AR084516A1 - METABOTROPIC GLUTAMATE RECEIVERS MODULATORS - Google Patents
METABOTROPIC GLUTAMATE RECEIVERS MODULATORSInfo
- Publication number
- AR084516A1 AR084516A1 ARP110104855A ARP110104855A AR084516A1 AR 084516 A1 AR084516 A1 AR 084516A1 AR P110104855 A ARP110104855 A AR P110104855A AR P110104855 A ARP110104855 A AR P110104855A AR 084516 A1 AR084516 A1 AR 084516A1
- Authority
- AR
- Argentina
- Prior art keywords
- amino
- dihydroquinazolin
- alkyl
- dimethyl
- methyl
- Prior art date
Links
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 title 1
- 229930195712 glutamate Natural products 0.000 title 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 14
- -1 amino, hydroxy Chemical group 0.000 abstract 12
- 229910052736 halogen Inorganic materials 0.000 abstract 8
- 150000002367 halogens Chemical class 0.000 abstract 8
- 125000001424 substituent group Chemical group 0.000 abstract 8
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 abstract 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 8
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 6
- 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 abstract 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract 6
- 125000000217 alkyl group Chemical group 0.000 abstract 6
- 229910052799 carbon Inorganic materials 0.000 abstract 4
- 150000001875 compounds Chemical class 0.000 abstract 4
- 229910052757 nitrogen Chemical group 0.000 abstract 4
- 229910052760 oxygen Inorganic materials 0.000 abstract 4
- 229910052717 sulfur Inorganic materials 0.000 abstract 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract 3
- 125000002252 acyl group Chemical group 0.000 abstract 3
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 abstract 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract 3
- 125000004432 carbon atom Chemical group C* 0.000 abstract 3
- 125000004093 cyano group Chemical group *C#N 0.000 abstract 3
- 125000005842 heteroatom Chemical group 0.000 abstract 3
- 239000001301 oxygen Chemical group 0.000 abstract 3
- 229920006395 saturated elastomer Polymers 0.000 abstract 3
- 239000011593 sulfur Substances 0.000 abstract 3
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 abstract 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 abstract 2
- 125000003545 alkoxy group Chemical group 0.000 abstract 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 abstract 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 2
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 abstract 1
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 abstract 1
- UVYRJNUVMYXOKP-UHFFFAOYSA-N 2-(2,4-dichloroanilino)-7-methyl-7,8-dihydro-6h-quinazolin-5-one Chemical compound N1=C2CC(C)CC(=O)C2=CN=C1NC1=CC=C(Cl)C=C1Cl UVYRJNUVMYXOKP-UHFFFAOYSA-N 0.000 abstract 1
- AYPHWSGHNQZCEV-UHFFFAOYSA-N 2-(2-methoxyanilino)-7,7-dimethyl-6,8-dihydroquinazolin-5-one Chemical compound COC1=CC=CC=C1NC1=NC=C(C(=O)CC(C)(C)C2)C2=N1 AYPHWSGHNQZCEV-UHFFFAOYSA-N 0.000 abstract 1
