OA12061A - Pyrazolo Ä4,3-DÜpyrimidine derivatives. - Google Patents
Pyrazolo Ä4,3-DÜpyrimidine derivatives. Download PDFInfo
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- OA12061A OA12061A OA1200200104A OA1200200104A OA12061A OA 12061 A OA12061 A OA 12061A OA 1200200104 A OA1200200104 A OA 1200200104A OA 1200200104 A OA1200200104 A OA 1200200104A OA 12061 A OA12061 A OA 12061A
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- OAPI
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- group
- compound
- alkyl
- formula
- ethyl
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- 150000001875 compounds Chemical class 0.000 claims abstract description 595
- 239000000651 prodrug Substances 0.000 claims abstract description 25
- 229940002612 prodrug Drugs 0.000 claims abstract description 25
- 201000001881 impotence Diseases 0.000 claims abstract description 12
- 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 6
- 239000000203 mixture Substances 0.000 claims description 183
- 238000006243 chemical reaction Methods 0.000 claims description 137
- 125000000217 alkyl group Chemical group 0.000 claims description 131
- 238000000034 method Methods 0.000 claims description 95
- -1 Ct to C4aikoxy Chemical group 0.000 claims description 79
- 239000002904 solvent Substances 0.000 claims description 74
- 125000003545 alkoxy group Chemical group 0.000 claims description 66
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 53
- 239000003795 chemical substances by application Substances 0.000 claims description 53
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 42
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 42
- 125000001424 substituent group Chemical group 0.000 claims description 40
- 230000008569 process Effects 0.000 claims description 39
- 229910052717 sulfur Inorganic materials 0.000 claims description 39
- 125000003342 alkenyl group Chemical group 0.000 claims description 38
- 125000005843 halogen group Chemical group 0.000 claims description 37
- 229910052760 oxygen Inorganic materials 0.000 claims description 36
- 239000002253 acid Substances 0.000 claims description 33
- 125000005842 heteroatom Chemical group 0.000 claims description 33
- 125000001188 haloalkyl group Chemical group 0.000 claims description 30
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
- 229910052757 nitrogen Inorganic materials 0.000 claims description 29
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 25
- 150000001412 amines Chemical class 0.000 claims description 21
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
- 230000001568 sexual effect Effects 0.000 claims description 19
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
- 101100240517 Caenorhabditis elegans nhr-11 gene Proteins 0.000 claims description 17
- 241000282414 Homo sapiens Species 0.000 claims description 17
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 17
- 230000015572 biosynthetic process Effects 0.000 claims description 16
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 238000009472 formulation Methods 0.000 claims description 14
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 14
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- 238000006073 displacement reaction Methods 0.000 claims description 13
- 125000004193 piperazinyl group Chemical group 0.000 claims description 13
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 13
- 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 description 11
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 10
- 125000006239 protecting group Chemical group 0.000 claims description 10
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 9
- 239000012351 deprotecting agent Substances 0.000 claims description 9
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 9
- UEYQJQVBUVAELZ-UHFFFAOYSA-N 2-Hydroxynicotinic acid Chemical compound OC(=O)C1=CC=CN=C1O UEYQJQVBUVAELZ-UHFFFAOYSA-N 0.000 claims description 8
- 239000003513 alkali Substances 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
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- 238000005859 coupling reaction Methods 0.000 claims description 7
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- 238000002638 palliative care Methods 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 125000003386 piperidinyl group Chemical group 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
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- 208000027520 Somatoform disease Diseases 0.000 claims description 6
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- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 125000002757 morpholinyl group Chemical group 0.000 claims description 5
- 125000001963 4 membered heterocyclic group Chemical group 0.000 claims description 4
- 206010024419 Libido decreased Diseases 0.000 claims description 4
- 208000006262 Psychological Sexual Dysfunctions Diseases 0.000 claims description 4
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 claims description 4
