BG106568A - 5-(2-заместени-5-хетероциклилсулфонилпирид-3-ил)-дихидропиразоло[4,3-d]пиримидин-7-они като фосфодиестеразни инхибитори - Google Patents

5-(2-заместени-5-хетероциклилсулфонилпирид-3-ил)-дихидропиразоло[4,3-d]пиримидин-7-они като фосфодиестеразни инхибитори Download PDF

Info

Publication number: BG106568A
Authority: BG; Bulgaria
Prior art keywords: lower alkyl; dihydro; pyrazolo; pyrimidin; ethyl
Prior art date: 1999-10-11

Application number

BG106568A

Other languages

Bulgarian (bg)

English (en)

Inventor

Charlotte ALLERTON

Christopher Barber

Graham MAW

David RAWSON

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

2002-04-02

Publication date

2002-12-29

1999-10-11 Priority claimed from GBGB9924041.8A external-priority patent/GB9924041D0/en

2000-07-28 Priority claimed from GB0018660A external-priority patent/GB0018660D0/en

2002-04-02 Application filed by Pfizer Inc. filed Critical Pfizer Inc.

2002-12-29 Publication of BG106568A publication Critical patent/BG106568A/bg

Links

229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 title description 2
239000002571 phosphodiesterase inhibitor Substances 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 603
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 7
230000005764 inhibitory process Effects 0.000 claims abstract description 6
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 pyrazol-4-yl Chemical group 0.000 claims description 215
125000000217 alkyl group Chemical group 0.000 claims description 184
239000000203 mixture Substances 0.000 claims description 141
238000000034 method Methods 0.000 claims description 135
125000005843 halogen group Chemical group 0.000 claims description 70
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 65
125000003118 aryl group Chemical group 0.000 claims description 63
125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 52
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 42
125000001424 substituent group Chemical group 0.000 claims description 42
229910052757 nitrogen Inorganic materials 0.000 claims description 41
150000003839 salts Chemical class 0.000 claims description 39
125000004093 cyano group Chemical group *C#N 0.000 claims description 38
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 36
238000006243 chemical reaction Methods 0.000 claims description 34
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 28
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 26
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 25
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 24
125000002877 alkyl aryl group Chemical group 0.000 claims description 24
229910052799 carbon Inorganic materials 0.000 claims description 20
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 19
125000000304 alkynyl group Chemical group 0.000 claims description 18
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 17
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 17
229910052739 hydrogen Inorganic materials 0.000 claims description 16
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 15
239000003814 drug Substances 0.000 claims description 14
125000000623 heterocyclic group Chemical group 0.000 claims description 14
201000001881 impotence Diseases 0.000 claims description 14
238000011282 treatment Methods 0.000 claims description 14
229910052760 oxygen Inorganic materials 0.000 claims description 13
238000007363 ring formation reaction Methods 0.000 claims description 13
239000012453 solvate Substances 0.000 claims description 13
229910052717 sulfur Inorganic materials 0.000 claims description 13
125000002252 acyl group Chemical group 0.000 claims description 12
WNWVKZTYMQWFHE-UHFFFAOYSA-N 4-ethylmorpholine Chemical group [CH2]CN1CCOCC1 WNWVKZTYMQWFHE-UHFFFAOYSA-N 0.000 claims description 11
208000010228 Erectile Dysfunction Diseases 0.000 claims description 11
239000003153 chemical reaction reagent Substances 0.000 claims description 11
125000004433 nitrogen atom Chemical group N* 0.000 claims description 11
125000002947 alkylene group Chemical group 0.000 claims description 10
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 10
235000001968 nicotinic acid Nutrition 0.000 claims description 9
239000011664 nicotinic acid Substances 0.000 claims description 9
239000000546 pharmaceutical excipient Substances 0.000 claims description 9
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 8
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
125000004432 carbon atom Chemical group C* 0.000 claims description 8
239000003795 chemical substances by application Substances 0.000 claims description 8
239000001301 oxygen Chemical group 0.000 claims description 8
206010057671 Female sexual dysfunction Diseases 0.000 claims description 7
125000003545 alkoxy group Chemical group 0.000 claims description 7
238000004132 cross linking Methods 0.000 claims description 7
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
208000006262 Psychological Sexual Dysfunctions Diseases 0.000 claims description 6
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
125000003342 alkenyl group Chemical group 0.000 claims description 6
230000004064 dysfunction Effects 0.000 claims description 6
125000005842 heteroatom Chemical group 0.000 claims description 6
230000007062 hydrolysis Effects 0.000 claims description 6
238000006460 hydrolysis reaction Methods 0.000 claims description 6
125000002346 iodo group Chemical group I* 0.000 claims description 6
230000001568 sexual effect Effects 0.000 claims description 6
125000003107 substituted aryl group Chemical group 0.000 claims description 6
