ZA200202723B - 5-(2-substituted-5-heterocyclylsulphonylpyrid-3-yl)-dihydropyrazolo[4,3-D]pyrimidin-7-ones as phosphodiesterase inhibitors. - Google Patents
5-(2-substituted-5-heterocyclylsulphonylpyrid-3-yl)-dihydropyrazolo[4,3-D]pyrimidin-7-ones as phosphodiesterase inhibitors. Download PDFInfo
- Publication number
- ZA200202723B ZA200202723B ZA200202723A ZA200202723A ZA200202723B ZA 200202723 B ZA200202723 B ZA 200202723B ZA 200202723 A ZA200202723 A ZA 200202723A ZA 200202723 A ZA200202723 A ZA 200202723A ZA 200202723 B ZA200202723 B ZA 200202723B
- Authority
- ZA
- South Africa
- Prior art keywords
- lower alkyl
- optionally substituted
- pyrimidin
- dihydro
- pyrazolo
- Prior art date
Links
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 title description 2
- 239000002571 phosphodiesterase inhibitor Substances 0.000 title description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 147
- 150000001875 compounds Chemical class 0.000 claims description 87
- 125000005843 halogen group Chemical group 0.000 claims description 64
- 125000003118 aryl group Chemical group 0.000 claims description 55
- 125000001424 substituent group Chemical group 0.000 claims description 37
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 34
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 28
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims description 22
- -1 pyrazol-4-yl Chemical group 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 13
- 125000000304 alkynyl group Chemical group 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- 125000002947 alkylene group Chemical group 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 10
- 125000000623 heterocyclic group Chemical group 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 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 description 7
- 238000006243 chemical reaction Methods 0.000 claims description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 239000001301 oxygen Chemical group 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000003107 substituted aryl group Chemical group 0.000 claims description 6
- 229910052717 sulfur Chemical group 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 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
- 201000001881 impotence Diseases 0.000 claims description 4
- 125000002346 iodo group Chemical group I* 0.000 claims description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 239000012453 solvate Substances 0.000 claims description 4
- 208000010228 Erectile Dysfunction Diseases 0.000 claims description 3
- 101150085511 PEDS1 gene Proteins 0.000 claims description 3
- 102100037592 Plasmanylethanolamine desaturase Human genes 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 230000005764 inhibitory process Effects 0.000 claims description 3
- 125000002757 morpholinyl group Chemical group 0.000 claims description 3
- 229920003199 poly(diethylsiloxane) Polymers 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 3
- 239000011593 sulfur Chemical group 0.000 claims description 3
- JYVJEWTWAUTFSV-NSHDSACASA-N (2s)-2-[[5-(1-methyl-7-oxo-3-propyl-4h-pyrazolo[4,3-d]pyrimidin-5-yl)-6-propoxypyridin-3-yl]amino]propanoic acid Chemical compound CCCOC1=NC=C(N[C@@H](C)C(O)=O)C=C1C(NC1=O)=NC2=C1N(C)N=C2CCC JYVJEWTWAUTFSV-NSHDSACASA-N 0.000 claims description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 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
- XTFVEDKZJWRHIZ-UHFFFAOYSA-N 5-(2-butoxy-5-iodopyridin-3-yl)-3-ethyl-2-(2-methoxyethyl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCCOC1=NC=C(I)C=C1C1=NC2=C(CC)N(CCOC)N=C2C(=O)N1 XTFVEDKZJWRHIZ-UHFFFAOYSA-N 0.000 claims description 2
