BG106678A - ПИРАЗОЛО [4,3 - d] ПИРИМИДИНОВИ ПРОИЗВОДНИ - Google Patents

ПИРАЗОЛО [4,3 - d] ПИРИМИДИНОВИ ПРОИЗВОДНИ Download PDF

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Publication number: BG106678A
Authority: BG; Bulgaria
Prior art keywords: ethyl; alkyl; ylsulfonyl; pyrazolo; dihydro
Prior art date: 1999-10-11

Application number

BG106678A

Other languages

Bulgarian (bg)

English (en)

Inventor

Mark Bunnage

Keith DEVRIES

Laurence HARRIS

Philip LEVETT

John Mathias

Joanna NEGRI

Stephen STREET

Albert Wood

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.)

1999-10-11

Filing date

2002-05-09

Publication date

2003-01-31

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=26244757&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=BG106678(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1999-10-11 Priority claimed from GBGB9924063.2A external-priority patent/GB9924063D0/en

2000-07-28 Priority claimed from GB0018656A external-priority patent/GB0018656D0/en

2002-05-09 Application filed by Pfizer Inc. filed Critical Pfizer Inc.

2003-01-31 Publication of BG106678A publication Critical patent/BG106678A/bg

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APXRHPDHORGIEB-UHFFFAOYSA-N 1H-pyrazolo[4,3-d]pyrimidine Chemical class N1=CN=C2C=NNC2=C1 APXRHPDHORGIEB-UHFFFAOYSA-N 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 639
150000003839 salts Chemical class 0.000 claims abstract description 90
239000012453 solvate Substances 0.000 claims abstract description 40
239000000651 prodrug Substances 0.000 claims abstract description 29
229940002612 prodrug Drugs 0.000 claims abstract description 29
ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 claims abstract description 23
201000001881 impotence Diseases 0.000 claims abstract description 22
238000011282 treatment Methods 0.000 claims abstract description 16
208000010228 Erectile Dysfunction Diseases 0.000 claims abstract description 14
102000004861 Phosphoric Diester Hydrolases Human genes 0.000 claims abstract description 8
108090001050 Phosphoric Diester Hydrolases Proteins 0.000 claims abstract description 8
101100189582 Dictyostelium discoideum pdeD gene Proteins 0.000 claims abstract 3
101150098694 PDE5A gene Proteins 0.000 claims abstract 3
102100029175 cGMP-specific 3',5'-cyclic phosphodiesterase Human genes 0.000 claims abstract 3
-1 piperazin-1-ylsulfonyl group Chemical group 0.000 claims description 342
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 164
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 140
238000000034 method Methods 0.000 claims description 108
238000006243 chemical reaction Methods 0.000 claims description 96
238000002360 preparation method Methods 0.000 claims description 89
239000002904 solvent Substances 0.000 claims description 79
125000001424 substituent group Chemical group 0.000 claims description 68
239000003795 chemical substances by application Substances 0.000 claims description 66
239000002585 base Substances 0.000 claims description 56
229910052739 hydrogen Inorganic materials 0.000 claims description 54
UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 54
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 47
125000005842 heteroatom Chemical group 0.000 claims description 47
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 47
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 46
125000000217 alkyl group Chemical group 0.000 claims description 41
229910052717 sulfur Inorganic materials 0.000 claims description 40
