BG107216A - 2-аминокарбонил-9н-пуринови производни - Google Patents

2-аминокарбонил-9н-пуринови производни Download PDF

Info

Publication number: BG107216A
Authority: BG; Bulgaria
Prior art keywords: compound; alkyl; formula; optionally substituted; amino
Prior art date: 2000-06-06

Application number

BG107216A

Other languages

Bulgarian (bg)

English (en)

Inventor

Simon MANTELL

Peter Stephenson

Original Assignee

Pfizer Inc.

Priority date (The priority date 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 date listed.)

2000-06-06

Filing date

2002-10-23

Publication date

2003-05-30

2000-06-06 Priority claimed from GB0014048A external-priority patent/GB0014048D0/en

2000-10-11 Priority claimed from GB0024920A external-priority patent/GB0024920D0/en

2002-10-23 Application filed by Pfizer Inc. filed Critical Pfizer Inc.

2003-05-30 Publication of BG107216A publication Critical patent/BG107216A/bg

Links

BMHHQPYFORGXQA-UHFFFAOYSA-N 7h-purine-2-carboxamide Chemical class NC(=O)C1=NC=C2N=CNC2=N1 BMHHQPYFORGXQA-UHFFFAOYSA-N 0.000 title description 4
150000001875 compounds Chemical class 0.000 claims abstract description 330
238000002360 preparation method Methods 0.000 claims abstract description 197
239000000203 mixture Substances 0.000 claims abstract description 109
238000000034 method Methods 0.000 claims abstract description 58
150000003839 salts Chemical class 0.000 claims abstract description 54
239000012453 solvate Substances 0.000 claims abstract description 32
230000008569 process Effects 0.000 claims abstract description 6
-1 piperidine -4-yl Chemical group 0.000 claims description 165
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 94
125000000579 2,2-diphenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(C1=C([H])C([H])=C([H])C([H])=C1[H])C([H])([H])* 0.000 claims description 69
229910052799 carbon Inorganic materials 0.000 claims description 67
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 60
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 58
229910052757 nitrogen Inorganic materials 0.000 claims description 50
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 49
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 47
229910052739 hydrogen Inorganic materials 0.000 claims description 45
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 43
125000004433 nitrogen atom Chemical group N* 0.000 claims description 42
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 41
125000006239 protecting group Chemical group 0.000 claims description 41
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 36
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 25
150000001412 amines Chemical class 0.000 claims description 24
125000004432 carbon atom Chemical group C* 0.000 claims description 24
125000005843 halogen group Chemical group 0.000 claims description 23
125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 22
239000003054 catalyst Substances 0.000 claims description 21
238000011282 treatment Methods 0.000 claims description 21
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 16
125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 16
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 16
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 15
125000000217 alkyl group Chemical group 0.000 claims description 14
229910002091 carbon monoxide Inorganic materials 0.000 claims description 14
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 13
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 12
125000002393 azetidinyl group Chemical group 0.000 claims description 12
125000004093 cyano group Chemical group *C#N 0.000 claims description 12
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 12
239000003814 drug Substances 0.000 claims description 12
125000003386 piperidinyl group Chemical group 0.000 claims description 12
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 11
206010006451 bronchitis Diseases 0.000 claims description 11
238000004519 manufacturing process Methods 0.000 claims description 11
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 10
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 10
206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 10
UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims description 10
201000004624 Dermatitis Diseases 0.000 claims description 10
208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 10
208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 10
201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 10
208000010668 atopic eczema Diseases 0.000 claims description 10
125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 claims description 10
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 10
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 10
125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 9
125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 9
208000007882 Gastritis Diseases 0.000 claims description 8
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 8
125000001309 chloro group Chemical group Cl* 0.000 claims description 8
125000001624 naphthyl group Chemical group 0.000 claims description 8
208000006673 asthma Diseases 0.000 claims description 7
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
125000000000 cycloalkoxy group Chemical group 0.000 claims description 7
201000010099 disease Diseases 0.000 claims description 7
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 7
239000001301 oxygen Substances 0.000 claims description 7
229910052760 oxygen Inorganic materials 0.000 claims description 7
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 6
101150051188 Adora2a gene Proteins 0.000 claims description 6
206010006458 Bronchitis chronic Diseases 0.000 claims description 6
125000003031 C5-C7 cycloalkylene group Chemical group 0.000 claims description 6