239000011593 sulfur Substances 0.000 claims description 6
229910052794 bromium Inorganic materials 0.000 claims description 5
229910052751 metal Inorganic materials 0.000 claims description 5
239000002184 metal Substances 0.000 claims description 5
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 5
DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 4
150000004703 alkoxides Chemical class 0.000 claims description 4
230000029936 alkylation Effects 0.000 claims description 4
238000005804 alkylation reaction Methods 0.000 claims description 4
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
229910052801 chlorine Inorganic materials 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 4
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
125000003386 piperidinyl group Chemical group 0.000 claims description 4
238000006467 substitution reaction Methods 0.000 claims description 4
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 3
206010024419 Libido decreased Diseases 0.000 claims description 3
235000004279 alanine Nutrition 0.000 claims description 3
208000035475 disorder Diseases 0.000 claims description 3
208000017020 hypoactive sexual desire disease Diseases 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
125000003226 pyrazolyl group Chemical group 0.000 claims description 3
IHJRYCMOFOKMBR-UHFFFAOYSA-N 2-[5-(5-acetyl-2-propoxypyridin-3-yl)-3-ethyl-7-oxo-4h-pyrazolo[4,3-d]pyrimidin-1-yl]acetic acid Chemical compound CCCOC1=NC=C(C(C)=O)C=C1C(NC1=O)=NC2=C1N(CC(O)=O)N=C2CC IHJRYCMOFOKMBR-UHFFFAOYSA-N 0.000 claims description 2
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical group [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 2
125000002757 morpholinyl group Chemical group 0.000 claims description 2
235000005152 nicotinamide Nutrition 0.000 claims description 2
239000011570 nicotinamide Substances 0.000 claims description 2
229960003966 nicotinamide Drugs 0.000 claims description 2
239000008194 pharmaceutical composition Substances 0.000 claims description 2
125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 2
125000004076 pyridyl group Chemical group 0.000 claims description 2
125000000547 substituted alkyl group Chemical group 0.000 claims description 2
125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims 1
RFXNKMOAYBNFKA-UHFFFAOYSA-N 5-[2-[2-(dimethylamino)ethyl]-3-ethyl-7-oxo-4h-pyrazolo[4,3-d]pyrimidin-5-yl]-6-ethoxypyridine-3-carboxylic acid Chemical compound CCOC1=NC=C(C(O)=O)C=C1C1=NC2=C(CC)N(CCN(C)C)N=C2C(=O)N1 RFXNKMOAYBNFKA-UHFFFAOYSA-N 0.000 claims 1
125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 claims 1
238000006880 cross-coupling reaction Methods 0.000 claims 1
125000001188 haloalkyl group Chemical group 0.000 claims 1
230000003993 interaction Effects 0.000 claims 1
239000008177 pharmaceutical agent Substances 0.000 claims 1
230000002265 prevention Effects 0.000 claims 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
102000004861 Phosphoric Diester Hydrolases Human genes 0.000 abstract description 9
108090001050 Phosphoric Diester Hydrolases Proteins 0.000 abstract description 9
238000011321 prophylaxis Methods 0.000 abstract description 3
ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 abstract description 2
238000009109 curative therapy Methods 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 527
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 386
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238000002360 preparation method Methods 0.000 description 182
239000000243 solution Substances 0.000 description 140
235000019439 ethyl acetate Nutrition 0.000 description 127
239000007787 solid Substances 0.000 description 118
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 98
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 87
239000011541 reaction mixture Substances 0.000 description 84
238000004458 analytical method Methods 0.000 description 73
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 70
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 64
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 63
150000002500 ions Chemical class 0.000 description 56
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 54
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 53
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 53
239000012267 brine Substances 0.000 description 53
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 52
239000002904 solvent Substances 0.000 description 44
238000003818 flash chromatography Methods 0.000 description 43
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 41
239000012074 organic phase Substances 0.000 description 41
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 41
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
238000004440 column chromatography Methods 0.000 description 36
230000002829 reductive effect Effects 0.000 description 36
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238000002844 melting Methods 0.000 description 31
230000008018 melting Effects 0.000 description 31
239000012044 organic layer Substances 0.000 description 31
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 30
102100024085 Alpha-aminoadipic semialdehyde dehydrogenase Human genes 0.000 description 29
239000000284 extract Substances 0.000 description 27
238000000746 purification Methods 0.000 description 26
238000010992 reflux Methods 0.000 description 26
101710135349 Venom phosphodiesterase Proteins 0.000 description 23
239000012043 crude product Substances 0.000 description 20
238000001914 filtration Methods 0.000 description 20
