HRP20110428T1 - Derivati piperidin-amino-benzimidazola kao inhibitori respiratorne sincitijalne virusne replikacije - Google Patents
Derivati piperidin-amino-benzimidazola kao inhibitori respiratorne sincitijalne virusne replikacije Download PDFInfo
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- HRP20110428T1 HRP20110428T1 HR20110428T HRP20110428T HRP20110428T1 HR P20110428 T1 HRP20110428 T1 HR P20110428T1 HR 20110428 T HR20110428 T HR 20110428T HR P20110428 T HRP20110428 T HR P20110428T HR P20110428 T1 HRP20110428 T1 HR P20110428T1
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- 241000725643 Respiratory syncytial virus Species 0.000 title 1
- 239000003112 inhibitor Substances 0.000 title 1
- 230000029812 viral genome replication Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract 27
- -1 aminocarbonyloxy Chemical group 0.000 claims abstract 25
- 125000001424 substituent group Chemical group 0.000 claims abstract 25
- 125000000217 alkyl group Chemical group 0.000 claims abstract 16
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 8
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims abstract 4
- 150000003839 salts Chemical class 0.000 claims abstract 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract 2
- 150000001204 N-oxides Chemical class 0.000 claims abstract 2
- 150000004696 coordination complex Chemical group 0.000 claims abstract 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 21
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 11
- 229910052739 hydrogen Inorganic materials 0.000 claims 9
- 239000001257 hydrogen Substances 0.000 claims 9
- 125000001475 halogen functional group Chemical group 0.000 claims 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 6
- 125000003386 piperidinyl group Chemical group 0.000 claims 6
- 125000005054 dihydropyrrolyl group Chemical group [H]C1=C([H])C([H])([H])C([H])([H])N1* 0.000 claims 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 5
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 5
- 125000005942 tetrahydropyridyl group Chemical group 0.000 claims 5
- 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims 4
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 4
- 125000000623 heterocyclic group Chemical group 0.000 claims 4
- 238000000034 method Methods 0.000 claims 4
- 125000003373 pyrazinyl group Chemical group 0.000 claims 4
- 125000004076 pyridyl group Chemical group 0.000 claims 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims 4
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 3
- 125000002883 imidazolyl group Chemical group 0.000 claims 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 3
- 125000004193 piperazinyl group Chemical group 0.000 claims 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims 3
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 2
- 125000003545 alkoxy group Chemical group 0.000 claims 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 2
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims 2
- 239000003153 chemical reaction reagent Substances 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 125000002950 monocyclic group Chemical group 0.000 claims 2
- 125000004043 oxo group Chemical group O=* 0.000 claims 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims 2
- 125000001425 triazolyl group Chemical group 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 125000004414 alkyl thio group Chemical group 0.000 claims 1
- 125000003277 amino group Chemical group 0.000 claims 1
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims 1
- 125000004093 cyano group Chemical group *C#N 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 125000002541 furyl group Chemical group 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 claims 1