229940121363 anti-inflammatory agent Drugs 0.000 claims description 6
239000002260 anti-inflammatory agent Substances 0.000 claims description 6
125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 6
208000007451 chronic bronchitis Diseases 0.000 claims description 6
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
230000000694 effects Effects 0.000 claims description 6
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 6
125000004043 oxo group Chemical group O=* 0.000 claims description 6
125000004263 tetrahydroisoquinolin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])C2=C([H])C([H])=C([H])C([H])=C2C1([H])* 0.000 claims description 6
BNMNQUBPZZSXQU-UHFFFAOYSA-N 1,3-dioxole-4-carboxylic acid Chemical compound OC(=O)C1=COCO1 BNMNQUBPZZSXQU-UHFFFAOYSA-N 0.000 claims description 5
201000006474 Brain Ischemia Diseases 0.000 claims description 5
206010008120 Cerebral ischaemia Diseases 0.000 claims description 5
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 5
206010009900 Colitis ulcerative Diseases 0.000 claims description 5
201000003883 Cystic fibrosis Diseases 0.000 claims description 5
206010012434 Dermatitis allergic Diseases 0.000 claims description 5
206010014561 Emphysema Diseases 0.000 claims description 5
208000010228 Erectile Dysfunction Diseases 0.000 claims description 5
208000007984 Female Infertility Diseases 0.000 claims description 5
206010020772 Hypertension Diseases 0.000 claims description 5
206010021928 Infertility female Diseases 0.000 claims description 5
208000007466 Male Infertility Diseases 0.000 claims description 5
208000018262 Peripheral vascular disease Diseases 0.000 claims description 5
208000028017 Psychotic disease Diseases 0.000 claims description 5
206010040070 Septic Shock Diseases 0.000 claims description 5
208000006011 Stroke Diseases 0.000 claims description 5
201000006704 Ulcerative Colitis Diseases 0.000 claims description 5
239000000556 agonist Substances 0.000 claims description 5
201000008937 atopic dermatitis Diseases 0.000 claims description 5
201000009267 bronchiectasis Diseases 0.000 claims description 5
206010008118 cerebral infarction Diseases 0.000 claims description 5
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
230000006378 damage Effects 0.000 claims description 5
206010012601 diabetes mellitus Diseases 0.000 claims description 5
206010015037 epilepsy Diseases 0.000 claims description 5
230000001771 impaired effect Effects 0.000 claims description 5
201000001881 impotence Diseases 0.000 claims description 5
239000000546 pharmaceutical excipient Substances 0.000 claims description 5
230000036303 septic shock Effects 0.000 claims description 5
125000001424 substituent group Chemical group 0.000 claims description 5
230000029663 wound healing Effects 0.000 claims description 5
208000011231 Crohn disease Diseases 0.000 claims description 4
201000004681 Psoriasis Diseases 0.000 claims description 4
125000002947 alkylene group Chemical group 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 4
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 4
125000000623 heterocyclic group Chemical group 0.000 claims description 4
230000002757 inflammatory effect Effects 0.000 claims description 4
230000000302 ischemic effect Effects 0.000 claims description 4
201000006417 multiple sclerosis Diseases 0.000 claims description 4
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
125000004193 piperazinyl group Chemical group 0.000 claims description 4
125000004574 piperidin-2-yl group Chemical group N1C(CCCC1)* 0.000 claims description 4
230000010410 reperfusion Effects 0.000 claims description 4
208000023504 respiratory system disease Diseases 0.000 claims description 4
206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
125000003545 alkoxy group Chemical group 0.000 claims description 3
238000005910 aminocarbonylation reaction Methods 0.000 claims description 3
210000001035 gastrointestinal tract Anatomy 0.000 claims description 3
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
229940044601 receptor agonist Drugs 0.000 claims description 3
239000000018 receptor agonist Substances 0.000 claims description 3
YVSWMCHIHVFURN-UHFFFAOYSA-N tert-butyl n-[2-[(1-pyridin-2-ylpiperidin-4-yl)carbamoylamino]ethyl]carbamate Chemical compound C1CC(NC(=O)NCCNC(=O)OC(C)(C)C)CCN1C1=CC=CC=N1 YVSWMCHIHVFURN-UHFFFAOYSA-N 0.000 claims description 3
125000004955 1,4-cyclohexylene group Chemical group [H]C1([H])C([H])([H])C([H])([*:1])C([H])([H])C([H])([H])C1([H])[*:2] 0.000 claims description 2
125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 2
239000005711 Benzoic acid Substances 0.000 claims description 2
125000004273 azetidin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])C1([H])* 0.000 claims description 2
235000010233 benzoic acid Nutrition 0.000 claims description 2
RWJFUQDRQOIAAF-UHFFFAOYSA-N ethyl 6-(2,2-diphenylethylamino)-7h-purine-2-carboxylate Chemical compound C=12N=CNC2=NC(C(=O)OCC)=NC=1NCC(C=1C=CC=CC=1)C1=CC=CC=C1 RWJFUQDRQOIAAF-UHFFFAOYSA-N 0.000 claims description 2
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
125000004356 hydroxy functional group Chemical group O* 0.000 claims 3
206010009137 Chronic sinusitis Diseases 0.000 claims 2
208000012895 Gastric disease Diseases 0.000 claims 2
208000027157 chronic rhinosinusitis Diseases 0.000 claims 2
208000004998 Abdominal Pain Diseases 0.000 claims 1
208000002881 Colic Diseases 0.000 claims 1
208000025865 Ulcer Diseases 0.000 claims 1
125000002252 acyl group Chemical group 0.000 claims 1
125000004429 atom Chemical group 0.000 claims 1
125000003944 tolyl group Chemical group 0.000 claims 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
125000005289 uranyl group Chemical group 0.000 claims 1
239000000543 intermediate Substances 0.000 abstract description 15
