CA2494975A1 - Substituted 1,4-pyrazine derivatives - Google Patents
Substituted 1,4-pyrazine derivatives Download PDFInfo
- Publication number
- CA2494975A1 CA2494975A1 CA002494975A CA2494975A CA2494975A1 CA 2494975 A1 CA2494975 A1 CA 2494975A1 CA 002494975 A CA002494975 A CA 002494975A CA 2494975 A CA2494975 A CA 2494975A CA 2494975 A1 CA2494975 A1 CA 2494975A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- substituted
- nr5r5
- cycloalkyl
- ring
- 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
- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 14
- 208000019901 Anxiety disease Diseases 0.000 claims abstract description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 84
- 150000001875 compounds Chemical class 0.000 claims description 50
- 229910052736 halogen Inorganic materials 0.000 claims description 50
- 125000001072 heteroaryl group Chemical group 0.000 claims description 49
- 150000002367 halogens Chemical class 0.000 claims description 47
- 125000003118 aryl group Chemical group 0.000 claims description 42
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 39
- 125000001424 substituent group Chemical group 0.000 claims description 39
- -1 alkylyne Chemical group 0.000 claims description 36
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 30
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 28
- 125000004432 carbon atom Chemical group C* 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 22
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 125000001188 haloalkyl group Chemical group 0.000 claims description 18
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 125000005349 heteroarylcycloalkyl group Chemical group 0.000 claims description 15
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
- 229940002612 prodrug Drugs 0.000 claims description 11
- 239000000651 prodrug Substances 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 10
- 229920006395 saturated elastomer Polymers 0.000 claims description 10
- 125000004350 aryl cycloalkyl group Chemical group 0.000 claims description 9
- 125000004429 atom Chemical group 0.000 claims description 9
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 9
- 230000027455 binding Effects 0.000 claims description 8
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 125000002950 monocyclic group Chemical group 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 125000006413 ring segment Chemical group 0.000 claims description 6
- CZDYVVMDBOUYST-JTHBVZDNSA-N 3,6-diethyl-n-[(1r,2s)-2-(2-fluoroethoxy)-2,3-dihydro-1h-inden-1-yl]-5-(4-methylpyridin-2-yl)oxypyrazin-2-amine Chemical compound CCC=1N=C(N[C@@H]2C3=CC=CC=C3C[C@@H]2OCCF)C(CC)=NC=1OC1=CC(C)=CC=N1 CZDYVVMDBOUYST-JTHBVZDNSA-N 0.000 claims description 5
- OHGDKOGPXYYKAS-LADGPHEKSA-N 5-(4,6-dimethylpyridin-2-yl)oxy-n-[(1r,2s)-2-ethoxy-2,3-dihydro-1h-inden-1-yl]-3,6-diethylpyrazin-2-amine Chemical compound N([C@@H]1C2=CC=CC=C2C[C@@H]1OCC)C(C(=N1)CC)=NC(CC)=C1OC1=CC(C)=CC(C)=N1 OHGDKOGPXYYKAS-LADGPHEKSA-N 0.000 claims description 4
- 230000036506 anxiety Effects 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 125000002619 bicyclic group Chemical group 0.000 claims description 3
- 150000001721 carbon Chemical group 0.000 claims description 3
- 230000001955 cumulated effect Effects 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- ZMRNNGNFCBYSLG-JTHBVZDNSA-N n-[(1r,2s)-2-ethoxy-2,3-dihydro-1h-inden-1-yl]-3,6-diethyl-5-(4-methylpyridin-2-yl)oxypyrazin-2-amine Chemical compound N([C@@H]1C2=CC=CC=C2C[C@@H]1OCC)C(C(=N1)CC)=NC(CC)=C1OC1=CC(C)=CC=N1 ZMRNNGNFCBYSLG-JTHBVZDNSA-N 0.000 claims description 3