- 125000001786 isothiazolyl group Chemical group 0.000 claims 1
- 125000000842 isoxazolyl group Chemical group 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims 1
- 125000001715 oxadiazolyl group Chemical group 0.000 claims 1
- 125000002971 oxazolyl group Chemical group 0.000 claims 1
- 125000003226 pyrazolyl group Chemical group 0.000 claims 1
- 125000002098 pyridazinyl group Chemical group 0.000 claims 1
- 125000004590 pyridopyridyl group Chemical group N1=C(C=CC2=C1C=CC=N2)* 0.000 claims 1
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims 1
- 230000010076 replication Effects 0.000 claims 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims 1
- 125000000335 thiazolyl group Chemical group 0.000 claims 1
- 125000001544 thienyl group Chemical group 0.000 claims 1
- 150000001412 amines Chemical group 0.000 abstract 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
- C07D401/14—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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- 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
-
- 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
-
- 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
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 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)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Virology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Spoj formule (I) njegov N-oksid, adicijska sol, kvaternarni amin, metalni kompleks ili stereokemijski izomerni oblik naznačen time da Q je C1-6alkil proizvoljno supstituiran sa jednim ili više supstituenta koji su svaki nezavisno odabrani iz skupine koji čine trifluorometil, C3-7cikloalkil, Ar2, hidroksi, C1-4alkoksi, C1-4alkiltio, Ar2-oksi-, Ar2-tio-, Ar2(CH2)noksi, Ar2(CH2)ntio, hidroksikarbonil, aminokarbonil, C1-4alkilkarbonil, Ar2karbonil, C1-4alkoksikarbonil, Ar2(CH2)nkarbonil, aminokarboniloksi, C1-4alkilkarbonil- oksi, Ar2karboniloksi, Ar2(CH2)nkarboniloksi,
Claims (21)
1. Spoj formule (I)
[image]
njegov N-oksid, adicijska sol, kvaternarni amin, metalni kompleks ili stereokemijski izomerni oblik naznačen time da
Q je C1-6alkil proizvoljno supstituiran sa jednim ili više supstituenta koji su svaki nezavisno odabrani iz skupine koji čine trifluorometil, C3-7cikloalkil, Ar2, hidroksi, C1-4alkoksi, C1-4alkiltio, Ar2-oksi-, Ar2-tio-, Ar2(CH2)noksi, Ar2(CH2)ntio, hidroksikarbonil, aminokarbonil, C1-4alkilkarbonil, Ar2karbonil, C1-4alkoksikarbonil, Ar2(CH2)nkarbonil, aminokarboniloksi, C1-4alkilkarbonil- oksi, Ar2karboniloksi, Ar2(CH2)nkarboniloksi, C1-4alkoksikarbonil(CH2)noksi, mono- ili di(C1-4alkil)aminokarbonil, mono- ili di(C1-4alkil)aminokarboniloksi, aminosulfonil, mono- ili di(C1-4alkil)aminosulfonil ili heterocikal odabran iz skupine koju čine pirolidinil, pirolil, dihidropirolil, imidazolil, triazolil, piperidinil, homopiperidinil, piperazinil, piridil i tetrahidro- piridil, pri čemu svaki od navedenih heterocikala može proizvoljno biti supstituiran sa okso ili C1-6alkilom; ili Q je C1-6alkil supstituiran sa dva supstituenta pri čemu jedan supstituent je odabran iz skupine koju čine amino, mono- i diC1-4alkil- amino i Ar2-C1-4alkilamino, a drugi supstituent je odabran iz skupine koju čine karboksil, C1-6alkiloksikarbonil, Ar2-C1-4alkiloksikarbonil, aminokarbonil i aminosulfonil;
G je direktna veza ili C1-10alkandiil proizvoljno supstituiran sa jednim ili više supstituenata nezavisno odabranih iz skupine koju čine hidroksi, C1-6alkiloksi, Ar1C1-6alkiloksi, C1-6alkiltio, Ar1C1-6alkiltio, HO(-CH2-CH2-O)n-, C1-6alkiloksi(-CH2-CH2-O)n- i Ar1C1-6alkiloksi(-CH2-CH2-O)n-;