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 330
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 198
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 183
239000000243 solution Substances 0.000 description 146
239000002904 solvent Substances 0.000 description 115
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 99
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 96
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 88
238000005160 1H NMR spectroscopy Methods 0.000 description 85
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 76
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 65
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 63
230000002829 reductive effect Effects 0.000 description 59
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 57
239000007787 solid Substances 0.000 description 56
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 54
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 53
238000006243 chemical reaction Methods 0.000 description 50
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 45
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 43
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 38
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
239000002253 acid Substances 0.000 description 35
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 34
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 30
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 30
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 29
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 27
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 25
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 24
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
239000011541 reaction mixture Substances 0.000 description 24
239000006260 foam Substances 0.000 description 23
239000000741 silica gel Substances 0.000 description 23
229910002027 silica gel Inorganic materials 0.000 description 23
238000001704 evaporation Methods 0.000 description 22
230000008020 evaporation Effects 0.000 description 22
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 18
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
238000010992 reflux Methods 0.000 description 18
239000000725 suspension Substances 0.000 description 18
239000002585 base Substances 0.000 description 17
229910000030 sodium bicarbonate Inorganic materials 0.000 description 17
235000017557 sodium bicarbonate Nutrition 0.000 description 17
238000003756 stirring Methods 0.000 description 17
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 17
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 16
235000011114 ammonium hydroxide Nutrition 0.000 description 16
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
229920006395 saturated elastomer Polymers 0.000 description 16
238000010898 silica gel chromatography Methods 0.000 description 16
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 15
239000010410 layer Substances 0.000 description 15
239000012299 nitrogen atmosphere Substances 0.000 description 15
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 14
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 14
239000000843 powder Substances 0.000 description 14
229910000029 sodium carbonate Inorganic materials 0.000 description 14
238000000451 chemical ionisation Methods 0.000 description 13
239000003153 chemical reaction reagent Substances 0.000 description 13
239000012043 crude product Substances 0.000 description 13
238000001914 filtration Methods 0.000 description 13
239000012074 organic phase Substances 0.000 description 13
239000000047 product Substances 0.000 description 13
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 12
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 12
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 12
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 12
239000012044 organic layer Substances 0.000 description 12
239000011734 sodium Substances 0.000 description 12
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 11
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 11
238000004440 column chromatography Methods 0.000 description 11
239000003921 oil Substances 0.000 description 11
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 10
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 10
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 10
238000007796 conventional method Methods 0.000 description 10
238000003818 flash chromatography Methods 0.000 description 10
210000000440 neutrophil Anatomy 0.000 description 10
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 10
229910052708 sodium Inorganic materials 0.000 description 10
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
239000005708 Sodium hypochlorite Substances 0.000 description 9
SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 9
239000007858 starting material Substances 0.000 description 9
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 8
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239000003765 sweetening agent Substances 0.000 description 1
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125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000005207 tetraalkylammonium group Chemical group 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000007751 thermal spraying Methods 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
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125000001425 triazolyl group Chemical group 0.000 description 1
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SIOVKLKJSOKLIF-HJWRWDBZSA-N trimethylsilyl (1z)-n-trimethylsilylethanimidate Chemical compound C[Si](C)(C)OC(/C)=N\[Si](C)(C)C SIOVKLKJSOKLIF-HJWRWDBZSA-N 0.000 description 1
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Classifications

