ES2647486T3 - Pirazolo[1,5-a]pirimidinas como agentes antivirales - Google Patents
Pirazolo[1,5-a]pirimidinas como agentes antivirales Download PDFInfo
- Publication number
- ES2647486T3 ES2647486T3 ES12814092.8T ES12814092T ES2647486T3 ES 2647486 T3 ES2647486 T3 ES 2647486T3 ES 12814092 T ES12814092 T ES 12814092T ES 2647486 T3 ES2647486 T3 ES 2647486T3
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- Prior art keywords
- compound
- alkyl
- formula
- cycloalkyl
- heterocyclyl
- Prior art date
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- 239000003443 antiviral agent Substances 0.000 title description 3
- LDIJKUBTLZTFRG-UHFFFAOYSA-N pyrazolo[1,5-a]pyrimidine Chemical class N1=CC=CN2N=CC=C21 LDIJKUBTLZTFRG-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 538
- 150000003839 salts Chemical class 0.000 claims abstract description 206
- 150000002148 esters Chemical class 0.000 claims abstract description 191
- -1 C2-C20 heterocyclyl Chemical group 0.000 claims abstract description 130
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 92
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 64
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 54
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 54
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims abstract description 52
- 229910017711 NHRa Inorganic materials 0.000 claims abstract description 45
- 101150073096 NRAS gene Proteins 0.000 claims abstract description 44
- 125000005884 carbocyclylalkyl group Chemical group 0.000 claims abstract description 39
- 125000006736 (C6-C20) aryl group Chemical group 0.000 claims abstract description 37
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 34
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 33
- 150000002367 halogens Chemical class 0.000 claims abstract description 33
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 31
- 150000001721 carbon Chemical group 0.000 claims abstract description 27
- 125000003118 aryl group Chemical group 0.000 claims abstract description 26
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims abstract description 19
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims abstract description 19
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 15
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 14
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 14
- 125000004452 carbocyclyl group Chemical group 0.000 claims abstract description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 13
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical group [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims abstract description 12
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 11
- MPVDXIMFBOLMNW-UHFFFAOYSA-N chembl1615565 Chemical compound OC1=CC=C2C=C(S(O)(=O)=O)C=C(S(O)(=O)=O)C2=C1N=NC1=CC=CC=C1 MPVDXIMFBOLMNW-UHFFFAOYSA-N 0.000 claims abstract description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 11
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 9
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 9
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims abstract description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract 4
- 239000000203 mixture Substances 0.000 claims description 144
- 238000000034 method Methods 0.000 claims description 104
- 239000003814 drug Substances 0.000 claims description 79
- 241000711904 Pneumoviridae Species 0.000 claims description 71
- 241000124008 Mammalia Species 0.000 claims description 60
- 229940124597 therapeutic agent Drugs 0.000 claims description 55
- 239000008194 pharmaceutical composition Substances 0.000 claims description 35
- 206010061603 Respiratory syncytial virus infection Diseases 0.000 claims description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 230000009385 viral infection Effects 0.000 claims description 26
- 238000011282 treatment Methods 0.000 claims description 25
- 208000030925 respiratory syncytial virus infectious disease Diseases 0.000 claims description 23
