ES2241994T3 - Compuestos pirazolo(4,3-d)pirimidinona como inhibidores de gmpc. - Google Patents
Compuestos pirazolo(4,3-d)pirimidinona como inhibidores de gmpc.Info
- Publication number
- ES2241994T3 ES2241994T3 ES02707031T ES02707031T ES2241994T3 ES 2241994 T3 ES2241994 T3 ES 2241994T3 ES 02707031 T ES02707031 T ES 02707031T ES 02707031 T ES02707031 T ES 02707031T ES 2241994 T3 ES2241994 T3 ES 2241994T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- het
- aryl
- terminated
- groups
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 194
- 239000003112 inhibitor Substances 0.000 title description 23
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 title description 5
- YCIPQJTZJGUXND-UHFFFAOYSA-N Aglaia odorata Alkaloid Natural products C1=CC(OC)=CC=C1C1(C(C=2C(=O)N3CCCC3=NC=22)C=3C=CC=CC=3)C2(O)C2=C(OC)C=C(OC)C=C2O1 YCIPQJTZJGUXND-UHFFFAOYSA-N 0.000 title description 4
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 98
- -1 oxatriazolyl Chemical group 0.000 claims abstract description 66
- 125000001424 substituent group Chemical group 0.000 claims abstract description 44
- 125000005843 halogen group Chemical group 0.000 claims abstract description 40
- 150000003839 salts Chemical class 0.000 claims abstract description 40
- 125000003118 aryl group Chemical group 0.000 claims abstract description 35
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 26
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 23
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 18
- 239000000651 prodrug Substances 0.000 claims abstract description 15
- 229940002612 prodrug Drugs 0.000 claims abstract description 15
- 239000012453 solvate Substances 0.000 claims abstract description 15
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 10
- 125000002393 azetidinyl group Chemical group 0.000 claims abstract description 9
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 8
- 125000003226 pyrazolyl group Chemical group 0.000 claims abstract description 7
- 125000002015 acyclic group Chemical group 0.000 claims abstract description 6
- 125000002883 imidazolyl group Chemical group 0.000 claims abstract description 6
- 125000001041 indolyl group Chemical group 0.000 claims abstract description 6
- 125000002757 morpholinyl group Chemical group 0.000 claims abstract description 6
- 125000004193 piperazinyl group Chemical group 0.000 claims abstract description 6
- 125000003386 piperidinyl group Chemical group 0.000 claims abstract description 6
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 6
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims abstract description 6
- 125000003831 tetrazolyl group Chemical group 0.000 claims abstract description 6
- 125000001425 triazolyl group Chemical group 0.000 claims abstract description 6
- 125000002877 alkyl aryl group Chemical group 0.000 claims abstract description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims abstract description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims abstract description 5
- 125000002541 furyl group Chemical group 0.000 claims abstract description 4
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims abstract description 4
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims abstract description 4
- 125000000842 isoxazolyl group Chemical group 0.000 claims abstract description 4
- 125000001715 oxadiazolyl group Chemical group 0.000 claims abstract description 4
- 125000002971 oxazolyl group Chemical group 0.000 claims abstract description 4
- 125000003373 pyrazinyl group Chemical group 0.000 claims abstract description 4
- 125000002098 pyridazinyl group Chemical group 0.000 claims abstract description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims abstract description 4
- 125000001113 thiadiazolyl group Chemical group 0.000 claims abstract description 4
- 125000005307 thiatriazolyl group Chemical group S1N=NN=C1* 0.000 claims abstract description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims abstract description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims abstract description 3
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims abstract description 3
- 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 abstract description 3
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims abstract description 3
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 10