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- 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
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- C07H19/16—Purine radicals
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Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pulmonology (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Biomedical Technology (AREA)
Reproductive Health (AREA)
Dermatology (AREA)
Endocrinology (AREA)
Cardiology (AREA)
Diabetes (AREA)
Heart & Thoracic Surgery (AREA)
Immunology (AREA)
Biochemistry (AREA)
Gynecology & Obstetrics (AREA)
Rheumatology (AREA)
Biotechnology (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
Hematology (AREA)
Orthopedic Medicine & Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Hospice & Palliative Care (AREA)
Oncology (AREA)
Communicable Diseases (AREA)

BG107216A 2000-06-06 2002-10-23 2-аминокарбонил-9н-пуринови производни BG107216A (bg)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
GB0014048A GB0014048D0 (en)	2000-06-06	2000-06-06	Purine derivatives
GB0018246A GB0018246D0 (en)	2000-06-06	2000-07-25	Purine derivatives
GB0024920A GB0024920D0 (en)	2000-06-06	2000-10-11	Purine derivatives
PCT/IB2001/000973 WO2001094368A1 (en)	2000-06-06	2001-06-05	2-aminocarbonyl-9h-purine derivatives

Publications (1)

Publication Number	Publication Date
BG107216A true BG107216A (bg)	2003-05-30

Family

ID=27255754

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BG107216A BG107216A (bg)	2000-06-06	2002-10-23	2-аминокарбонил-9н-пуринови производни

Country Status (33)

Country	Link
EP (1)	EP1292604B1 (pl)
JP (2)	JP4129176B2 (pl)
KR (1)	KR100484704B1 (pl)
CN (1)	CN1249074C (pl)
AR (1)	AR030289A1 (pl)
AT (1)	ATE431356T1 (pl)
AU (2)	AU2001260537B2 (pl)
BG (1)	BG107216A (pl)
BR (1)	BR0111263A (pl)
CA (1)	CA2414018C (pl)
CU (1)	CU23240B7 (pl)
CZ (1)	CZ20023875A3 (pl)
DE (1)	DE60138702D1 (pl)
DK (1)	DK1292604T3 (pl)
DZ (1)	DZ3439A1 (pl)
EA (1)	EA004983B1 (pl)
EE (1)	EE200200678A (pl)
ES (1)	ES2324816T3 (pl)
GC (1)	GC0000287A (pl)
HR (1)	HRP20020960A2 (pl)
HU (1)	HUP0301330A3 (pl)
IL (2)	IL152783A0 (pl)
IS (1)	IS6599A (pl)
MA (1)	MA26910A1 (pl)
MX (1)	MXPA02012033A (pl)
NO (1)	NO324426B1 (pl)
NZ (1)	NZ522184A (pl)
OA (1)	OA12279A (pl)
PA (1)	PA8518801A1 (pl)
PL (1)	PL360435A1 (pl)
SK (1)	SK16752002A3 (pl)
TW (1)	TWI227240B (pl)
WO (1)	WO2001094368A1 (pl)

