AR076707A1 - Derivados amino-propionicos sustituidos como inhibidores de neprilisina - Google Patents

Derivados amino-propionicos sustituidos como inhibidores de neprilisina

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Publication number
AR076707A1
AR076707A1 ARP100101809A ARP100101809A AR076707A1 AR 076707 A1 AR076707 A1 AR 076707A1 AR P100101809 A ARP100101809 A AR P100101809A AR P100101809 A ARP100101809 A AR P100101809A AR 076707 A1 AR076707 A1 AR 076707A1
Authority
AR
Argentina
Prior art keywords
alkyl
halogen
heteroaryl
alkoxy
independently selected
Prior art date
Application number
ARP100101809A
Other languages
English (en)
Original Assignee
Novartis Ag
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=42313042&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=AR076707(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Novartis Ag filed Critical Novartis Ag
Publication of AR076707A1 publication Critical patent/AR076707A1/es

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
    • C07D317/32—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D317/34—Oxygen atoms
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    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
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Abstract

Se refiere a un método para la fabricacion de los compuestos de la solicitud, y a sus usos terapéuticos. La presente solicitud proporciona además una combinacion de agentes farmacologicamente activos y una composicion farmacéutica. Reivindicacion 1: Un compuesto de la formula (1) o una sal farmacéuticamente aceptable del mismo, en donde R1 es H, alquilo C1-7, hidroxilo, alcoxilo C1-7, halogeno, -SH, -S-alquilo C1-7 o NRaRb; R2 por cada presentacion, es independientemente alquilo C1-7, halogeno, NO2, CN, alcanoílo C1-7-amino, cicloalquilo C3-7, hidroxilo, alcoxilo C1-7, halo-alquilo C1-7, NRaRb, arilo C6-10, heteroarilo o heterociclilo; en donde Ra y Rb por cada presentacion, son independientemente H o alquilo C1-7; R3 es A1-C(O)X1 o A2-R4; R4 es arilo C6-10, o un heteroarilo, el cual puede ser monocíclico o bicíclico, y el cual puede estar opcionalmente sustituido con uno o más sustituyentes seleccionados independientemente a partir de hidroxilo, hidroxi-alquilo C1-7, nitro, NRaRb, -C(O)-alquilo C1-7, -C(O)-O-alquilo C1-7, alcoxilo C1-7, halogeno, alquilo C1-7, halo-alquilo C1-7, alquenilo C2-7, arilo C6-10, heteroarilo, -NHS(O)2-alquilo C1-7, y bencilo; o R4 es un heterociclilo, el cual puede estar opcionalmente sustituido con uno o más sustituyentes seleccionados independientemente a partir del grupo que consiste en oxo, hidroxilo, hidroxi-alquilo C1-7, amino, C(O)-O-alquilo C1-7, alcoxilo C1-7, halogeno, alquilo C1-7, halo-alquilo C1-7, arilo C6-10, heteroarilo, -NHSO2-alquilo C1-7 y bencilo; R5 es H, halogeno, hidroxilo, alcoxilo C1-7, halogeno, alquilo C1-7, o halo-alquilo C1-7; y X y X1 son independientemente OH, -O-alquilo C1-7, NRaRb, -NHS(O)2-alquilo C1-7, -NHS(O)2-bencilo u -O-arilo C6-10; en donde el alquilo está opcionalmente sustituido con uno o más sustituyentes seleccionados independientemente a partir del grupo que consiste en arilo C6-10, heteroarilo, heterociclilo, -C(O)NH2, -C(O)NH-alquilo C1-6, y -C(O)N(alquilo C1-6)2; B1 es -C(O)NH- o -NHC(O)-; A1 es un enlace o un alquileno C1-7 lineal o ramificado, que está opcionalmente sustituido con uno o más sustituyentes seleccionados independientemente a partir del grupo que consiste en halogeno, cicloalquilo C3-7, alcoxilo C1-7, hidroxilo, y O-acetato, en donde dos grupos alquilo geminales pueden combinarse opcionalmente para formar un cicloalquilo C3-7; o A1 es un alquenileno C1-7 lineal o ramificado; o A1 es un alquileno lineal C1-4 en donde uno o más átomos de carbono son reemplazados con un heteroátomo seleccionado a partir de O, NRc; y A1 está opcionalmente sustituido con uno o más sustituyentes seleccionados independientemente a partir del grupo que consiste en halogeno y alquilo C1-7; en donde Rc por cada presentacion, es independientemente H, alquilo C1-7, -C(O)-O-alquilo C1-7, o -CH2C(O)OH; o A1 es un fenilo o un heteroarilo; cada uno de los cuales está opcionalmente sustituido con uno o más sustituyentes seleccionados independientemente a partir del grupo que consiste en alquilo C1-7, cicloalquilo C3-7, halo-alquilo C1-7, hidroxilo, alcoxilo C1-7, halogeno, NRaRb, -OCH2CO2H, y -OCH2C(O)NH2; o A1 es un cicloalquilo C3-7; o A1 es -alquileno C1-4-arilo C6-10-, -alquileno C1-4-heteroaril- o -alquileno C1-4-heterociclil-, en donde A1 puede estar en cualquier direccion; y A2 es un enlace o un alquileno C1-7 lineal o ramificado, que está opcionalmente sustituido con uno o más sustituyentes seleccionados independientemente a partir del grupo que consiste en halogeno, alcoxilo C1-7, hidroxilo, O-acetato, y cicloalquilo C3-7; n es 0, 1, 2, 3, 4 o 5; en donde cada heteroarilo es un anillo aromático monocíclico o bicíclico que comprende de 5 a 10 átomos del anillo seleccionados a partir de átomos de carbono, y de 1 a 5 heteroátomos, y cada heterociclilo es una fraccion monocíclica saturada parcialmente saturada, pero no aromática, la cual comprende de 4 a 7 átomos del anillo seleccionados a partir de átomos de carbono, y de 1 a 5 heteroátomos, en donde cada heteroátomo de un heteroarilo o de un heterociclilo se selecciona independientemente a partir de O, N y S.
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