- 241000725643 Respiratory syncytial virus Species 0.000 claims description 20
- 230000001225 therapeutic effect Effects 0.000 claims description 16
- 125000001624 naphthyl group Chemical group 0.000 claims description 11
- 125000004076 pyridyl group Chemical group 0.000 claims description 10
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 7
- 125000001544 thienyl group Chemical group 0.000 claims description 7
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 6
- 125000001041 indolyl group Chemical group 0.000 claims description 6
- 238000013160 medical therapy Methods 0.000 claims description 6
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 6
- 229960000329 ribavirin Drugs 0.000 claims description 6
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- MTPVBMVUENFFLL-HXUWFJFHSA-N 1-(2-fluorophenyl)-3-[(3s)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]urea Chemical compound FC1=CC=CC=C1NC(=O)N[C@@H]1C(=O)NC2=CC=CC=C2C(C=2C=CC=CC=2)=N1 MTPVBMVUENFFLL-HXUWFJFHSA-N 0.000 claims description 5
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 5
- 229960000402 palivizumab Drugs 0.000 claims description 5
- 238000011321 prophylaxis Methods 0.000 claims description 5
- 125000005493 quinolyl group Chemical group 0.000 claims description 5
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 5
- KSHJXDWYTZJUEI-UHFFFAOYSA-N 1-cyclopropyl-3-[[1-(4-hydroxybutyl)benzimidazol-2-yl]methyl]imidazo[4,5-c]pyridin-2-one Chemical compound N=1C2=CC=CC=C2N(CCCCO)C=1CN(C1=O)C2=CN=CC=C2N1C1CC1 KSHJXDWYTZJUEI-UHFFFAOYSA-N 0.000 claims description 4
- 229960001521 motavizumab Drugs 0.000 claims description 4
- 125000006648 (C1-C8) haloalkyl group Chemical group 0.000 claims description 3
- BLUJRJMLDHEMRX-UHFFFAOYSA-N 2-[[2-hydroxy-5-[(5-methyltetrazol-1-yl)iminomethyl]phenyl]-(4-hydroxyphenyl)methyl]-4-[(5-methyltetrazol-1-yl)iminomethyl]phenol Chemical compound Cc1nnnn1N=Cc1ccc(O)c(c1)C(c1ccc(O)cc1)c1cc(C=Nn2nnnc2C)ccc1O BLUJRJMLDHEMRX-UHFFFAOYSA-N 0.000 claims description 3
- 108700002314 gontivimab Proteins 0.000 claims description 3
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 108
- 239000000543 intermediate Substances 0.000 description 99
- 239000000243 solution Substances 0.000 description 68
- 241000282414 Homo sapiens Species 0.000 description 63
- 208000015181 infectious disease Diseases 0.000 description 62
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 59
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 53
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- 239000011541 reaction mixture Substances 0.000 description 48
- 239000004480 active ingredient Substances 0.000 description 47
- 238000002360 preparation method Methods 0.000 description 44
- 238000009472 formulation Methods 0.000 description 43
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 41
- 235000019439 ethyl acetate Nutrition 0.000 description 41
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 38
- 210000004027 cell Anatomy 0.000 description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 31
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 31
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 28
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 27
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 25
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 24
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 23
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 23
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 23
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 22
- 241000700605 Viruses Species 0.000 description 22
- 238000006243 chemical reaction Methods 0.000 description 21
- 230000002458 infectious effect Effects 0.000 description 21
- 239000008177 pharmaceutical agent Substances 0.000 description 21
- 239000000843 powder Substances 0.000 description 21
- 230000002829 reductive effect Effects 0.000 description 21
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 21