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US6921753B2 (en)	2000-06-27	2005-07-26	Pfizer Inc	Purine derivatives
US20030013675A1 (en) *	2001-05-25	2003-01-16	Boehringer Ingelheim Pharma Kg	Combination of an adenosine A2A-receptor agonist and tiotropium or a derivative thereof for treating obstructive airways and other inflammatory diseases
EP1434782A2 (en)	2001-10-01	2004-07-07	University of Virginia Patent Foundation	2-propynyl adenosine analogs having a2a agonist activity and compositions thereof
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US6974803B2 (en)	2001-12-06	2005-12-13	Pfizer Inc	Pharmaceutical combination
GB0129273D0 (en) *	2001-12-06	2002-01-23	Pfizer Ltd	Crystalline drug form
AU2003234716A1 (en) *	2002-04-10	2003-10-27	Joel M. Linden	Use of a2a adenosine receptor agonists for the treatment of inflammatory diseases
WO2004081005A1 (en) *	2003-03-07	2004-09-23	Neurocrine Biosciences, Inc.	Melanin-concentrating hormone receptor antagonists and compositions and methods related thereto
WO2004080411A2 (en) *	2003-03-07	2004-09-23	Neurocrine Biosciences, Inc.	Melanin-concentrating hormone receptor antagonists and compositions and methods related thereto
TW200519106A (en)	2003-05-02	2005-06-16	Novartis Ag	Organic compounds
US7335648B2 (en)	2003-10-21	2008-02-26	Inspire Pharmaceuticals, Inc.	Non-nucleotide composition and method for inhibiting platelet aggregation
GB2422782A (en)	2003-10-21	2006-08-09	Inspire Pharmaceuticals Inc	Non-nucleotide compositions and method for treating pain
US7749981B2 (en)	2003-10-21	2010-07-06	Inspire Pharmaceuticals, Inc.	Drug-eluting stents coated with non-nucleotide P2Y12 receptor antagonist compound
AU2004284098B2 (en)	2003-10-21	2009-07-16	Inspire Pharmaceuticals, Inc.	Tetrahydro-furo [3,4-d] dioxole compounds and compositions and method for inhibiting platelet aggregation
GB0401334D0 (en)	2004-01-21	2004-02-25	Novartis Ag	Organic compounds
GB0411056D0 (en)	2004-05-18	2004-06-23	Novartis Ag	Organic compounds
AU2005267706B2 (en)	2004-08-02	2011-12-08	University Of Virginia Patent Foundation	2-propynyl adenosine analogs with modified 5'-ribose groups having A2A agonist activity
US7576069B2 (en)	2004-08-02	2009-08-18	University Of Virginia Patent Foundation	2-polycyclic propynyl adenosine analogs having A2A agonist activity
US7442687B2 (en)	2004-08-02	2008-10-28	The University Of Virginia Patent Foundation	2-polycyclic propynyl adenosine analogs having A2A agonist activity
GT200500281A (es)	2004-10-22	2006-04-24	Novartis Ag	Compuestos organicos.
GB0424284D0 (en)	2004-11-02	2004-12-01	Novartis Ag	Organic compounds
GB0426164D0 (en)	2004-11-29	2004-12-29	Novartis Ag	Organic compounds
US7932376B2 (en)	2005-05-05	2011-04-26	Inspire Pharmaceuticals, Inc.	Pyrimidine-based non-nucleotide composition and method for inhibiting platelet aggregation
GB0510390D0 (en)	2005-05-20	2005-06-29	Novartis Ag	Organic compounds
RU2421464C2 (ru)	2005-10-21	2011-06-20	Новартис Аг	Человеческие антитела к il-13 и их терапевтическое применение
GB0601951D0 (en)	2006-01-31	2006-03-15	Novartis Ag	Organic compounds
EP2322525B1 (en)	2006-04-21	2013-09-18	Novartis AG	Purine derivatives for use as adenosin A2A receptor agonists
WO2008037477A1 (en)	2006-09-29	2008-04-03	Novartis Ag	Pyrazolopyrimidines as p13k lipid kinase inhibitors
CN101522682A (zh)	2006-10-30	2009-09-02	诺瓦提斯公司	作为抗炎剂的杂环化合物
MX2010007604A (es)	2008-01-11	2010-08-02	Novartis Ag	Pirimidinas como inhibidores de cinasa.
CN102123990B (zh)	2008-06-19	2014-07-09	武田药品工业株式会社	杂环化合物及其用途
PT2391366E (pt)	2009-01-29	2013-02-05	Novartis Ag	Benzimidazoles substituídos para o tratamento de astrocitomas
CN102448978A (zh)	2009-05-29	2012-05-09	辉瑞有限公司	新颖的糖皮质激素受体激动剂
US8389526B2 (en)	2009-08-07	2013-03-05	Novartis Ag	3-heteroarylmethyl-imidazo[1,2-b]pyridazin-6-yl derivatives
JP5781510B2 (ja)	2009-08-12	2015-09-24	ノバルティスアーゲー	ヘテロ環式ヒドラゾン化合物および癌および炎症の処置のためのそれらの使用
PE20121148A1 (es)	2009-08-17	2012-09-07	Intellikine Llc	Compuestos heterociclicos y usos de los mismos
JP5775871B2 (ja)	2009-08-20	2015-09-09	ノバルティスアーゲー	ヘテロ環式オキシム化合物
WO2012034095A1 (en)	2010-09-09	2012-03-15	Irm Llc	Compounds and compositions as trk inhibitors
US8637516B2 (en)	2010-09-09	2014-01-28	Irm Llc	Compounds and compositions as TRK inhibitors
WO2012107500A1 (en)	2011-02-10	2012-08-16	Novartis Ag	[1, 2, 4] triazolo [4, 3 -b] pyridazine compounds as inhibitors of the c-met tyrosine kinase
WO2012116237A2 (en)	2011-02-23	2012-08-30	Intellikine, Llc	Heterocyclic compounds and uses thereof
WO2012116217A1 (en)	2011-02-25	2012-08-30	Irm Llc	Compounds and compositions as trk inhibitors
EA026655B1 (ru)	2011-09-15	2017-05-31	Новартис Аг	6-ЗАМЕЩЕННЫЕ 3-(ХИНОЛИН-6-ИЛТИО)[1,2,4]ТРИАЗОЛО[4,3-a]ПИРИДИНЫ В КАЧЕСТВЕ ИНГИБИТОРОВ c-MET ТИРОЗИНКИНАЗЫ
CA2856803A1 (en)	2011-11-23	2013-05-30	Intellikine, Llc	Enhanced treatment regimens using mtor inhibitors
JP2015512425A (ja)	2012-04-03	2015-04-27	ノバルティスアーゲー	チロシンキナーゼ阻害剤との組合せ製品及びそれらの使用
EP2968340A4 (en)	2013-03-15	2016-08-10	Intellikine Llc	COMBINING KINASE INHIBITORS AND USES THEREOF
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WO2016011658A1 (en)	2014-07-25	2016-01-28	Novartis Ag	Combination therapy
ES2831416T3 (es)	2014-07-31	2021-06-08	Novartis Ag	Terapia de combinación de un inhibidor de MET y un inhibidor de EGFR
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TW202140550A (zh)	2020-01-29	2021-11-01	瑞士商諾華公司	使用抗ｔｓｌｐ抗體治療炎性或阻塞性氣道疾病之方法

