CA2936338A1 - (r)-3-((3s,4s)-3-fluoro-4-(4-hydroxyphenyl)piperidin-1-yl)-1-(4-methylbenzyl)pyrrolidin-2-one and its prodrugs for the treatment of psychiatric disorders - Google Patents
(r)-3-((3s,4s)-3-fluoro-4-(4-hydroxyphenyl)piperidin-1-yl)-1-(4-methylbenzyl)pyrrolidin-2-one and its prodrugs for the treatment of psychiatric disorders Download PDFInfo
- Publication number
- CA2936338A1 CA2936338A1 CA2936338A CA2936338A CA2936338A1 CA 2936338 A1 CA2936338 A1 CA 2936338A1 CA 2936338 A CA2936338 A CA 2936338A CA 2936338 A CA2936338 A CA 2936338A CA 2936338 A1 CA2936338 A1 CA 2936338A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- mmol
- piperidin
- alkyl
- fluoro
- 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
Links
- 229940002612 prodrug Drugs 0.000 title claims description 10
- 239000000651 prodrug Substances 0.000 title claims description 10
- 208000020016 psychiatric disease Diseases 0.000 title description 2
- UNVYDSCXINFREZ-BHDDXSALSA-N (3R)-3-[(3S,4S)-3-fluoro-4-(4-hydroxyphenyl)piperidin-1-yl]-1-[(4-methylphenyl)methyl]pyrrolidin-2-one Chemical compound F[C@@H]1CN(CC[C@H]1C1=CC=C(C=C1)O)[C@H]1C(N(CC1)CC1=CC=C(C=C1)C)=O UNVYDSCXINFREZ-BHDDXSALSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 62
- 238000000034 method Methods 0.000 claims abstract description 21
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- -1 amino acid esters Chemical group 0.000 claims description 29
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 125000005907 alkyl ester group Chemical group 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 125000001475 halogen functional group Chemical group 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 4
- 125000001188 haloalkyl group Chemical group 0.000 claims description 4
- 150000003009 phosphonic acids Chemical group 0.000 claims description 4
- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical class NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 208000004296 neuralgia Diseases 0.000 claims description 3
- 208000021722 neuropathic pain Diseases 0.000 claims description 3
- 208000018737 Parkinson disease Diseases 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims description 2
- 125000002393 azetidinyl group Chemical group 0.000 claims description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 2
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 208000020401 Depressive disease Diseases 0.000 claims 2
- ZPUVTBAQHJFPHE-BHDDXSALSA-N [4-[(3S,4S)-3-fluoro-1-[(3R)-1-[(4-methylphenyl)methyl]-2-oxopyrrolidin-3-yl]piperidin-4-yl]phenyl] dihydrogen phosphate Chemical compound P(=O)(OC1=CC=C(C=C1)[C@H]1[C@@H](CN(CC1)[C@H]1C(N(CC1)CC1=CC=C(C=C1)C)=O)F)(O)O ZPUVTBAQHJFPHE-BHDDXSALSA-N 0.000 claims 2
- BYFQSSVDKAZZCU-BEDMTGONSA-N (2S)-2-amino-4-[4-[(3S,4S)-3-fluoro-1-[(3R)-1-[(4-methylphenyl)methyl]-2-oxopyrrolidin-3-yl]piperidin-4-yl]phenoxy]-4-oxobutanoic acid hydrochloride Chemical compound Cl.N[C@H](C(=O)O)CC(=O)OC1=CC=C(C=C1)[C@H]1[C@@H](CN(CC1)[C@H]1C(N(CC1)CC1=CC=C(C=C1)C)=O)F BYFQSSVDKAZZCU-BEDMTGONSA-N 0.000 claims 1
- AHEPHJOEWHVSSS-BKZZESQVSA-N [4-[(3S,4S)-3-fluoro-1-[(3R)-1-[(4-methylphenyl)methyl]-2-oxopyrrolidin-3-yl]piperidin-4-yl]phenyl] (2S)-2-amino-3-methylbutanoate hydrochloride Chemical compound Cl.N[C@H](C(=O)OC1=CC=C(C=C1)[C@H]1[C@@H](CN(CC1)[C@H]1C(N(CC1)CC1=CC=C(C=C1)C)=O)F)C(C)C AHEPHJOEWHVSSS-BKZZESQVSA-N 0.000 claims 1
- IBBDQKGDANXVOA-CXWZADJDSA-N [4-[(3S,4S)-3-fluoro-1-[(3R)-1-[(4-methylphenyl)methyl]-2-oxopyrrolidin-3-yl]piperidin-4-yl]phenyl] (2S)-2-aminopropanoate hydrochloride Chemical compound Cl.N[C@H](C(=O)OC1=CC=C(C=C1)[C@H]1[C@@H](CN(CC1)[C@H]1C(N(CC1)CC1=CC=C(C=C1)C)=O)F)C IBBDQKGDANXVOA-CXWZADJDSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 31
- 210000003169 central nervous system Anatomy 0.000 abstract description 6
- 239000003446 ligand Substances 0.000 abstract description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 3
- 108010054200 NR2B NMDA receptor Proteins 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 73
