HRP20220427T1 - Farmaceutski spojevi - Google Patents
Farmaceutski spojevi Download PDFInfo
- Publication number
- HRP20220427T1 HRP20220427T1 HRP20220427TT HRP20220427T HRP20220427T1 HR P20220427 T1 HRP20220427 T1 HR P20220427T1 HR P20220427T T HRP20220427T T HR P20220427TT HR P20220427 T HRP20220427 T HR P20220427T HR P20220427 T1 HRP20220427 T1 HR P20220427T1
- Authority
- HR
- Croatia
- Prior art keywords
- acid
- benzodiazol
- dihydro
- methyl
- chloro
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims 16
- -1 1-{[5-Chloro-1-(4,4,4-trifluorobutyl)-1H-1,3-benzodiazol-2-yl]methyl}-3,3-difluoro-2,3-dihydro-1H-indole Chemical compound 0.000 claims 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims 3
- 239000003814 drug Substances 0.000 claims 3
- 238000000034 method Methods 0.000 claims 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 3
- 235000018102 proteins Nutrition 0.000 claims 3
- 108090000623 proteins and genes Proteins 0.000 claims 3
- 102000004169 proteins and genes Human genes 0.000 claims 3
- 150000003839 salts Chemical class 0.000 claims 3
- 229940124597 therapeutic agent Drugs 0.000 claims 3
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 2
- 206010061603 Respiratory syncytial virus infection Diseases 0.000 claims 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 2
- 239000003085 diluting agent Substances 0.000 claims 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims 2
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims 1
- MPIZTHAVPXBSOB-UHFFFAOYSA-N 1-[[5-(aminomethyl)-1-(3-methylbutyl)benzimidazol-2-yl]methyl]-4-chloro-3,3-difluoroindol-2-one Chemical compound NCC1=CC2=C(N(C(=N2)CN2C(C(C3=C(C=CC=C23)Cl)(F)F)=O)CCC(C)C)C=C1 MPIZTHAVPXBSOB-UHFFFAOYSA-N 0.000 claims 1
- OCHZUKBJYDHNIO-UHFFFAOYSA-N 1-[[5-chloro-1-(1-ethylsulfonylpiperidin-4-yl)benzimidazol-2-yl]methyl]-3,3-difluoroindol-2-one Chemical compound C(S(=O)(=O)N1CCC(CC1)N1C2=C(C=C(Cl)C=C2)N=C1CN1C2=C(C(C1=O)(F)F)C=CC=C2)C OCHZUKBJYDHNIO-UHFFFAOYSA-N 0.000 claims 1
- IWRAZCQCAJTGID-UHFFFAOYSA-N 1-[[5-chloro-1-(1-methylsulfonylpiperidin-4-yl)benzimidazol-2-yl]methyl]-3,3-difluoroindol-2-one Chemical compound CS(=O)(=O)N1CCC(N2C3=C(C=C(C=C3)Cl)N=C2CN2C3=C(C(C2=O)(F)F)C=CC=C3)CC1 IWRAZCQCAJTGID-UHFFFAOYSA-N 0.000 claims 1
- SHTSNBVPDPZMCF-UHFFFAOYSA-N 1-[[5-chloro-1-(3-methylsulfonylpropyl)benzimidazol-2-yl]methyl]-3,3-difluoroindol-2-one Chemical compound CS(=O)(=O)CCCN1C2=C(C=C(C=C2)Cl)N=C1CN1C2=C(C(C1=O)(F)F)C=CC=C2 SHTSNBVPDPZMCF-UHFFFAOYSA-N 0.000 claims 1
- YIPLIWFLDCEIIW-UHFFFAOYSA-N 1-[[5-chloro-1-(oxan-4-yl)benzimidazol-2-yl]methyl]-3,3,7-trifluoroindol-2-one Chemical compound C1CC(N2C3=C(C=C(C=C3)Cl)N=C2CN2C3=C(F)C=CC=C3C(C2=O)(F)F)CCO1 YIPLIWFLDCEIIW-UHFFFAOYSA-N 0.000 claims 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims 1
- 108010068327 4-hydroxyphenylpyruvate dioxygenase Proteins 0.000 claims 1
- CKLJMWTZIZZHCS-UHFFFAOYSA-N Aspartic acid Chemical compound OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 claims 1
- HSURRMCXESEWJO-UHFFFAOYSA-N ClC1=CC2=C(N(C(=N2)CN2C(C(C3=CC=CC=C23)(F)F)=O)CCCN2CC(CC2)S(=O)(=O)C)C=C1 Chemical compound ClC1=CC2=C(N(C(=N2)CN2C(C(C3=CC=CC=C23)(F)F)=O)CCCN2CC(CC2)S(=O)(=O)C)C=C1 HSURRMCXESEWJO-UHFFFAOYSA-N 0.000 claims 1
- CODDRBRIALPJFP-UHFFFAOYSA-N ClC1=CC2=C(N(C(=N2)CN2C(C(C3=CC=CC=C23)(F)F)=O)CCCNCCS(=O)(=O)C)C=C1 Chemical compound ClC1=CC2=C(N(C(=N2)CN2C(C(C3=CC=CC=C23)(F)F)=O)CCCNCCS(=O)(=O)C)C=C1 CODDRBRIALPJFP-UHFFFAOYSA-N 0.000 claims 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims 1
- 102000007982 Phosphoproteins Human genes 0.000 claims 1
