CA2339189A1 - Nitrosated and nitrosylated phosphodiesterase inhibitors, compositions and methods of use - Google Patents
Nitrosated and nitrosylated phosphodiesterase inhibitors, compositions and methods of use Download PDFInfo
- Publication number
- CA2339189A1 CA2339189A1 CA002339189A CA2339189A CA2339189A1 CA 2339189 A1 CA2339189 A1 CA 2339189A1 CA 002339189 A CA002339189 A CA 002339189A CA 2339189 A CA2339189 A CA 2339189A CA 2339189 A1 CA2339189 A1 CA 2339189A1
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- CA
- Canada
- Prior art keywords
- nitrosated
- nitrosylated
- compound
- group
- formula
- 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.)
- Abandoned
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- 238000000034 method Methods 0.000 title claims abstract description 200
- 239000000203 mixture Substances 0.000 title claims abstract description 79
- 239000002571 phosphodiesterase inhibitor Substances 0.000 title claims abstract description 61
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 title abstract description 17
- 150000001875 compounds Chemical class 0.000 claims abstract description 217
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 55
- 201000010099 disease Diseases 0.000 claims abstract description 41
- 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 30
- 201000001880 Sexual dysfunction Diseases 0.000 claims abstract description 21
- 231100000872 sexual dysfunction Toxicity 0.000 claims abstract description 21
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims description 242
- 125000003118 aryl group Chemical group 0.000 claims description 148
- 239000002253 acid Substances 0.000 claims description 136
- 125000000217 alkyl group Chemical group 0.000 claims description 136
- -1 aryl carboxylic acid Chemical class 0.000 claims description 127
- 150000002148 esters Chemical class 0.000 claims description 116
- 239000001257 hydrogen Substances 0.000 claims description 110
- 229910052739 hydrogen Inorganic materials 0.000 claims description 110
- 239000003795 chemical substances by application Substances 0.000 claims description 86
- 150000002431 hydrogen Chemical class 0.000 claims description 80
- 229910052702 rhenium Inorganic materials 0.000 claims description 72
- 150000002367 halogens Chemical class 0.000 claims description 63
- 229910052736 halogen Inorganic materials 0.000 claims description 62
- 239000004215 Carbon black (E152) Substances 0.000 claims description 60
- 125000003545 alkoxy group Chemical group 0.000 claims description 60
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 60
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 57
- 230000015572 biosynthetic process Effects 0.000 claims description 55
- 229920006395 saturated elastomer Polymers 0.000 claims description 55
- 125000000623 heterocyclic group Chemical group 0.000 claims description 54
- ICRHORQIUXBEPA-UHFFFAOYSA-N thionitrous acid Chemical compound SN=O ICRHORQIUXBEPA-UHFFFAOYSA-N 0.000 claims description 52
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 50
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 48
- 229940099471 Phosphodiesterase inhibitor Drugs 0.000 claims description 46
- 125000005518 carboxamido group Chemical group 0.000 claims description 43
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 41
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 claims description 40
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 40
- 229910052760 oxygen Inorganic materials 0.000 claims description 39
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 38
- 239000001301 oxygen Substances 0.000 claims description 38
- 239000000066 endothelium dependent relaxing factor Substances 0.000 claims description 37
- 238000012546 transfer Methods 0.000 claims description 37
- 102000008299 Nitric Oxide Synthase Human genes 0.000 claims description 36
- 108010021487 Nitric Oxide Synthase Proteins 0.000 claims description 36
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 36
- 239000000758 substrate Substances 0.000 claims description 36
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 34
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 33
- 238000004519 manufacturing process Methods 0.000 claims description 32
- 125000005596 alkyl carboxamido group Chemical group 0.000 claims description 31
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- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 26
- 125000005533 aryl carboxamido group Chemical group 0.000 claims description 26
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- 229930195733 hydrocarbon Natural products 0.000 claims description 18
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- 125000000747 amidyl group Chemical group [H][N-]* 0.000 claims description 17
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- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 13