- JCKWQYINBVNSQH-UHFFFAOYSA-N 2-(2-methoxyanilino)-7-methyl-7,8-dihydro-6h-quinazolin-5-one Chemical compound COC1=CC=CC=C1NC1=NC=C(C(=O)CC(C)C2)C2=N1 JCKWQYINBVNSQH-UHFFFAOYSA-N 0.000 abstract 1
- BVCITABAYKSHIA-UHFFFAOYSA-N 2-(3,4-dimethylanilino)-7-methyl-7,8-dihydro-6h-quinazolin-5-one Chemical compound N1=C2CC(C)CC(=O)C2=CN=C1NC1=CC=C(C)C(C)=C1 BVCITABAYKSHIA-UHFFFAOYSA-N 0.000 abstract 1
- DYSMSOZGDSBFGJ-UHFFFAOYSA-N 2-(3-methylanilino)-7,8-dihydro-6h-quinazolin-5-one Chemical compound CC1=CC=CC(NC=2N=C3CCCC(=O)C3=CN=2)=C1 DYSMSOZGDSBFGJ-UHFFFAOYSA-N 0.000 abstract 1
- OUWOUICAXVWGOV-UHFFFAOYSA-N 2-(4-ethylanilino)-7,7-dimethyl-6,8-dihydroquinazolin-5-one Chemical compound C1=CC(CC)=CC=C1NC1=NC=C(C(=O)CC(C)(C)C2)C2=N1 OUWOUICAXVWGOV-UHFFFAOYSA-N 0.000 abstract 1
- VXCOZWHCCMPUAM-UHFFFAOYSA-N 2-(4-ethylanilino)-7-methyl-7,8-dihydro-6h-quinazolin-5-one Chemical compound C1=CC(CC)=CC=C1NC1=NC=C(C(=O)CC(C)C2)C2=N1 VXCOZWHCCMPUAM-UHFFFAOYSA-N 0.000 abstract 1
- DEEMVIYBZUVSSY-UHFFFAOYSA-N 2-(4-fluoroanilino)-7,7-dimethyl-6,8-dihydroquinazolin-5-one Chemical compound N1=C2CC(C)(C)CC(=O)C2=CN=C1NC1=CC=C(F)C=C1 DEEMVIYBZUVSSY-UHFFFAOYSA-N 0.000 abstract 1
- KBVOQEPNTWNERF-UHFFFAOYSA-N 2-(4-fluoroanilino)-7,8-dihydro-6h-quinazolin-5-one Chemical compound C1=CC(F)=CC=C1NC1=NC=C(C(=O)CCC2)C2=N1 KBVOQEPNTWNERF-UHFFFAOYSA-N 0.000 abstract 1
- RNPRKYWGEVJQMP-UHFFFAOYSA-N 2-(4-fluoroanilino)-7-methyl-7,8-dihydro-6h-quinazolin-5-one Chemical compound N1=C2CC(C)CC(=O)C2=CN=C1NC1=CC=C(F)C=C1 RNPRKYWGEVJQMP-UHFFFAOYSA-N 0.000 abstract 1
- WYHYXVIMEYVIAO-UHFFFAOYSA-N 2-(4-methoxyanilino)-7,7-dimethyl-6,8-dihydroquinazolin-5-one Chemical compound C1=CC(OC)=CC=C1NC1=NC=C(C(=O)CC(C)(C)C2)C2=N1 WYHYXVIMEYVIAO-UHFFFAOYSA-N 0.000 abstract 1
- IWTAOVDGCFFSAF-UHFFFAOYSA-N 2-(4-methoxyanilino)-7,8-dihydro-6h-quinazolin-5-one Chemical compound C1=CC(OC)=CC=C1NC1=NC=C(C(=O)CCC2)C2=N1 IWTAOVDGCFFSAF-UHFFFAOYSA-N 0.000 abstract 1
- FAZOGWIEGACWAA-UHFFFAOYSA-N 2-(4-methoxyanilino)-7-methyl-7,8-dihydro-6h-quinazolin-5-one Chemical compound C1=CC(OC)=CC=C1NC1=NC=C(C(=O)CC(C)C2)C2=N1 FAZOGWIEGACWAA-UHFFFAOYSA-N 0.000 abstract 1
- GSYOTFDFISKQPY-UHFFFAOYSA-N 2-(4-methylanilino)-7,8-dihydro-6h-quinazolin-5-one Chemical compound C1=CC(C)=CC=C1NC1=NC=C(C(=O)CCC2)C2=N1 GSYOTFDFISKQPY-UHFFFAOYSA-N 0.000 abstract 1
- APMVGNPBLZECRV-UHFFFAOYSA-N 2-(cyclopentylamino)-7,7-dimethyl-6,8-dihydroquinazolin-5-one Chemical compound N1=C2CC(C)(C)CC(=O)C2=CN=C1NC1CCCC1 APMVGNPBLZECRV-UHFFFAOYSA-N 0.000 abstract 1
- GNGCMRJKOOHKLT-UHFFFAOYSA-N 2-[3-(trifluoromethyl)anilino]-7,8-dihydro-6h-quinazolin-5-one Chemical compound FC(F)(F)C1=CC=CC(NC=2N=C3CCCC(=O)C3=CN=2)=C1 GNGCMRJKOOHKLT-UHFFFAOYSA-N 0.000 abstract 1
- HWIYZTJLAMSYNO-UHFFFAOYSA-N 2-anilino-7,7-dimethyl-6,8-dihydroquinazolin-5-one Chemical compound N1=C2CC(C)(C)CC(=O)C2=CN=C1NC1=CC=CC=C1 HWIYZTJLAMSYNO-UHFFFAOYSA-N 0.000 abstract 1