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 20
- 239000000047 product Substances 0.000 description 20
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 20
- 239000012453 solvate Substances 0.000 description 20
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 20
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 19
- 125000001424 substituent group Chemical group 0.000 description 19
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 18
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 18
- 230000000670 limiting effect Effects 0.000 description 18
- 239000002245 particle Substances 0.000 description 18
- 239000000546 pharmaceutical excipient Substances 0.000 description 18
- 238000005160 1H NMR spectroscopy Methods 0.000 description 17
- 229940079593 drug Drugs 0.000 description 17
- 238000004128 high performance liquid chromatography Methods 0.000 description 17
- 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 description 17
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- 239000000651 prodrug Substances 0.000 description 16
- 229940002612 prodrug Drugs 0.000 description 16
- 230000000241 respiratory effect Effects 0.000 description 16
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 15
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 15
- 239000000741 silica gel Substances 0.000 description 15
- 229910002027 silica gel Inorganic materials 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 14
- AMFYRKOUWBAGHV-UHFFFAOYSA-N 1h-pyrazolo[4,3-b]pyridine Chemical compound C1=CN=C2C=NNC2=C1 AMFYRKOUWBAGHV-UHFFFAOYSA-N 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- 239000000443 aerosol Substances 0.000 description 14
- 125000003545 alkoxy group Chemical group 0.000 description 14
- YWBFPKPWMSWWEA-UHFFFAOYSA-O triazolopyrimidine Chemical compound BrC1=CC=CC(C=2N=C3N=CN[N+]3=C(NCC=3C=CN=CC=3)C=2)=C1 YWBFPKPWMSWWEA-UHFFFAOYSA-O 0.000 description 14
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- 230000000840 anti-viral effect Effects 0.000 description 13
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
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- 239000000126 substance Substances 0.000 description 11
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- DATJETPTDKFEEF-UHFFFAOYSA-N pyrrolidine-3-carbonitrile Chemical compound N#CC1CCNC1 DATJETPTDKFEEF-UHFFFAOYSA-N 0.000 description 10
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- 238000012360 testing method Methods 0.000 description 10
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 9
- MJQSRSOTRPMVKB-UHFFFAOYSA-N 5h-imidazo[4,5-c]pyridazine Chemical compound C1=NNC2=NC=NC2=C1 MJQSRSOTRPMVKB-UHFFFAOYSA-N 0.000 description 9
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
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- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
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Classifications
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/538—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with carbocyclic ring systems
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- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- C07D—HETEROCYCLIC COMPOUNDS
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- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
- 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
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Applications Claiming Priority (5)
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|---|---|---|---|
| US201161579625P | 2011-12-22 | 2011-12-22 | |
| US201161579625P | 2011-12-22 | ||
| US201261618510P | 2012-03-30 | 2012-03-30 | |
| US201261618510P | 2012-03-30 | ||
| PCT/US2012/071065 WO2013096681A1 (en) | 2011-12-22 | 2012-12-20 | Pyrazolo[1,5-a]pyrimidines as antiviral agents |
Publications (1)
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|---|---|
| ES2647486T3 true ES2647486T3 (es) | 2017-12-21 |