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- 125000005343 heterocyclic alkyl group Chemical group 0.000 claims description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
- ZRHUHDUEXWHZMA-UHFFFAOYSA-N 1,4-dihydropyrazol-5-one Chemical class O=C1CC=NN1 ZRHUHDUEXWHZMA-UHFFFAOYSA-N 0.000 claims description 12
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- KJMFQJFNQYWQAV-UHFFFAOYSA-N 3h-imidazo[4,5-h]quinazoline Chemical class C1=NC=NC2=C(NC=N3)C3=CC=C21 KJMFQJFNQYWQAV-UHFFFAOYSA-N 0.000 claims description 9
- 239000007926 intracavernous injection Substances 0.000 claims description 9
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Classifications
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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
- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
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- Heart & Thoracic Surgery (AREA)
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- Endocrinology (AREA)
- Biomedical Technology (AREA)
- Reproductive Health (AREA)
- Neurology (AREA)
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- Vascular Medicine (AREA)
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- Rheumatology (AREA)
- Gynecology & Obstetrics (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/145,142 US5958926A (en) | 1996-11-01 | 1998-09-01 | Nitrosated and nitrosylated phosphodiesterase inhibitor compounds, compositions and their uses |
| US09/145,142 | 1998-09-01 | ||
| PCT/US1999/020024 WO2000012076A1 (en) | 1998-09-01 | 1999-09-01 | Nitrosated and nitrosylated phosphodiesterase inhibitors, compositions and methods of use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2339189A1 true CA2339189A1 (en) | 2000-03-09 |
Family
ID=22511772
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002339189A Abandoned CA2339189A1 (en) | 1998-09-01 | 1999-09-01 | Nitrosated and nitrosylated phosphodiesterase inhibitors, compositions and methods of use |
Country Status (6)
| Country | Link |
|---|---|
| US (11) | US5958926A (enExample) |
| EP (1) | EP1109543A4 (enExample) |
| JP (1) | JP2002523450A (enExample) |
| AU (1) | AU773269B2 (enExample) |
| CA (1) | CA2339189A1 (enExample) |
| WO (1) | WO2000012076A1 (enExample) |
Families Citing this family (59)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5645839A (en) * | 1995-06-07 | 1997-07-08 | Trustees Of Boston University | Combined use of angiotensin inhibitors and nitric oxide stimulators to treat fibrosis |
| US6331543B1 (en) * | 1996-11-01 | 2001-12-18 | Nitromed, Inc. | Nitrosated and nitrosylated phosphodiesterase inhibitors, compositions and methods of use |
| US5958926A (en) | 1996-11-01 | 1999-09-28 | Nitromed, Inc. | Nitrosated and nitrosylated phosphodiesterase inhibitor compounds, compositions and their uses |
| AU740758B2 (en) * | 1997-10-28 | 2001-11-15 | Vivus, Inc. | Treatment of female sexual dysfunction |
| US6472425B1 (en) | 1997-10-31 | 2002-10-29 | Nitromed, Inc. | Methods for treating female sexual dysfunctions |
| IT1301759B1 (it) * | 1998-06-19 | 2000-07-07 | Nicox Sa | Sali nitrati di farmaci antiipertensivi |
| IL132460A0 (en) * | 1999-10-19 | 2001-03-19 | Laniado Shlomo | Sildenafil preparation |
| IL139456A0 (en) | 1999-11-08 | 2001-11-25 | Pfizer | Compounds for the treatment of female sexual dysfunction |
| US20040254153A1 (en) * | 1999-11-08 | 2004-12-16 | Pfizer Inc | Compounds for the treatment of female sexual dysfunction |
| GB0000561D0 (en) * | 2000-01-11 | 2000-03-01 | Pfizer Ltd | Treatment of diabetic ulcers |
| US6476037B1 (en) * | 2000-03-23 | 2002-11-05 | The Regents Of The University Of California | L-arginine and phosphodiesterase (PDE) inhibitor synergism |
| CA2417552C (en) | 2000-06-27 | 2014-05-13 | Qualilife Pharmaceuticals Inc. | Compositions and methods for treating females sexual response |
| IT1318673B1 (it) * | 2000-08-08 | 2003-08-27 | Nicox Sa | Farmaci per le disfunzioni sessuali. |
| US6953774B2 (en) * | 2000-08-11 | 2005-10-11 | Applied Research Systems Ars Holding N.V. | Methods of inducing ovulation |
| US6821978B2 (en) | 2000-09-19 | 2004-11-23 | Schering Corporation | Xanthine phosphodiesterase V inhibitors |
| CA2425489C (en) * | 2000-10-16 | 2011-05-17 | Duke University | Therapeutic use of aerosolized s-nitrosoglutathione in cystic fibrosis |
| MXPA03007960A (es) * | 2001-03-06 | 2003-12-04 | Cellegy Pharma Inc | Compuestos y metodos para el tratamiento de desordenes urogenitales. |
| EP1408757A4 (en) * | 2001-07-02 | 2006-12-27 | Wisconsin Alumni Res Found | METHOD AND COMPOSITION FOR EXTENDING DRUG STAY TIME IN INTESTINE |
| US6444237B1 (en) | 2001-09-13 | 2002-09-03 | Pamela A. Heleen | Herbal composition for enhancing sexual response |
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| US6177428B1 (en) | 2001-01-23 |
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| EP1109543A4 (en) | 2006-03-08 |
| JP2002523450A (ja) | 2002-07-30 |
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