CO5180639A1 - Amidas de acidos carboxilicos medicamentos que contienen estos compuestos su utilizacion y su prepracion - Google Patents

Amidas de acidos carboxilicos medicamentos que contienen estos compuestos su utilizacion y su prepracion

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Publication number
CO5180639A1
CO5180639A1 CO00056547A CO00056547A CO5180639A1 CO 5180639 A1 CO5180639 A1 CO 5180639A1 CO 00056547 A CO00056547 A CO 00056547A CO 00056547 A CO00056547 A CO 00056547A CO 5180639 A1 CO5180639 A1 CO 5180639A1
Authority
CO
Colombia
Prior art keywords
group
alkyl
amino
substituted
phenyl
Prior art date
Application number
CO00056547A
Other languages
English (en)
Inventor
Norbert Hauel
Priepke Henning
Michael Damm
Schnapp Andras
Original Assignee
Boehringer Ingleheim Pharma Kg
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 Boehringer Ingleheim Pharma Kg filed Critical Boehringer Ingleheim Pharma Kg
Publication of CO5180639A1 publication Critical patent/CO5180639A1/es

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • 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
    • C07D295/182—Radicals derived from carboxylic acids
    • C07D295/192—Radicals derived from carboxylic acids from aromatic carboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • 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
    • C07C233/53—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 six-membered aromatic ring
    • C07C233/55—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 six-membered aromatic ring having the carbon atom of the carboxamide group bound to a carbon atom of an unsaturated carbon skeleton
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/57—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings
    • 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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    • C07C233/00—Carboxylic acid amides
    • C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C233/81—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of 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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    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/32—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
    • C07C235/38—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
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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
    • C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
    • C07C237/30—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to hydrogen atoms or to acyclic carbon atoms
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    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
    • C07C237/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
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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
    • C07C237/52—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the nitrogen atom of at least one of the carboxamide groups further acylated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C243/00—Compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes
    • C07C243/24—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids
    • C07C243/38—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids with acylating carboxyl groups bound to carbon atoms of six-membered aromatic rings
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/24—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the same saturated acyclic carbon skeleton
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    • C07—ORGANIC CHEMISTRY
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    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids
    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/20—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by nitrogen atoms not being part of nitro or nitroso groups
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    • C07C271/06—Esters of carbamic acids
    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/26—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring
    • C07C271/28—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring to a carbon atom of a non-condensed six-membered aromatic ring
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    • C07C275/42—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by carboxyl groups
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    • C07C309/28—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C309/45—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing nitrogen atoms, not being part of nitro or nitroso groups, bound to the carbon skeleton
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    • C07C309/64—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to acyclic carbon atoms
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    • C07C311/08—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
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    • C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C311/21—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
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    • C07C311/30—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
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    • C07C311/38—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton
    • C07C311/39—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
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    • 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
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    • C07D213/72—Nitrogen atoms
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    • C07D213/78—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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    • C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
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Abstract

