BRPI0710655A2

BRPI0710655A2 - compostos orgánicos

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Info

Publication number: BRPI0710655A2
Authority: BR; Brazil
Prior art keywords: optionally substituted; amino; alkyl; formula; purin
Prior art date: 2006-04-21

Application number

BRPI0710655-6A

Other languages

English (en)

Portuguese (pt)

Inventor

Robin Alec Fairhurst

Roger John Taylor

Original Assignee

Novartis Ag

Priority date

2006-04-21

Filing date

2007-04-19

Publication date

2011-08-16

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

2011-08-16 Publication of BRPI0710655A2 publication Critical patent/BRPI0710655A2/pt

Links

150000002894 organic compounds Chemical class 0.000 title abstract description 3
150000001875 compounds Chemical class 0.000 claims abstract description 354
150000003839 salts Chemical class 0.000 claims abstract description 35
-1 substituted Chemical class 0.000 claims description 278
125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 63
125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 60
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 54
229910052757 nitrogen Inorganic materials 0.000 claims description 48
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 45
125000005842 heteroatom Chemical group 0.000 claims description 45
229910052760 oxygen Inorganic materials 0.000 claims description 45
239000001301 oxygen Chemical group 0.000 claims description 45
229910052717 sulfur Chemical group 0.000 claims description 44
239000011593 sulfur Chemical group 0.000 claims description 44
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 43
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 38
239000003795 chemical substances by application Substances 0.000 claims description 34
229910052739 hydrogen Inorganic materials 0.000 claims description 30
239000001257 hydrogen Substances 0.000 claims description 30
230000002757 inflammatory effect Effects 0.000 claims description 19
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 17
125000000041 C6-C10 aryl group Chemical group 0.000 claims description 16
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
125000000217 alkyl group Chemical group 0.000 claims description 13
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 13
239000003814 drug Substances 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 12
125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 11
230000004913 activation Effects 0.000 claims description 9
125000003282 alkyl amino group Chemical group 0.000 claims description 9
230000000694 effects Effects 0.000 claims description 9
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
125000003118 aryl group Chemical group 0.000 claims description 7
125000000623 heterocyclic group Chemical group 0.000 claims description 7
125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 6
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 6
125000004093 cyano group Chemical group *C#N 0.000 claims description 6
125000004043 oxo group Chemical group O=* 0.000 claims description 6
238000002560 therapeutic procedure Methods 0.000 claims description 6
230000029663 wound healing Effects 0.000 claims description 6
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
101150051188 Adora2a gene Proteins 0.000 claims description 5
206010063837 Reperfusion injury Diseases 0.000 claims description 5
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
208000027866 inflammatory disease Diseases 0.000 claims description 4
208000028867 ischemia Diseases 0.000 claims description 4
208000011580 syndromic disease Diseases 0.000 claims description 4
102000007471 Adenosine A2A receptor Human genes 0.000 claims description 3
108010085277 Adenosine A2A receptor Proteins 0.000 claims description 3
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 3
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
125000004390 alkyl sulfonyl group Chemical group 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
238000003384 imaging method Methods 0.000 claims description 3
230000004054 inflammatory process Effects 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
230000001404 mediated effect Effects 0.000 claims description 3
210000000056 organ Anatomy 0.000 claims description 3
244000052769 pathogen Species 0.000 claims description 3
208000005069 pulmonary fibrosis Diseases 0.000 claims description 3
208000002815 pulmonary hypertension Diseases 0.000 claims description 3
125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 2
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 2
125000006730 (C2-C5) alkynyl group Chemical group 0.000 claims description 2
206010011089 Coronary artery stenosis Diseases 0.000 claims description 2
208000016192 Demyelinating disease Diseases 0.000 claims description 2
229940123038 Integrin antagonist Drugs 0.000 claims description 2
229940124158 Protease/peptidase inhibitor Drugs 0.000 claims description 2
125000005167 cycloalkylaminocarbonyl group Chemical group 0.000 claims description 2
239000012216 imaging agent Substances 0.000 claims description 2
239000004090 neuroprotective agent Substances 0.000 claims description 2
239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 2
229930024421 Adenine Natural products 0.000 claims 1
GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims 1
229960000643 adenine Drugs 0.000 claims 1
230000002285 radioactive effect Effects 0.000 claims 1
238000002360 preparation method Methods 0.000 abstract description 42
239000000825 pharmaceutical preparation Substances 0.000 abstract description 2
229940127557 pharmaceutical product Drugs 0.000 abstract description 2
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 117
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 112
238000006243 chemical reaction Methods 0.000 description 107
238000000034 method Methods 0.000 description 99
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 76
229940080818 propionamide Drugs 0.000 description 73
239000011541 reaction mixture Substances 0.000 description 64
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 60
239000002904 solvent Substances 0.000 description 60
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 60
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 59
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 57
239000000243 solution Substances 0.000 description 54
239000000203 mixture Substances 0.000 description 52
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 45
239000002253 acid Substances 0.000 description 44
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 40
239000000543 intermediate Substances 0.000 description 38
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 38