- GPVKSROWFGDUKP-UHFFFAOYSA-N 2-anilino-7,8-dihydro-6h-quinazolin-5-one Chemical compound N=1C=C2C(=O)CCCC2=NC=1NC1=CC=CC=C1 GPVKSROWFGDUKP-UHFFFAOYSA-N 0.000 abstract 1
- JPPUUZHXXFEOQF-UHFFFAOYSA-N 2-anilino-7-methyl-7,8-dihydro-6h-quinazolin-5-one Chemical compound N1=C2CC(C)CC(=O)C2=CN=C1NC1=CC=CC=C1 JPPUUZHXXFEOQF-UHFFFAOYSA-N 0.000 abstract 1
- SCEIRFNZRFIPRN-UHFFFAOYSA-N 7,7-dimethyl-2-(3-methylanilino)-6,8-dihydroquinazolin-5-one Chemical compound CC1=CC=CC(NC=2N=C3CC(C)(C)CC(=O)C3=CN=2)=C1 SCEIRFNZRFIPRN-UHFFFAOYSA-N 0.000 abstract 1
- QNTJTLOEIHXVSM-UHFFFAOYSA-N 7,7-dimethyl-2-(4-methylanilino)-6,8-dihydroquinazolin-5-one Chemical compound C1=CC(C)=CC=C1NC1=NC=C(C(=O)CC(C)(C)C2)C2=N1 QNTJTLOEIHXVSM-UHFFFAOYSA-N 0.000 abstract 1
- DBHTVYKJUZBVHY-UHFFFAOYSA-N 7,7-dimethyl-2-[3-(trifluoromethyl)anilino]-6,8-dihydroquinazolin-5-one Chemical compound N1=C2CC(C)(C)CC(=O)C2=CN=C1NC1=CC=CC(C(F)(F)F)=C1 DBHTVYKJUZBVHY-UHFFFAOYSA-N 0.000 abstract 1
- BAFPXHFNDNHTER-UHFFFAOYSA-N 7-methyl-2-(4-methylanilino)-7,8-dihydro-6h-quinazolin-5-one Chemical compound N1=C2CC(C)CC(=O)C2=CN=C1NC1=CC=C(C)C=C1 BAFPXHFNDNHTER-UHFFFAOYSA-N 0.000 abstract 1
- CUFHWQVDBWBXRN-UHFFFAOYSA-N 7-methyl-2-(4-phenoxyanilino)-7,8-dihydro-6h-quinazolin-5-one Chemical compound N1=C2CC(C)CC(=O)C2=CN=C1NC(C=C1)=CC=C1OC1=CC=CC=C1 CUFHWQVDBWBXRN-UHFFFAOYSA-N 0.000 abstract 1
- XXGQHSSAOZBHJU-UHFFFAOYSA-N 7-methyl-2-[3-(trifluoromethyl)anilino]-7,8-dihydro-6h-quinazolin-5-one Chemical compound N1=C2CC(C)CC(=O)C2=CN=C1NC1=CC=CC(C(F)(F)F)=C1 XXGQHSSAOZBHJU-UHFFFAOYSA-N 0.000 abstract 1
- RVKXYKKWPRUSGZ-UHFFFAOYSA-N CC1(CC2=NC(=NC=C2C(=O)C1)NC3=CC(=CC(=C3)OC)OC)C Chemical compound CC1(CC2=NC(=NC=C2C(=O)C1)NC3=CC(=CC(=C3)OC)OC)C RVKXYKKWPRUSGZ-UHFFFAOYSA-N 0.000 abstract 1
- 102000012777 Metabotropic Glutamate 5 Receptor Human genes 0.000 abstract 1
- 108010065028 Metabotropic Glutamate 5 Receptor Proteins 0.000 abstract 1
- 208000012902 Nervous system disease Diseases 0.000 abstract 1
- 208000025966 Neurological disease Diseases 0.000 abstract 1
- 230000001154 acute effect Effects 0.000 abstract 1
- 125000003118 aryl group Chemical group 0.000 abstract 1
- 230000001684 chronic effect Effects 0.000 abstract 1
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 abstract 1
- 125000001072 heteroaryl group Chemical group 0.000 abstract 1
- 125000000623 heterocyclic group Chemical group 0.000 abstract 1
- 150000004677 hydrates Chemical class 0.000 abstract 1
- 229910052739 hydrogen Inorganic materials 0.000 abstract 1
- 125000002950 monocyclic group Chemical group 0.000 abstract 1
- 230000003287 optical effect Effects 0.000 abstract 1
- 230000002265 prevention Effects 0.000 abstract 1
- 229940002612 prodrug Drugs 0.000 abstract 1
- 239000000651 prodrug Substances 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 239000012453 solvate Substances 0.000 abstract 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/84—Nitrogen atoms