- QZKBQGKELRAWEN-UHFFFAOYSA-N 5-(2-butoxy-5-iodopyridin-3-yl)-3-ethyl-2-(2-morpholin-4-ylethyl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCCOC1=NC=C(I)C=C1C(NC(=O)C1=N2)=NC1=C(CC)N2CCN1CCOCC1 QZKBQGKELRAWEN-UHFFFAOYSA-N 0.000 claims description 2
- VSENBPHLXIVGAC-UHFFFAOYSA-N 5-(5-acetyl-2-butoxypyridin-3-yl)-3-ethyl-2-(1-methylpiperidin-4-yl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCCOC1=NC=C(C(C)=O)C=C1C1=NC2=C(CC)N(C3CCN(C)CC3)N=C2C(=O)N1 VSENBPHLXIVGAC-UHFFFAOYSA-N 0.000 claims description 2
- JOUAVWDHDYEWSY-UHFFFAOYSA-N 5-[5-(1-methyl-7-oxo-3-propyl-4h-pyrazolo[4,3-d]pyrimidin-5-yl)-6-propoxypyridin-3-yl]-1,2-oxazol-3-one Chemical compound C1=C(C=2NC(=O)C=3N(C)N=C(CCC)C=3N=2)C(OCCC)=NC=C1C1=CC(O)=NO1 JOUAVWDHDYEWSY-UHFFFAOYSA-N 0.000 claims description 2
- SNLFNBCMIOHUJK-UHFFFAOYSA-N 5-[5-(2-hydroxyacetyl)-2-(2-methylpropoxy)pyridin-3-yl]-2-methyl-3-propyl-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCC=1N(C)N=C(C(N2)=O)C=1N=C2C1=CC(C(=O)CO)=CN=C1OCC(C)C SNLFNBCMIOHUJK-UHFFFAOYSA-N 0.000 claims description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 2
- 229910052751 metal Inorganic materials 0.000 claims description 2
- 239000002184 metal Substances 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
- 235000001968 nicotinic acid Nutrition 0.000 claims description 2
- 239000011664 nicotinic acid Substances 0.000 claims description 2
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 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
- 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims 5
- 238000006880 cross-coupling reaction Methods 0.000 claims 3
- 206010057671 Female sexual dysfunction Diseases 0.000 claims 2
- 150000004703 alkoxides Chemical group 0.000 claims 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 2
- 239000003153 chemical reaction reagent Substances 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 230000004064 dysfunction Effects 0.000 claims 2
- 230000001568 sexual effect Effects 0.000 claims 2
- XQVHDNHIJPAMJF-UHFFFAOYSA-N 1-methyl-5-[2-propoxy-5-(2h-tetrazol-5-yl)pyridin-3-yl]-3-propyl-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound C1=C(C=2NC(=O)C=3N(C)N=C(CCC)C=3N=2)C(OCCC)=NC=C1C1=NN=NN1 XQVHDNHIJPAMJF-UHFFFAOYSA-N 0.000 claims 1
- WNWVKZTYMQWFHE-UHFFFAOYSA-N 4-ethylmorpholine Chemical group [CH2]CN1CCOCC1 WNWVKZTYMQWFHE-UHFFFAOYSA-N 0.000 claims 1
- FXMZTDRRWLKQBN-UHFFFAOYSA-N 5-(1-methyl-7-oxo-3-propyl-4h-pyrazolo[4,3-d]pyrimidin-5-yl)-6-propoxypyridine-3-carbonitrile Chemical compound CCCOC1=NC=C(C#N)C=C1C(NC1=O)=NC2=C1N(C)N=C2CCC FXMZTDRRWLKQBN-UHFFFAOYSA-N 0.000 claims 1
- IITHDGLRFLQMIE-UHFFFAOYSA-N 5-(5-acetyl-2-butoxypyridin-3-yl)-3-ethyl-2-(2-methoxyethyl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCCOC1=NC=C(C(C)=O)C=C1C1=NC2=C(CC)N(CCOC)N=C2C(=O)N1 IITHDGLRFLQMIE-UHFFFAOYSA-N 0.000 claims 1
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- 208000021663 Female sexual arousal disease Diseases 0.000 claims 1
- 206010024419 Libido decreased Diseases 0.000 claims 1
- 208000006262 Psychological Sexual Dysfunctions Diseases 0.000 claims 1
- 208000027520 Somatoform disease Diseases 0.000 claims 1
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- 238000009109 curative therapy Methods 0.000 claims 1
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- 239000003085 diluting agent Substances 0.000 claims 1
- REQPQFUJGGOFQL-UHFFFAOYSA-N dimethylcarbamothioyl n,n-dimethylcarbamodithioate Chemical compound CN(C)C(=S)SC(=S)N(C)C REQPQFUJGGOFQL-UHFFFAOYSA-N 0.000 claims 1
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- 208000017020 hypoactive sexual desire disease Diseases 0.000 claims 1