- 239000000243 solution Substances 0.000 description 57
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 43
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- 239000000543 intermediate Substances 0.000 description 41
- 239000011541 reaction mixture Substances 0.000 description 39
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 38
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 38
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 36
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 34
- 239000002904 solvent Substances 0.000 description 33
- 238000005160 1H NMR spectroscopy Methods 0.000 description 26
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 24
- 239000000047 product Substances 0.000 description 23
- 239000007787 solid Substances 0.000 description 23
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- 239000012043 crude product Substances 0.000 description 20
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 20
- 239000012044 organic layer Substances 0.000 description 20
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 16
- 239000003814 drug Substances 0.000 description 16
- 239000010410 layer Substances 0.000 description 16
- 229940079593 drug Drugs 0.000 description 15
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 13
- 102100022630 Glutamate receptor ionotropic, NMDA 2B Human genes 0.000 description 12
- 108010038912 Retinoid X Receptors Proteins 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 10
- 241001465754 Metazoa Species 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
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- 230000027455 binding Effects 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 238000010898 silica gel chromatography Methods 0.000 description 10
- 229910052938 sodium sulfate Inorganic materials 0.000 description 10
- 235000011152 sodium sulphate Nutrition 0.000 description 10
- 238000003556 assay Methods 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 239000012528 membrane Substances 0.000 description 9
- 238000004808 supercritical fluid chromatography Methods 0.000 description 9
- 238000004293 19F NMR spectroscopy Methods 0.000 description 8
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 7
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 7
- 239000008186 active pharmaceutical agent Substances 0.000 description 7
- 210000004556 brain Anatomy 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 108091006146 Channels Proteins 0.000 description 6
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- 235000001014 amino acid Nutrition 0.000 description 6
- 229940024606 amino acid Drugs 0.000 description 6
- 238000012048 forced swim test Methods 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 6
- 210000002381 plasma Anatomy 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 229910052796 boron Inorganic materials 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000004108 freeze drying Methods 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- CMPQUABWPXYYSH-UHFFFAOYSA-N phenyl phosphate Chemical compound OP(O)(=O)OC1=CC=CC=C1 CMPQUABWPXYYSH-UHFFFAOYSA-N 0.000 description 5
- 238000004007 reversed phase HPLC Methods 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000000935 antidepressant agent Substances 0.000 description 4
- 229940005513 antidepressants Drugs 0.000 description 4
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- 150000003951 lactams Chemical class 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- QEJCHYKXNFQQSM-QMMMGPOBSA-N (3s)-3-[tert-butyl(dimethyl)silyl]oxypyrrolidin-2-one Chemical compound CC(C)(C)[Si](C)(C)O[C@H]1CCNC1=O QEJCHYKXNFQQSM-QMMMGPOBSA-N 0.000 description 3
- SKGCWFWNKKTPSN-UHFFFAOYSA-N 2,4-dibromo-n-[(4-fluorophenyl)methyl]butanamide Chemical compound FC1=CC=C(CNC(=O)C(Br)CCBr)C=C1 SKGCWFWNKKTPSN-UHFFFAOYSA-N 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
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- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 3