- 125000006528 (C2-C6) alkyl group Chemical group 0.000 claims abstract 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract 2
- 239000000203 mixture Substances 0.000 claims description 47
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 32
- 239000003814 drug Substances 0.000 claims description 27
- 229940079593 drug Drugs 0.000 claims description 23
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 17
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 17
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 16
- 241001465754 Metazoa Species 0.000 claims description 9
- 238000009472 formulation Methods 0.000 claims description 7
- 230000001568 sexual effect Effects 0.000 claims description 7
- 230000004064 dysfunction Effects 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 5
- 201000001881 impotence Diseases 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 208000010228 Erectile Dysfunction Diseases 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 201000001880 Sexual dysfunction Diseases 0.000 claims description 2
- 208000027520 Somatoform disease Diseases 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 208000027753 pain disease Diseases 0.000 claims description 2
- 231100000872 sexual dysfunction Toxicity 0.000 claims description 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims 1
- 206010011953 Decreased activity Diseases 0.000 claims 1
- 208000021663 Female sexual arousal disease Diseases 0.000 claims 1
- 208000030047 Sexual desire disease Diseases 0.000 claims 1
- 125000000304 alkynyl group Chemical group 0.000 claims 1
- 238000009109 curative therapy Methods 0.000 claims 1
- 238000011321 prophylaxis Methods 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
- 125000004429 atom Chemical group 0.000 abstract description 6
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 abstract description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 121
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 54
- 238000002360 preparation method Methods 0.000 description 54
- 238000006243 chemical reaction Methods 0.000 description 49
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 47
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- 239000000243 solution Substances 0.000 description 45
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 41
- 238000000034 method Methods 0.000 description 40
- 239000007787 solid Substances 0.000 description 35
- 230000002829 reductive effect Effects 0.000 description 34
- 239000002253 acid Substances 0.000 description 33
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 31
- 102100024085 Alpha-aminoadipic semialdehyde dehydrogenase Human genes 0.000 description 28
- 239000002904 solvent Substances 0.000 description 28
- 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 description 27
- 238000005481 NMR spectroscopy Methods 0.000 description 27
- ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 27
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- 238000010992 reflux Methods 0.000 description 25
- 239000000047 product Substances 0.000 description 22
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 20
- 101710135349 Venom phosphodiesterase Proteins 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
- 239000002585 base Substances 0.000 description 17
- 241000282414 Homo sapiens Species 0.000 description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 13
- 238000004452 microanalysis Methods 0.000 description 13
- 239000000741 silica gel Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- 238000004440 column chromatography Methods 0.000 description 12
- 238000005859 coupling reaction Methods 0.000 description 12
- 150000002148 esters Chemical group 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- 238000011282 treatment Methods 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 11
- 229910000024 caesium carbonate Inorganic materials 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 239000007832 Na2SO4 Substances 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- 239000000556 agonist Substances 0.000 description 10
- 229910021529 ammonia Inorganic materials 0.000 description 10
- 239000012267 brine Substances 0.000 description 10
- 239000000460 chlorine Substances 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 229910052938 sodium sulfate Inorganic materials 0.000 description 10
- 235000011152 sodium sulphate Nutrition 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 10