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 37
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
239000003960 organic solvent Substances 0.000 description 35
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 34
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 31
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 30
QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 29
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
239000002585 base Substances 0.000 description 28
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 28
238000000746 purification Methods 0.000 description 28
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 25
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 24
239000012300 argon atmosphere Substances 0.000 description 23
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
238000004440 column chromatography Methods 0.000 description 21
230000002441 reversible effect Effects 0.000 description 21
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 20
229910052786 argon Inorganic materials 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 20
208000006673 asthma Diseases 0.000 description 19
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 19
238000006467 substitution reaction Methods 0.000 description 19
150000001412 amines Chemical class 0.000 description 17
OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 16
239000003054 catalyst Substances 0.000 description 15
230000008569 process Effects 0.000 description 14
239000000047 product Substances 0.000 description 14
239000000377 silicon dioxide Substances 0.000 description 14
239000012948 isocyanate Substances 0.000 description 13
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 13
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 12
229910000041 hydrogen chloride Inorganic materials 0.000 description 12
150000002513 isocyanates Chemical class 0.000 description 12
239000012044 organic layer Substances 0.000 description 12
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 12
125000004899 1-ethylpropylamino group Chemical group C(C)C(CC)N* 0.000 description 11
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 11
YMYJWRNXFNUREO-TXDVJWISSA-N n-[(1s,2r,3s,4r)-4-[6-(2,2-diphenylethylamino)-2-[[(2s)-1-hydroxy-3-phenylpropan-2-yl]amino]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(N[C@H](CO)CC=3C=CC=CC=3)=NC(NCC(C=3C=CC=CC=3)C=3C=CC=CC=3)=C2N=C1 YMYJWRNXFNUREO-TXDVJWISSA-N 0.000 description 11
AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 10
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 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
229910052799 carbon Inorganic materials 0.000 description 10
MIVFLRKONVQVSU-DRABBMOASA-N n-[(1s,2r,3s,4r)-4-[2-chloro-6-(pentan-3-ylamino)purin-9-yl]-2,3-dihydroxycyclopentyl]propanamide Chemical compound C1=NC=2C(NC(CC)CC)=NC(Cl)=NC=2N1[C@@H]1C[C@H](NC(=O)CC)[C@@H](O)[C@H]1O MIVFLRKONVQVSU-DRABBMOASA-N 0.000 description 10
235000009518 sodium iodide Nutrition 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
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
CJNRGSHEMCMUOE-UHFFFAOYSA-N 2-piperidin-1-ylethanamine Chemical compound NCCN1CCCCC1 CJNRGSHEMCMUOE-UHFFFAOYSA-N 0.000 description 8
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical group [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
239000012298 atmosphere Substances 0.000 description 8
238000004587 chromatography analysis Methods 0.000 description 8
TXWOGHSRPAYOML-UHFFFAOYSA-N cyclobutanecarboxylic acid Chemical compound OC(=O)C1CCC1 TXWOGHSRPAYOML-UHFFFAOYSA-N 0.000 description 8
YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 8
229940043279 diisopropylamine Drugs 0.000 description 8
201000010099 disease Diseases 0.000 description 8
238000003818 flash chromatography Methods 0.000 description 8
230000000414 obstructive effect Effects 0.000 description 8
208000023504 respiratory system disease Diseases 0.000 description 8
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
125000004911 3,3-dimethylbutylamino group Chemical group CC(CCN*)(C)C 0.000 description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 7
239000005557 antagonist Substances 0.000 description 7
125000004432 carbon atom Chemical group C* 0.000 description 7
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 7
150000002148 esters Chemical class 0.000 description 7
150000002431 hydrogen Chemical group 0.000 description 7
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
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
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
238000009472 formulation Methods 0.000 description 6
229940047889 isobutyramide Drugs 0.000 description 6
150000004702 methyl esters Chemical class 0.000 description 6
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 6
229910052762 osmium Inorganic materials 0.000 description 6
SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 description 6
239000007787 solid Substances 0.000 description 6
238000003756 stirring Methods 0.000 description 6
239000000126 substance 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
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
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 5
239000007983 Tris buffer Substances 0.000 description 5
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 5
230000000172 allergic effect Effects 0.000 description 5
230000003110 anti-inflammatory effect Effects 0.000 description 5
208000010668 atopic eczema Diseases 0.000 description 5
230000003182 bronchodilatating effect Effects 0.000 description 5
239000004202 carbamide Substances 0.000 description 5
150000001721 carbon Chemical group 0.000 description 5
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 5
239000000460 chlorine Substances 0.000 description 5
229910052801 chlorine Inorganic materials 0.000 description 5
239000012043 crude product Substances 0.000 description 5
210000003979 eosinophil Anatomy 0.000 description 5
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 5
125000002883 imidazolyl group Chemical group 0.000 description 5
229960004592 isopropanol Drugs 0.000 description 5
229910052943 magnesium sulfate Inorganic materials 0.000 description 5
235000019341 magnesium sulphate Nutrition 0.000 description 5
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
239000011734 sodium Substances 0.000 description 5
229910052708 sodium Inorganic materials 0.000 description 5
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 4
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-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
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 4
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