229910052760 oxygen Inorganic materials 0.000 claims description 38
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 36
229910052757 nitrogen Inorganic materials 0.000 claims description 34
238000007363 ring formation reaction Methods 0.000 claims description 32
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 28
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 27
125000000623 heterocyclic group Chemical group 0.000 claims description 27
125000003545 alkoxy group Chemical group 0.000 claims description 25
239000003814 drug Substances 0.000 claims description 25
125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 24
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 24
229910052736 halogen Inorganic materials 0.000 claims description 24
229920006395 saturated elastomer Polymers 0.000 claims description 24
150000001412 amines Chemical class 0.000 claims description 23
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 23
150000002367 halogens Chemical class 0.000 claims description 21
JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 20
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 19
239000002253 acid Substances 0.000 claims description 18
229910052799 carbon Inorganic materials 0.000 claims description 18
125000004432 carbon atom Chemical group C* 0.000 claims description 18
125000005843 halogen group Chemical group 0.000 claims description 18
XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 claims description 17
230000015572 biosynthetic process Effects 0.000 claims description 17
208000035475 disorder Diseases 0.000 claims description 17
125000001188 haloalkyl group Chemical group 0.000 claims description 17
125000004193 piperazinyl group Chemical group 0.000 claims description 17
239000002552 dosage form Substances 0.000 claims description 16
125000006239 protecting group Chemical group 0.000 claims description 16
238000006467 substitution reaction Methods 0.000 claims description 16
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
208000006262 Psychological Sexual Dysfunctions Diseases 0.000 claims description 13
125000000753 cycloalkyl group Chemical group 0.000 claims description 13
125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 claims description 13
125000003342 alkenyl group Chemical group 0.000 claims description 12
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 12
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 12
201000001880 Sexual dysfunction Diseases 0.000 claims description 11
239000003112 inhibitor Substances 0.000 claims description 11
231100000872 sexual dysfunction Toxicity 0.000 claims description 11
125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 10
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 10
125000003386 piperidinyl group Chemical group 0.000 claims description 10
230000008569 process Effects 0.000 claims description 10
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 10
125000003118 aryl group Chemical group 0.000 claims description 9
229910052801 chlorine Inorganic materials 0.000 claims description 9
201000010099 disease Diseases 0.000 claims description 9
230000004064 dysfunction Effects 0.000 claims description 9
125000004438 haloalkoxy group Chemical group 0.000 claims description 9
238000011321 prophylaxis Methods 0.000 claims description 9
208000012201 sexual and gender identity disease Diseases 0.000 claims description 9
208000015891 sexual disease Diseases 0.000 claims description 9
230000036299 sexual function Effects 0.000 claims description 9
