CA2165192C - Fluoroalkoxy-substituted benzamides and their use as cyclic nucleotide phosphodiesterase inhibitors - Google Patents
Fluoroalkoxy-substituted benzamides and their use as cyclic nucleotide phosphodiesterase inhibitors Download PDFInfo
- Publication number
- CA2165192C CA2165192C CA002165192A CA2165192A CA2165192C CA 2165192 C CA2165192 C CA 2165192C CA 002165192 A CA002165192 A CA 002165192A CA 2165192 A CA2165192 A CA 2165192A CA 2165192 C CA2165192 C CA 2165192C
- Authority
- CA
- Canada
- Prior art keywords
- halogen
- alkoxy
- alkyl
- hydrogen
- compound
- 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
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- 239000002571 phosphodiesterase inhibitor Substances 0.000 title description 6
- 229940054066 benzamide antipsychotics Drugs 0.000 title description 5
- 150000003936 benzamides Chemical class 0.000 title description 5
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 title description 5
- 101000909851 Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) cAMP/cGMP dual specificity phosphodiesterase Rv0805 Proteins 0.000 title description 3
- -1 cyano, carboxyl Chemical group 0.000 claims abstract description 173
- 150000001875 compounds Chemical class 0.000 claims abstract description 78
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 71
- 150000002367 halogens Chemical class 0.000 claims abstract description 71
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 60
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 51
- 239000001257 hydrogen Substances 0.000 claims abstract description 51
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 28
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 23
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 21
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 18
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims abstract description 17
- 239000003814 drug Substances 0.000 claims abstract description 14
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 14
- 125000001424 substituent group Chemical group 0.000 claims abstract description 3
- 150000003839 salts Chemical class 0.000 claims description 57
- 229910052731 fluorine Inorganic materials 0.000 claims description 26
- 239000011737 fluorine Substances 0.000 claims description 26
- 125000001153 fluoro group Chemical group F* 0.000 claims description 25
- 238000011282 treatment Methods 0.000 claims description 22
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- 238000000034 method Methods 0.000 claims description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- 208000035475 disorder Diseases 0.000 claims description 12
- SCEVBRBKKQZTKM-UHFFFAOYSA-N 5-[[6-chloro-5-(1-methylindol-5-yl)-1H-benzimidazol-2-yl]oxy]-N-hydroxy-2-methylbenzamide Chemical compound ClC=1C(=CC2=C(NC(=N2)OC=2C=CC(=C(C(=O)NO)C=2)C)C=1)C=1C=C2C=CN(C2=CC=1)C SCEVBRBKKQZTKM-UHFFFAOYSA-N 0.000 claims description 9
- APJAEXGNDLFGPD-AWCRTANDSA-N 3-amino-n-{4-[2-(2,6-dimethyl-phenoxy)-acetylamino]-3-hydroxy-1-isobutyl-5-phenyl-pentyl}-benzamide Chemical compound C([C@@H]([C@@H](O)C[C@H](CC(C)C)NC(=O)C=1C=CC(N)=CC=1)NC(=O)COC=1C(=CC=CC=1C)C)C1=CC=CC=C1 APJAEXGNDLFGPD-AWCRTANDSA-N 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 8
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- KLIDCXVFHGNTTM-UHFFFAOYSA-N 2,6-dimethoxyphenol Chemical group COC1=CC=CC(OC)=C1O KLIDCXVFHGNTTM-UHFFFAOYSA-N 0.000 claims description 6
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
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- WQUBEIMCFHCJCO-AWCRTANDSA-N 4-amino-n-{4-[2-(2,6-dimethyl-phenoxy)-acetylamino]-3-hydroxy-1-isobutyl-5-phenyl-pentyl}-benzamide Chemical compound C([C@@H]([C@@H](O)C[C@H](CC(C)C)NC(=O)C=1C=C(N)C=CC=1)NC(=O)COC=1C(=CC=CC=1C)C)C1=CC=CC=C1 WQUBEIMCFHCJCO-AWCRTANDSA-N 0.000 claims description 3
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- 229940079593 drug Drugs 0.000 abstract 1
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- 239000002253 acid Substances 0.000 description 12
- 239000003921 oil Substances 0.000 description 11
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- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 8
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
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- ZCNMBDBEKFFBGL-UHFFFAOYSA-N 3-(cyclobutylmethoxy)-4-(difluoromethoxy)benzoic acid Chemical compound OC(=O)C1=CC=C(OC(F)F)C(OCC2CCC2)=C1 ZCNMBDBEKFFBGL-UHFFFAOYSA-N 0.000 description 2
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- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 2
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- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000009121 systemic therapy Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 210000000626 ureter Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C235/56—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Hydrogenated Pyridines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicinal Preparation (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1996/93-9 | 1993-07-02 | ||
| CH199693 | 1993-07-02 | ||
| PCT/EP1994/002169 WO1995001338A1 (de) | 1993-07-02 | 1994-07-02 | Fluoralkoxy substituierte benzamide und ihre verwendung als zyklisch-nukleotid phosphodiesterase-inhibitoren |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2165192A1 CA2165192A1 (en) | 1995-01-12 |
| CA2165192C true CA2165192C (en) | 2001-04-24 |
Family
ID=4223466
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002165192A Expired - Lifetime CA2165192C (en) | 1993-07-02 | 1994-07-02 | Fluoroalkoxy-substituted benzamides and their use as cyclic nucleotide phosphodiesterase inhibitors |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US5712298A (enExample) |
| EP (1) | EP0706513B1 (enExample) |
| JP (1) | JP3093271B2 (enExample) |
| KR (1) | KR100331255B1 (enExample) |
| CN (1) | CN1046939C (enExample) |
| AT (1) | ATE217612T1 (enExample) |
| AU (1) | AU687087B2 (enExample) |
| CA (1) | CA2165192C (enExample) |
| CY (2) | CY2389B1 (enExample) |
| CZ (1) | CZ290266B6 (enExample) |
| DE (2) | DE59410119D1 (enExample) |
| DK (1) | DK0706513T3 (enExample) |
| ES (1) | ES2176252T3 (enExample) |
| FI (1) | FI112864B (enExample) |
| FR (1) | FR10C0052I2 (enExample) |
| HU (1) | HU220041B (enExample) |
| LU (1) | LU91709I2 (enExample) |
| LV (1) | LV13074B (enExample) |
| NO (2) | NO305598B1 (enExample) |
| NZ (1) | NZ271316A (enExample) |
| PL (1) | PL178314B1 (enExample) |
| PT (1) | PT706513E (enExample) |
| RU (1) | RU2137754C1 (enExample) |
| SG (1) | SG143011A1 (enExample) |
| SI (1) | SI0706513T1 (enExample) |
| SK (1) | SK283263B6 (enExample) |
| WO (1) | WO1995001338A1 (enExample) |
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| US6096768A (en) * | 1992-01-28 | 2000-08-01 | Rhone-Poulenc Rorer Limited | Compounds containing phenyl linked to aryl or heteroaryl by an aliphatic- or heteroatom-containing linking group |
| AU6526896A (en) * | 1995-07-22 | 1997-02-18 | Rhone-Poulenc Rorer Limited | Substituted aromatic compounds and their pharmaceutical use |
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| EP0941086A4 (en) * | 1996-11-01 | 2000-07-12 | Nitromed Inc | NITROSIZED AND NITROSYLATED PHOSPHODIESTERASE INHIBITING COMPOUNDS, COMPOSITIONS AND THEIR USE |
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