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Neurology (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
La presente se relaciona además con un proceso para la preparación de dichos compuestos. Los compuestos de la presente son moduladores de mGluR5 y por ello son de utilidad para el control y la prevención de trastornos neurológicos agudos y/o crónicos.Reivindicación 1: Un compuesto caracterizado porque se selecciona entre los de la fórmula (1), donde: X representa CH2 o C=O; Y representa CR6R7, NR8, O ó S; R1 representa H, alquilo C1-6, o F; R2 representa H, alquilo C1-6, o F; o R1 y R2 junto con el átomo de carbono al cual se encuentran unidos forman un anillo de entre 3 y 7 miembros que puede ser saturado o insaturado, donde el anillo opcionalmente puede contener uno o dos heteroátomos seleccionados entre azufre, oxígeno, y nitrógeno y donde el anillo puede estar opcionalmente sustituido con uno o más sustituyentes seleccionados entre halógeno, trifluorometilo, trifluorometoxi, alquilo C1-6, alcoxi C1-6, amino, hidroxi, ciano, acilo, alquil C1-6amino, di-(alquil C1-6)amino, alquil C1-6carbonilamino, y oxo; R3 representa H, alquilo C1-6, o F; R4 representa H, alquilo C1-6, o F; o R3 y R4 junto con el átomo de carbono al cual se encuentran unidos forman un anillo de entre 3 y 7 miembros que puede ser saturado o insaturado, donde el anillo opcionalmente puede contener uno o dos heteroátomos seleccionados entre azufre, oxígeno, y nitrógeno y donde el anillo puede estar opcionalmente sustituido con uno o más sustituyentes seleccionados entre halógeno, trifluorometilo, trifluorometoxi, alquilo C1-6, alcoxi C1-6, amino, hidroxi, ciano, acilo, alquil C1-6amino, di-(alquil C1-6)amino, alquil C1-6carbonilamino, y oxo; R5 representa una porción monocíclica seleccionada entre arilo, heteroarilo, cicloalquilo C3-6, y heterociclilo; R6 representa H, alquilo C1-6, o F; R7 representa H, alquilo C1-6, o F; o R6 y R7 junto con el átomo de carbono al cual se encuentran unidos forman un anillo de entre 3 y 7 miembros que puede ser saturado o insaturado, donde el anillo opcionalmente puede contener uno o dos heteroátomos seleccionados entre azufre, oxígeno, y nitrógeno y donde el anillo puede estar opcionalmente sustituido con uno o más sustituyentes seleccionados entre halógeno, trifluorometilo, trifluorometoxi, alquilo C1-6, alcoxi C1-6, amino, hidroxi, ciano, acilo, alquil C1-6amino, di-(alquil C1-6)amino, alquil C1-6carbonilamino, y oxo; R8 representa H, alquilo C1-6 que puede estar opcionalmente sustituido con uno o más sustituyentes seleccionados entre halógeno, trifluorometilo, trifluorometoxi, alcoxi C1-6, amino, hidroxi, alquil C1-6amino, y di-(alquil C1-6)amino, cicloalquilo C3-6, alquilcarbonilo C1-6 que puede estar opcionalmente sustituido con uno o más sustituyentes seleccionados entre