- OROWAFDBBMNLPV-JTHBVZDNSA-N n-[(1r,2s)-2-ethoxy-2,3-dihydro-1h-inden-1-yl]-3,6-diethyl-5-(5-methylpyridin-2-yl)oxypyrazin-2-amine Chemical compound N([C@@H]1C2=CC=CC=C2C[C@@H]1OCC)C(C(=N1)CC)=NC(CC)=C1OC1=CC=C(C)C=N1 OROWAFDBBMNLPV-JTHBVZDNSA-N 0.000 claims description 3
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- 150000002978 peroxides Chemical class 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- JRZYFNWKXMUXEA-LADGPHEKSA-N 3,6-diethyl-5-(4-methylpyridin-2-yl)oxy-n-[(1r,2s)-2-propoxy-2,3-dihydro-1h-inden-1-yl]pyrazin-2-amine Chemical compound N([C@@H]1C2=CC=CC=C2C[C@@H]1OCCC)C(C(=N1)CC)=NC(CC)=C1OC1=CC(C)=CC=N1 JRZYFNWKXMUXEA-LADGPHEKSA-N 0.000 claims description 2
- CLKQAGKKYHGBPF-UHFFFAOYSA-N n-(2-ethoxy-2,3-dihydro-1h-inden-1-yl)-3,6-diethyl-5-(4-methylphenyl)sulfanylpyrazin-2-amine Chemical compound CCOC1CC2=CC=CC=C2C1NC(C(=N1)CC)=NC(CC)=C1SC1=CC=C(C)C=C1 CLKQAGKKYHGBPF-UHFFFAOYSA-N 0.000 claims description 2
- 108091005471 CRHR1 Proteins 0.000 claims 2
- SKFGLBGENUOICG-LADGPHEKSA-N 3,6-diethyl-5-(4-methylpyridin-2-yl)oxy-n-[(1r,2s)-2-propan-2-yloxy-2,3-dihydro-1h-inden-1-yl]pyrazin-2-amine Chemical compound CCC=1N=C(N[C@@H]2C3=CC=CC=C3C[C@@H]2OC(C)C)C(CC)=NC=1OC1=CC(C)=CC=N1 SKFGLBGENUOICG-LADGPHEKSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
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- 208000020401 Depressive disease Diseases 0.000 abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 40
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 36
- 108010022152 Corticotropin-Releasing Hormone Proteins 0.000 description 34
- 102000012289 Corticotropin-Releasing Hormone Human genes 0.000 description 34
- 238000002360 preparation method Methods 0.000 description 19
- 235000019439 ethyl acetate Nutrition 0.000 description 17
- 208000035475 disorder Diseases 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 11
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 7
- 239000005557 antagonist Substances 0.000 description 7
- 230000000949 anxiolytic effect Effects 0.000 description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
- 230000003542 behavioural effect Effects 0.000 description 6
- 238000006555 catalytic reaction Methods 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 210000003169 central nervous system Anatomy 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- XFTQRUTUGRCSGO-UHFFFAOYSA-N pyrazin-2-amine Chemical compound NC1=CN=CC=N1 XFTQRUTUGRCSGO-UHFFFAOYSA-N 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
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- 239000000463 material Substances 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 238000000159 protein binding assay Methods 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 5
- 229910052723 transition metal Inorganic materials 0.000 description 5
- 150000003624 transition metals Chemical class 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 208000019022 Mood disease Diseases 0.000 description 4
- DRBBFCLWYRJSJZ-UHFFFAOYSA-N N-phosphocreatine Chemical compound OC(=O)CN(C)C(=N)NP(O)(O)=O DRBBFCLWYRJSJZ-UHFFFAOYSA-N 0.000 description 4
- 208000012902 Nervous system disease Diseases 0.000 description 4
- 208000025966 Neurological disease Diseases 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 150000004703 alkoxides Chemical class 0.000 description 4
- 150000001504 aryl thiols Chemical class 0.000 description 4
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