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| ES12814092.8T Active ES2647486T3 (es) | 2011-12-22 | 2012-12-20 | Pirazolo[1,5-a]pirimidinas como agentes antivirales |
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|---|---|
| US (3) | US8946238B2 (cg-RX-API-DMAC7.html) |
| EP (1) | EP2794611B1 (cg-RX-API-DMAC7.html) |
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| AU (1) | AU2012358805B2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2858096C (cg-RX-API-DMAC7.html) |
| ES (1) | ES2647486T3 (cg-RX-API-DMAC7.html) |
| PT (1) | PT2794611T (cg-RX-API-DMAC7.html) |
| WO (1) | WO2013096681A1 (cg-RX-API-DMAC7.html) |
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| US8486938B2 (en) | 2010-06-24 | 2013-07-16 | Gilead Sciences, Inc. | Pyrazolo[1,5-a]pyrimidines for antiviral treatment |
| CA2858096C (en) | 2011-12-22 | 2020-06-23 | Gilead Sciences, Inc. | Pyrazolo[1,5-a]pyrimidines as antiviral agents |
| CN106986869A (zh) | 2012-04-17 | 2017-07-28 | 吉利德科学公司 | 用于抗病毒治疗的化合物和方法 |
| HK1225716A1 (zh) | 2013-08-21 | 2017-09-15 | Alios Biopharma, Inc. | 抗病毒化合物 |
| CA2957017A1 (en) * | 2014-08-05 | 2016-02-11 | Alios Biopharma, Inc. | Combination therapy for treating a paramyxovirus |
| CA2963051C (en) * | 2014-12-08 | 2023-10-17 | Janssen Sciences Ireland Uc | Piperidine substituted pyrazolo[1,5-a]pyrimidine derivatives with inhibitory activity on the replication of the respiratory syncytial virus (rsv) |
| KR102486023B1 (ko) * | 2014-12-08 | 2023-01-05 | 얀센 사이언시즈 아일랜드 언리미티드 컴퍼니 | 호흡기 세포융합 바이러스 （ｒｓｖ）의 복제에 대하여 저해 활성을 갖는 피페리딘 치환된 삼환식 피라졸로［１，５―ａ］피리미딘 유도체 |
| CN107427529A (zh) | 2014-12-26 | 2017-12-01 | 埃莫里大学 | N4‑羟基胞苷和衍生物及与其相关的抗病毒用途 |
| MA41614A (fr) | 2015-02-25 | 2018-01-02 | Alios Biopharma Inc | Composés antiviraux |
| JP2018076234A (ja) * | 2015-03-16 | 2018-05-17 | 大正製薬株式会社 | ピラゾロ［１，５−ａ］ピリミジン化合物 |
| MX381798B (es) | 2015-07-22 | 2025-03-13 | Enanta Pharm Inc | Derivados de benzodiazepina como inhibidores de rsv |
| EP3402799B1 (en) | 2016-01-15 | 2022-05-04 | Enanta Pharmaceuticals, Inc. | Heterocyclic compounds as rsv inhibitors |
| EP3454862B1 (en) | 2016-05-10 | 2024-09-11 | C4 Therapeutics, Inc. | Spirocyclic degronimers for target protein degradation |
| WO2017197055A1 (en) | 2016-05-10 | 2017-11-16 | C4 Therapeutics, Inc. | Heterocyclic degronimers for target protein degradation |
| WO2017197046A1 (en) | 2016-05-10 | 2017-11-16 | C4 Therapeutics, Inc. | C3-carbon linked glutarimide degronimers for target protein degradation |
| EP3455219A4 (en) | 2016-05-10 | 2019-12-18 | C4 Therapeutics, Inc. | AMINE-RELATED C3-GLUTARIMIDE DEGRONIMERS FOR TARGET PROTEIN REDUCTION |
| EP3458455B1 (en) * | 2016-05-20 | 2021-06-16 | F. Hoffmann-La Roche AG | Novel pyrazine compounds with oxygen, sulfur and nitrogen linker for the treatment of infectious diseases |
| KR102473491B1 (ko) | 2016-10-06 | 2022-12-05 | 오버스 쎄라퓨틱스, 인코포레이티드 | 에플로르니틴의 투여를 위한 제형 |
| CN110809472B (zh) | 2017-02-16 | 2023-05-23 | 英安塔制药有限公司 | 用于制备苯二氮䓬衍生物的方法 |
| CN110769822A (zh) | 2017-06-20 | 2020-02-07 | C4医药公司 | 用于蛋白降解的n/o-连接的降解决定子和降解决定子体 |
| WO2019006295A1 (en) | 2017-06-30 | 2019-01-03 | Enanta Pharmaceuticals, Inc. | HETEROCYCLIC COMPOUNDS AS RSV INHIBITORS |
| DK3684767T3 (da) | 2017-09-22 | 2024-07-15 | Jubilant Epipad LLC | Heterocykliske forbindelser som pad-inhibitorer |
| US10881666B2 (en) | 2017-09-29 | 2021-01-05 | Enanta Pharmaceuticals, Inc. | Combination pharmaceutical agents as RSV inhibitors |
| AU2018352142B2 (en) | 2017-10-18 | 2022-08-25 | Jubilant Epipad LLC | Imidazo-pyridine compounds as PAD inhibitors |
| CN111386265A (zh) | 2017-11-06 | 2020-07-07 | 朱比连特普罗德尔有限责任公司 | 作为pd1/pd-l1活化的抑制剂的嘧啶衍生物 |
| JP7228588B2 (ja) | 2017-11-13 | 2023-02-24 | エナンタ ファーマシューティカルズ インコーポレイテッド | ベンゾジアゼピン－２－オンおよびベンゾアゼピン－２－オン誘導体の分割方法 |
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| US9278975B2 (en) | 2016-03-08 |
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| AU2012358805A1 (en) | 2014-06-19 |
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