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AU5879299A (en) *	1998-10-16	2000-05-08	Monaghan, Sandra Marina	Adenine derivatives
GB9913932D0 (en) *	1999-06-15	1999-08-18	Pfizer Ltd	Purine derivatives
TWI227240B (en) *	2000-06-06	2005-02-01	Pfizer	2-aminocarbonyl-9H-purine derivatives

2001
- 2001-05-31 TW TW090113146A patent/TWI227240B/zh not_active IP Right Cessation
- 2001-06-04 AR ARP010102656A patent/AR030289A1/es active IP Right Grant
- 2001-06-05 AT AT01934242T patent/ATE431356T1/de not_active IP Right Cessation
- 2001-06-05 WO PCT/IB2001/000973 patent/WO2001094368A1/en not_active Ceased
- 2001-06-05 PL PL36043501A patent/PL360435A1/pl not_active Application Discontinuation
- 2001-06-05 DK DK01934242T patent/DK1292604T3/da active
- 2001-06-05 ES ES01934242T patent/ES2324816T3/es not_active Expired - Lifetime
- 2001-06-05 HU HU0301330A patent/HUP0301330A3/hu unknown
- 2001-06-05 EP EP01934242A patent/EP1292604B1/en not_active Expired - Lifetime
- 2001-06-05 AU AU2001260537A patent/AU2001260537B2/en not_active Ceased
- 2001-06-05 EA EA200201179A patent/EA004983B1/ru not_active IP Right Cessation
- 2001-06-05 BR BR0111263-5A patent/BR0111263A/pt not_active IP Right Cessation
- 2001-06-05 CA CA002414018A patent/CA2414018C/en not_active Expired - Fee Related
- 2001-06-05 IL IL15278301A patent/IL152783A0/xx active IP Right Grant
- 2001-06-05 DE DE60138702T patent/DE60138702D1/de not_active Expired - Lifetime
- 2001-06-05 AU AU6053701A patent/AU6053701A/xx active Pending
- 2001-06-05 CZ CZ20023875A patent/CZ20023875A3/cs unknown
- 2001-06-05 GC GCP20011415 patent/GC0000287A/en active
- 2001-06-05 MX MXPA02012033A patent/MXPA02012033A/es active IP Right Grant
- 2001-06-05 OA OA1200200363A patent/OA12279A/en unknown
- 2001-06-05 SK SK1675-2002A patent/SK16752002A3/sk unknown
- 2001-06-05 DZ DZ013439A patent/DZ3439A1/fr active
- 2001-06-05 NZ NZ522184A patent/NZ522184A/en unknown
- 2001-06-05 HR HR20020960A patent/HRP20020960A2/hr not_active Application Discontinuation
- 2001-06-05 EE EEP200200678A patent/EE200200678A/xx unknown
- 2001-06-05 JP JP2002501916A patent/JP4129176B2/ja not_active Expired - Fee Related
- 2001-06-05 KR KR10-2002-7016606A patent/KR100484704B1/ko not_active Expired - Fee Related
- 2001-06-05 CN CNB018108024A patent/CN1249074C/zh not_active Expired - Fee Related
- 2001-06-06 PA PA20018518801A patent/PA8518801A1/es unknown
2002
- 2002-10-23 BG BG107216A patent/BG107216A/bg unknown
- 2002-10-29 IS IS6599A patent/IS6599A/is unknown
- 2002-11-26 CU CU20020281A patent/CU23240B7/es not_active IP Right Cessation
- 2002-12-02 MA MA26930A patent/MA26910A1/fr unknown
- 2002-12-04 NO NO20025821A patent/NO324426B1/no not_active IP Right Cessation
2007
- 2007-06-21 IL IL184144A patent/IL184144A/en not_active IP Right Cessation
2008
- 2008-01-15 JP JP2008005804A patent/JP2008150383A/ja active Pending