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229910000030 sodium bicarbonate Inorganic materials 0.000 description 20
229960000583 acetic acid Drugs 0.000 description 19
239000008346 aqueous phase Substances 0.000 description 19
238000010828 elution Methods 0.000 description 19
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239000002253 acid Substances 0.000 description 18
239000007864 aqueous solution Substances 0.000 description 18
239000000725 suspension Substances 0.000 description 18
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
238000009835 boiling Methods 0.000 description 17
239000010410 layer Substances 0.000 description 17
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JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
229910021529 ammonia Inorganic materials 0.000 description 16
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 15
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 15
229910000024 caesium carbonate Inorganic materials 0.000 description 15
239000002244 precipitate Substances 0.000 description 15
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
WOEQSXAIPTXOPY-UHFFFAOYSA-N tert-butyl 4-methylsulfonyloxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(OS(C)(=O)=O)CC1 WOEQSXAIPTXOPY-UHFFFAOYSA-N 0.000 description 14
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 13
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 13
238000003756 stirring Methods 0.000 description 13
239000000126 substance Substances 0.000 description 13
239000002585 base Substances 0.000 description 12
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
238000005859 coupling reaction Methods 0.000 description 12
239000002552 dosage form Substances 0.000 description 12
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CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 12
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 11
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
239000003054 catalyst Substances 0.000 description 11
239000000460 chlorine Substances 0.000 description 11
238000001816 cooling Methods 0.000 description 11
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125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 11
IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 11
UZKWTJUDCOPSNM-UHFFFAOYSA-N 1-ethenoxybutane Chemical compound CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 10
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
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WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
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238000003786 synthesis reaction Methods 0.000 description 9
238000004809 thin layer chromatography Methods 0.000 description 9
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230000000694 effects Effects 0.000 description 8
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NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 8
239000007858 starting material Substances 0.000 description 8
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 8
241001465754 Metazoa Species 0.000 description 7
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 7
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239000001257 hydrogen Substances 0.000 description 7
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JIVZKJJQOZQXQB-UHFFFAOYSA-N tolazoline Chemical compound C=1C=CC=CC=1CC1=NCCN1 JIVZKJJQOZQXQB-UHFFFAOYSA-N 0.000 description 1
229960002312 tolazoline Drugs 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
230000007704 transition Effects 0.000 description 1
125000004665 trialkylsilyl group Chemical group 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
229940029284 trichlorofluoromethane Drugs 0.000 description 1
RXJKFRMDXUJTEX-UHFFFAOYSA-N triethylphosphine Chemical compound CCP(CC)CC RXJKFRMDXUJTEX-UHFFFAOYSA-N 0.000 description 1
YNZXWQJZEDLQEG-UHFFFAOYSA-N trimazosin Chemical compound N1=C2C(OC)=C(OC)C(OC)=CC2=C(N)N=C1N1CCN(C(=O)OCC(C)(C)O)CC1 YNZXWQJZEDLQEG-UHFFFAOYSA-N 0.000 description 1
229960002906 trimazosin Drugs 0.000 description 1
FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
229910052722 tritium Inorganic materials 0.000 description 1
229960000281 trometamol Drugs 0.000 description 1
230000002792 vascular Effects 0.000 description 1
229940124549 vasodilator Drugs 0.000 description 1
229960005080 warfarin Drugs 0.000 description 1
PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 1
239000001993 wax Substances 0.000 description 1
238000005550 wet granulation Methods 0.000 description 1
239000003871 white petrolatum Substances 0.000 description 1
239000000230 xanthan gum Substances 0.000 description 1
229920001285 xanthan gum Polymers 0.000 description 1
229940082509 xanthan gum Drugs 0.000 description 1
235000010493 xanthan gum Nutrition 0.000 description 1
239000000811 xylitol Substances 0.000 description 1
HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
235000010447 xylitol Nutrition 0.000 description 1
229960002675 xylitol Drugs 0.000 description 1
VWQVUPCCIRVNHF-UHFFFAOYSA-N yttrium atom Chemical compound [Y] VWQVUPCCIRVNHF-UHFFFAOYSA-N 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Reproductive Health (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Life Sciences & Earth Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Engineering & Computer Science (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Endocrinology (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Gynecology & Obstetrics (AREA)
Pregnancy & Childbirth (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