R1 je Ar1 ili monociklički ili biciklički heterocikal koji je odabran od piperidinila, piperazinila, piridila, pirazinila, piridazinila, pirimidinila, furanila, tetrahidrofuranila, tienila, pirolila, tiazolila, oksazolila, imidazolila, izotiazolila, pirazolila, izoksazolila, oksadiazolila, kvinolinila, kvinoksalinila, benzofuranila, benzotienila, benzimidazolila, benzoksazolila, benztiazolila, piridopiridila, naftiridinila, 1H imidazo[4,5-b]piridinil, 3H-imidazo[4,5-b]piridinil, imidazo[1,2-a]- piridinil, 2,3-dihidro-1,4-dioksino[2,3-b]piridil ili radikal prema formuli
[image]
[image]
[image]
pri čemu svaki navedeni monociklički ili biciklički heterocikal može proizvoljno biti supstituiran sa 1 ili gdje je moguće više, na primjer sa 2, 3, 4 ili 5, supstituenata nezavisno odabranih iz skupine supstituenata koji čine halo, hidroksi, amino, cijano, karboksil, C1-6alkil, C1-6alkiloksi, C1-6alkiltio, C1-6alkiloksiC1-6alkil, Ar1, Ar1C1-6alkil, Ar1C1-6alkiloksi, hidroksiC1-6alkil, mono-ili di(C1-6alkil)amino, mono-ili di(C1-6alkil)aminoC1-6alkil, polihaloC1-6alkil, C1-6alkilkarbonilamino, C1-6alkil-SO2-NR4a-, Ar1-SO2,-NR4a-, C1-6alkiloksikarbonil, -C(=O)-NR4aR4b, HO(-CH2-CH2-O)n-, halo(-CH2-CH2-O)n-, C1-6alkiloksi(-CH2-CH2-O)n-, Ar1C1-6alkiloksi(-CH2-CH2-O)n- i mono-ili di(C1-6alkil)amino(-CH2-CH2-O)n-;
svaki n nezavisno je 1, 2, 3 ili 4;
jedan od R2a i R3a je C1-6alkil, a drugi od R2a i R3a je vodik;
u slučaju da R2a je različito od vodika tada R2b je C1-6alkil, i R3b je vodik;
u slučaju da R3a je različito od vodika tada R3b je C1-6alkil, i R2b je vodik; ili
R3b je C1-6alkil; i R3a, R2a, R2b svi su vodik;
R4a i R4b mogu biti isti ili mogu biti različiti jedan u odnosu na drugi, i svaki su nezavisno vodik ili C1-6alkil; ili
R4a i R4buzeti zajedno mogu tvoriti bivalentni radikal prema formuli -(CH2)s-;
R5 je vodik ili C1-6alkil;
m je 1 ili 2;
p je 1 ili 2;
s je 4 ili 5;
t je 1, 2 ili 3;
Ar1 je fenil ili fenil supstituiran sa 1 ili više, kao što je 2, 3 ili 4, supstituenata odabranih od halo, hidroksi, C1-6alkil, hidroksiC1-6alkil, polihaloC1-6alkil, i C1-6alkiloksi;
Ar2 je fenil ili fenil supstituiran sa 1 ili više, kao što je 2, 3 ili 4, supstituenata odabranih od skupine koju čine halo, hidroksi, amino, cijano, C1-6alkil, hidroksiC1-6alkil, polihaloC1-6alkil, aminoC1-6alkil, C1-6alkiloksi, amino- sulfonil, aminokarbonil, hidroksikarbonil, C1-4alkilkarbonil, mono- ili di(C1-4alkil)amino, mono- ili di(C1-4alkil)aminokarbonil, mono- ili di(C1-4alkil)aminosulfonil, mono- ili di(C1-4alkil)aminoC1-6alkil i C 1-4alkoksikarbonil.
2. Spoj prema zahtjevu 1, naznačen time da spoj ima formulu
[image]
pri čemu Q, t, R5, G i R1 su kako je definirano u zahtjevu 1; i
R2a je C1-6alkil;
R2b je C1-6alkil.
3. Spoj prema zahtjevu 1, naznačen time da spoj ima formulu
[image]
pri čemu Q, t, R5, G i R1 su kako je definirano u zahtjevu 1; i
R3a je C1-6alkil;
R3b je C1-6alkil.
4. Spoj prema zahtjevu 1, naznačen time da spoj ima formulu
[image]
pri čemu Q, t, R5, G i R1 su kako je definirano u zahtjevu 1; i
R3b je C1-6alkil.
5. Spoj prema bilo kojem od zahtjeva 1 do 4 naznačen time da t je 2.
6. Spoj prema bilo kojem od zahtjeva 1 do 5 naznačen time da G je C1-10alkandiil.
7. Spoj prema bilo kojem od zahtjeva 1 - 5, naznačen time da G je metilen.
8. Spoj prema bilo kojem od zahtjeva 1 - 7, naznačen time da R1 je piridil proizvoljno supstituiran sa 1 ili 2 supstituenta nezavisno odabran iz skupine koju čine halo, hidroksi, amino, cijano, karboksil, C1-6alkil, C1-6alkiloksi, C1-6alkiltio, C1-6alkiloksiC1-6alkil, Ar1, Ar1C1-6alkil, Ar1C1-6alkiloksi, hidroksiC1-6alkil, mono-ili di(C1-6alkil)amino, mono-ili di(C1-6alkil)amino-C1-6alkil, polihaloC1-6alkil, C1-6alkilkarbonilamino, C1-6alkil-SO2-NR4a-, Ar1-SO2-NR4a-, C1-6alkiloksikarbonil, -C(=O)-NR4aR4b, HO(-CH2-CH2-O)n-, halo(-CH2-CH2-O)n-, C1-6alkiloksi(-CH2-CH2-O)n-, Ar1C1-6alkiloksi(-CH2CH2-O)n- i mono-ili di(C1-6alkil)amino(-CH2-CH2-O)n-.
