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AR093091A1 - HETEROCICLICAL COMPOUNDS CONTAINING NITROGEN - Google Patents

HETEROCICLICAL COMPOUNDS CONTAINING NITROGEN

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Publication number
AR093091A1
AR093091A1 ARP130103824A ARP130103824A AR093091A1 AR 093091 A1 AR093091 A1 AR 093091A1 AR P130103824 A ARP130103824 A AR P130103824A AR P130103824 A ARP130103824 A AR P130103824A AR 093091 A1 AR093091 A1 AR 093091A1
Authority
AR
Argentina
Prior art keywords
optionally substituted
methyl
oxo
pyrido
carboxamide
Prior art date
Application number
ARP130103824A
Other languages
Spanish (es)
Inventor
Sasaki Shigekazu
Taniguchi Takahiko
Nomura Izumi
Ashizawa Tomoko
Mikami Satoshi
Nakamura Shinji
Original Assignee
Takeda Pharmaceuticals Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from PCT/JP2013/062140 external-priority patent/WO2013161913A1/en
Application filed by Takeda Pharmaceuticals Co filed Critical Takeda Pharmaceuticals Co
Publication of AR093091A1 publication Critical patent/AR093091A1/en

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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

La presente tiene una acción inhibidora selectiva de la PDE2A, el cual es útil como agente para la profilaxis o tratamiento de esquizofrenia, la enfermedad de Alzheimer y similar. Reivindicación 1: Un compuesto representado por la fórmula (1), caracterizado porque R¹ es un átomo de hidrógeno o un grupo alquilo C₁₋₆ opcionalmente sustituido; R² y R³ son cada uno de ellos independientemente un átomo de hidrógeno o un grupo alquilo C₁₋₆ opcionalmente sustituido, o R² y R³ en combinación forman opcionalmente, junto el átomo de carbono adyacente, un anillo opcionalmente sustituido; X es un enlace o un grupo alquileno C₁₋₆ opcionalmente sustituido; A es un grupo cíclico opcionalmente sustituido; Z¹ es un grupo representado por CRZ¹ en donde RZ¹ es un átomo de hidrógeno, un átomo de halógeno un grupo alquilo C₁₋₆ opcionalmente sustituido, un grupo alquenilo C₂₋₆ opcionalmente sustituido, un grupo alquinilo C₂₋₆ opcionalmente sustituido, un grupo alcoxi C₁₋₆ opcionalmente sustituido, un grupo amino opcionalmente sustituido, un grupo ciano o un grupo cíclico opcionalmente sustituido, o un átomo de nitrógeno; Z² es un grupo representado por CRZ² en donde RZ² es un átomo de hidrógeno, un átomo de halógeno un grupo alquilo C₁₋₆ opcionalmente sustituido, un grupo alquenilo C₂₋₆ opcionalmente sustituido, un grupo alquinilo C₂₋₆ opcionalmente sustituido, un grupo alcoxi C₁₋₆ opcionalmente sustituido, un grupo amino opcionalmente sustituido, un grupo ciano o un grupo cíclico opcionalmente sustituido, o un átomo de nitrógeno; Z³ es un grupo representado por CRZ³ en donde RZ³ es un átomo de hidrógeno, un átomo de halógeno un grupo alquilo C₁₋₆ opcionalmente