CA2246753C - Non-peptidyl vasopressin v1a antagonists - Google Patents
Non-peptidyl vasopressin v1a antagonists Download PDFInfo
- Publication number
- CA2246753C CA2246753C CA002246753A CA2246753A CA2246753C CA 2246753 C CA2246753 C CA 2246753C CA 002246753 A CA002246753 A CA 002246753A CA 2246753 A CA2246753 A CA 2246753A CA 2246753 C CA2246753 C CA 2246753C
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- amino
- optionally substituted
- phenyl
- hydroxy
- 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
- 239000005557 antagonist Substances 0.000 title description 38
- 108010004977 Vasopressins Proteins 0.000 title description 30
- GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 title description 29
- 102000002852 Vasopressins Human genes 0.000 title description 29
- 229960003726 vasopressin Drugs 0.000 title description 29
- 102000004136 Vasopressin Receptors Human genes 0.000 claims abstract description 16
- 108090000643 Vasopressin Receptors Proteins 0.000 claims abstract description 16
- 230000008485 antagonism Effects 0.000 claims abstract description 9
- RZRRJTZLVKZGRN-UHFFFAOYSA-N 2-(2-oxoazetidin-1-yl)acetic acid Chemical class OC(=O)CN1CCC1=O RZRRJTZLVKZGRN-UHFFFAOYSA-N 0.000 claims abstract description 6
- -1 phenoxyacetyl Chemical group 0.000 claims description 199
- 150000001875 compounds Chemical class 0.000 claims description 180
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 122
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 71
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 62
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 61
- 125000002947 alkylene group Chemical group 0.000 claims description 45
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 43
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 36
- 125000001424 substituent group Chemical group 0.000 claims description 36
- 125000000217 alkyl group Chemical group 0.000 claims description 32
- 239000002253 acid Substances 0.000 claims description 31
- 239000001257 hydrogen Substances 0.000 claims description 30
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 27
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 24
- 229910052736 halogen Inorganic materials 0.000 claims description 24
- 150000002367 halogens Chemical group 0.000 claims description 24
- 238000011282 treatment Methods 0.000 claims description 22
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims description 17
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
- 150000002431 hydrogen Chemical group 0.000 claims description 14
- 125000003386 piperidinyl group Chemical group 0.000 claims description 14
- 125000001624 naphthyl group Chemical group 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 11
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 10
- 125000005518 carboxamido group Chemical group 0.000 claims description 10
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
- 125000004193 piperazinyl group Chemical group 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 8
- 125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 8
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 7
- 125000004423 acyloxy group Chemical group 0.000 claims description 7
- 125000002541 furyl group Chemical group 0.000 claims description 7
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 5
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 125000003368 amide group Chemical group 0.000 claims description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 4
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 4
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000012453 solvate Substances 0.000 claims description 4
- 125000004665 trialkylsilyl group Chemical group 0.000 claims description 4
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 3
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 3
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
- 125000002757 morpholinyl group Chemical group 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 3
- 125000002971 oxazolyl group Chemical group 0.000 claims description 3
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 3
- 125000005544 phthalimido group Chemical group 0.000 claims description 3
- 125000006239 protecting group Chemical group 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- 125000005493 quinolyl group Chemical group 0.000 claims description 3
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 claims description 3
