N1C2=NC(Cl)=NC(NCC(C=3C=CC=CC=3)C=3C=CC=CC=3)=C2N=C1 WOWFIILXWFHMGC-ZSXPUABSSA-N 0.000 description 13
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 13
229910000041 hydrogen chloride Inorganic materials 0.000 description 13
150000002513 isocyanates Chemical class 0.000 description 13
239000000377 silicon dioxide Substances 0.000 description 13
239000012044 organic layer Substances 0.000 description 12
210000002345 respiratory system Anatomy 0.000 description 12
201000010099 disease Diseases 0.000 description 11
150000002148 esters Chemical class 0.000 description 11
229910052943 magnesium sulfate Inorganic materials 0.000 description 11
235000019341 magnesium sulphate Nutrition 0.000 description 11
229910000489 osmium tetroxide Inorganic materials 0.000 description 11
230000002829 reductive effect Effects 0.000 description 11
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 10
239000012267 brine Substances 0.000 description 10
238000003818 flash chromatography Methods 0.000 description 10
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
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
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-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
125000004494 ethyl ester group Chemical group 0.000 description 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 8
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 8
150000001721 carbon Chemical class 0.000 description 8
TXWOGHSRPAYOML-UHFFFAOYSA-N cyclobutanecarboxylic acid Chemical compound OC(=O)C1CCC1 TXWOGHSRPAYOML-UHFFFAOYSA-N 0.000 description 8
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 8
229940079593 drug Drugs 0.000 description 8
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
FELUVMYOCCMHCR-QIZZFAIBSA-N 2-[(1S,2R,3S,4R)-4-[2-chloro-6-(pentan-3-ylamino)purin-9-yl]-2,3-dihydroxycyclopentyl]propanamide Chemical compound ClC1=NC(=C2N=CN(C2=N1)[C@H]1[C@@H]([C@@H]([C@@H](C1)C(C(=O)N)C)O)O)NC(CC)CC FELUVMYOCCMHCR-QIZZFAIBSA-N 0.000 description 7
CJNRGSHEMCMUOE-UHFFFAOYSA-N 2-piperidin-1-ylethanamine Chemical compound NCCN1CCCCC1 CJNRGSHEMCMUOE-UHFFFAOYSA-N 0.000 description 7
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 7
239000005557 antagonist Substances 0.000 description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
238000009472 formulation Methods 0.000 description 7
VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
229940047889 isobutyramide Drugs 0.000 description 7
230000000414 obstructive effect Effects 0.000 description 7
239000012285 osmium tetroxide Substances 0.000 description 7
125000003386 piperidinyl group Chemical group 0.000 description 7
125000004076 pyridyl group Chemical group 0.000 description 7
238000003756 stirring Methods 0.000 description 7
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
101100515517 Arabidopsis thaliana XI-I gene Proteins 0.000 description 6
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 6
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IJDYOKVVRXZCFD-RQJHMYQMSA-N [(1r,4s)-4-hydroxycyclopent-2-en-1-yl] acetate Chemical compound CC(=O)O[C@@H]1C[C@H](O)C=C1 IJDYOKVVRXZCFD-RQJHMYQMSA-N 0.000 description 6
229940124630 bronchodilator Drugs 0.000 description 6
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-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
239000012043 crude product Substances 0.000 description 6
229910052740 iodine Inorganic materials 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
DKCWQRKXTQSULZ-UHFFFAOYSA-N 1h-imidazole;urea Chemical compound NC(N)=O.C1=CNC=N1 DKCWQRKXTQSULZ-UHFFFAOYSA-N 0.000 description 5
RXMTUVIKZRXSSM-UHFFFAOYSA-N 2,2-diphenylethanamine Chemical compound C=1C=CC=CC=1C(CN)C1=CC=CC=C1 RXMTUVIKZRXSSM-UHFFFAOYSA-N 0.000 description 5
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
230000003110 anti-inflammatory effect Effects 0.000 description 5
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 5
BUZRUIZTMOKRPB-UHFFFAOYSA-N carboxycarbamic acid Chemical compound OC(=O)NC(O)=O BUZRUIZTMOKRPB-UHFFFAOYSA-N 0.000 description 5
150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
230000003197 catalytic effect Effects 0.000 description 5
239000000460 chlorine Substances 0.000 description 5
229910052801 chlorine Inorganic materials 0.000 description 5
210000003979 eosinophil Anatomy 0.000 description 5
125000002883 imidazolyl group Chemical group 0.000 description 5
RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 5
125000006239 protecting group Chemical group 0.000 description 5
125000000719 pyrrolidinyl group Chemical group 0.000 description 5
230000005855 radiation Effects 0.000 description 5
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
OKRROXQXGNEUSS-UHFFFAOYSA-N 1h-imidazol-1-ium-1-carboxylate Chemical compound OC(=O)N1C=CN=C1 OKRROXQXGNEUSS-UHFFFAOYSA-N 0.000 description 4
RMFWVOLULURGJI-UHFFFAOYSA-N 2,6-dichloro-7h-purine Chemical compound ClC1=NC(Cl)=C2NC=NC2=N1 RMFWVOLULURGJI-UHFFFAOYSA-N 0.000 description 4
206010027654 Allergic conditions Diseases 0.000 description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-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
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
239000000556 agonist Substances 0.000 description 4
125000006193 alkinyl group Chemical group 0.000 description 4
125000005907 alkyl ester group Chemical group 0.000 description 4
125000003277 amino group Chemical group 0.000 description 4
239000000739 antihistaminic agent Substances 0.000 description 4
125000004104 aryloxy group Chemical group 0.000 description 4
230000001363 autoimmune Effects 0.000 description 4
235000013877 carbamide Nutrition 0.000 description 4
WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 4
229940088679 drug related substance Drugs 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
239000012458 free base Substances 0.000 description 4
150000004820 halides Chemical class 0.000 description 4
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238000004949 mass spectrometry Methods 0.000 description 4
125000001624 naphthyl group Chemical group 0.000 description 4
150000007524 organic acids Chemical class 0.000 description 4
239000007800 oxidant agent Substances 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
208000023504 respiratory system disease Diseases 0.000 description 4
238000004366 reverse phase liquid chromatography Methods 0.000 description 4
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