halógeno, trifluorometilo, trifluorometoxi, alcoxi C1-6, amino, hidroxi, alquil C1-6amino, y di-(alquil C1-6)amino, cicloalquil C3-6carbonilo, alcoxicarbonilo C1-6 que puede estar opcionalmente sustituido con uno o más sustituyentes seleccionados entre halógeno, trifluorometilo, trifluorometoxi, alcoxi C1-6, amino, hidroxi, alquil C1-6amino, y di-(alquil C1-6)amino, aminocarbonilo, N-alquil C1-6aminocarbonilo donde la porción alquilo puede estar opcionalmente sustituida con uno o más sustituyentes seleccionados entre halógeno, trifluorometilo, trifluorometoxi, alcoxi C1-6, amino, hidroxi, alquil C1-6amino, y di-(alquil C1-6)amino, N,N-di-(alquil C1-6)aminocarbonilo, donde las porciones alquilo pueden estar opcionalmente sustituidas con uno o más sustituyentes seleccionados entre halógeno, trifluorometilo, trifluorometoxi, alcoxi C1-6, amino, hidroxi, alquil C1-6amino, y di-(alquil C1-6)amino; e isómeros ópticos, prodrogas, sales aceptables farmacéuticamente, hidratos, solvatos, y polimorfos del mismo; donde debe comprenderse que el compuesto de fórmula (1) no puede representar: 2-((2,4-diclorofenil)amino)-7-metil-7,8-dihidroquinazolin-5(6H)-ona, 2-((2,4-dimetilfenil)amino)-7-metil-7,8-dihidroquinazolin-5(6H)-ona, 2-((2-metoxifenil)amino)-7,7-dimetil-7,8-dihidroquinazolin-5(6H)-ona, 2-((2-metoxifenil)amino)-7-metil-7,8-dihidroquinazolin-5(6H)-ona, 2-((3-(trifluorometil)fenil)amino)-7,8-dihidroquinazolin-5(6H)-ona, 2-((3,4-dimetilfenil)amino)-7-metil-7,8-dihidroquinazolin-5(6H)-ona, 2-((3,5-dimetoxifenil)amino)-7,7-dimetil-7,8-dihidroquinazolin-5(6H)-ona, 2-((4-etilfenil)amino)-7,7-dimetil-7,8-dihidroquinazolin-5(6H)-ona, 2-((4-etilfenil)amino)-7-metil-7,8-dihidroquinazolin-5(6H)-ona, 2-((4-fluorofenil)amino)-7,7-dimetil-7,8-dihidroquinazolin-5(6H)-ona, 2-((4-fluorofenil)amino)-7,8-dihidroquinazolin-5(6H)-ona, 2-((4-fluorofenil)amino)-7-metil-7,8-dihidroquinazolin-5(6H)-ona, 2-((4-metoxifenil)amino)-7,7-dimetil-7,8-dihidroquinazolin-5(6H)-ona, 2-((4-metoxifenil)amino)-7,8-dihidroquinazolin-5(6H)ona, 2-((4-metoxifenil)amino)-7-metil-7,8-dihidroquinazolin-5(6H)-ona, 2-(ciclopentilamino)-7,7-dimetil-7,8-dihidroquinazolin-5(6H)-ona, 2-(ciclopropilamino)-7,7-dimetil-7,8-dihidroquinazolin.-5(6H)-ona, 2-(m-tolilamino)-7,8-dihidroquinazolin-5(6H)-ona, 2-(fenilamino)-7,8-dihidroquinazolin-5(6H)-ona, 2-(p-tolilamino)-7,8-dihidroquinazolin-5(6H)-ona, 7,7-dimetil-2-((3-(trifluorometil)fenil)amino)-7,8-dihidroquinazolin-5(6H)-ona, 7,7-dimetil-2-((4-fenoxifenil)amino)-7,8-dihidroquinazolin-5(6H)-ona, 7,7-dimetil-2-(m-tolilamino)-7,8-dihidroquinazolin-5(6H)-ona, 7,7-dimetil-2-(fenilamino)-7,8-dihidroquinazolin-5(6H)-ona, 7-metil-2-((4-fenoxifenil)amino)-7,8-dihidroquinazolin-5(6H)-ona, 7-metil-2-(p-tolilamino)-7,8-dihidroquinazolin-5(6H)-ona, 7,7-dimetil-2-(p-tolilamino)-7,8-dihidroquinazolin-5(6H)-ona, 7-metil-2-(fenilamino)-7,8-dihidroquinazolin-5(6H)-ona, 