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
- 108090000028 Neprilysin Proteins 0.000 description 9
- 102000003729 Neprilysin Human genes 0.000 description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- 230000008878 coupling Effects 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 8
- 238000010168 coupling process Methods 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 8
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 7
- 108010003205 Vasoactive Intestinal Peptide Proteins 0.000 description 7
- 102000055135 Vasoactive Intestinal Peptide Human genes 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 229910052740 iodine Inorganic materials 0.000 description 7
- 150000002576 ketones Chemical group 0.000 description 7
- 239000000546 pharmaceutical excipient Substances 0.000 description 7
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- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 125000006239 protecting group Chemical group 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
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- 229940124639 Selective inhibitor Drugs 0.000 description 6
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- URPYMXQQVHTUDU-OFGSCBOVSA-N nucleopeptide y Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 URPYMXQQVHTUDU-OFGSCBOVSA-N 0.000 description 6
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Landscapes
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0106651 | 2001-03-16 | ||
| GB0106561A GB0106561D0 (en) | 2001-03-16 | 2001-03-16 | Pharmaceutically active compounds |
| GB0106651A GB0106651D0 (en) | 2001-03-16 | 2001-03-16 | Pharmaceutically active compounds |
| GB0106561 | 2001-03-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2241994T3 true ES2241994T3 (es) | 2005-11-01 |
Family
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Family Applications (1)
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| EP (1) | EP1372656B1 (enExample) |
| JP (1) | JP2004527510A (enExample) |
| AT (1) | ATE298238T1 (enExample) |
| BR (1) | BR0208078A (enExample) |
| CA (1) | CA2436911A1 (enExample) |
| DE (1) | DE60204760T2 (enExample) |
| ES (1) | ES2241994T3 (enExample) |
| MX (1) | MXPA03006310A (enExample) |
| WO (1) | WO2002074312A1 (enExample) |
Families Citing this family (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2341240T3 (es) | 2002-12-13 | 2010-06-17 | Warner-Lambert Company Llc | Ligando alfa-2-delta para tratar los sintomas del tracto urinario inferior. |
| WO2004082667A1 (en) * | 2003-03-17 | 2004-09-30 | Pfizer Products Inc. | Treatment of type 1 diabetes with pde5 inhibitors |
| US7141669B2 (en) | 2003-04-23 | 2006-11-28 | Pfizer Inc. | Cannabiniod receptor ligands and uses thereof |
| BRPI0412259B1 (pt) | 2003-07-22 | 2019-08-20 | Astex Therapeutics Limited | Compostos de 1H-pirazol 3,4-dissubstituídos como moduladores de quinases dependentes de ciclina (CDK), seus usos, processo para a preparação dos mesmos e composição farmacêutica |
| JP2007504243A (ja) * | 2003-09-03 | 2007-03-01 | ニューロジェン・コーポレーション | ５−アリール−ピラゾロ［４，３−ｄ］ピリミジン類、ピリジン類、ピラジン類及び関連化合物 |
| AR054425A1 (es) | 2005-01-21 | 2007-06-27 | Astex Therapeutics Ltd | Sales de adicion de piperidin 4-il- amida de acido 4-(2,6-dicloro-benzoilamino) 1h-pirazol-3-carboxilico. |
| US8404718B2 (en) | 2005-01-21 | 2013-03-26 | Astex Therapeutics Limited | Combinations of pyrazole kinase inhibitors |
| CN103467471A (zh) | 2005-06-06 | 2013-12-25 | 武田药品工业株式会社 | 有机化合物 |
| ATE522518T1 (de) * | 2006-05-31 | 2011-09-15 | Takeda San Diego Inc | Indazol- und isoindolderivate als glucokinaseaktivierende stoffe |
| US9255099B2 (en) | 2006-06-06 | 2016-02-09 | Intra-Cellular Therapies, Inc. | Pyrazolo[3,4-D]pyrimidine-4,6(5H,7H)-diones as phosphodiesterase 1 inhibitors |
| WO2008070095A1 (en) | 2006-12-05 | 2008-06-12 | Intra-Cellular Therapies, Inc. | Novel uses |
| ES2588238T3 (es) | 2007-12-06 | 2016-10-31 | Intra-Cellular Therapies, Inc. | Derivados de pirazolopirimidin-4,6-diona y su uso como producto farmacéutico |
| JP5813511B2 (ja) | 2008-12-06 | 2015-11-17 | イントラ−セルラー・セラピーズ・インコーポレイテッドＩｎｔｒａ−Ｃｅｌｌｕｌａｒ Ｔｈｅｒａｐｉｅｓ， Ｉｎｃ． | 有機化合物 |
| US8927556B2 (en) | 2008-12-06 | 2015-01-06 | Intra-Cellular Therapies, Inc. | 1H-pyrrolo[3,4-D]pyrimidin-2(6H)-one compounds |
| US8633180B2 (en) | 2008-12-06 | 2014-01-21 | Intra-Cellular Therapies, Inc. | Organic compounds |