241000124008 Mammalia Species 0.000 claims description 8
240000008042 Zea mays Species 0.000 claims description 8
235000002017 Zea mays subsp mays Nutrition 0.000 claims description 8
125000002757 morpholinyl group Chemical group 0.000 claims description 8
230000035946 sexual desire Effects 0.000 claims description 8
125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 7
125000001963 4 membered heterocyclic group Chemical group 0.000 claims description 7
235000005824 Zea mays ssp. parviglumis Nutrition 0.000 claims description 7
235000005822 corn Nutrition 0.000 claims description 7
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 7
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 7
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
238000002638 palliative care Methods 0.000 claims description 7
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 6
206010011953 Decreased activity Diseases 0.000 claims description 6
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 6
229910052783 alkali metal Inorganic materials 0.000 claims description 6
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 6
229910052794 bromium Inorganic materials 0.000 claims description 6
238000005859 coupling reaction Methods 0.000 claims description 6
239000003085 diluting agent Substances 0.000 claims description 6
238000004519 manufacturing process Methods 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 6
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 6
WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 claims description 5
229940123333 Phosphodiesterase 5 inhibitor Drugs 0.000 claims description 5
208000029901 Sexual arousal disease Diseases 0.000 claims description 5
125000002393 azetidinyl group Chemical group 0.000 claims description 5
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 5
230000007062 hydrolysis Effects 0.000 claims description 5
238000006460 hydrolysis reaction Methods 0.000 claims description 5
125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
239000002590 phosphodiesterase V inhibitor Substances 0.000 claims description 5
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
230000001568 sexual effect Effects 0.000 claims description 5
239000000126 substance Substances 0.000 claims description 5
UEYQJQVBUVAELZ-UHFFFAOYSA-N 2-Hydroxynicotinic acid Chemical compound OC(=O)C1=CC=CN=C1O UEYQJQVBUVAELZ-UHFFFAOYSA-N 0.000 claims description 4
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 4
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
125000005279 aryl sulfonyloxy group Chemical group 0.000 claims description 4
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 4
239000007788 liquid Substances 0.000 claims description 4
125000001453 quaternary ammonium group Chemical group 0.000 claims description 4
125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 4
230000001225 therapeutic effect Effects 0.000 claims description 4
125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 3
YPFZMBHKIVDSNR-UHFFFAOYSA-N 5-[2-ethoxy-5-(4-ethylpiperazin-1-yl)sulfonylpyridin-3-yl]-3-ethyl-2-(2-methoxyethyl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound C1=C(C=2NC(=O)C3=NN(CCOC)C(CC)=C3N=2)C(OCC)=NC=C1S(=O)(=O)N1CCN(CC)CC1 YPFZMBHKIVDSNR-UHFFFAOYSA-N 0.000 claims description 3
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
230000002265 prevention Effects 0.000 claims description 3