2-((3,5-dimetilfeni))amino)-7,8-dihidroquinazolin-5(6H)-ona, 7-metil-2-(m-tolilamino)-7,8-dihidroquinazolin-5(6H)-ona, o 7-metil-2-((3-(trifluorometil)fenil)amino)-7,8-dihidroquinazolin-5(6H)-ona.This also relates to a process for the preparation of said compounds. The compounds herein are mGluR5 modulators and are therefore useful for the control and prevention of acute and / or chronic neurological disorders. Claim 1: A compound characterized in that it is selected from those of the formula (1), wherein: X represents CH2 or C = O; Y represents CR6R7, NR8, O or S; R1 represents H, C1-6 alkyl, or F; R2 represents H, C1-6 alkyl, or F; or R1 and R2 together with the carbon atom to which they are attached form a ring of between 3 and 7 members that can be saturated or unsaturated, where the ring can optionally contain one or two heteroatoms selected from sulfur, oxygen, and nitrogen and where the ring may be optionally substituted with one or more substituents selected from halogen, trifluoromethyl, trifluoromethoxy, C1-6 alkyl, C1-6 alkoxy, amino, hydroxy, cyano, acyl, C1-6 alkyl, di- (C1-6 alkyl ) amino, C 1-6 alkylcarbonylamino, and oxo; R3 represents H, C1-6 alkyl, or F; R4 represents H, C1-6 alkyl, or F; or R3 and R4 together with the carbon atom to which they are attached form a ring of between 3 and 7 members that can be saturated or unsaturated, where the ring can optionally contain one or two heteroatoms selected from sulfur, oxygen, and nitrogen and where the ring may be optionally substituted with one or more substituents selected from halogen, trifluoromethyl, trifluoromethoxy, C1-6 alkyl, C1-6 alkoxy, amino, hydroxy, cyano, acyl, C1-6 alkyl, di- (C1-6 alkyl ) amino, C 1-6 alkylcarbonylamino, and oxo; R5 represents a monocyclic portion selected from aryl, heteroaryl, C3-6 cycloalkyl, and heterocyclyl; R6 represents H, C1-6 alkyl, or F; R7 represents H, C1-6 alkyl, or F; or R6 and R7 together with the carbon atom to which they are attached form a ring of between 3 and 7 members that can be saturated or unsaturated, where the ring can optionally contain one or two heteroatoms selected from sulfur, oxygen, and nitrogen and where the ring may be optionally substituted with one or more substituents selected from halogen, trifluoromethyl, trifluoromethoxy, C1-6 alkyl, C1-6 alkoxy, amino, hydroxy, cyano, acyl, C1-6 alkyl, di- (C1-6 alkyl ) amino, C 1-6 alkylcarbonylamino, and oxo; R 8 represents H, C 1-6 alkyl which may be optionally substituted with one or more substituents selected from halogen, trifluoromethyl, trifluoromethoxy, C 1-6 alkoxy, amino, hydroxy, C 1-6 alkyl, and di- (C 1-6 alkyl) amino , C3-6 cycloalkyl, C1-6 alkylcarbonyl which may be optionally substituted with one or more substituents selected from halogen, trifluoromethyl, trifluoromethoxy, C1-6 alkoxy, amino, hydroxy, C1-6 alkyl, and di- (C1-6 alkyl ) amino, C 3-6 cycloalkylcarbonyl, C 1-6 alkoxycarbonyl which