- 108010089430 Phosphoproteins Proteins 0.000 claims 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims 1
- 102000002689 Toll-like receptor Human genes 0.000 claims 1
- 108020000411 Toll-like receptor Proteins 0.000 claims 1
- 241000700605 Viruses Species 0.000 claims 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims 1
- 230000003110 anti-inflammatory effect Effects 0.000 claims 1
- 230000002128 anti-rhinoviral effect Effects 0.000 claims 1
- 239000003443 antiviral agent Substances 0.000 claims 1
- 229940121357 antivirals Drugs 0.000 claims 1
- 235000003704 aspartic acid Nutrition 0.000 claims 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims 1
- 229940092714 benzenesulfonic acid Drugs 0.000 claims 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims 1
- 235000015165 citric acid Nutrition 0.000 claims 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 claims 1
- 235000019253 formic acid Nutrition 0.000 claims 1
- 239000001530 fumaric acid Substances 0.000 claims 1
- 235000013922 glutamic acid Nutrition 0.000 claims 1
- 239000004220 glutamic acid Substances 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims 1
- 229940071870 hydroiodic acid Drugs 0.000 claims 1
- 230000002519 immonomodulatory effect Effects 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 claims 1
- 239000004310 lactic acid Substances 0.000 claims 1
- 235000014655 lactic acid Nutrition 0.000 claims 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims 1
- 239000011976 maleic acid Substances 0.000 claims 1
- 239000001630 malic acid Substances 0.000 claims 1
- 235000011090 malic acid Nutrition 0.000 claims 1
- 229940098779 methanesulfonic acid Drugs 0.000 claims 1
- 229910017604 nitric acid Inorganic materials 0.000 claims 1
- 235000006408 oxalic acid Nutrition 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 235000019260 propionic acid Nutrition 0.000 claims 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 229940121649 protein inhibitor Drugs 0.000 claims 1
- 239000012268 protein inhibitor Substances 0.000 claims 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims 1
- 230000000241 respiratory effect Effects 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
- 239000011975 tartaric acid Substances 0.000 claims 1
- 235000002906 tartaric acid Nutrition 0.000 claims 1
- SQERPUKJDQOIMS-UHFFFAOYSA-N tert-butyl 4-[5-chloro-2-[(3,3-difluoro-2-oxoindol-1-yl)methyl]benzimidazol-1-yl]piperidine-1-carboxylate Chemical compound CC(OC(=O)N1CCC(CC1)N1C2=C(C=C(C=C2)Cl)N=C1CN1C2=C(C(C1=O)(F)F)C=CC=C2)(C)C SQERPUKJDQOIMS-UHFFFAOYSA-N 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/42—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum viral
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- 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
- C07D401/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Claims (15)
1. Spoj koji je benzimidazol formule (I):
[image]
u kojem:
R1 je -(CH2)m-R7,
[image]
R2 je H, halo, -(CH2)m-NH2, -(CH2)n-C(=NH)-NH2 ili -(CH2)n-NH-(CH2)m-NHR9;
R3je H, F ili Cl;
svaki od R4, R5 i R6 je nezavisno H ili F;
R7 je C1-C6 alkil, CF3, -SO2R11, -NH-(CH2)2-(NH)r-R8, -NH-CH(R8R9) ili grupa sljedeće formule (A):
[image]
W je -(CH2)m-, -CH2-O-CH2-, -CH2-S-CH2-, -(CH2)r-S(O)2-CH2- ili -(CH2)r-NR8-CH2-;
m je cijeli broj od 1 do 3;
n je 1 ili 2;
p je 1 i V je CH; ili p je 0 i V je N;
q je 0 ili 1;
r je 0 ili 1;
R8 je H, -SO2R11, -SO2CF3, -COR11, -C(O)OR11, -CON(R9)2 ili -(CH2)nSO2R11;
R9 je H ili C1-C6 alkil, svaki R9 je isti ili različit kada su prisutna dva;
R10 je -SO2R11, -SO2CF3, -COR11, -CON(R9)2 ili -(CH2)nSO2R11; i
R11 je C1-C6 alkil;
ili njegova farmaceutski prihvatljiva sol.