- 238000009109 curative therapy Methods 0.000 claims description 4
- 208000017020 hypoactive sexual desire disease Diseases 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 229910052698 phosphorus Inorganic materials 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 claims description 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 239000012954 diazonium Substances 0.000 claims description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical group [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 claims description 3
- 230000001404 mediated effect Effects 0.000 claims description 3
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 3
- 125000004423 acyloxy group Chemical group 0.000 claims description 2
- 239000000010 aprotic solvent Substances 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- 230000003301 hydrolyzing effect Effects 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 9
- SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 3
- TVEXGJYMHHTVKP-UHFFFAOYSA-N 6-oxabicyclo[3.2.1]oct-3-en-7-one Chemical compound C1C2C(=O)OC1C=CC2 TVEXGJYMHHTVKP-UHFFFAOYSA-N 0.000 claims 1
- 101150110608 HAT1 gene Proteins 0.000 claims 1
- 101100226116 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) esa-1 gene Proteins 0.000 claims 1
- 241000009298 Trigla lyra Species 0.000 claims 1
- 230000001856 erectile effect Effects 0.000 claims 1
- 125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 claims 1
- 101150009274 nhr-1 gene Proteins 0.000 claims 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 230000000630 rising effect Effects 0.000 claims 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims 1
- 150000003839 salts Chemical class 0.000 abstract description 34
- 206010057671 Female sexual dysfunction Diseases 0.000 abstract description 15
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 abstract description 7
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 abstract description 7
- 238000011282 treatment Methods 0.000 abstract description 7
- 208000010228 Erectile Dysfunction Diseases 0.000 abstract description 5
- 230000003389 potentiating effect Effects 0.000 abstract description 5
- 101100189582 Dictyostelium discoideum pdeD gene Proteins 0.000 abstract 1
- 101150098694 PDE5A gene Proteins 0.000 abstract 1
- 229940124639 Selective inhibitor Drugs 0.000 abstract 1
- 102100029175 cGMP-specific 3',5'-cyclic phosphodiesterase Human genes 0.000 abstract 1
- ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 abstract 1
- 239000012453 solvate Substances 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 306
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 291
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 255
- 229910052739 hydrogen Inorganic materials 0.000 description 185
- 239000000243 solution Substances 0.000 description 172
- 230000002829 reductive effect Effects 0.000 description 129
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 82
- 239000007787 solid Substances 0.000 description 81
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 74
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 72
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 70
- 238000002360 preparation method Methods 0.000 description 64
- 229960001866 silicon dioxide Drugs 0.000 description 63
- 239000000741 silica gel Substances 0.000 description 62
- 229910002027 silica gel Inorganic materials 0.000 description 62
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 60
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 55
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 54
- 239000002585 base Substances 0.000 description 52
- 238000004440 column chromatography Methods 0.000 description 46
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 44
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 38
- 235000019341 magnesium sulphate Nutrition 0.000 description 37
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 36
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- 235000002639 sodium chloride Nutrition 0.000 description 36
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 35
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 34
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 30
- 239000000284 extract Substances 0.000 description 29
- 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 29
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 18
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- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 7
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Classifications
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
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- 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
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Landscapes
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Applications Claiming Priority (2)
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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 |