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 3
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 3
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 125000004001 thioalkyl group Chemical group 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 150000004677 hydrates Chemical class 0.000 claims description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 2
- 150000002596 lactones Chemical class 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 16
- 125000001475 halogen functional group Chemical group 0.000 claims 12
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 2
- 125000002252 acyl group Chemical group 0.000 claims 2
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 1
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 1
- 229940124530 sulfonamide Drugs 0.000 claims 1
- 150000003456 sulfonamides Chemical class 0.000 claims 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 54
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 110
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 96
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 76
- 239000000203 mixture Substances 0.000 description 64
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 58
- 230000002829 reductive effect Effects 0.000 description 57
- 239000000243 solution Substances 0.000 description 52
- 239000011541 reaction mixture Substances 0.000 description 48
- 239000007787 solid Substances 0.000 description 45
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 44
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 40
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 39
- 229940093499 ethyl acetate Drugs 0.000 description 36
- 235000019439 ethyl acetate Nutrition 0.000 description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
- 238000006243 chemical reaction Methods 0.000 description 32
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 30
- 210000004027 cell Anatomy 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
- 238000003556 assay Methods 0.000 description 26
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- 238000007792 addition Methods 0.000 description 22
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 22
- 239000003795 chemical substances by application Substances 0.000 description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 21
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 21
- 229920006395 saturated elastomer Polymers 0.000 description 21
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 20
- 238000002360 preparation method Methods 0.000 description 20
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- 229940022663 acetate Drugs 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical compound CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 17
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- 208000002193 Pain Diseases 0.000 description 17
- 230000036407 pain Effects 0.000 description 17
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 16
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 16
- 150000002466 imines Chemical class 0.000 description 16
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 16
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 16
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- 238000012360 testing method Methods 0.000 description 15
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- 239000012131 assay buffer Substances 0.000 description 14
- XNOPRXBHLZRZKH-DSZYJQQASA-N oxytocin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@H](N)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 XNOPRXBHLZRZKH-DSZYJQQASA-N 0.000 description 14
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- 150000008064 anhydrides Chemical class 0.000 description 13
- 239000006260 foam Substances 0.000 description 13
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- 231100000673 dose–response relationship Toxicity 0.000 description 7
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
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- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Heart & Thoracic Surgery (AREA)
- Rheumatology (AREA)
- Immunology (AREA)
- Cardiology (AREA)
- Psychiatry (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pulmonology (AREA)
- Urology & Nephrology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Ultra Sonic Daignosis Equipment (AREA)
- Bidet-Like Cleaning Device And Other Flush Toilet Accessories (AREA)