2. Spoj prema zahtjevu 1 gdje R1 je -(CH2)m-R7 u kojoj m je 2 ili 3 i R7 je izabran između:
(i) -NH-(CH2)2-(NH)r-R8 gdje r je 0 ili 1 i R8 je izabran između -SO2Me, -SO2Et i -SO2CF3;
(ii) C1-C6 alkil, CF3 ili -SO2R11;
(iii) -NH-CH(R8R9) gdje R8 je -CONH2 ili -CONMe2 i R9 je C1-C6 alkil.
(iv) grupa formule (A) u kojoj p je 1, q je 0, V je CH i W je -(CH2)r-S(O)2-CH2- ili -(CH2)r-NR8-CH2- u kojoj r je 0 i R8 je -SO2Me ili -SO2Et;
(v) grupa formule (A) u kojoj p je 0, V je N, W je -(CH2)m-u kojoj m je cijeli broj od 1 do 3, q je 1 i R10 je -SO2Me, -SO2Et, -CONH2 ili -CONMe2; i
(vi) grupa formule (A) u kojoj p je 0, V je N, q je 0 i W je -CH2-O-CH2-, -CH2-S-CH2-, -(CH2)r-S(O)2-CH2-ili -(CH2)r-NR8-CH2-u kojoj r je 0 ili 1 i R8 je -SO2Me, -SO2Et ili -COMe.
3. Spoj prema zahtjevu 1 u kojem:
R1 je
[image]
u kojem R8 je H, -SO2R11, -COMe, -C(O)OR11, -CON(R9)2 ili -(CH2)nSO2R11.
4. Spoj prema zahtjevu 3 gdje
-SO2R11 je -SO2Me ili -SO2Et;
-CON(R9)2 je -CONH2 ili -CONMe2; i
-(CH2)nSO2R11 je -CH2CH2SO2Me.
5. Spoj prema bilo kojem od zahtjeva 1 do 3 u kojem R2 je Cl ili -CH2NH2.
6. Spoj prema zahtjevu 1 ili 2 gdje je grupa formule (A) izabrana između sljedećih struktura:
[image]
7. Spoj prema zahtjevu 1, koji je izabran između:
1-{[5-Kloro-1-(4,4,4-trifluorobutil)-1H-1,3-benzodiazol-2-il]metil}-3,3-difluoro-2,3-dihidro-1H-indol-2-ona;
1-({5-Kloro-1-[3-(-(4-metansulfonilpiperazin-1-il)propil]-1H-1,3-benzodiazol-2-il}metil)-3,3-difluoro-2,3-dihidro-1H-indol-2-ona;
1-[(5-Kloro-1-{3-[(2-metansulfoniletil)amino]propil}-1H-1,3-benzodiazol-2-il)metil]-3,3-difluoro-2,3-dihidro-1H-indol-2-ona;
1-({5-Kloro-1-[3-(3-metansulfonilpirolidin-1-il)propil]-1H-1,3-benzodiazol-2-il}metil)-3,3-difluoro-2,3-dihidro-1H-indol-2-ona;
1-{[5-Kloro-1-(3-metansulfonilpropil)-1H-1,3-benzodiazol-2-il]metil}-3,3-difluoro-2,3-dihidro-1H-indol-2-ona;
terc-Butil 4-{5-Kloro-2-[(3,3-difluoro-2-okso-2,3-dihidro-1H-indol-1-il)metil]-1H-1,3-benzodiazol-1-il}piperidin-1-karboksilata;
1-{[5-Kloro-1-(piperidin-4-il)-1H-1,3-benzodiazol-2-il]metil}-3,3-difluoro-2,3-dihidro-1H-indol-2-ona;
1-{[5-Kloro-1-(1-metansulfonilpiperidin-4-il)-1H-1,3-benzodiazol-2-il]metil}-3,3-difluoro-2,3-dihidro-1H-indol-2-on;
1-({5-Kloro-1-[1-(etansulfonil)piperidin-4-il]-1H-1,3-benzodiazol-2-il}metil)-3,3-difluoro-2,3-dihidro-1H-indol-2-ona;
1-{[5-Kloro-1-(oksan-4-il)-1H-1,3-benzodiazol-2-il]metil}-3,3-difluoro-2,3-dihidro-1H-indol-2-ona;
1-{[5-Kloro-1-(oksan-4-il)-1H-1,3-benzodiazol-2-yl]metil}-3,3,6-trifluoro-2,3-dihidro-1H-indol-2-ona;
1-{[5-Kloro-1-(oksan-4-il)-1H-1,3-benzodiazol-2-il]metil}-3,3,7-trifluoro-2,3-dihidro-1H-indol-2-on;
1-{[5-(Aminometil)-1-(3-metilbutil)-1H-1,3-benzodiazol-2-il]metil}-3,3-difluoro-2,3-dihidro-1H-indol-2-ona;
1-{[5-(Aminometil)-1-(3-metilbutil)-1H-1,3-benzodiazol-2-il]metil}-3,3,4-trifluoro-2,3-dihidro-1H-indol-2-ona;
1-{[5-(Aminometil)-1-(3-metilbutil)-1H-1,3-benzodiazol-2-yl]metil} -4-kloro-3,3-difluoro-2,3-dihidro-1H-indol-2-ona; i
1-{[5-(Aminometil)-1-(3-metilbutil)-1H-1,3-benzodiazol-2-yl]metil}-3,3,5-trifluoro-2,3-dihidro-1H-indol-2-ona;
i njihovih farmaceutski prihvatljivih soli.