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- 125000000547 substituted alkyl group Chemical group 0.000 claims 1
- XGFVXYNIPZJDPD-UHFFFAOYSA-N tert-butyl 2-[3-ethyl-5-(5-iodo-2-propoxypyridin-3-yl)-7-oxo-4h-pyrazolo[4,3-d]pyrimidin-1-yl]acetate Chemical compound CCCOC1=NC=C(I)C=C1C(NC1=O)=NC2=C1N(CC(=O)OC(C)(C)C)N=C2CC XGFVXYNIPZJDPD-UHFFFAOYSA-N 0.000 claims 1
- FWPZDJJCMBDPCU-UHFFFAOYSA-N tert-butyl 4-[5-(2-butoxy-5-iodopyridin-3-yl)-3-ethyl-7-oxo-4h-pyrazolo[4,3-d]pyrimidin-2-yl]piperidine-1-carboxylate Chemical compound CCCCOC1=NC=C(I)C=C1C1=NC2=C(CC)N(C3CCN(CC3)C(=O)OC(C)(C)C)N=C2C(=O)N1 FWPZDJJCMBDPCU-UHFFFAOYSA-N 0.000 claims 1
- 125000004122 cyclic group Chemical group 0.000 description 8
- 238000001640 fractional crystallisation Methods 0.000 description 5
- 125000002015 acyclic group Chemical group 0.000 description 4
- ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 4
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- 231100000252 nontoxic Toxicity 0.000 description 2
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- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- UNLXVOHLFVMSHA-UHFFFAOYSA-N 5-(2-butoxy-5-iodopyridin-3-yl)-3-ethyl-1-(2-methoxyethyl)-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCCOC1=NC=C(I)C=C1C(NC1=O)=NC2=C1N(CCOC)N=C2CC UNLXVOHLFVMSHA-UHFFFAOYSA-N 0.000 description 1
- WOJHPCPARYCLQS-UHFFFAOYSA-N 5-(5-amino-2-propoxypyridin-3-yl)-1-methyl-3-propyl-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound CCCOC1=NC=C(N)C=C1C(NC1=O)=NC2=C1N(C)N=C2CCC WOJHPCPARYCLQS-UHFFFAOYSA-N 0.000 description 1
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- SHVBOOIDTHDYJY-UHFFFAOYSA-N 6-phenylpyrazolo[3,4-d]pyrimidin-3-one Chemical class N=1C=C2C(=O)N=NC2=NC=1C1=CC=CC=C1 SHVBOOIDTHDYJY-UHFFFAOYSA-N 0.000 description 1
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- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical class OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 229940029575 guanosine Drugs 0.000 description 1
- 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 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 229940001447 lactate Drugs 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 150000004712 monophosphates Chemical class 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 150000002829 nitrogen Chemical class 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- NSQYMQABPXEHOY-UHFFFAOYSA-N pyrazolo[3,4-d]pyrimidin-3-one Chemical class C1=NC=C2C(=O)N=NC2=N1 NSQYMQABPXEHOY-UHFFFAOYSA-N 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000005307 thiatriazolyl group Chemical group S1N=NN=C1* 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9924041.8A GB9924041D0 (en) | 1999-10-11 | 1999-10-11 | Pharmaceutically active compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200202723B true ZA200202723B (en) | 2003-04-08 |
Family
ID=10862532
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200202723A ZA200202723B (en) | 1999-10-11 | 2002-04-08 | 5-(2-substituted-5-heterocyclylsulphonylpyrid-3-yl)-dihydropyrazolo[4,3-D]pyrimidin-7-ones as phosphodiesterase inhibitors. |
Country Status (3)
| Country | Link |
|---|---|
| EC (1) | ECSP003706A (es) |
| GB (1) | GB9924041D0 (es) |
| ZA (1) | ZA200202723B (es) |
-
1999
- 1999-10-11 GB GBGB9924041.8A patent/GB9924041D0/en not_active Ceased
-
2000
- 2000-10-10 EC ECSP003706 patent/ECSP003706A/es unknown
-
2002
- 2002-04-08 ZA ZA200202723A patent/ZA200202723B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ECSP003706A (es) | 2002-05-23 |
| GB9924041D0 (en) | 1999-12-15 |
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