Applications Claiming Priority (13)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US1214996P | 1996-02-23 | 1996-02-23 | |
| US1218896P | 1996-02-23 | 1996-02-23 | |
| US1221596P | 1996-02-23 | 1996-02-23 | |
| US60/012,149 | 1996-02-23 | ||
| US60/012,188 | 1996-02-23 | ||
| US60/012,215 | 1996-02-23 | ||
| GB9605044.8 | 1996-03-09 | ||
| GB9605045.5 | 1996-03-09 | ||
| GB9605046.3 | 1996-03-09 | ||
| GBGB9605045.5A GB9605045D0 (en) | 1996-03-09 | 1996-03-09 | Method and non-peptidyl agents for modulation of the oxytocin receptor |
| GBGB9605044.8A GB9605044D0 (en) | 1996-03-09 | 1996-03-09 | Method and non-peptidyl agents for modulation of the vasopressin v1a receptor |
| GBGB9605046.3A GB9605046D0 (en) | 1996-03-09 | 1996-03-09 | Method for antagonism of the tachykinin receptor with non-peptide agents |
| PCT/US1997/003039 WO1997030707A1 (en) | 1996-02-23 | 1997-02-20 | NON-PEPTIDYL VASOPRESSIN V1a ANTAGONISTS |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2246753A1 CA2246753A1 (en) | 1997-08-28 |
| CA2246753C true CA2246753C (en) | 2005-05-10 |
Family
ID=27547258
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002246753A Expired - Lifetime CA2246753C (en) | 1996-02-23 | 1997-02-20 | Non-peptidyl vasopressin v1a antagonists |
Country Status (10)
| Country | Link |
|---|---|
| US (3) | US6204260B1 (https=) |
| EP (1) | EP0939632B1 (https=) |
| JP (1) | JP4212112B2 (https=) |
| AT (1) | ATE305781T1 (https=) |
| AU (1) | AU1977997A (https=) |
| CA (1) | CA2246753C (https=) |
| DE (1) | DE69734321T2 (https=) |
| DK (1) | DK0939632T3 (https=) |
| ES (1) | ES2248840T3 (https=) |
| WO (1) | WO1997030707A1 (https=) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2258980T3 (es) | 1999-08-16 | 2006-09-16 | Revaax Pharmaceuticals Llc | Composiciones farmaceuticas que comprenden acido clavulanico o derivados del mismo para el tratamiento de trastornos del comportamiento. |
| US6489319B2 (en) * | 1999-08-16 | 2002-12-03 | Revaax Pharmaceuticals, Llc | Neurotherapeutic use of carboxypeptidase inhibitors |
| US6426342B2 (en) * | 1999-08-16 | 2002-07-30 | Revaax Pharmaceuticals, Llc | Use of β-lactamase inhibitors as neuroprotectants |
| YU32702A (sh) | 1999-11-04 | 2005-06-10 | Ortho-Mcneil Pharmaceutical Inc. | Nepeptidni supstituisani benzotiazepini kao antagonisti vazopresina |
| AR036053A1 (es) | 2001-06-15 | 2004-08-04 | Versicor Inc | Compuestos de n-formil-hidroxilamina, un proceso para su preparacion y composiciones farmaceuticas |
| ES2283589T3 (es) | 2001-06-15 | 2007-11-01 | Vicuron Pharmaceuticals, Inc. | Compuestos biciclicos de pirrolidina. |
| ES2666188T3 (es) * | 2001-10-12 | 2018-05-03 | Azevan Pharmaceuticals, Inc. | Antagonistas del v1a de vasopresina beta-lactámicos |
| AU2002359761A1 (en) * | 2001-12-18 | 2003-06-30 | Invenux, Inc. | Antibiotic compounds |
| KR20120032574A (ko) * | 2002-10-03 | 2012-04-05 | 탈자진 인코포레이티드 | 혈관항상성 유지제 및 그의 사용 방법 |
| US20050282814A1 (en) * | 2002-10-03 | 2005-12-22 | Targegen, Inc. | Vasculostatic agents and methods of use thereof |
| WO2005035492A1 (en) * | 2003-10-03 | 2005-04-21 | Serenix Pharmaceuticals, Llc. | 3-SUBSTITUTED β-LACTAMYL VASOPRESSIN V1A ANTAGONISTS |
| KR20070011458A (ko) * | 2004-04-08 | 2007-01-24 | 탈자진 인코포레이티드 | 키나제의 벤조트리아진 억제제 |
| PL382308A1 (pl) | 2004-08-25 | 2007-08-20 | Targegen, Inc. | Związki heterocykliczne i sposoby stosowania |
| AU2013206201B2 (en) * | 2005-03-22 | 2016-06-16 | Azevan Pharmaceuticals, Inc. | Beta-lactamylalkanoic acids for treating premenstrual disorders |
| AU2006227199A1 (en) * | 2005-03-22 | 2006-09-28 | Azevan Pharmaceuticals, Inc. | Beta-lactamylalkanoic acids for treating premenstrual disorders |
| NZ563984A (en) * | 2005-06-08 | 2011-11-25 | Targegen Inc | Methods and compositions for the treatment of ocular disorders |
| KR101523776B1 (ko) * | 2005-07-19 | 2015-05-28 | 아제반 파마슈티칼스, 인코퍼레이티드 | 베타-락타민 페닐알라닌, 시스테인 그리고 세린 바소프레신길항물질 |
| US8133900B2 (en) * | 2005-11-01 | 2012-03-13 | Targegen, Inc. | Use of bi-aryl meta-pyrimidine inhibitors of kinases |
| CN103626742B (zh) | 2005-11-01 | 2017-04-26 | 塔格根公司 | 激酶的联-芳基间-嘧啶抑制剂 |
| US8604042B2 (en) * | 2005-11-01 | 2013-12-10 | Targegen, Inc. | Bi-aryl meta-pyrimidine inhibitors of kinases |
| US7691858B2 (en) * | 2006-04-25 | 2010-04-06 | Targegen, Inc. | Kinase inhibitors and methods of use thereof |
| WO2008034032A2 (en) * | 2006-09-14 | 2008-03-20 | Azevan Pharmaceuticals, Inc. | Beta-lactam cannabinoid receptor modulators |
