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AR083872A1 - Derivados de acido carbamoil-cicloalquil-acetico sustituidos como inhibidores de nep - Google Patents

Derivados de acido carbamoil-cicloalquil-acetico sustituidos como inhibidores de nep

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Publication number
AR083872A1
AR083872A1 ARP110104249A ARP110104249A AR083872A1 AR 083872 A1 AR083872 A1 AR 083872A1 AR P110104249 A ARP110104249 A AR P110104249A AR P110104249 A ARP110104249 A AR P110104249A AR 083872 A1 AR083872 A1 AR 083872A1
Authority
AR
Argentina
Prior art keywords
alkyl
heteroaryl
alkoxy
halogen
independently selected
Prior art date
Application number
ARP110104249A
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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
Application filed by Novartis Ag filed Critical Novartis Ag
Publication of AR083872A1 publication Critical patent/AR083872A1/es

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    • C07C233/45—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
    • C07C233/52—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a ring other than a six-membered aromatic ring
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    • A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
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    • C07C233/63—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C237/22—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
    • C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/55—Acids; Esters
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    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
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    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
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Abstract

Se proporciona además una composición farmacéutica de los compuestos de la presente, y una combinación de agentes famacológicamente activos. Su uso como medicamento para el tratamiento de enfermedades mediadas por NEP.Reivindicación 1: Un compuesto de la fórmula (1) o una sal farmacéuticamente aceptable del mismo, en donde: R3 y R4 son H, o R3 y R4 junto con los átomos de carbono con los que están unidos, forman un anillo de fenilo; n es 0 ó 1; R1, por cada presentación, es independientemente halógeno, alquilo C1-6, alcoxilo C1-6, hidroxilo, heteroarilo o fenilo; en donde el heteroarilo y fenilo pueden estar opcionalmente sustituidos con uno o más sustituyentes seleccionados independientemente a partir de halógeno, alquilo C1-6, halo-alquilo C1-6, ciano, alcoxilo C1-6, hidroxilo y NRcRd; en donde Rc y Rd son independientemente H o alquilo C1-6; o dos grupos R1 adyacentes forman, junto con los átomos de carbono con los que están unidos, un anillo de heteroarilo de 5 ó 6 miembros opcionalmente sustituido con uno o más sustituyentes independientemente seleccionados a partir de halógeno, alquilo C1-6, halo-alquilo C1-6, ciano, hidroxilo y alcoxilo C1-6; R2 es (CH2)pC(O)X1 o (CH2)s-heteroarilo; en donde el heteroarilo es un anillo de heteroarilo mono- o bi-cíclico que contiene de 5 a 10 miembros del anillo seleccionados a partir de átomos de carbono, y de 1 a 5 heteroátomos, y cada heteroátomo se selecciona independientemente a partir de O, N o S, en donde S y N se pueden oxidar hasta diferentes estados de oxidación, y el heteroarilo está opcionalmente sustituido con uno o más sustituyentes seleccionados independientemente a partir de halógeno, alquilo C1-6, halo-alquilo C1-6, ciano, hidroxilo, alcoxilo C1-6, carboxilo y C(O)O-alquilo C1-6; R5 es H, alquilo C1-6, o arilo C6-10-alquilo C1-6; p es 0 ó 1; s es 0, 1, 2, 3 ó 4; m es 0, 1, 2, 3, 4 ó 5; X y X1 son independientemente OH, O-alquilo C1-6, O-bencilo o NRaRb, en donde Ra y Rb son independientemente H, alquilo C1-6 opcionalmente sustituido con uno o más sustituyentes seleccionados independientemente a partir de halógeno, hidroxilo, alcoxilo C1-6, y carboxilo; o Ra y Rb, junto con el átomo de nitrógeno con el que están unidos, forman un heterociclilo de 5 ó 6 miembros opcionalmente sustituido con uno o más sustituyentes seleccionados independientemente a partir de alquilo C1-6, halógeno, hidroxilo, alcoxilo C1-6, carboxilo, C(O)O-alquilo C1-6, y C(O)O-bencilo; y B es C(O)NH o NHC(O), con la condición de que el compuesto no es el ácido 4-(bisfenil-4-il)-3-(1-carboxi-metil)-ciclopentan-carboxamido)-butanoico, el ácido 4-([1,1’-bifenil]-4-il)-3-(1-(2-(benciloxi)-2-oxo-etil)-ciclopentan-carboxamido)-butanoico, ni el 4-([1,1’-bifenil]-4-il)-3-(1-(2-(benciloxi)-2-oxo-etil)-ciclopentan-carboxamido)-butanoato de terbutilo.
ARP110104249A 2010-11-16 2011-11-14 Derivados de acido carbamoil-cicloalquil-acetico sustituidos como inhibidores de nep AR083872A1 (es)

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US41417110P 2010-11-16 2010-11-16

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AR083872A1 true AR083872A1 (es) 2013-03-27

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US (1) US8877815B2 (es)
EP (1) EP2640689A1 (es)
JP (1) JP2014507372A (es)
CN (1) CN103249715A (es)
AR (1) AR083872A1 (es)
TW (1) TW201300353A (es)
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