may be optionally substituted with one or more substituents selected from halogen, trifluoromethyl, trifluoromethoxy, C 1-6 alkoxy, amino, hydroxy, C 1-6 alkyl, and di- (C 1-6 alkyl) -6) amino, aminocarbonyl, N-C1-6 aminocarbonyl where the alkyl portion may be optionally substituted with one or more substituents selected from halogen, trifluoromethyl, trifluoromethoxy, C1-6 alkoxy, amino, hydroxy, C1-6amino alkyl, and di - (alkyl C1-6) amino, N, N-di- (C1-6 alkyl) aminocarbonyl, where the alkyl portions may be optionally substituted with one or more substituents selected from halogen, trifluoromethyl, trifluoromethoxy, C1-6 alkoxy, amino, hydroxy, C 1-6 alkyl, and di- (C 1-6 alkyl) amino; and optical isomers, prodrugs, pharmaceutically acceptable salts, hydrates, solvates, and polymorphs thereof; where it should be understood that the compound of formula (1) cannot represent: 2 - ((2,4-dichlorophenyl) amino) -7-methyl-7,8-dihydroquinazolin-5 (6H) -one, 2 - ((2 , 4-dimethylphenyl) amino) -7-methyl-7,8-dihydroquinazolin-5 (6H) -one, 2 - ((2-methoxyphenyl) amino) -7,7-dimethyl-7,8-dihydroquinazolin-5 ( 6H) -one, 2 - ((2-methoxyphenyl) amino) -7-methyl-7,8-dihydroquinazolin-5 (6H) -one, 2 - ((3- (trifluoromethyl) phenyl) amino) -7.8 -dihydroquinazolin-5 (6H) -one, 2 - ((3,4-dimethylphenyl) amino) -7-methyl-7,8-dihydroquinazolin-5 (6H) -one, 2 - ((3,5-dimethoxyphenyl) amino) -7,7-dimethyl-7,8-dihydroquinazolin-5 (6H) -one, 2 - ((4-ethylphenyl) amino) -7,7-dimethyl-7,8-dihydroquinazolin-5 (6H) - one, 2 - ((4-ethylphenyl) amino) -7-methyl-7,8-dihydroquinazolin-5 (6H) -one, 2 - ((4-fluorophenyl) amino) -7,7-dimethyl-7,8 -dihydroquinazolin-5 (6H) -one, 2 - ((4-fluorophenyl) amino) -7,8-dihydroquinazolin-5 (6H) -one, 2 - ((4-fluorophenyl) amino) -7-methyl-7 , 8-dihydroquinazolin-5 (6H) -one, 2 - ((4-methoxyphenyl) amino) -7,7-dimethyl-7,8-dihydroquinazolin-5 (6H) -one, 2 - ((4-methoxyphenyl) amino) -7,8-dihydroquin azolin-5 (6H) one, 2 - ((4-methoxyphenyl) amino) -7-methyl-7,8-dihydroquinazolin-5 (6H) -one, 2- (cyclopentylamino) -7,7-dimethyl-7, 8-dihydroquinazolin-5 (6H) -one, 2- (cyclopropylamino) -7,7-dimethyl-7,8-dihydroquinazolin.-5 (6H) -one, 2- (m-tolylamino) -7,8-dihydroquinazolin -5 (6H) -one, 2- (phenylamino) -7,8-dihydroquinazolin-5 (6H) -one, 2- (p-tolylamino) -7,8-dihydroquinazolin-5 (6H) -one, 7, 7-dimethyl-2 - ((3- (trifluoromethyl) phenyl) amino) -7,8-dihydroquinazolin-5 (6H) -one, 7,7-dimethyl-2 - ((4-phenoxyphenyl) amino) -7, 8-dihydroquinazolin-5 (6H) -one, 7,7-dimethyl-2- (m-tolylamino) -7,8-dihydroquinazolin-5 (6H) -one, 7,7-dimethyl-2- (phenylamino) - 7,8-dihydroquinazolin-5 (6H) -one, 7-methyl-2 - ((4-phenoxyphenyl) amino) -7,8-dihydroquinazolin-5 (6H) -one, 7-methyl-2- (p- tolylamino) -7,8-dihydroquinazolin-5 (6H) -one, 7,7-dimethyl-2- (p-tolylamino) -7,8-dihydroquinazolin-5 (6H) -one, 7-methyl-2- ( phenylamino) -7,8-dihydroquinazolin-5 (6H) -one, 2 - ((3,5-dimethylpheni)) amino) -7,8-dihydroquinazolin-5 (6H) -one, 7-methyl-2- ( m-tolylamino) -7,8-dihydroquinazolin-5 (6H) -one, or 7 -methyl-2 - ((3- (trifluoromethyl) phenyl) amino) -7,8-dihydroquinazolin-5 (6H) -one.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201061459976P | 2010-12-22 | 2010-12-22 | |