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- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 3
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- 238000001914 filtration Methods 0.000 description 3
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- 239000012535 impurity Substances 0.000 description 3
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- NCFGJGLKTINFDI-UHFFFAOYSA-N phenyl 2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound CC(C)(C)OC(=O)NC(C)C(=O)OC1=CC=CC=C1 NCFGJGLKTINFDI-UHFFFAOYSA-N 0.000 description 3
- HCRMTRJXSDDOIK-UHFFFAOYSA-N phenyl 2-aminopropanoate Chemical compound CC(N)C(=O)OC1=CC=CC=C1 HCRMTRJXSDDOIK-UHFFFAOYSA-N 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
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- GSBRQFAQWICXFO-UONOGXRCSA-N tert-butyl (3S,4S)-3-fluoro-4-(4-hydroxyphenyl)piperidine-1-carboxylate Chemical compound F[C@@H]1CN(CC[C@H]1C1=CC=C(C=C1)O)C(=O)OC(C)(C)C GSBRQFAQWICXFO-UONOGXRCSA-N 0.000 description 3
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- 238000004679 31P NMR spectroscopy Methods 0.000 description 2
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- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D401/02—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 containing two hetero rings
- C07D401/04—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 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/59—Hydrogenated pyridine rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201461925405P | 2014-01-09 | 2014-01-09 | |
| US61/925,405 | 2014-01-09 | ||
| PCT/US2015/010552 WO2015105929A1 (en) | 2014-01-09 | 2015-01-08 | (r)-3-((3s,4s)-3-fluoro-4-(4-hydroxyphenyl)piperidin-1-yl)-1-(4-methylbenzyl)pyrrolidin-2-one and its prodrugs for the treatment of psychiatric disorders |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2936338A1 true CA2936338A1 (en) | 2015-07-16 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2936338A Abandoned CA2936338A1 (en) | 2014-01-09 | 2015-01-08 | (r)-3-((3s,4s)-3-fluoro-4-(4-hydroxyphenyl)piperidin-1-yl)-1-(4-methylbenzyl)pyrrolidin-2-one and its prodrugs for the treatment of psychiatric disorders |
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| EP (2) | EP3677578A1 (enExample) |
| JP (1) | JP6629738B2 (enExample) |
| KR (1) | KR102331120B1 (enExample) |
| AR (1) | AR102019A1 (enExample) |
| AU (1) | AU2015204785A1 (enExample) |
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| EA (1) | EA201691133A1 (enExample) |
| ES (1) | ES2771825T3 (enExample) |
| HR (1) | HRP20200161T1 (enExample) |
| HU (1) | HUE048750T2 (enExample) |
| IL (1) | IL246596A0 (enExample) |
| LT (1) | LT3092223T (enExample) |
| MX (1) | MX2016008715A (enExample) |
| PE (1) | PE20160898A1 (enExample) |
| PL (1) | PL3092223T3 (enExample) |
| PT (1) | PT3092223T (enExample) |
| RS (1) | RS59858B1 (enExample) |
| SG (1) | SG11201605620QA (enExample) |
| SI (1) | SI3092223T1 (enExample) |
| SM (1) | SMT202000094T1 (enExample) |
| TW (1) | TW201612169A (enExample) |
| UY (1) | UY35946A (enExample) |
| WO (1) | WO2015105929A1 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US9187506B2 (en) * | 2014-01-09 | 2015-11-17 | Bristol-Myers Squibb Company | (R)-3-((3S,4S)-3-fluoro-4-(4-hydroxyphenyl)piperidin-1-yl)-1-(4-methylbenzyl)pyrrolidin-2-one and its prodrugs for the treatment of psychiatric disorders |
| AU2016340237A1 (en) * | 2015-10-14 | 2018-05-31 | Bristol-Myers Squibb Company | Selective NR2B antagonists |
| CA3001894A1 (en) | 2015-10-14 | 2017-04-20 | Bristol-Myers Squibb Company | Selective nr2b antagonists |
| CA3096145A1 (en) * | 2019-10-11 | 2021-04-11 | Royal Bank Of Canada | System and method of machine learning using embedding networks |
| WO2024197289A1 (en) * | 2023-03-22 | 2024-09-26 | Gilgamesh Pharmaceuticals, Inc. | Negative allosteric modulators of glun2b receptors and methods of making and using the same |
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| US6476041B1 (en) | 1999-10-29 | 2002-11-05 | Merck & Co., Inc. | 1,4 substituted piperidinyl NMDA/NR2B antagonists |