| BRPI1013901A2 (pt) * | 2009-04-29 | 2019-09-24 | Rexahn Pharmaceuticals Inc | formulação de clavulanato para neuroproteção e tratamento de distúrbios neurodegenerativos |
| WO2012003436A1 (en) | 2010-07-01 | 2012-01-05 | Azevan Pharmaceuticals, Inc. | Methods for treating post traumatic stress disorder |
| CA2816957A1 (en) | 2010-11-07 | 2012-05-10 | Targegen, Inc. | Compositions and methods for treating myelofibrosis |
| NZ724718A (en) | 2014-03-28 | 2023-04-28 | Azevan Pharmaceuticals Inc | Compositions and methods for treating neurodegenerative diseases |
| WO2019055913A1 (en) | 2017-09-15 | 2019-03-21 | Azevan Pharmaceuticals, Inc. | COMPOSITIONS AND METHODS FOR TREATMENT OF BRAIN INJURY |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4751299A (en) | 1983-11-18 | 1988-06-14 | Takeda Chemical Industries, Ltd. | Optically active β-lactams and method of their production |
| US4665171A (en) | 1985-07-17 | 1987-05-12 | Harvard University | Process and intermediates for β-lactam antibiotics |
| US4673737A (en) | 1985-08-02 | 1987-06-16 | Harvard University | 7-acylamino-(or 7-amino)-3-trifluoromethylsulfonyloxy-1-carba(1-dethia)-3-cephem-4-carboxylic acids and esters thereof |
| DK429986A (da) | 1985-09-09 | 1987-03-10 | Otsuka Pharma Co Ltd | 2-oxa-isocephemforbindelser |
| US4734498A (en) | 1986-07-10 | 1988-03-29 | Eli Lilly And Company | 3β-succinimidoazetidinones as chiral intermediates |
| US4772694A (en) * | 1986-07-24 | 1988-09-20 | Eli Lilly And Company | Chiral 3-(1,2,5-trisubstituted imidazolidinone) azetidinone antibiotic intermediates |
| DK123488A (da) | 1987-03-09 | 1988-09-10 | Otsuka Pharma Co Ltd | 2-oxa-isocephemforbindelser, praeparater indeholdende dem, og fremgangsmaader til fremstilling af dem |
| US5373089A (en) | 1988-09-02 | 1994-12-13 | Northwestern University | Oxytocin antagonist |
| US5068232A (en) | 1990-04-10 | 1991-11-26 | American Cyanamid Company | Novel 2-substituted alkyl-3-carboxy carbapenems as antibiotics and a method of producing them |
| US5521307A (en) * | 1992-02-18 | 1996-05-28 | Eli Lilly And Company | Methods and compounds for the preparation of carbacephems |
| AU5587594A (en) * | 1992-10-27 | 1994-05-24 | Merck & Co., Inc. | New substituted azetidinones as anti-inflammatory and antidegenerative agents |
| US5631365A (en) * | 1993-09-21 | 1997-05-20 | Schering Corporation | Hydroxy-substituted azetidinone compounds useful as hypocholesterolemic agents |
| WO1996016333A1 (en) * | 1994-11-23 | 1996-05-30 | Affymax Technologies, N.V. | METHODS FOR SYNTHESIZING DIVERSE COLLECTIONS OF β-LACTAM COMPOUNDS |
| JPH11503728A (ja) * | 1995-03-31 | 1999-03-30 | シンファー ラボラトリーズ，インコーポレーティッド | システイン・プロテイナーゼ阻害剤として有用な新規な４−置換−３−ペプチジル−アゼチジン−２−オン誘導体 |
| AU5487496A (en) * | 1995-05-03 | 1996-11-21 | Eli Lilly And Company | Combinatorial process for synthesizing azetidinone analogs |
-
1997
- 1997-02-20 EP EP97907895A patent/EP0939632B1/en not_active Expired - Lifetime
- 1997-02-20 CA CA002246753A patent/CA2246753C/en not_active Expired - Lifetime
- 1997-02-20 DK DK97907895T patent/DK0939632T3/da active
- 1997-02-20 WO PCT/US1997/003039 patent/WO1997030707A1/en not_active Ceased
- 1997-02-20 AU AU19779/97A patent/AU1977997A/en not_active Abandoned
- 1997-02-20 US US09/125,737 patent/US6204260B1/en not_active Expired - Lifetime
- 1997-02-20 ES ES97907895T patent/ES2248840T3/es not_active Expired - Lifetime
- 1997-02-20 DE DE69734321T patent/DE69734321T2/de not_active Expired - Lifetime
- 1997-02-20 JP JP52964797A patent/JP4212112B2/ja not_active Expired - Lifetime
- 1997-02-20 AT AT97907895T patent/ATE305781T1/de active
-
2000
- 2000-12-08 US US09/733,430 patent/US6521611B2/en not_active Expired - Lifetime
-
2002
- 2002-12-20 US US10/327,240 patent/US6610680B1/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| EP0939632A4 (en) | 2002-09-25 |
| US20020049187A1 (en) | 2002-04-25 |
| EP0939632B1 (en) | 2005-10-05 |
| DE69734321D1 (de) | 2006-02-16 |
| ES2248840T3 (es) | 2006-03-16 |
| DK0939632T3 (da) | 2006-01-30 |
| US6610680B1 (en) | 2003-08-26 |
| ATE305781T1 (de) | 2005-10-15 |
| US6204260B1 (en) | 2001-03-20 |
| JP4212112B2 (ja) | 2009-01-21 |
| EP0939632A1 (en) | 1999-09-08 |
| JP2000504731A (ja) | 2000-04-18 |
| US6521611B2 (en) | 2003-02-18 |
| AU1977997A (en) | 1997-09-10 |
| DE69734321T2 (de) | 2006-08-10 |
| CA2246753A1 (en) | 1997-08-28 |
| WO1997030707A1 (en) | 1997-08-28 |
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