| EP2358204B1 (en) | 2008-12-06 | 2015-08-05 | Intra-Cellular Therapies, Inc. | 4,5,7,8-tetrahydro-4-oxo-2H-imidazo[1,2-a]pyrrolo[3,4-e]pyrimidine compounds as PDE1 inhibitors. |
| ES2638912T3 (es) | 2008-12-06 | 2017-10-24 | Intra-Cellular Therapies, Inc. | Compuestos orgánicos |
| JP5710493B2 (ja) | 2008-12-06 | 2015-04-30 | イントラ−セルラー・セラピーズ・インコーポレイテッドＩｎｔｒａ−Ｃｅｌｌｕｌａｒ Ｔｈｅｒａｐｉｅｓ， Ｉｎｃ． | 有機化合物 |
| EP2379076B1 (en) | 2008-12-23 | 2014-11-12 | The Trustees of Columbia University in the City of New York | Phosphodiesterase inhibitors and uses thereof |
| JP2012526810A (ja) | 2009-05-13 | 2012-11-01 | イントラ−セルラー・セラピーズ・インコーポレイテッド | 有機化合物 |
| WO2011153135A1 (en) | 2010-05-31 | 2011-12-08 | Intra-Cellular Therapies, Inc. | Organic compounds |
| EP2575817A4 (en) | 2010-05-31 | 2014-01-08 | Intra Cellular Therapies Inc | ORGANIC CONNECTIONS |
| EP2576551A4 (en) | 2010-05-31 | 2014-04-16 | Intra Cellular Therapies Inc | ORGANIC CONNECTIONS |
| TW201206937A (en) | 2010-05-31 | 2012-02-16 | Intra Cellular Therapies Inc | Organic compounds |
| US10561656B2 (en) | 2011-06-10 | 2020-02-18 | Intra-Cellular Therapies, Inc. | Organic compounds |
| WO2014127331A1 (en) | 2013-02-17 | 2014-08-21 | Intra-Cellular Therapies, Inc. | Novel uses |
| EP3479825B1 (en) | 2013-03-15 | 2021-02-17 | Intra-Cellular Therapies, Inc. | Pde1 inhibitors for use in the treatment and/or prevention of cns or pns diseases or disorders |
| US9598426B2 (en) | 2013-03-15 | 2017-03-21 | Intra-Cellular Therapies, Inc. | Organic compounds |
| WO2015196186A1 (en) | 2014-06-20 | 2015-12-23 | Intra-Cellular Therapies, Inc. | Organic compounds |
| JP6591530B2 (ja) | 2014-08-07 | 2019-10-16 | イントラ−セルラー・セラピーズ・インコーポレイテッドＩｎｔｒａ−Ｃｅｌｌｕｌａｒ Ｔｈｅｒａｐｉｅｓ， Ｉｎｃ． | 有機化合物 |
| US10285992B2 (en) | 2014-08-07 | 2019-05-14 | Intra-Cellular Therapies, Inc. | Combinations of PDE1 inhibitors and NEP inhibitors and associated methods |
| US9546175B2 (en) | 2014-08-07 | 2017-01-17 | Intra-Cellular Therapies, Inc. | Organic compounds |
| ES2857567T3 (es) | 2014-09-17 | 2021-09-29 | Intra Cellular Therapies Inc | Derivados de 7,8-dihidro-[2h]-imidazo-[1,2-a]pirazolo[4,3-e]pirimidin-4(5h)-ona como inhibidores de fosfodiesterasa 1 (PDE1) para tratar enfermedades, trastornos o lesiones del sistema nervioso central (SNC) |
| WO2016192083A1 (en) * | 2015-06-04 | 2016-12-08 | Merck Sharp & Dohme Corp. | Dihydropyrazolopyrimidinone compounds as pde2 inhibitors |
| JP2019510039A (ja) | 2016-03-28 | 2019-04-11 | イントラ−セルラー・セラピーズ・インコーポレイテッドＩｎｔｒａ−Ｃｅｌｌｕｌａｒ Ｔｈｅｒａｐｉｅｓ， Ｉｎｃ． | 新規組成物および方法 |
| EP3970719A1 (en) | 2016-09-12 | 2022-03-23 | Intra-Cellular Therapies, Inc. | Pde1 inhibitor for use in a method of treatment or prophylaxis of inflammation and/or an inflammatory disease or disorder |
| US11839614B2 (en) | 2018-01-31 | 2023-12-12 | Intra-Cellular Therapies, Inc. | Methods for treating or mitigating cardiotoxicity characterized by inhibition of adenosine A2 signaling and/or adenosine A2 receptor expression |
| US12410175B2 (en) | 2019-09-03 | 2025-09-09 | Intra-Cellular Therapies, Inc. | Compounds |
| US12364695B2 (en) | 2020-06-02 | 2025-07-22 | Intra-Cellular Therapies, Inc. | Methods of treating inflammatory disease |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9114760D0 (en) * | 1991-07-09 | 1991-08-28 | Pfizer Ltd | Therapeutic agents |
| GB9311920D0 (en) * | 1993-06-09 | 1993-07-28 | Pfizer Ltd | Therapeutic agents |
-
2002
- 2002-03-07 WO PCT/IB2002/000679 patent/WO2002074312A1/en not_active Ceased
- 2002-03-07 ES ES02707031T patent/ES2241994T3/es not_active Expired - Lifetime
- 2002-03-07 JP JP2002573019A patent/JP2004527510A/ja active Pending
- 2002-03-07 BR BR0208078-8A patent/BR0208078A/pt not_active IP Right Cessation
- 2002-03-07 DE DE60204760T patent/DE60204760T2/de not_active Expired - Fee Related
- 2002-03-07 CA CA002436911A patent/CA2436911A1/en not_active Abandoned
- 2002-03-07 EP EP02707031A patent/EP1372656B1/en not_active Expired - Lifetime
- 2002-03-07 AT AT02707031T patent/ATE298238T1/de not_active IP Right Cessation
- 2002-03-07 MX MXPA03006310A patent/MXPA03006310A/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CA2436911A1 (en) | 2002-09-26 |
| DE60204760T2 (de) | 2006-05-18 |
| ATE298238T1 (de) | 2005-07-15 |
| MXPA03006310A (es) | 2003-09-16 |
| JP2004527510A (ja) | 2004-09-09 |
| EP1372656A1 (en) | 2004-01-02 |
| DE60204760D1 (de) | 2005-07-28 |
| BR0208078A (pt) | 2004-03-02 |
| EP1372656B1 (en) | 2005-06-22 |
| WO2002074312A1 (en) | 2002-09-26 |
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