9. Spoj prema bilo kojem od zahtjeva 1 - 7, naznačen time da R1 je piridil supstituiran sa 1 ili 2 supstituenta nezavisno odabrana iz skupine koju čine hidroksi i C1-6alkil.
10. Spoj prema bilo kojem od zahtjeva 1 - 7, naznačen time da R1 je Ar1, kvinolinil, benzimidazolil, radikal formule
[image]
ili pirazinil; pri čemu svaki od radikala Ar1, kvinolinil, benzimidazolil, (c-4), ili pirazinil mogu proizvoljno biti supstituirani sa supstituentima navedenih radikala kako je zatraženo u zahtjevu 1.
11. Spoj prema bilo kojem od zahtjeva 1-7, naznačen time da R1 je fenil proizvoljno supstituiran sa jednim, dva ili tri radikala odabranih iz skupine koju čine halo, hidroksi, C1-6alkil, C1-6alkiloksi; kvinolinil; radikal (c-4) pri čemu m je 2, proizvoljno supstituiran sa do dva radikala odabranih od C1-6alkila; benzimidazolil proizvoljno supstituiran sa C1-6alkilom; pirazinil proizvoljno supstituiran sa do tri radikala odabranih od C1-6alkila.
12. Spoj prema bilo kojem od zahtjeva 1 - 11, naznačen time da R5 je vodik.
13. Spoj prema bilo kojem od zahtjeva 1 - 12, naznačen time da Q je C1-6alkil proizvoljno supstituiran sa jednim ili dva supstituenta koji su svaki nezavisno odabrani od trifluorometil, C3-7cikloalkil, Ar2, hidroksi, C1-4alkoksi, Ar2-oksi-, Ar2(CH2)noksi, hidroksikarbonil, aminokarbonil, C1-4alkilkarbonil, C1-4alkoksikarbonil, aminokarboniloksi, M(CH2)nkarboniloksi, C1-4alkoksikarbonil-(CH2)noksi, mono- ili di(C1-4alkil)aminokarbonil, aminosulfonil, mono- ili di(C1-4alkil)aminosulfonil ili heterocikal odabran od pirolidinila, pirolila, dihidropirolila, imidazolila, triazolila, piperidinila, homopiperidinila, piperazinila i tetrahidropiridila, pri čemu svaki navedeni heterocikal može proizvoljno biti supstituiran sa okso ili C1-6alkilom; ili Q je C1-6alkil supstituiran sa dva supstituenta pri čemu jedan supstituent je odabran od amino, a drugi supstituent je odabran od karboksila i C1-6alkiloksikarbonila.
14. Spoj prema bilo kojem od zahtjeva 1-12, naznačen time da Q je C1-6alkil proizvoljno supstituiran sa jednim ili dva supstituenta koji su svaki nezavisno odabrani od aminokarbonil, C1-4alkoksikarbonil, aminokarboniloksi, Ar2(CH2)nkarboniloksi, mono- ili di(C1-4alkilaminokarbonil, aminosulfonil, mono- ili di(C1-4alkilaminosulfonil, pirolidinil, dihidropirolil, piperidinil, homopiperidinil i tetrahidropiridil; ili Q je C1-6alkil supstituiran sa dva supstituenta pri čemu je jedan amino, a drugi supstituent je odabran od karboksila i C1-6alkiloksikarbonila.
15. Spoj prema bilo kojem od zahtjeva 1-12, naznačen time da Q je C1-6alkil proizvoljno supstituiran sa jednim supstituentom odabranim od aminokarbonil, C1-4alkoksikarbonil, aminokarboniloksi, Ar2(CH2)nkarboniloksi, mono- ili di(C1-4alkil)-aminokarbonil, aminosulfonil, mono- ili di(C1-4alkilaminosulfonil, pirolidinil, dihidropirolil, piperidinil, homopiperidinil i tetrahidropiridil, i proizvoljno sa drugim supstituentom koji je hidroksi ili Q je C1-6alkil supstituiran sa dva supstituenta pri čemu jedan supstituent je amino, a drugi supstituent je odabran od karboksila i C1-6alkiloksikarbonil.