IIOTWDDVVSFHRF-UHFFFAOYSA-N 2-[2-(dimethylamino)ethyl]-5-[2-ethoxy-5-(4-ethylpiperazin-1-yl)sulfonylpyridin-3-yl]-3-ethyl-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound C1=C(C=2NC(=O)C3=NN(CCN(C)C)C(CC)=C3N=2)C(OCC)=NC=C1S(=O)(=O)N1CCN(CC)CC1 IIOTWDDVVSFHRF-UHFFFAOYSA-N 0.000 claims description 2
125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 2
VYGYAGDQYNLXDJ-UHFFFAOYSA-N 3-ethyl-2-(1-ethylazetidin-3-yl)-5-[5-(4-ethylpiperazin-1-yl)sulfonyl-2-phenylmethoxypyridin-3-yl]-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound C1N(CC)CC1N1C(CC)=C(N=C(NC2=O)C=3C(=NC=C(C=3)S(=O)(=O)N3CCN(CC)CC3)OCC=3C=CC=CC=3)C2=N1 VYGYAGDQYNLXDJ-UHFFFAOYSA-N 0.000 claims description 2
KPSBFMNMIOHYPY-UHFFFAOYSA-N 3-ethyl-5-[2-(2-methoxyethoxy)-5-(4-methylpiperazin-1-yl)sulfonylpyridin-3-yl]-2-(2-methylpropyl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCC=1N(CC(C)C)N=C(C(N2)=O)C=1N=C2C(C(=NC=1)OCCOC)=CC=1S(=O)(=O)N1CCN(C)CC1 KPSBFMNMIOHYPY-UHFFFAOYSA-N 0.000 claims description 2
VYFHWUGIGFPUHL-UHFFFAOYSA-N 3-ethyl-5-[5-(4-ethylpiperazin-1-yl)sulfonyl-2-(2-methoxyethoxy)pyridin-3-yl]-2-(2-methoxyethyl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound C1CN(CC)CCN1S(=O)(=O)C1=CN=C(OCCOC)C(C=2NC(=O)C3=NN(CCOC)C(CC)=C3N=2)=C1 VYFHWUGIGFPUHL-UHFFFAOYSA-N 0.000 claims description 2
RQYWQMXXGVLLGB-UHFFFAOYSA-N 3-ethyl-5-[5-(4-ethylpiperazin-1-yl)sulfonyl-2-propoxypyridin-3-yl]-2-(2-methoxyethyl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound C1=C(C=2NC(=O)C3=NN(CCOC)C(CC)=C3N=2)C(OCCC)=NC=C1S(=O)(=O)N1CCN(CC)CC1 RQYWQMXXGVLLGB-UHFFFAOYSA-N 0.000 claims description 2
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
WRAPEVAEFSIHPM-UHFFFAOYSA-N 5-[2-butoxy-5-(4-ethylpiperazin-1-yl)sulfonylpyridin-3-yl]-3-ethyl-2-(1-ethylazetidin-3-yl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCCOC1=NC=C(S(=O)(=O)N2CCN(CC)CC2)C=C1C(NC(=O)C1=N2)=NC1=C(CC)N2C1CN(CC)C1 WRAPEVAEFSIHPM-UHFFFAOYSA-N 0.000 claims description 2
OBEWPUCJDXQPSA-UHFFFAOYSA-N 5-[2-butoxy-5-(4-ethylpiperazin-1-yl)sulfonylpyridin-3-yl]-3-ethyl-2-(2-methoxyethyl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound C1=C(C=2NC(=O)C3=NN(CCOC)C(CC)=C3N=2)C(OCCCC)=NC=C1S(=O)(=O)N1CCN(CC)CC1 OBEWPUCJDXQPSA-UHFFFAOYSA-N 0.000 claims description 2
JMIOIYJBQYLMRL-UHFFFAOYSA-N 5-[2-ethoxy-5-(4-ethylpiperazin-1-yl)sulfonylpyridin-3-yl]-3-ethyl-2-(1-methoxypropan-2-yl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound C1=C(C=2NC(=O)C3=NN(C(CC)=C3N=2)C(C)COC)C(OCC)=NC=C1S(=O)(=O)N1CCN(CC)CC1 JMIOIYJBQYLMRL-UHFFFAOYSA-N 0.000 claims description 2
CVJJVQHDUKHESY-UHFFFAOYSA-N 5-[2-ethoxy-5-(4-ethylpiperazin-1-yl)sulfonylpyridin-3-yl]-3-ethyl-2-[2-(methylamino)ethyl]-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound C1=C(C=2NC(=O)C3=NN(CCNC)C(CC)=C3N=2)C(OCC)=NC=C1S(=O)(=O)N1CCN(CC)CC1 CVJJVQHDUKHESY-UHFFFAOYSA-N 0.000 claims description 2
WHZLAQCYTKWPJL-UHFFFAOYSA-N 5-[5-(4-ethylpiperazin-1-yl)sulfonyl-2-(2-methylpropoxy)pyridin-3-yl]-2-(2-methoxyethyl)-3-propyl-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCC=1N(CCOC)N=C(C(N2)=O)C=1N=C2C(C(=NC=1)OCC(C)C)=CC=1S(=O)(=O)N1CCN(CC)CC1 WHZLAQCYTKWPJL-UHFFFAOYSA-N 0.000 claims description 2
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
230000037007 arousal Effects 0.000 claims description 2
125000004104 aryloxy group Chemical group 0.000 claims description 2
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
239000012954 diazonium Substances 0.000 claims description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical group [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 claims description 2