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- TWSYWYSTOISQDZ-DLBZAZTESA-N n-[(1r,2s)-2-ethoxy-2,3-dihydro-1h-inden-1-yl]-3,6-diethyl-5-iodopyrazin-2-amine Chemical compound N([C@@H]1C2=CC=CC=C2C[C@@H]1OCC)C1=NC(CC)=C(I)N=C1CC TWSYWYSTOISQDZ-DLBZAZTESA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
- 238000012552 review Methods 0.000 description 4
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 208000017194 Affective disease Diseases 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 102100027467 Pro-opiomelanocortin Human genes 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
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- KVKFRMCSXWQSNT-UHFFFAOYSA-N n,n'-dimethylethane-1,2-diamine Chemical compound CNCCNC KVKFRMCSXWQSNT-UHFFFAOYSA-N 0.000 description 3
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- 150000003335 secondary amines Chemical class 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
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- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 2
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- APIXJSLKIYYUKG-UHFFFAOYSA-N 3 Isobutyl 1 methylxanthine Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N=CN2 APIXJSLKIYYUKG-UHFFFAOYSA-N 0.000 description 2
- OHKRYVAKYCCYNX-UHFFFAOYSA-N 3-chloro-2,5-diethylpyrazine Chemical compound CCC1=CN=C(CC)C(Cl)=N1 OHKRYVAKYCCYNX-UHFFFAOYSA-N 0.000 description 2
- FSPIBFKGESGOLU-UHFFFAOYSA-N 4,6-dimethyl-1h-pyridin-2-one Chemical compound CC1=CC(C)=NC(O)=C1 FSPIBFKGESGOLU-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
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- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
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- 229910052740 iodine Inorganic materials 0.000 description 2
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- DELOIKUHVLMGAZ-FCHUYYIVSA-N n-[(1r,2s)-2-ethoxy-2,3-dihydro-1h-inden-1-yl]-3,6-diethyl-5-(3-methylpyridin-2-yl)oxypyrazin-2-amine Chemical compound N([C@@H]1C2=CC=CC=C2C[C@@H]1OCC)C(C(=N1)CC)=NC(CC)=C1OC1=NC=CC=C1C DELOIKUHVLMGAZ-FCHUYYIVSA-N 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
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- XKMLYUALXHKNFT-UHFFFAOYSA-N rGTP Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O XKMLYUALXHKNFT-UHFFFAOYSA-N 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000003938 response to stress Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
Classifications
-
- 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
- C07D401/12—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 linked by a chain containing hetero atoms as chain links
-
- 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
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P25/24—Antidepressants
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members 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
- C07D241/20—Nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Addiction (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US41026102P | 2002-09-12 | 2002-09-12 | |
| US60/410,261 | 2002-09-12 | ||
| PCT/US2003/024805 WO2004024719A1 (en) | 2002-09-12 | 2003-08-27 | Substituted 1,4-pyrazine derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2494975A1 true CA2494975A1 (en) | 2004-03-25 |
Family
ID=31994096
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002494975A Abandoned CA2494975A1 (en) | 2002-09-12 | 2003-08-27 | Substituted 1,4-pyrazine derivatives |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US20040116444A1 (https=) |