BG106568A 1999-10-11 2002-04-02 5-(2-заместени-5-хетероциклилсулфонилпирид-3-ил)-дихидропиразоло[4,3-d]пиримидин-7-они като фосфодиестеразни инхибитори BG106568A (bg)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
GBGB9924041.8A GB9924041D0 (en)	1999-10-11	1999-10-11	Pharmaceutically active compounds
GB0018660A GB0018660D0 (en)	2000-07-28	2000-07-28	Pharmaceutically active compounds
PCT/IB2000/001430 WO2001027112A1 (en)	1999-10-11	2000-10-04	5-(2-substituted-5-heterocyclylsulphonylpyrid-3-yl)-dihydropyrazolo[4,3-d]pyrimidin-7-ones as phosphodiesterase inhibitors

Publications (1)

Publication Number	Publication Date
BG106568A true BG106568A (bg)	2002-12-29

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ID=26244758

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BG106568A BG106568A (bg)	1999-10-11	2002-04-02	5-(2-заместени-5-хетероциклилсулфонилпирид-3-ил)-дихидропиразоло[4,3-d]пиримидин-7-они като фосфодиестеразни инхибитори

Country Status (34)

Country	Link
US (1)	US6756373B1 (et)
EP (1)	EP1222190A1 (et)
JP (1)	JP2003511452A (et)
KR (1)	KR20020038941A (et)
CN (1)	CN1378547A (et)
AP (1)	AP2002002455A0 (et)
AR (1)	AR022665A1 (et)
AU (1)	AU7547900A (et)
BG (1)	BG106568A (et)
BR (1)	BR0014695A (et)
CA (1)	CA2387353A1 (et)
CO (1)	CO5261539A1 (et)
CZ (1)	CZ20021151A3 (et)
DZ (1)	DZ3218A1 (et)
EA (1)	EA200200240A1 (et)
EE (1)	EE200200192A (et)
GT (1)	GT200000168A (et)
HK (1)	HK1049834A1 (et)
HU (1)	HUP0203438A3 (et)
IL (1)	IL149025A0 (et)
IS (1)	IS6288A (et)
MA (1)	MA26824A1 (et)
NO (1)	NO20021695L (et)
NZ (1)	NZ517324A (et)
OA (1)	OA12058A (et)
PA (1)	PA8504401A1 (et)
PE (1)	PE20010736A1 (et)
PL (1)	PL357522A1 (et)
SK (1)	SK4562002A3 (et)
SV (1)	SV2002000192A (et)
TN (1)	TNSN00198A1 (et)
TR (1)	TR200200954T2 (et)
UY (1)	UY26383A1 (et)
WO (1)	WO2001027112A1 (et)