sustituido, un grupo alquenilo C₂₋₆ opcionalmente sustituido, un grupo alquinilo C₂₋₆ opcionalmente sustituido, un grupo alcoxi C₁₋₆ opcionalmente sustituido, un grupo amino opcionalmente sustituido, un grupo ciano, un grupo alquilo C₁₋₆-carbonilo opcionalmente sustituido o un grupo cíclico opcionalmente sustituido, o un átomo de nitrógeno; y B es un heterociclo aromático que contiene nitrógeno que contiene 1 o 2 átomos de nitrógeno; siempre que 2,3-dihidro-1-metil-2-oxo-N-2-tiazolil-6-[3-(trifluorometil)fenil]-pirido[2,3-b]pirazina-4(1H)carboxamida, 2,3-dihidro-1-metil-N-(4-metil-2-tiazolil)-2-oxo-6-[3-(trifluorometil)fenil]-pirido[2,3-b]pirazina-4(1H)carboxamida, 2,3-dihidro-1-metil-2-oxo-N-(tetrahidro-2-oxo-3-furanil)-6-[3-(trifluorometil)fenil]-pirido[2,3-b]pirazina-4(1H)carboxamida, 2,3-dihidro-1-metil-N-2-oxazolil-2-oxo-6-[3-(trifluorometil)fenil]-pirido[2,3-b]pirazina-4(1H)carboxamida, 2,3-dihidro-1-metil-2-oxo-N-1H-1,2,4-triazol-3-il-6-[3-(trifluorometil)-fenil-1-pirido[2,3-b]pirazina-4(1H)carboxamida, 2,3-dihidro-1-metil-2-oxo-N-4-piridinil-6-[3-(trifluorometil)fenil]-pirido[2,3-b]pirazina-4(1H)-carboxamida, 2,3-dihidro-1-metil-2-oxo-N-4-pirimidinil-6-[3-(trifluorometil)fenil]-pirido[2,3-b]pirazina-4(1H)carboxamida, 2,3-dihidro-1-metil-2-oxo-N-5-pirimidinil-6-[3-(trifluorometil)-fenil]-pirido[2,3-b]pirazina-4(1H)carboxamida, 2,3-dihidro-1-metil-2-oxo-N-3-piridazinil-6-[3-(trifluorometil)fenil]-pirido[2,3-b]pirazina-4(1H)carboxamida, 2,3-dihidro-1-metil-N-[6-(4-morfolinil)-2-piridinil]-2-oxo-6-[3-(trifluorometil)fenil]-pirido[2,3-b]pirazina-4(1H)carboxamida, N-(4,5-dimetil-2-tiazolil)-2,3-dihidro-1-metil-2-oxo-6-[3-(trifluorometil)fenil]-pirido[2,3-b]pirazina-4(1H)carboxamida, 2,3-dihidro-1-metil-N-(5-metil-2-tiazolil)-2-oxo-6-[3-(trifluorometil)fenil]-pirido[2,3-b]pirazina-4(1H)carboxamida, N-[5-[(dimetilamino)carbonil]-4-metil-tiazolil]-2,3-dihidro-1-metil-2-oxo-6-[3-(trifluorometil)-fenil]-pirido[2,3-b]pirazina-4-(1H)carboxamida, N-(4,6-dimetil-2-piridinil)-2,3-dihidro-1-metil-2-oxo-6-[3-(trifluorometil)fenil]-pirido[2,3-b]pirazina-4(1H)carboxamida, 2,3-dihidro-1-metil-2-oxo-N-2-pirazinil-6-[3-(trifluorometil)fenil-1-pirido[2,3-b]pirazina-4(1H)carboxamida, 2,3-dihidro-1-metil-2-oxo-N-2-pirazinil-6-[3-(trifluorometil)fenil]-pirido[2,3-b]pirazina-4(1H)carboxamida, 2,3-dihidro-1-metil-2-oxo-N-2-pirimidinil-6-[3-(trifluorometil)fenil]-pirido[2,3-b]pirazin-4(H)carboxamida, N-[2-(1-azetidinil)-4-piridinil]-2,3-dihidro-1-metil-2-oxo-6-[3-(trifluorometil)fenil-1-pirido[2,3-b]pirazina-4(1H)carboxamida, 2,3-dihidro-1-metil-N-[6-(4-morfolinilmetil)-2-piridinil]-2-oxo-6-[3-(trifluorometil)-fenil-1-pirido[2,3-b]pirazina-4-(1H)-carboxamida, y N-[6-(1-azetidinil)-2-piridinil]-2,3-dihidro-1-metil-2-oxo-6-[3-(trifluorometil)-fenil]-pirido[2,3-b]pirazina-4(1H)carboxamida se excluyen; o una sal del mismo.The