125000002541 furyl group Chemical group 0.000 claims description 2
229910052500 inorganic mineral Inorganic materials 0.000 claims description 2
239000011707 mineral Substances 0.000 claims description 2
101150009274 nhr-1 gene Proteins 0.000 claims description 2
229910017604 nitric acid Inorganic materials 0.000 claims description 2
239000003960 organic solvent Substances 0.000 claims description 2
229910052698 phosphorus Inorganic materials 0.000 claims description 2
239000003586 protic polar solvent Substances 0.000 claims description 2
125000004076 pyridyl group Chemical group 0.000 claims description 2
125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 9
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 3
CJWRCAPGMZJIBS-UHFFFAOYSA-N 1,4-dihydropyrazolo[4,3-d]pyrimidin-7-one;2-methoxyethanol Chemical compound COCCO.O=C1N=CNC2=C1NN=C2 CJWRCAPGMZJIBS-UHFFFAOYSA-N 0.000 claims 2
230000001771 impaired effect Effects 0.000 claims 2
KTGFLVDKXVWJDH-UHFFFAOYSA-N 1-(azetidin-1-yl)ethanone Chemical compound CC(=O)N1CCC1 KTGFLVDKXVWJDH-UHFFFAOYSA-N 0.000 claims 1
JQXAVRJTJOJMSE-UHFFFAOYSA-N 2-(cyclobutylmethyl)-3-ethyl-5-[2-(2-methoxyethoxy)-5-(4-methylpiperazin-1-yl)sulfonylpyridin-3-yl]-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound N1=C(C(NC(=N2)C=3C(=NC=C(C=3)S(=O)(=O)N3CCN(C)CC3)OCCOC)=O)C2=C(CC)N1CC1CCC1 JQXAVRJTJOJMSE-UHFFFAOYSA-N 0.000 claims 1
OZRATLVKWROBMN-UHFFFAOYSA-N 2-(cyclobutylmethyl)-5-[2-ethoxy-5-(4-ethylpiperazin-1-yl)sulfonylpyridin-3-yl]-3-ethyl-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCOC1=NC=C(S(=O)(=O)N2CCN(CC)CC2)C=C1C(NC(=O)C1=N2)=NC1=C(CC)N2CC1CCC1 OZRATLVKWROBMN-UHFFFAOYSA-N 0.000 claims 1
AWXZPTUDNDPUMO-UHFFFAOYSA-N 3-ethyl-5-[5-(4-ethylpiperazin-1-yl)sulfonyl-2-propan-2-yloxypyridin-3-yl]-2-(2-methoxyethyl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound C1CN(CC)CCN1S(=O)(=O)C1=CN=C(OC(C)C)C(C=2NC(=O)C3=NN(CCOC)C(CC)=C3N=2)=C1 AWXZPTUDNDPUMO-UHFFFAOYSA-N 0.000 claims 1
KYLOFMQLLNEPBT-UHFFFAOYSA-N 5-[2-butoxy-5-(4-ethylpiperazin-1-yl)sulfonylpyridin-3-yl]-2-[2-(dimethylamino)ethyl]-3-ethyl-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound C1=C(C=2NC(=O)C3=NN(CCN(C)C)C(CC)=C3N=2)C(OCCCC)=NC=C1S(=O)(=O)N1CCN(CC)CC1 KYLOFMQLLNEPBT-UHFFFAOYSA-N 0.000 claims 1
COVMDAYFLBAMRZ-UHFFFAOYSA-N 5-[2-butoxy-5-(4-ethylpiperazin-1-yl)sulfonylpyridin-3-yl]-3-ethyl-2-(1-methylazetidin-3-yl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCCOC1=NC=C(S(=O)(=O)N2CCN(CC)CC2)C=C1C(NC(=O)C1=N2)=NC1=C(CC)N2C1CN(C)C1 COVMDAYFLBAMRZ-UHFFFAOYSA-N 0.000 claims 1
USCAQVLUGMUUDT-UHFFFAOYSA-N 5-[2-ethoxy-5-(4-ethylpiperazin-1-yl)sulfonylpyridin-3-yl]-2-(2-methoxyethyl)-3-propyl-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCC=1N(CCOC)N=C(C(N2)=O)C=1N=C2C(C(=NC=1)OCC)=CC=1S(=O)(=O)N1CCN(CC)CC1 USCAQVLUGMUUDT-UHFFFAOYSA-N 0.000 claims 1
238000007259 addition reaction Methods 0.000 claims 1
238000010976 amide bond formation reaction Methods 0.000 claims 1
238000005915 ammonolysis reaction Methods 0.000 claims 1
238000009109 curative therapy Methods 0.000 claims 1
230000003993 interaction Effects 0.000 claims 1
238000007912 intraperitoneal administration Methods 0.000 claims 1
230000001404 mediated effect Effects 0.000 claims 1
GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 claims 1
QYCUDRKEQFHGDK-UHFFFAOYSA-N spiro[1,3-oxazolidine-5,9'-fluorene]-2,4-dione Chemical compound O1C(=O)NC(=O)C21C1=CC=CC=C1C1=CC=CC=C12 QYCUDRKEQFHGDK-UHFFFAOYSA-N 0.000 claims 1
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Classifications