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2000
- 2000-10-04 EA EA200200240A patent/EA200200240A1/ru unknown
- 2000-10-04 CA CA002387353A patent/CA2387353A1/en not_active Abandoned
- 2000-10-04 SK SK456-2002A patent/SK4562002A3/sk unknown
- 2000-10-04 AP APAP/P/2002/002455A patent/AP2002002455A0/en unknown
- 2000-10-04 EP EP00964557A patent/EP1222190A1/en not_active Withdrawn
- 2000-10-04 CN CN00814083A patent/CN1378547A/zh active Pending
- 2000-10-04 KR KR1020027004589A patent/KR20020038941A/ko not_active Ceased
- 2000-10-04 TR TR2002/00954T patent/TR200200954T2/xx unknown
- 2000-10-04 DZ DZ003218A patent/DZ3218A1/fr active
- 2000-10-04 JP JP2001530330A patent/JP2003511452A/ja not_active Withdrawn
- 2000-10-04 CZ CZ20021151A patent/CZ20021151A3/cs unknown
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- 2000-10-04 OA OA1200200101A patent/OA12058A/en unknown
- 2000-10-04 AU AU75479/00A patent/AU7547900A/en not_active Abandoned
- 2000-10-04 NZ NZ517324A patent/NZ517324A/en unknown
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- 2000-10-04 WO PCT/IB2000/001430 patent/WO2001027112A1/en not_active Ceased
- 2000-10-04 PL PL00357522A patent/PL357522A1/xx not_active Application Discontinuation
- 2000-10-04 EE EEP200200192A patent/EE200200192A/et unknown
- 2000-10-04 HU HU0203438A patent/HUP0203438A3/hu unknown
- 2000-10-04 BR BR0014695-1A patent/BR0014695A/pt not_active IP Right Cessation
- 2000-10-06 US US09/684,228 patent/US6756373B1/en not_active Expired - Fee Related
- 2000-10-09 UY UY26383A patent/UY26383A1/es not_active Application Discontinuation
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- 2000-10-10 GT GT200000168A patent/GT200000168A/es unknown
- 2000-10-10 TN TNTNSN00198A patent/TNSN00198A1/fr unknown
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2002
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- 2002-04-02 BG BG106568A patent/BG106568A/bg unknown
- 2002-04-04 MA MA26585A patent/MA26824A1/fr unknown
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Also Published As

Publication number	Publication date
TR200200954T2 (tr)	2002-09-23
UY26383A1 (es)	2001-05-31
NO20021695L (no)	2002-06-07
HUP0203438A2 (hu)	2003-01-28
IS6288A (is)	2002-02-26
AU7547900A (en)	2001-04-23
PE20010736A1 (es)	2001-07-19
CA2387353A1 (en)	2001-04-19
AR022665A1 (es)	2002-09-04
PL357522A1 (en)	2004-07-26
HK1049834A1 (zh)	2003-05-30
CZ20021151A3 (cs)	2003-03-12
NZ517324A (en)	2003-09-26
SV2002000192A (es)	2002-07-16
BR0014695A (pt)	2002-06-18
IL149025A0 (en)	2002-11-10
AP2002002455A0 (en)	2002-06-30
PA8504401A1 (es)	2002-04-25
OA12058A (en)	2006-05-03
NO20021695D0 (no)	2002-04-10
MA26824A1 (fr)	2004-12-20
WO2001027112A1 (en)	2001-04-19
US6756373B1 (en)	2004-06-29
TNSN00198A1 (fr)	2002-05-30
DZ3218A1 (fr)	2001-04-19
SK4562002A3 (en)	2003-04-01
JP2003511452A (ja)	2003-03-25
EA200200240A1 (ru)	2002-10-31
EE200200192A (et)	2003-06-16
EP1222190A1 (en)	2002-07-17
HUP0203438A3 (en)	2003-05-28
KR20020038941A (ko)	2002-05-24
GT200000168A (es)	2002-04-03
CO5261539A1 (es)	2003-03-31
CN1378547A (zh)	2002-11-06

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