| EP10196573 | 2010-12-22 |
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| Publication Number | Publication Date |
|---|---|
| AR084516A1 true AR084516A1 (en) | 2013-05-22 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP110104855A AR084516A1 (en) | 2010-12-22 | 2011-12-21 | METABOTROPIC GLUTAMATE RECEIVERS MODULATORS |
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| Country | Link |
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| AR (1) | AR084516A1 (en) |
| WO (1) | WO2012085166A1 (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| JP6256469B2 (en) * | 2012-08-03 | 2018-01-10 | 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 | Process for the preparation of spiro [2.5] octane-5,7-dione |
| CN104262265B (en) * | 2014-07-21 | 2016-04-13 | 湖南华腾制药有限公司 | A kind of preparation method of tetrahydro quinazoline derivative |
| US9938228B2 (en) | 2014-09-09 | 2018-04-10 | Boehringer Ingelheim International Gmbh | Process for the preparation of spiro[2.5]octane-5,7-dione and spiro[3.5]nonane-6,8-dione |
| US20200123127A1 (en) * | 2016-04-25 | 2020-04-23 | Everon Biosciences, Inc. | Removal of senescence-associated macrophages |
| WO2021146543A1 (en) * | 2020-01-15 | 2021-07-22 | The Trustees Of Princeton University | Inhibitors of glucose-6-phosphate dehydrogenase and uses thereof |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH603545A5 (en) | 1972-04-20 | 1978-08-31 | Merz & Co | |
| DE2856393C2 (en) | 1978-12-27 | 1983-04-28 | Merz + Co GmbH & Co, 6000 Frankfurt | Medicines used to treat Parkinson's disease |
| ES2059602T3 (en) | 1989-04-14 | 1994-11-16 | Merz & Co Gmbh & Co | USE OF ADAMANTANE DERIVATIVES FOR THE PREVENTION AND TREATMENT OF BRAIN ISCHEMIA. |
| DE102004020908A1 (en) * | 2004-04-28 | 2005-11-17 | Grünenthal GmbH | Substituted 5,6,7,8-tetrahydropyrido [4,3-d] pyrimidin-2-yl and 5,6,7,8-tetrahydroquinazolin-2-yl compounds |
| WO2007071358A1 (en) * | 2005-12-20 | 2007-06-28 | Novartis Ag | Nicotinic acid derivatives as modulators of metabotropic glutamate receptors |
| ATE539075T1 (en) * | 2007-08-02 | 2012-01-15 | Recordati Ireland Ltd | NEW HETEROCYCLIC COMPOUNDS AS MGLU5 ANTAGONISTS |
| AU2009203773B2 (en) * | 2008-01-11 | 2013-04-18 | F. Hoffmann-La Roche Ag | Modulators for amyloid beta |
-
2011
- 2011-12-21 AR ARP110104855A patent/AR084516A1/en not_active Application Discontinuation
- 2011-12-21 WO PCT/EP2011/073711 patent/WO2012085166A1/en not_active Ceased
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| WO2012085166A1 (en) | 2012-06-28 |
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