| EP (1) | EP1539736A1 (https=) |
| JP (1) | JP2006506350A (https=) |
| AR (1) | AR041125A1 (https=) |
| AU (1) | AU2003269949A1 (https=) |
| BR (1) | BR0314139A (https=) |
| CA (1) | CA2494975A1 (https=) |
| MX (1) | MXPA05002418A (https=) |
| TW (1) | TW200503717A (https=) |
| WO (1) | WO2004024719A1 (https=) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004099201A1 (en) * | 2003-05-09 | 2004-11-18 | Pharmacia & Upjohn Company Llc | Compounds as crf1 receptor antagonists |
| US20060211710A1 (en) * | 2005-03-17 | 2006-09-21 | Pfizer Inc | Substituted aryl 1,4-pyrazine derivatives |
| KR102598895B1 (ko) | 2016-07-12 | 2023-11-07 | 레볼루션 메디슨즈, 인크. | 다른자리 입체성 shp2 억제제로서의 2,5-이치환 3-메틸 피라진 및 2,5,6-3치환 3-메틸 피라진 |
| MX2019008695A (es) | 2017-01-23 | 2019-09-11 | Revolution Medicines Inc | Compuestos biciclicos como inhibidores alostericos de shp2. |
| MX2019008696A (es) | 2017-01-23 | 2019-09-13 | Revolution Medicines Inc | Compuestos de piridina como inhibidores de shp2 alostericos. |
| CA3074690A1 (en) | 2017-09-07 | 2019-03-14 | Revolution Medicines, Inc. | Shp2 inhibitor compositions and methods for treating cancer |
| MX2020003579A (es) | 2017-10-12 | 2020-07-22 | Revolution Medicines Inc | Compuestos de piridina, pirazina, y triazina como inhibidores de shp2 alostericos. |
| BR112020009757A2 (pt) | 2017-12-15 | 2020-11-03 | Revolution Medicines, Inc. | compostos policíclicos como inibidores alostéricos de shp2 |
| IL300091A (en) | 2018-05-01 | 2023-03-01 | Revolution Medicines Inc | C40-, c28-, and c-32-linked rapamycin analogs as mtor inhibitors |
| CN112368289B (zh) | 2018-05-01 | 2024-02-20 | 锐新医药公司 | 作为mtor抑制剂的c26-连接的雷帕霉素类似物 |
| AU2023275778A1 (en) | 2022-05-25 | 2024-12-12 | Revolution Medicines, Inc. | Methods of treating cancer with an mtor inhibitor |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6159980A (en) * | 1996-09-16 | 2000-12-12 | Dupont Pharmaceuticals Company | Pyrazinones and triazinones and their derivatives thereof |
| PA8467401A1 (es) * | 1998-02-17 | 2000-09-29 | Pfizer Prod Inc | Procedimiento para tratar la insuficiencia cardiaca |
| CO5271670A1 (es) * | 1999-10-29 | 2003-04-30 | Pfizer Prod Inc | Antagonistas del factor de liberacion de corticitropina y composiciones relacionadas |
| CN1231473C (zh) * | 2000-02-16 | 2005-12-14 | 神经能质公司 | 取代的芳基吡嗪 |
-
2003
- 2003-08-27 US US10/649,299 patent/US20040116444A1/en not_active Abandoned
- 2003-08-27 EP EP03751841A patent/EP1539736A1/en not_active Withdrawn
- 2003-08-27 CA CA002494975A patent/CA2494975A1/en not_active Abandoned
- 2003-08-27 JP JP2004536018A patent/JP2006506350A/ja not_active Abandoned
- 2003-08-27 AU AU2003269949A patent/AU2003269949A1/en not_active Abandoned
- 2003-08-27 WO PCT/US2003/024805 patent/WO2004024719A1/en not_active Ceased
- 2003-08-27 BR BR0314139-0A patent/BR0314139A/pt not_active IP Right Cessation
- 2003-08-27 MX MXPA05002418A patent/MXPA05002418A/es not_active Application Discontinuation
- 2003-09-02 AR ARP030103176A patent/AR041125A1/es unknown
- 2003-09-10 TW TW092125064A patent/TW200503717A/zh unknown
Also Published As
| Publication number | Publication date |
|---|---|
| MXPA05002418A (es) | 2005-05-27 |
| US20040116444A1 (en) | 2004-06-17 |
| BR0314139A (pt) | 2005-07-12 |
| JP2006506350A (ja) | 2006-02-23 |
| AR041125A1 (es) | 2005-05-04 |
| TW200503717A (en) | 2005-02-01 |
| AU2003269949A1 (en) | 2004-04-30 |
| EP1539736A1 (en) | 2005-06-15 |
| WO2004024719A1 (en) | 2004-03-25 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |