AR103818A2 - MYELOPEROXIDASE INHIBITORS PIRROLOPIRIMIDINE DERIVATIVES (MPO) - Google Patents

MYELOPEROXIDASE INHIBITORS PIRROLOPIRIMIDINE DERIVATIVES (MPO)

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Publication number
AR103818A2
AR103818A2 ARP160100534A ARP160100534A AR103818A2 AR 103818 A2 AR103818 A2 AR 103818A2 AR P160100534 A ARP160100534 A AR P160100534A AR P160100534 A ARP160100534 A AR P160100534A AR 103818 A2 AR103818 A2 AR 103818A2
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Argentina
Prior art keywords
alkoxy
alkyl
optionally substituted
optionally
halogen
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ARP160100534A
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Spanish (es)
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Astrazeneca Ab
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Publication date
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Publication of AR103818A2 publication Critical patent/AR103818A2/en

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Abstract

Sus sales farmacéuticamente aceptables; junto con procesos para su preparación, composiciones que los contienen y su uso terapéutico. Los compuestos son inhibidores de la enzima MPO y, por ello, son particularmente útiles en el tratamiento o la prevención de trastornos neuroinflamatorios, trastornos cardiovasculares y trastornos respiratorios. Reivindicación 1: Un compuesto de la fórmula (1) donde: al menos uno de X e Y representa S y el otro representa O ó S; L representa un enlace directo o alquileno C₁₋₇, donde dicho alquileno incorpora opcionalmente un heteroátomo seleccionado de O, S(O)ₙ y NR⁶ y dicho alquileno incorpora opcionalmente uno o dos enlaces dobles carbono-carbono, y dicho alquileno está opcionalmente sustituido con uno o varios sustituyentes seleccionados, de modo independiente, de OH, halógeno, CN y NR⁴R⁵, alquilo C₁₋₆ y alcoxi C₁₋₆, donde dicho alcoxi incorpora opcionalmente un carbonilo adyacente al oxígeno; n representa un número entero 0, 1 o 2; R¹ representa hidrógeno o i) un anillo saturado o parcialmente insaturado de 3 a 7 miembros que opcionalmente incorpora uno o dos heteroátomos seleccionados, de modo independiente, de O, N y S, y que opcionalmente incorpora un grupo carbonilo, opcionalmente sustituido con uno o varios sustituyentes seleccionados de halógeno, SO₂R⁹, SO₂NR⁹R¹⁰, OH, alquilo C₁₋₇, alcoxi C₁₋₇, CN, CONR²R³, NR²COR³ y COR³, donde dicho alcoxi está también opcionalmente sustituido con alcoxi C₁₋₆ y donde dicho alcoxi incorpora opcionalmente un carbonilo adyacente al oxígeno y dicho alquilo está también opcionalmente sustituido con hidroxi o alcoxi C₁₋₆ y dicho alquilo o alcoxi incorpora opcionalmente un carbonilo adyacente al oxígeno o en cualquier posición en el alquilo o ii) un sistema de anillos aromáticos seleccionado de fenilo, bifenilo, naftilo o una estructura de anillo heteroaromática monocíclica o bicíclica que contiene 1 a 3 heteroátomos seleccionados, de modo independiente, de O, N y S, donde dicho sistema de anillo aromático está opcionalmente sustituido con uno o varios sustituyentes seleccionados de halógeno, SO₂R⁹, SO₂NR⁹R¹⁰, OH, alquilo C₁₋₇, alcoxi C₁₋₇, CN, CONR²R³, NR²COR³ y COR³; donde dicho alcoxi está también opcionalmente sustituido con alcoxi C₁₋₆ y donde dicho alcoxi incorpora opcionalmente un carbonilo adyacente al oxígeno y dicho alquilo está también opcionalmente sustituido con hidroxi o alcoxi C₁₋₆ y dicho alquilo o alcoxi incorpora opcionalmente un carbonilo adyacente al oxígeno o en cualquier posición en el alquilo; R¹² representa hidrógeno o halógeno o un carbono opcionalmente sustituido con uno a tres átomos de halógeno; en cada aparición, R², R³, R⁴, R⁵, R⁶, R⁹ y R¹⁰ representan, de modo independiente, hidrógeno, alquilo C₁₋₆ o alcoxi C₁₋₆ donde dicho alcoxi incorpora opcionalmente un carbonilo adyacente al oxígeno, y dicho alquilo está también opcionalmente sustituido con halógeno, alcoxi C₁₋₆, CHO, alcanoílo C₂₋₆, OH, CONR⁷R⁸ y NR⁷COR⁸; o los grupos NR²R³, NR⁴R⁵ y NR⁹R¹⁰ representan cada uno, de modo independiente, un anillo azacíclico saturado de 5 a 7 miembros que opcionalmente incorpora un heteroátomo adicional seleccionado de O, S y NR¹¹, donde dicho anillo está también opcionalmente sustituido con halógeno, alcoxi C₁₋₆, CHO, alcanoílo C₂₋₆, OH, CONR⁷R⁸ y NR⁷COR⁸; en cada aparición R⁷, R⁸ y R¹¹ representan, de modo independiente, hidrógeno o alquilo C₁₋₆, o el grupo NR⁷R⁸ representa un anillo azacíclico saturado de 5 a 7 miembros que opcionalmente incorpora un heteroátomo adicional seleccionado de O, S y NR¹¹; y sus sales farmacéuticamente aceptables; con la condición de que se excluyan los compuestos 1-b-D-ribofuranosil-2-oxopirrolo[3,2-d]pirimidin-4(3H,5H)-tiona, 1-(2,3,5-tri-O-benzoil-1-b-D-ribofuranosil)-2-oxopirrolo[3,2-d]pirimidin-4(3H,5H)-tiona y 5,7-dimercapto-1,4,6-triazaindeno.Its pharmaceutically acceptable salts; together with processes for their preparation, compositions that contain them and their therapeutic use. The compounds are inhibitors of the MPO enzyme and, therefore, are particularly useful in the treatment or prevention of neuroinflammatory disorders, cardiovascular disorders and respiratory disorders. Claim 1: A compound of the formula (1) wherein: at least one of X and Y represents S and the other represents O or S; L represents a direct bond or C₁₋₇ alkylene, wherein said alkylene optionally incorporates a heteroatom selected from O, S (O) ⁶ and NR⁶ and said alkylene optionally incorporates one or two carbon-carbon double bonds, and said alkylene is optionally substituted with one or more substituents independently selected from OH, halogen, CN and NR⁴R⁵, C₁₋₆ alkyl and C₁₋₆ alkoxy, wherein said alkoxy optionally incorporates a carbonyl adjacent to oxygen; n represents an integer 0, 1 or 2; R¹ represents hydrogen or i) a saturated or partially unsaturated ring of 3 to 7 members that optionally incorporates one or two heteroatoms selected, independently, from O, N and S, and that optionally incorporates a carbonyl group, optionally substituted with one or more substituents selected from halogen, SO₂R⁹, SO₂NR⁹R¹⁰, OH, C₁₋₇ alkyl, C₁₋₇ alkoxy, CN, CONR²R³, NR²COR³ and COR³, wherein said alkoxy is also optionally substituted with C₁₋₆ alkoxy and wherein said alkoxy optionally incorporates an adjacent carbonyl to the oxygen and said alkyl is also optionally substituted with hydroxy or C₁₋₆ alkoxy and said alkyl or alkoxy optionally incorporates a carbonyl adjacent to the oxygen or at any position in the alkyl or ii) an aromatic ring system selected from phenyl, biphenyl, naphthyl or a monocyclic or bicyclic heteroaromatic ring structure containing 1 to 3 selected heteroatoms ionically, independently, of O, N and S, wherein said aromatic ring system is optionally substituted with one or more substituents selected from halogen, SO₂R⁹, SO₂NR⁹R¹⁰, OH, C₁₋₇ alkyl, C₁₋₇ alkoxy, CN, CONR²R³ , NR²COR³ and COR³; wherein said alkoxy is also optionally substituted with C₁₋₆ alkoxy and where said alkoxy optionally incorporates a carbonyl adjacent to oxygen and said alkyl is also optionally substituted with hydroxy or C₁₋₆ alkoxy and said alkyl or alkoxy optionally incorporates a carbonyl adjacent to oxygen or in any position in the alkyl; R² represents hydrogen or halogen or a carbon optionally substituted with one to three halogen atoms; at each occurrence, R², R³, R⁴, R⁵, R⁶, R⁹ and R¹⁰ independently represent hydrogen, C₁₋₆ alkyl or C₁₋₆ alkoxy where said alkoxy optionally incorporates a carbonyl adjacent to oxygen, and said alkyl is also optionally substituted with halogen, C₁₋₆ alkoxy, CHO, C₂₋₆ alkanoyl, OH, CONR⁷R⁸ and NR⁷COR⁸; or the groups NR²R³, NR⁴R⁵ and NR⁹R¹⁰ each independently represent a saturated 5 to 7-membered azacyclic ring that optionally incorporates an additional heteroatom selected from O, S and NR¹¹, where said ring is also optionally substituted with halogen, alkoxy C₁₋₆, CHO, Cno alkanoyl, OH, CONR⁷R⁸ and NR⁷COR⁸; at each occurrence R⁷, R⁸ and R¹¹ independently represent hydrogen or C₁₋₆ alkyl, or the NR⁷R⁸ group represents a saturated 5- to 7-membered azacyclic ring that optionally incorporates an additional heteroatom selected from O, S and NR¹¹; and its pharmaceutically acceptable salts; with the proviso that the 1-bD-ribofuranosyl-2-oxopyrrolo [3,2-d] pyrimidin-4 (3H, 5H) -thiona, 1- (2,3,5-tri-O-benzoyl) compounds are excluded -1-bD-ribofuranosyl) -2-oxopyrrolo [3,2-d] pyrimidin-4 (3H, 5H) -thiona and 5,7-dimercapto-1,4,6-triazaindene.

ARP160100534A 2004-12-06 2016-03-01 MYELOPEROXIDASE INHIBITORS PIRROLOPIRIMIDINE DERIVATIVES (MPO) AR103818A2 (en)

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Application Number Priority Date Filing Date Title
SE0402972A SE0402972D0 (en) 2004-12-06 2004-12-06 Novel compounds

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AR103818A2 true AR103818A2 (en) 2017-06-07

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SE (1) SE0402972D0 (en)
ZA (1) ZA200705000B (en)

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ZA200705000B (en) 2008-09-25
SE0402972D0 (en) 2004-12-06

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