8. Farmaceutski sastav koji sadrži spoj kao što je definirano prema bilo kojem od zahtjeva 1 do 7 i farmaceutski prihvatljiv nosač ili razblaživač.
9. Spoj kao što je definiran prema bilo kojem od zahtjeva 1-7, za upotrebu u liječenju ljudskog ili životinjskog tijela terapijom.
10. Spoj kako je definirano prema bilo kojem od zahtjeva 1 do 7 za upotrebu u liječenju ili prevenciji RSV infekcije.
11. Proizvod koji sadrži:
(a) spoj koji je definiran prema bilo kojem od zahtjeva 1 do 7; i
(b) jedno ili više drugih terapeutskih sredstava;
za simultanu, odvojenu ili sekvencionalnu upotrebu u liječenju subjekta koji pati od ili je podložan RSV infekciji.
12. Proizvod prema zahtjevu 11, gdje je drugo terapeutsko sredstvo:
(i) RSV inhibitor (N)-proteina nukleokapsida;
(ii) inhibitor proteina, kao što je onaj koji inhibira fosfoproteinski (P) protein i/ili veliki (L) protein;
(iii) anti-RSV monoklonalna antitijela, kao što je antitijelo F-proteina;
(iv) imunomodulatorni spoj receptora sličnog tolu;
(v) anti-virusni lijekovi respiratornog virusa, kao što su spojevi protiv grupa i/ili protiv rinovirusa; i/ili
(vi) anti-inflamatorni spoj.
13. Farmaceutski sastav koji sadrži (a) spoj kao što je definirano u bilo kojem od zahtjeva 1 do 7, i (b) jedno ili više terapeutskih sredstava kao što je definirano prema zahtjevu 12, zajedno s farmaceutski prihvatljivim nosačem ili razblaživačem.
14. Postupak za dobivanje farmaceutski prihvatljive soli kao što je definirano prema zahtjevu 1, gdje postupak obuhvaća tretiranje benzimidazola formule (I) kako je definirano u zahtjevu 1 s pogodnom kiselinom u pogodnom rastvaraču.
15. Postupak prema zahtjevu 14, gdje je kiselina izabrana između klorovodonične kiseline, bromovodonične kiseline, jodovodonične kiseline, sumporne kiseline, dušikove kiseline, fosforne kiseline, metansulfonske kiseline, benzensulfonske kiseline, mravlje kiseline, octene kiseline, trifluorooctene kiseline, propionske kiseline, oksalne kiseline, malonske kiseline, sukcinske kiseline, fumarne kiseline, maleinske kiseline, mliječne kiseline, jabučne kiseline, vinske kiseline, limunske kiseline, etansulfonske kiseline, asparaginske i glutaminske kiseline.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1721812.4A GB201721812D0 (en) | 2017-12-22 | 2017-12-22 | Pharmaceutical compounds |
| PCT/GB2018/053756 WO2019122928A1 (en) | 2017-12-22 | 2018-12-21 | Pharmaceutical compounds |
| EP18829962.2A EP3728220B1 (en) | 2017-12-22 | 2018-12-21 | Pharmaceutical compounds |
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| HRP20220427T1 true HRP20220427T1 (hr) | 2022-06-24 |
| HRP20220427T8 HRP20220427T8 (hr) | 2022-07-22 |
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| US (1) | US11141406B2 (hr) |
| EP (1) | EP3728220B1 (hr) |
| JP (1) | JP2021508341A (hr) |
| CY (1) | CY1125097T1 (hr) |
| DK (1) | DK3728220T3 (hr) |
| ES (1) | ES2905650T3 (hr) |
| GB (1) | GB201721812D0 (hr) |
| HR (1) | HRP20220427T8 (hr) |
| HU (1) | HUE058039T2 (hr) |
| LT (1) | LT3728220T (hr) |
| PL (1) | PL3728220T3 (hr) |
| PT (1) | PT3728220T (hr) |
| RS (1) | RS63049B1 (hr) |
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| EP1263754A1 (en) | 2000-02-01 | 2002-12-11 | Millennium Pharmaceuticals, Inc. | INDALONE AND BENZIMIDAZOLONE INHIBITORS OF FACTOR Xa |
| US6774134B2 (en) | 2000-12-20 | 2004-08-10 | Bristol-Myers Squibb Company | Heterocyclic substituted 2-methyl-benzimidazole antiviral agents |
| US6919331B2 (en) | 2001-12-10 | 2005-07-19 | Bristol-Myers Squibb Company | Substituted 2-methyl-benzimidazole respiratory syncytial virus antiviral agents |
| WO2010103306A1 (en) | 2009-03-10 | 2010-09-16 | Astrazeneca Uk Limited | Benzimidazole derivatives and their use as antivaral agents |
| GB201119538D0 (en) * | 2011-11-10 | 2011-12-21 | Viral Ltd | Pharmaceutical compounds |
| EP2997028A1 (en) | 2013-05-14 | 2016-03-23 | F.Hoffmann-La Roche Ag | Aza-oxo-indoles for the treatment and prophylaxis of respiratory syncytial virus infection |
| JPWO2015012400A1 (ja) | 2013-07-26 | 2017-03-02 | 大正製薬株式会社 | グリシントランスポーター阻害物質 |
| CA2914541A1 (en) * | 2013-08-15 | 2015-02-19 | F. Hoffmann-La Roche Ag | Novel aza-oxo-indoles for the treatment and prophylaxis of respiratory syncytial virus infection |
| TWI671299B (zh) * | 2014-04-14 | 2019-09-11 | 愛爾蘭商健生科學愛爾蘭無限公司 | 作為ｒｓｖ抗病毒化合物之螺脲化合物 |
| GB201417707D0 (en) * | 2014-10-07 | 2014-11-19 | Viral Ltd | Pharmaceutical compounds |
-
2017
- 2017-12-22 GB GBGB1721812.4A patent/GB201721812D0/en not_active Ceased
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2018
- 2018-12-21 PL PL18829962T patent/PL3728220T3/pl unknown
- 2018-12-21 US US16/955,568 patent/US11141406B2/en active Active
- 2018-12-21 EP EP18829962.2A patent/EP3728220B1/en active Active
- 2018-12-21 RS RS20220286A patent/RS63049B1/sr unknown
- 2018-12-21 DK DK18829962.2T patent/DK3728220T3/da active
- 2018-12-21 HU HUE18829962A patent/HUE058039T2/hu unknown
- 2018-12-21 HR HRP20220427TT patent/HRP20220427T8/hr unknown
- 2018-12-21 ES ES18829962T patent/ES2905650T3/es active Active
- 2018-12-21 WO PCT/GB2018/053756 patent/WO2019122928A1/en unknown
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- 2018-12-21 JP JP2020554951A patent/JP2021508341A/ja not_active Withdrawn
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| Publication number | Publication date |
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| HRP20220427T8 (hr) | 2022-07-22 |
| GB201721812D0 (en) | 2018-02-07 |
| PL3728220T3 (pl) | 2022-05-09 |
| LT3728220T (lt) | 2022-01-25 |
| ES2905650T3 (es) | 2022-04-11 |
| DK3728220T3 (da) | 2022-02-07 |
| US11141406B2 (en) | 2021-10-12 |
| SI3728220T1 (sl) | 2022-04-29 |
| RS63049B1 (sr) | 2022-04-29 |
| WO2019122928A1 (en) | 2019-06-27 |
| CY1125097T1 (el) | 2024-02-16 |
| HUE058039T2 (hu) | 2022-06-28 |
| EP3728220B1 (en) | 2022-01-05 |
| PT3728220T (pt) | 2022-01-19 |
| US20200316030A1 (en) | 2020-10-08 |
| EP3728220A1 (en) | 2020-10-28 |
| JP2021508341A (ja) | 2021-03-04 |
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