Also Published As

Publication number	Publication date
AU6053701A (en)	2001-12-17
IL184144A0 (en)	2007-10-31
IL152783A0 (en)	2003-06-24
CU23240B7 (es)	2007-10-17
AU2001260537B2 (en)	2006-05-25
IL184144A (en)	2008-11-26
TWI227240B (en)	2005-02-01
JP2008150383A (ja)	2008-07-03
CZ20023875A3 (cs)	2004-02-18
MA26910A1 (fr)	2004-12-20
EE200200678A (et)	2004-06-15
WO2001094368A1 (en)	2001-12-13
HRP20020960A2 (en)	2005-02-28
BR0111263A (pt)	2003-06-17
PA8518801A1 (es)	2002-09-17
DK1292604T3 (da)	2009-06-15
DE60138702D1 (de)	2009-06-25
CA2414018A1 (en)	2001-12-13
PL360435A1 (pl)	2004-09-06
EA200201179A1 (ru)	2003-04-24
IS6599A (is)	2002-10-29
JP2003535871A (ja)	2003-12-02
NO20025821D0 (no)	2002-12-04
EP1292604A1 (en)	2003-03-19
EP1292604B1 (en)	2009-05-13
CN1434830A (zh)	2003-08-06
EA004983B1 (ru)	2004-10-28
ES2324816T3 (es)	2009-08-17
HUP0301330A3 (en)	2005-02-28
NO20025821L (no)	2003-02-04
HK1089447A1 (zh)	2006-12-01
MXPA02012033A (es)	2003-04-25
GC0000287A (en)	2006-11-01
DZ3439A1 (fr)	2001-12-13
NO324426B1 (no)	2007-10-08
OA12279A (en)	2003-01-01
ATE431356T1 (de)	2009-05-15
AR030289A1 (es)	2003-08-20
NZ522184A (en)	2004-05-28
KR100484704B1 (ko)	2005-04-22
HUP0301330A2 (hu)	2003-08-28
SK16752002A3 (sk)	2004-05-04
HK1054042A1 (en)	2003-11-14
CA2414018C (en)	2007-10-16
KR20030032962A (ko)	2003-04-26
CN1249074C (zh)	2006-04-05
JP4129176B2 (ja)	2008-08-06

Publication	Publication Date	Title
BG107216A (bg)	2003-05-30	2-аминокарбонил-9н-пуринови производни
AU2001260537A1 (en)	2002-03-07	2-aminocarbonyl-9H-purine derivatives
AU764106B2 (en)	2003-08-07	Purine derivatives
US6753322B2 (en)	2004-06-22	2-aminocarbonyl-9H-purine derivatives
US6525032B2 (en)	2003-02-25	Purine derivatives
US6350735B1 (en)	2002-02-26	Purine derivatives
IL152783A (en)	2008-11-26	2-aminocarbonyl-9h-purine derivatives
HK1089447B (en)	2008-08-22	A process for the preparation of 2-aminocarbonyl-9h-purine derivatives and the intermediates thereof