16. Spoj prema bilo kojem od zahtjeva 1 - 12, naznačen time da Q je C1-6alkil supstituiran sa aminokarbonilom, C1-4alkoksikarbonilom, aminokarboniloksi, mono- ili di(C1-4alkil)aminokarbonilom, aminosulfonil, mono- ili di(C1-4alkil)aminosulfonilom, pirolidinilom, dihidropirolilom, piperidinilom, homopiperidinilom ili tetrahidropiridilom.
17. Spoj prema bilo kojem od zahtjeva 1 do 16 naznačen time da je za upotrebu kao lijek.
18. Farmaceutski pripravak naznačen time da sadrži farmaceutski prihvatljiv nosač, i kao aktivni sastojak terapeutski učinkovitu količinu spoja prema bilo kojem od zahtjeva 1 do 16.
19. Postupak dobivanja farmaceutskog pripravka prema zahtjevu 18, naznačen time da navedeni postupak sadrži blisko miješanje farmaceutski prihvatljivog nosača sa terapeutski učinkovitom količinom spoja prema bilo kojem od zahtjeva 1 do 16.
20. Upotreba spoja prema bilo kojem od zahtjeva 1 do 16 naznačena time da je za proizvodnju lijeka za inhibiciju RSV replikacije.
21. Postupak dobivanja spoja prema bilo kojem od zahtjeva 1 do 23, naznačen time da navedeni postupak sadrži
(a) reakciju intermedijera formule (II) sa reagensom (III) kao što je prikazano u slijedećoj reakcijskoj shemi:
[image]
(b) reakciju intermedijera formule (IV) sa reagensom (V) kao što je prikazano u slijedećoj reakcijskoj shemi:
[image]
pri čemu Q, G, t, R1 R2a, R2b, R3a, R3b, R5 su kako je zatraženo u bilo kojem od zahtjeva 1 do 16; i proizvoljno pretvaranja tako dobivenih spojeva formule (I) u njihov farmaceutski prihvatljiv oblik bazno-adicijske ili kisele adicijske soli tretmanom sa pogodnom bazom ili kiselinom i obrnuto tretiranja bazno-adicijskog ili kiselo adicijskog oblika soli sa kiselinom ili bazom kako bi se dobio slobodan oblik spoja prema formuli (I).
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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EP03104802 | 2003-12-18 | ||
US56683504P | 2004-04-30 | 2004-04-30 | |
PCT/EP2004/053606 WO2005058873A1 (en) | 2003-12-18 | 2004-12-20 | Piperidine-amino-benzimidazole derivatives as inhibitors of respiratory syncytial virus replication |
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HRP20110428T1 true HRP20110428T1 (hr) | 2011-08-31 |
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HR20110428T HRP20110428T1 (hr) | 2003-12-18 | 2011-06-08 | Derivati piperidin-amino-benzimidazola kao inhibitori respiratorne sincitijalne virusne replikacije |
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Country | Link |
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US (2) | US7355051B2 (hr) |
EP (1) | EP1723136B1 (hr) |
JP (1) | JP2007514715A (hr) |
KR (1) | KR101074334B1 (hr) |
CN (2) | CN1894239A (hr) |
AR (1) | AR046771A1 (hr) |
AT (1) | ATE501135T1 (hr) |
AU (1) | AU2004298456B2 (hr) |
BR (1) | BRPI0417668A (hr) |
CA (1) | CA2548654C (hr) |
DE (1) | DE602004031776D1 (hr) |
DK (1) | DK1723136T3 (hr) |
HR (1) | HRP20110428T1 (hr) |
MX (1) | MXPA06007109A (hr) |
RU (1) | RU2381224C2 (hr) |
TW (1) | TWI349007B (hr) |
WO (1) | WO2005058873A1 (hr) |
Families Citing this family (49)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
HU230382B1 (hu) * | 2001-02-24 | 2016-03-29 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Xantinszármazékok, előállításuk és alkalmazásuk gyógyszerként |
US7407955B2 (en) | 2002-08-21 | 2008-08-05 | Boehringer Ingelheim Pharma Gmbh & Co., Kg | 8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions |