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OA1200200104A OA12061A (en) | 1999-10-11 | 2000-10-11 | Pyrazolo Ä4,3-DÜpyrimidine derivatives. |
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US7235625B2 (en) | 1999-06-29 | 2007-06-26 | Palatin Technologies, Inc. | Multiple agent therapy for sexual dysfunction |
TWI265925B (en) | 1999-10-11 | 2006-11-11 | Pfizer | Pyrazolo[4,3-d]pyrimidin-7-ones useful in inhibiting type 5 cyclic guanosine 3',5'-monophosphate phosphodiesterases(cGMP PDE5), process and intermediates for their preparation, their uses and composition comprising them |
GB0000561D0 (en) * | 2000-01-11 | 2000-03-01 | Pfizer Ltd | Treatment of diabetic ulcers |
MXPA02010322A (es) * | 2000-04-19 | 2004-09-10 | Univ Johns Hopkins | Metodos para la prevencion y tratamiento de trastornos gastrointestinales. |
US6271228B1 (en) * | 2000-04-28 | 2001-08-07 | Pfizer Inc. | Blood pressure stabilization during hemodialysis |
US6407259B1 (en) | 2000-07-28 | 2002-06-18 | Pfizer Inc. | Process for the preparation of pyrazoles |
EP1176142A1 (en) * | 2000-07-28 | 2002-01-30 | Pfizer Inc. | Process for the preparation of pyrazoles |
US6420557B1 (en) | 2000-07-28 | 2002-07-16 | Pfizer Inc. | Crystalline therapeutic agent |
EE200300045A (et) * | 2000-07-28 | 2004-12-15 | Pfizer Inc. | Kristalne ravimaine |
US6548508B2 (en) | 2000-10-20 | 2003-04-15 | Pfizer, Inc. | Use of PDE V inhibitors for improved fecundity in mammals |
GB0025782D0 (en) * | 2000-10-20 | 2000-12-06 | Pfizer Ltd | Use of inhibitors |
FR2820319B3 (fr) * | 2001-02-08 | 2003-12-05 | Ellipse Pharmaceuticals | Procede de fabrication d'un comprime flottant incluant de l'alfuzosine et comprime obtenu |
DE10135815A1 (de) * | 2001-07-23 | 2003-02-06 | Bayer Ag | Verwendung von 2-Alkoxyphenyl-substituierten Imidazotriazinonen |
AU2003223071A1 (en) * | 2002-05-23 | 2003-12-12 | Pfizer Inc. | Pharmaceutical combination of PDE5 inhibitors with ACE inhibitors |
GB0214784D0 (en) * | 2002-06-26 | 2002-08-07 | Pfizer Ltd | Novel combination |
DE10229778A1 (de) * | 2002-07-03 | 2004-01-29 | Bayer Ag | Neue Verwendung von Imidazotriazinonen |
GB0219961D0 (en) | 2002-08-28 | 2002-10-02 | Pfizer Ltd | Oxytocin inhibitors |
US7323462B2 (en) | 2002-12-10 | 2008-01-29 | Pfizer Inc. | Morpholine dopamine agonists |
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- 2000-10-11 WO PCT/IB2000/001457 patent/WO2001027113A2/en active Application Filing
- 2000-10-11 GE GEAP20005578A patent/GEP20033068B/en unknown
- 2000-10-11 PL PL00357536A patent/PL357536A1/xx not_active Application Discontinuation
- 2000-10-11 SK SK460-2002A patent/SK4602002A3/sk unknown
- 2000-10-11 CZ CZ20021158A patent/CZ20021158A3/cs unknown
- 2000-10-11 KR KR1020027004643A patent/KR100549152B1/ko not_active Expired - Fee Related
- 2000-10-11 AP APAP/P/2002/002456A patent/AP1238A/en active
- 2000-10-11 OA OA1200200104A patent/OA12061A/en unknown
- 2000-10-11 PE PE2000001090A patent/PE20010737A1/es not_active Application Discontinuation
- 2000-10-11 PT PT00966347T patent/PT1220856E/pt unknown
- 2000-10-11 EA EA200200337A patent/EA004982B1/ru not_active IP Right Cessation
- 2000-10-11 AT AT00966347T patent/ATE284404T1/de not_active IP Right Cessation
- 2000-10-11 HR HR20020317A patent/HRP20020317B1/xx not_active IP Right Cessation
- 2000-10-11 DK DK00966347T patent/DK1220856T3/da active
- 2000-10-11 DE DE60016615T patent/DE60016615T2/de not_active Expired - Lifetime
-
2002
- 2002-03-21 CU CU20020060A patent/CU23198A3/es not_active IP Right Cessation
- 2002-03-21 IS IS6320A patent/IS2181B/is unknown
- 2002-03-28 IN IN385MU2002 patent/IN2002MU00385A/en unknown
- 2002-04-05 MA MA26586A patent/MA26825A1/fr unknown
- 2002-04-08 CR CR6617A patent/CR6617A/es not_active Application Discontinuation
- 2002-04-08 IL IL149026A patent/IL149026A/en not_active IP Right Cessation
- 2002-04-10 NO NO20021694A patent/NO322856B1/no not_active IP Right Cessation
- 2002-04-10 MX MXPA02003627 patent/MX228340B/es active IP Right Grant
- 2002-05-09 BG BG106678A patent/BG106678A/bg unknown
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2004
- 2004-01-06 US US10/753,199 patent/US7176311B2/en not_active Expired - Fee Related
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2005
- 2005-01-28 IN IN80MU2005 patent/IN2005MU00080A/en unknown
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2006
- 2006-03-08 IN IN264MU2006 patent/IN2006MU00264A/en unknown
- 2006-08-11 US US11/463,931 patent/US20060293347A1/en not_active Abandoned
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2007
- 2007-04-19 IN IN567MU2007 patent/IN2007MU00567A/en unknown
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2008
- 2008-08-08 CR CR10191A patent/CR10191A/es not_active Application Discontinuation
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2009
- 2009-05-20 US US12/469,311 patent/US20100035891A1/en not_active Abandoned
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