present has a selective inhibitory action of PDE2A, which is useful as an agent for the prophylaxis or treatment of schizophrenia, Alzheimer's disease and the like. Claim 1: A compound represented by the formula (1), characterized in that R¹ is a hydrogen atom or an optionally substituted C₁₋₆ alkyl group; R² and R³ are each independently a hydrogen atom or an optionally substituted C₁₋₆ alkyl group, or R² and R³ in combination optionally, together with the adjacent carbon atom, an optionally substituted ring; X is an optionally substituted C₁₋₆ alkylene group or bond; A is an optionally substituted cyclic group; Z¹ is a group represented by CRZ¹ wherein RZ¹ is a hydrogen atom, a halogen atom an optionally substituted C₁₋₆ alkyl group, an optionally substituted C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an alkoxy group Optionally substituted C₁₋₆, an optionally substituted amino group, a cyano group or an optionally substituted cyclic group, or a nitrogen atom; Z² is a group represented by CRZ² where RZ² is a hydrogen atom, a halogen atom an optionally substituted C₁₋₆ alkyl group, an optionally substituted C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an alkoxy group Optionally substituted C₁₋₆, an optionally substituted amino group, a cyano group or an optionally substituted cyclic group, or a nitrogen atom; Z³ is a group represented by CRZ³ wherein RZ³ is a hydrogen atom, a halogen atom an optionally substituted C₁₋₆ alkyl group, an optionally substituted C₂₋₆ alkenyl group, an optionally substituted C₂₋₆ alkynyl group, an alkoxy group Optionally substituted C₁₋₆, an optionally substituted amino group, a cyano group, an optionally substituted C₁₋₆-carbonyl alkyl group or an optionally substituted cyclic group, or a nitrogen atom; and B is a nitrogen-containing aromatic heterocycle containing 1 or 2 nitrogen atoms; provided that 2,3-dihydro-1-methyl-2-oxo-N-2-thiazolyl-6- [3- (trifluoromethyl) phenyl] -pyrido [2,3-b] pyrazine-4 (1H) carboxamide, 2 , 3-dihydro-1-methyl-N- (4-methyl-2-thiazolyl) -2-oxo-6- [3- (trifluoromethyl) phenyl] -pyrido [2,3-b] pyrazine-4 (1H) carboxamide, 2,3-dihydro-1-methyl-2-oxo-N- (tetrahydro-2-oxo-3-furanyl) -6- [3- (trifluoromethyl) phenyl] -pyrido [2,3-b] pyrazine -4 (1H) carboxamide, 2,3-dihydro-1-methyl-N-2-oxazolyl-2-oxo-6- [3- (trifluoromethyl) phenyl] -pyrido [2,3-b] pyrazine-4 ( 1H) carboxamide, 2,3-dihydro-1-methyl-2-oxo-N-1H-1,2,4-triazol-3-yl-6- [3- (trifluoromethyl) -phenyl-1-pyrido [2 , 3-b] pyrazine-4 (1 H) carboxamide, 2,3-dihydro-1-methyl-2-oxo-N-4-pyridinyl-6- [3- (trifluoromethyl) phenyl] -pyrido [2,3- b] pyrazine-4 (1 H) -carboxamide, 2,3-dihydro-1-methyl-2-oxo-N-4-pyrimidinyl-6- [3- (trifluoromethyl) phenyl] -pyrido [2,3-b] pyrazine-4 (1H) carboxamide, 2,3-dihydro-1-methyl-2-oxo-N-5-pyrimidinyl-6- [3- (trifluoromethyl) -phenyl] -pyrido [2,3-b] pyrazine- 4 (1H) carboxamide, 2,3-dihydro-1-methyl-2-oxo-N-3-pyridazinyl-6- [3- (trifluoromethyl) phenyl] -pyrido [2,3-b ] pyrazine-4 (1H) carboxamide, 2,3-dihydro-1-methyl-N- [6- (4-morpholinyl) -2-pyridinyl] -2-oxo-6- [3- (trifluoromethyl) phenyl] - pyrido [2,3-b] pyrazine-4 (1 H) carboxamide, N- (4,5-dimethyl-2-thiazolyl) -2,3-dihydro-1-methyl-2-oxo-6- [3- ( trifluoromethyl) phenyl] -pyrido [2,3-b] pyrazine-4 (1 H) carboxamide, 2,3-dihydro-1-methyl-N- (5-methyl-2-thiazolyl) -2-oxo-6- [ 3- (trifluoromethyl) phenyl] -pyrido [2,3-b] pyrazine-4 (1 H) carboxamide, N- [5 - [(dimethylamino) carbonyl] -4-methyl-thiazolyl] -2,3-dihydro-1 -methyl-2-oxo-6- [3- (trifluoromethyl) -phenyl] -pyrido [2,3-b] pyrazine-4- (1 H) carboxamide, N- (4,6-dimethyl-2-pyridinyl) - 2,3-dihydro-1-methyl-2-oxo-6- [3- (trifluoromethyl) phenyl] -pyrido [2,3-b] pyrazine-4 (1H) carboxamide, 2,3-dihydro-1-methyl -2-oxo-N-2-pyrazinyl-6- [3- (trifluoromethyl) phenyl-1-pyrido [2,3-b] pyrazine-4 (1H) carboxamide, 2,3-dihydro-1-methyl-2 -oxo-N-2-pyrazinyl-6- [3- (trifluoromethyl) phenyl] -pyrido [2,3-b] pyrazine-4 (1H) carboxamide, 2,3-dihydro-1-methyl-2-oxo- N-2-pyrimidinyl-6- [3- (trifluoromethyl) phenyl] -pyrido [2,3-b] pyrazin-4 (H) carboxamide, N- [2- (1-azetidin il) -4-pyridinyl] -2,3-dihydro-1-methyl-2-oxo-6- [3- (trifluoromethyl) phenyl-1-pyrido [2,3-b] pyrazine-4 (1H) carboxamide, 2,3-dihydro-1-methyl-N- [6- (4-morpholinylmethyl) -2-pyridinyl] -2-oxo-6- [3- (trifluoromethyl) -phenyl-1-pyrido [2,3-b ] pyrazine-4- (1H) -carboxamide, and N- [6- (1-azetidinyl) -2-pyridinyl] -2,3-dihydro-1-methyl-2-oxo-6- [3- (trifluoromethyl) -phenyl] -pyrido [2,3-b] pyrazine-4 (1 H) carboxamide are excluded; or a salt thereof.

ARP130103824A 2012-12-26 2013-10-22 HETEROCICLICAL COMPOUNDS CONTAINING NITROGEN AR093091A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2012283470 2012-12-26
PCT/JP2013/062140 WO2013161913A1 (en) 2012-04-25 2013-04-24 Nitrogenated heterocyclic compound

Publications (1)

Publication Number Publication Date
AR093091A1 true AR093091A1 (en) 2015-05-20

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Application Number Title Priority Date Filing Date
ARP130103824A AR093091A1 (en) 2012-12-26 2013-10-22 HETEROCICLICAL COMPOUNDS CONTAINING NITROGEN

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Country Link
AR (1) AR093091A1 (en)
GE (1) GEP201606554B (en)
TW (1) TWI613200B (en)
UY (1) UY35095A (en)

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2779303A1 (en) * 2009-10-29 2011-05-19 Sirtris Pharmaceuticals, Inc. Bicyclic pyridines and analogs as sirtuin modulators

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TW201427979A (en) 2014-07-16
TWI613200B (en) 2018-02-01
GEP201606554B (en) 2016-10-10
UY35095A (en) 2014-07-31

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