US7569574B2 (en) | 2002-08-22 | 2009-08-04 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Purine derivatives, the preparation thereof and their use as pharmaceutical compositions |
US7495005B2 (en) * | 2002-08-22 | 2009-02-24 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Xanthine derivatives, their preparation and their use in pharmaceutical compositions |
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DE10254304A1 (de) * | 2002-11-21 | 2004-06-03 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Xanthinderivate, deren Herstellung und deren Verwendung als Arzneimittel |
US7566707B2 (en) * | 2003-06-18 | 2009-07-28 | Boehringer Ingelheim International Gmbh | Imidazopyridazinone and imidazopyridone derivatives, the preparation thereof and their use as pharmaceutical compositions |
DE10355304A1 (de) | 2003-11-27 | 2005-06-23 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue 8-(Piperazin-1-yl)-und 8-([1,4]Diazepan-1-yl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel |
US7501426B2 (en) * | 2004-02-18 | 2009-03-10 | Boehringer Ingelheim International Gmbh | 8-[3-amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical compositions |
DE102004009039A1 (de) * | 2004-02-23 | 2005-09-08 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 8-[3-Amino-piperidin-1-yl]-xanthine, deren Herstellung und Verwendung als Arzneimittel |
US7393847B2 (en) * | 2004-03-13 | 2008-07-01 | Boehringer Ingleheim International Gmbh | Imidazopyridazinediones, their preparation and their use as pharmaceutical compositions |
US7179809B2 (en) * | 2004-04-10 | 2007-02-20 | Boehringer Ingelheim International Gmbh | 2-Amino-imidazo[4,5-d]pyridazin-4-ones, their preparation and their use as pharmaceutical compositions |
US7439370B2 (en) | 2004-05-10 | 2008-10-21 | Boehringer Ingelheim International Gmbh | Imidazole derivatives, their preparation and their use as intermediates for the preparation of pharmaceutical compositions and pesticides |
DE102004030502A1 (de) * | 2004-06-24 | 2006-01-12 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Imidazole und Triazole, deren Herstellung und Verwendung als Arzneimittel |
DE102004043944A1 (de) * | 2004-09-11 | 2006-03-30 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue 8-(3-Amino-piperidin-1-yl)-7-(but-2-inyl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel |
DE102004044221A1 (de) * | 2004-09-14 | 2006-03-16 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue 3-Methyl-7-butinyl-xanthine, deren Herstellung und deren Verwendung als Arzneimittel |
DE102004054054A1 (de) * | 2004-11-05 | 2006-05-11 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verfahren zur Herstellung chiraler 8-(3-Amino-piperidin-1-yl)-xanthine |
TWI370820B (en) | 2005-04-27 | 2012-08-21 | Takeda Pharmaceutical | Fused heterocyclic compounds |
DE102005035891A1 (de) * | 2005-07-30 | 2007-02-08 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | 8-(3-Amino-piperidin-1-yl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel |
NZ619413A (en) | 2006-05-04 | 2015-08-28 | Boehringer Ingelheim Int | Polymorphs of a dpp-iv enzyme inhibitor |
PE20110235A1 (es) | 2006-05-04 | 2011-04-14 | Boehringer Ingelheim Int | Combinaciones farmaceuticas que comprenden linagliptina y metmorfina |
EP1852108A1 (en) | 2006-05-04 | 2007-11-07 | Boehringer Ingelheim Pharma GmbH & Co.KG | DPP IV inhibitor formulations |
WO2008017670A1 (en) | 2006-08-08 | 2008-02-14 | Boehringer Ingelheim International Gmbh | Pyrrolo [3, 2 -d] pyrimidines as dpp-iv inhibitors for the treatment of diabetes mellitus |