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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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BG106678A 1999-10-11 2002-05-09 ПИРАЗОЛО [4,3 - d] ПИРИМИДИНОВИ ПРОИЗВОДНИ BG106678A (bg)

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GBGB9924063.2A GB9924063D0 (en)	1999-10-11	1999-10-11	Pharmaceutically active compounds
GB0018656A GB0018656D0 (en)	2000-07-28	2000-07-28	Pharmaceutically active compounds
PCT/IB2000/001457 WO2001027113A2 (en)	1999-10-11	2000-10-11	PYRAZOLO `4,3-d! PYRIMIDINE DERIVATIVES

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AP (1)	AP1238A (et)
AT (1)	ATE284404T1 (et)
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Publication number	Publication date
CU23198A3 (es)	2007-03-23
HK1050367A1 (en)	2003-06-20
PT1220856E (pt)	2005-02-28
NO20021694L (no)	2002-05-27
HUP0203450A3 (en)	2003-05-28
AP1238A (en)	2004-01-29
SV2002000195A (es)	2002-07-16
US20060293347A1 (en)	2006-12-28
CR6617A (es)	2004-02-23
CN1680378A (zh)	2005-10-12
JP3834236B2 (ja)	2006-10-18
CN100383141C (zh)	2008-04-23
US20100035891A1 (en)	2010-02-11
WO2001027113A3 (en)	2001-10-25
US6677335B1 (en)	2004-01-13
MY130319A (en)	2007-06-29
JP2003511453A (ja)	2003-03-25
IL149026A (en)	2010-05-17
IS2181B (is)	2006-12-15
OA12061A (en)	2006-05-03
PL357536A1 (en)	2004-07-26
IN2006MU00264A (et)	2007-06-08
IS6320A (is)	2002-03-21
MXPA02003627A (en)	2002-08-01
NO20021694D0 (no)	2002-04-10
MX228340B (en)	2005-06-07
AP2002002456A0 (en)	2002-06-30
IN2002MU00385A (et)	2005-08-26
HK1069577A1 (zh)	2005-05-27
EP1220856B1 (en)	2004-12-08
DE60016615T2 (de)	2005-12-22
HK1078574A1 (zh)	2006-03-17
GEP20033068B (en)	2003-09-25
WO2001027113A2 (en)	2001-04-19
CO5251477A1 (es)	2003-02-28
YU31402A (sh)	2005-03-15
EE200200195A (et)	2003-08-15
US7176311B2 (en)	2007-02-13
NO322856B1 (no)	2006-12-11
PH12000002783B1 (en)	2006-02-21
CN1572792A (zh)	2005-02-02
CZ20021158A3 (cs)	2003-03-12
IL149026A0 (en)	2002-11-10
CN1204138C (zh)	2005-06-01
EE05181B1 (et)	2009-06-15
ES2232502T3 (es)	2005-06-01
EA200200337A1 (ru)	2002-10-31
TWI265925B (en)	2006-11-11
DZ3220A1 (fr)	2001-04-19
IN2007MU00567A (et)	2007-08-31
GEP20033142B (en)	2003-12-25
HRP20020317B1 (en)	2007-08-31
CN100378100C (zh)	2008-04-02
DK1220856T3 (da)	2005-03-14
HRP20020317A2 (en)	2004-04-30
CA2387357A1 (en)	2001-04-19
PE20010737A1 (es)	2001-07-19
CA2387357C (en)	2007-10-02
PA8504501A1 (es)	2003-06-30
MA26825A1 (fr)	2004-12-20
BR0014698A (pt)	2002-06-18
AU7678400A (en)	2001-04-23
EP1220856A2 (en)	2002-07-10
KR100549152B1 (ko)	2006-02-06
EG24411A (en)	2009-05-25
GT200000171A (es)	2002-04-03
NZ518078A (en)	2003-10-31
IN2005MU00080A (et)	2006-05-19
SI1220856T1 (en)	2005-06-30
AU779065B2 (en)	2005-01-06
TR200200989T2 (tr)	2002-09-23
SK4602002A3 (en)	2003-04-01
DE60016615D1 (de)	2005-01-13
KR20020038942A (ko)	2002-05-24
ATE284404T1 (de)	2004-12-15
RS50476B (sr)	2010-03-02
CN1387531A (zh)	2002-12-25
US20040152712A1 (en)	2004-08-05
HUP0203450A2 (hu)	2003-01-28
EA004982B1 (ru)	2004-10-28
TNSN00199A1 (fr)	2002-05-30
CR10191A (es)	2008-10-10

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