| ATE337292T1 (de) | 2000-04-26 | 2006-09-15 | Warner Lambert Co | Trans-n- 4-(4-hydroxyphenyl)cyclohexylö-3- phenylpropionamid als subtyp-selektiver nmda rezeptor antagonist |
| WO2003035641A1 (en) | 2001-10-22 | 2003-05-01 | Shionogi & Co., Ltd. | Novel carbamoylpyrrolidone derivative |
| CN1798744A (zh) | 2003-06-04 | 2006-07-05 | 麦克公司 | 作为nmda/nr2b拮抗剂的3－氟－哌啶化合物 |
| BRPI0415113A (pt) | 2003-10-08 | 2006-11-28 | Pfizer | compostos de lactama condensados |
| US7935706B2 (en) | 2006-02-23 | 2011-05-03 | Shionogi & Co., Ltd. | Nitrogen-containing heterocycle derivatives substituted with cyclic group |
| EP2170334B1 (en) | 2007-06-29 | 2021-03-17 | Emory University | Nmda receptor antagonists for neuroprotection |
| WO2009064747A2 (en) * | 2007-11-13 | 2009-05-22 | Vertex Pharmaceuticals Incorporated | 4(-3-(-2-(phenyl)morpholino)-2-oxopyrrolidin-1-yl)-n-(thiazol-2-yl)benzenesulfonamide derivati ves and related compounds as modulators of ion channels for the treatment of pain |
| US9187506B2 (en) * | 2014-01-09 | 2015-11-17 | Bristol-Myers Squibb Company | (R)-3-((3S,4S)-3-fluoro-4-(4-hydroxyphenyl)piperidin-1-yl)-1-(4-methylbenzyl)pyrrolidin-2-one and its prodrugs for the treatment of psychiatric disorders |
-
2015
- 2015-01-07 US US14/591,372 patent/US9187506B2/en active Active
- 2015-01-08 PE PE2016001105A patent/PE20160898A1/es unknown
- 2015-01-08 WO PCT/US2015/010552 patent/WO2015105929A1/en not_active Ceased
- 2015-01-08 DK DK15702312.8T patent/DK3092223T3/da active
- 2015-01-08 SG SG11201605620QA patent/SG11201605620QA/en unknown
- 2015-01-08 PT PT157023128T patent/PT3092223T/pt unknown
- 2015-01-08 SI SI201531064T patent/SI3092223T1/sl unknown
- 2015-01-08 RS RS20200109A patent/RS59858B1/sr unknown
- 2015-01-08 CA CA2936338A patent/CA2936338A1/en not_active Abandoned
- 2015-01-08 JP JP2016545818A patent/JP6629738B2/ja not_active Expired - Fee Related
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- 2015-01-08 AU AU2015204785A patent/AU2015204785A1/en not_active Abandoned
- 2015-01-08 EP EP19212924.5A patent/EP3677578A1/en not_active Withdrawn
- 2015-01-08 KR KR1020167021355A patent/KR102331120B1/ko not_active Expired - Fee Related
- 2015-01-08 HU HUE15702312A patent/HUE048750T2/hu unknown
- 2015-01-08 ES ES15702312T patent/ES2771825T3/es active Active
- 2015-01-08 HR HRP20200161TT patent/HRP20200161T1/hr unknown
- 2015-01-08 SM SM20200094T patent/SMT202000094T1/it unknown
- 2015-01-08 EP EP15702312.8A patent/EP3092223B1/en active Active
- 2015-01-08 EA EA201691133A patent/EA201691133A1/ru unknown
- 2015-01-08 LT LTEP15702312.8T patent/LT3092223T/lt unknown
- 2015-01-08 MX MX2016008715A patent/MX2016008715A/es unknown
- 2015-01-09 AR ARP150100067A patent/AR102019A1/es unknown
- 2015-01-09 UY UY0001035946A patent/UY35946A/es unknown
- 2015-10-13 US US14/881,932 patent/US20160030456A1/en not_active Abandoned
-
2016
- 2016-07-04 IL IL246596A patent/IL246596A0/en unknown
- 2016-07-07 CL CL2016001744A patent/CL2016001744A1/es unknown
- 2016-11-21 US US15/357,102 patent/US20170065573A1/en not_active Abandoned
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2017
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- 2017-08-17 US US15/679,847 patent/US20170340653A1/en not_active Abandoned
- 2017-12-19 US US15/846,914 patent/US20180104265A1/en not_active Abandoned
-
2018
- 2018-05-04 US US15/971,049 patent/US20180250316A1/en not_active Abandoned
- 2018-12-19 US US16/225,631 patent/US20190125770A1/en not_active Abandoned
-
2019
- 2019-06-27 US US16/454,843 patent/US20190314392A1/en not_active Abandoned
-
2020
- 2020-01-31 US US16/778,960 patent/US20200297742A1/en not_active Abandoned
- 2020-02-07 CY CY20201100120T patent/CY1122768T1/el unknown
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Legal Events
| Date | Code | Title | Description |
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| FZDE | Discontinued |
Effective date: 20210831 |
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| FZDE | Discontinued |
Effective date: 20210831 |