AR071175A1 (es) | 2008-04-03 | 2010-06-02 | Boehringer Ingelheim Int | Composicion farmaceutica que comprende un inhibidor de la dipeptidil-peptidasa-4 (dpp4) y un farmaco acompanante |
UY32030A (es) | 2008-08-06 | 2010-03-26 | Boehringer Ingelheim Int | "tratamiento para diabetes en pacientes inapropiados para terapia con metformina" |
KR20190016601A (ko) | 2008-08-06 | 2019-02-18 | 베링거 인겔하임 인터내셔날 게엠베하 | 메트포르민 요법이 부적합한 환자에서의 당뇨병 치료 |
RU2011113823A (ru) | 2008-09-10 | 2012-10-20 | БЕРИНГЕР ИНГЕЛЬХАЙМ ИНТЕРНАЦИОНАЛЬ ГмбХ (DE) | Комбинированная терапия, предназначенная для лечения диабета и связанных с ним состояний |
US20200155558A1 (en) | 2018-11-20 | 2020-05-21 | Boehringer Ingelheim International Gmbh | Treatment for diabetes in patients with insufficient glycemic control despite therapy with an oral antidiabetic drug |
JP2012512848A (ja) | 2008-12-23 | 2012-06-07 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 有機化合物の塩の形態 |
AR074990A1 (es) | 2009-01-07 | 2011-03-02 | Boehringer Ingelheim Int | Tratamiento de diabetes en pacientes con un control glucemico inadecuado a pesar de la terapia con metformina |
WO2011016576A1 (en) | 2009-08-04 | 2011-02-10 | Takeda Pharmaceutical Company Limited | Alanine derivatives as inhibitors of apoptosis proteins |
JP2013512229A (ja) | 2009-11-27 | 2013-04-11 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 遺伝子型が同定された糖尿病患者のリナグリプチン等のddp−iv阻害薬による治療 |
BR112012028136A2 (pt) | 2010-05-05 | 2016-08-09 | Boehringer Ingelheim Int | terapia de combinaçao |
EP3725325B1 (en) | 2010-06-24 | 2023-05-31 | Boehringer Ingelheim International GmbH | Diabetes therapy |
US9034883B2 (en) | 2010-11-15 | 2015-05-19 | Boehringer Ingelheim International Gmbh | Vasoprotective and cardioprotective antidiabetic therapy |
WO2012174312A2 (en) * | 2011-06-15 | 2012-12-20 | Glaxosmithkline Llc | Benzimidazole derivatives as antiviral agents |
CN103781788B (zh) | 2011-07-15 | 2016-08-17 | 勃林格殷格翰国际有限公司 | 经取代的喹唑啉、其制备及其在药物组合物中的用途 |
US9555001B2 (en) | 2012-03-07 | 2017-01-31 | Boehringer Ingelheim International Gmbh | Pharmaceutical composition and uses thereof |
EP3685839A1 (en) | 2012-05-14 | 2020-07-29 | Boehringer Ingelheim International GmbH | Linagliptin for use in the treatment of albuminuria and kidney related diseases |
WO2013174767A1 (en) | 2012-05-24 | 2013-11-28 | Boehringer Ingelheim International Gmbh | A xanthine derivative as dpp -4 inhibitor for use in modifying food intake and regulating food preference |
EP3110449B1 (en) | 2014-02-28 | 2023-06-28 | Boehringer Ingelheim International GmbH | Medical use of a dpp-4 inhibitor |
MA41614A (fr) * | 2015-02-25 | 2018-01-02 | Alios Biopharma Inc | Composés antiviraux |
MX2018015089A (es) | 2016-06-10 | 2019-05-13 | Boehringer Ingelheim Int | Combinacion de linagliptina y metformina. |
TW201825465A (zh) | 2016-09-23 | 2018-07-16 | 美商基利科學股份有限公司 | 磷脂醯肌醇3-激酶抑制劑 |
TW201815787A (zh) | 2016-09-23 | 2018-05-01 | 美商基利科學股份有限公司 | 磷脂醯肌醇3-激酶抑制劑 |
TW201813963A (zh) | 2016-09-23 | 2018-04-16 | 美商基利科學股份有限公司 | 磷脂醯肌醇3-激酶抑制劑 |
KR102296703B1 (ko) | 2017-03-20 | 2021-09-01 | 포르마 세라퓨틱스 인크. | 피루베이트 키나제 (pkr) 활성화제로서의 피롤로피롤 조성물 |
BR112021005188A2 (pt) | 2018-09-19 | 2021-06-08 | Forma Therapeutics, Inc. | tratamento de anemia falciforme com um composto de ativação de piruvato cinase r |
US20230055923A1 (en) | 2018-09-19 | 2023-02-23 | Forma Therapeutics, Inc. | Activating pyruvate kinase r |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4219559A (en) * | 1979-01-10 | 1980-08-26 | Janssen Pharmaceutica N.V. | N-Heterocyclyl-4-piperidinamines |
CA1140119A (en) * | 1978-04-03 | 1983-01-25 | Joseph Torremans | N-heterocyclyl-4-piperidinamines |
US4556660A (en) | 1982-07-12 | 1985-12-03 | Janssen Pharmaceutica N.V. | N-(Bicyclic heterocyclyl)-4-piperidinamines |
US4634704A (en) | 1983-10-06 | 1987-01-06 | Janssen Pharmaceutica, N.V. | Anti-allergic five membered heterocyclic ring containing N-(bicyclic heterocycyl)-4-piperidinamines |
KR100190299B1 (ko) | 1990-07-19 | 1999-06-01 | 디르크 반테 | 신규한 옥사졸릴 유도체 |
CA2376785A1 (en) * | 1999-06-28 | 2001-01-04 | Janssen Pharmaceutica N.V. | Benzimidazoles and imidazopyridines as respiratory syncytial virus replication inhibitors |
SK18942001A3 (sk) | 1999-06-28 | 2002-10-08 | Janssen Pharmaceutica N. V. | Inhibítory replikácie respiračného syncytiálneho vírusu |
UA74787C2 (en) * | 1999-06-28 | 2006-02-15 | Janssen Pharmaceutica Nv | Respiratory syncytial virus replication inhibitors |
-
2004
- 2004-12-20 DK DK04804942.3T patent/DK1723136T3/da active
- 2004-12-20 MX MXPA06007109A patent/MXPA06007109A/es active IP Right Grant
- 2004-12-20 CN CNA2004800372846A patent/CN1894239A/zh active Pending
- 2004-12-20 TW TW093139922A patent/TWI349007B/zh not_active IP Right Cessation
- 2004-12-20 BR BRPI0417668-5A patent/BRPI0417668A/pt not_active IP Right Cessation
- 2004-12-20 AT AT04804942T patent/ATE501135T1/de not_active IP Right Cessation
- 2004-12-20 US US10/596,519 patent/US7355051B2/en active Active
- 2004-12-20 DE DE602004031776T patent/DE602004031776D1/de active Active
- 2004-12-20 AR ARP040104809A patent/AR046771A1/es not_active Application Discontinuation
- 2004-12-20 WO PCT/EP2004/053606 patent/WO2005058873A1/en active Application Filing
- 2004-12-20 CN CN201310195044XA patent/CN103450159A/zh active Pending
- 2004-12-20 JP JP2006544461A patent/JP2007514715A/ja not_active Withdrawn
- 2004-12-20 AU AU2004298456A patent/AU2004298456B2/en not_active Ceased
- 2004-12-20 CA CA2548654A patent/CA2548654C/en not_active Expired - Fee Related
- 2004-12-20 EP EP04804942A patent/EP1723136B1/en active Active
- 2004-12-20 RU RU2006125720/04A patent/RU2381224C2/ru not_active IP Right Cessation
-
2006
- 2006-06-30 KR KR1020067013313A patent/KR101074334B1/ko not_active IP Right Cessation
-
2008
- 2008-02-13 US US12/030,483 patent/US20080146613A1/en not_active Abandoned
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2011
- 2011-06-08 HR HR20110428T patent/HRP20110428T1/hr unknown
Also Published As
Publication number | Publication date |
---|---|
US7355051B2 (en) | 2008-04-08 |
AU2004298456A1 (en) | 2005-06-30 |
MXPA06007109A (es) | 2006-08-23 |
DK1723136T3 (da) | 2011-06-27 |
JP2007514715A (ja) | 2007-06-07 |
BRPI0417668A (pt) | 2007-04-03 |
TW200533669A (en) | 2005-10-16 |
EP1723136A1 (en) | 2006-11-22 |
EP1723136B1 (en) | 2011-03-09 |
TWI349007B (en) | 2011-09-21 |
CN103450159A (zh) | 2013-12-18 |
RU2381224C2 (ru) | 2010-02-10 |
WO2005058873A1 (en) | 2005-06-30 |
KR101074334B1 (ko) | 2011-10-17 |
DE602004031776D1 (de) | 2011-04-21 |
RU2006125720A (ru) | 2008-01-27 |
CN1894239A (zh) | 2007-01-10 |
US20080146613A1 (en) | 2008-06-19 |
ATE501135T1 (de) | 2011-03-15 |
AU2004298456B2 (en) | 2011-04-07 |
AR046771A1 (es) | 2005-12-21 |
CA2548654A1 (en) | 2005-06-30 |
CA2548654C (en) | 2012-08-07 |
US20070093659A1 (en) | 2007-04-26 |
KR20060117985A (ko) | 2006-11-17 |
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