1. Utilización de las amidas de ácidos carboxílicos de la fórmula general <EMI FILE="00056547_1" ID="1" IMF=JPEG >en la queR1 significa un átomo de hidrógeno, un grupo alquilo C1 3 o trifluorometilo, R2 significa un átomo de hidrógeno, flúor, cloro o bromo, un grupo alquilo C1 3, cicloalquilo C3 7 o alcoxi C1 3, o también, cuando R4 y R5 representan en cada caso un átomo de hidrógeno, R1 y R2 significan en común un grupo n alquileno C1 3 eventualmente sustituido con un grupo alquilo C1 3, R3 significa un átomo de hidrógeno o un grupo alquilo C1 5,R4 y R5 significan en cada caso un átomo de hidrógeno o en común otro enlace de carbono con carbono,A significa un grupo fenilo, naftilo o tetrahidronaftilo sustituido con un átomo de flúor, cloro, bromo o yodo, o con un grupo alquilo C1 6, cicloalquilo C3 7, fenilo, alcoxi C1 3, ciano, trifluorometilo o nitro, pudiendo los grupos fenilo y naftilo monosustituidos precedentemente mencionados estar sustituidos adicionalmente con un átomo de flúor, cloro o bromo, o con un grupo alquilo C1 3 o alcoxi C1 3, y pudiendo los grupos fenilo disustituidos precedentemente mencionados estar sustituidos adicionalmente con un grupo alquilo C1 3 o alcoxi C1 3, significa un grupo naftilo, significa un grupo de cromano o cromeno, en el que un grupo metileno puede estar reemplazado por un grupo carbonilo, significa un grupo heteroarilo de 5 ó 6 miembros, eventualmente sustituido en el entramado de carbonos con un átomo de flúor, cloro o bromo, o con un grupo alquilo C1 3 o alcoxi C1 3, conteniendo los grupos heteroarilo de 6 miembros uno, dos o tres átomos de nitrógeno y conteniendo los grupos heteroarilo de 5 miembros un grupo imino eventualmente sustituido con un grupo alquilo C1 3, un átomo de oxígeno o azufre o un grupo imino eventualmente sustituido con un grupo alquilo C1 3 y un átomo de oxígeno o azufre o uno o dos átomos de nitrógeno, y pudiendo estar condensado adicionalmente con los grupos heteroarilo monocíclicos precedentemente - 2 -mencionados a través de dos átomos de carbono contiguos un anillo de fenilo, que puede estar sustituido también en el entramado de carbonos con un átomo de flúor, cloro o bromo, o con un grupo alquilo C1 3 o alcoxi C1 3, significa un grupo fenil vinilo, o R1, en común con A y con el átomo de carbono situado entremedias, significa un grupo cicloalquilideno C5 7, con el que puede estar condensado a través de dos átomos de carbono contiguos un anillo de fenilo, que puede estar sustituido adicionalmente con uno o dos grupos alquilo C1 3 o alcoxi C1 3, pudiendo los sustituyentes ser iguales o diferentes, y B significa un grupo heteroarilo de 5 ó 6 miembros sustituido con un grupo carboxi o con un grupo transformable in vivo en un grupo carboxi,significa un grupo fenilo o naftilo, los cuales en cada caso pueden estar sustituidos con un grupo carboxi, con un grupo transformable in vivo en un grupo carboxi o con un grupo cargado negativamente en condiciones fisiológicas, pudiendo los grupos fenilo precedentemente mencionados estar sustituidos adicionalmente con un átomo de flúor, cloro, bromo o yodo, con un grupo alquilo C1 3, trifluorometilo, fenilo, hidroxi, alcoxi C1 3, alquil C1 3 sulfonil oxi, fenil sulfonil oxi, carboxi, alcoxi C1 3 carbonilo, formilo, alquil C1 3 carbonilo, alquil C1 3 sulfonilo, fenil sulfonilo, nitro, pirrolidino, piperidino, morfolino, N (alquil C1 3) piperazino, amino sulfonilo, alquil C1 3 amino sulfonilo o di (alquil C1 3) amino sulfonilo, con un grupo alquilo C1 3, que está sustituido con un grupo hidroxi, alcoxi C1 3, amino, alquil C1 4 amino, di (alquil C1 4) amino, cicloalquil C3 7 amino, pirrolidino, piperidino, morfolino, piperazino o N (alquil C1 3) piperazino, con un grupo alcoxi C2 3, alquenilo C2-3 o alquinilo C2-3 sustituido con un grupo di (alquil C1 3) amino en la posición 2 ó 3, con un grupo amino, con un grupo N (alquil C1 3) amino o N,N di (alquil C1 3) amino, en el que la parte de alquilo puede estar sustituida con un grupo alcoxi C1 3 en cada caso en la posición 2 ó 3, referida al átomo de nitrógeno, con un grupo N fenil amino, N (fenil alquil C1 3) amino o N (piridil alquil C1 3) amino, en los cuales en cada caso un átomo de hidrógeno de los grupos amino precedentemente mencionados puede estar reemplazado por un grupo alquil C1 3 sulfonilo, fenil alquil C1 3 sulfonilo o fenil sulfonilo, o con un grupo alquilo C1 7, que en las posiciones 2 a 5 puede estar reemplazado por un grupo alcoxi C1 3, ciano, amino, alquil C1 3 amino, di (alquil C1 3) amino o tetrazolilo, con un grupo amino carbonilo o alquil C1 3 amino carbonilo, los cuales en cada caso pueden estar sustituidos en el átomo de nitrógeno de amino con un grupo alquilo C1 4, que puede estar sustituido con un grupo vinilo, etinilo, fenilo, piridilo, imidazolilo, carboxi o trifluorometilo, o con excepción de la posición 2 referida al átomo de nitrógeno de amino carbonilo, puede estar sustituido con un grupo hidroxi, alcoxi C1 3, alquil C1 3 tio, amino, alquil C1 3 amino, di (alquil C1 3) amino, alcanoil C1 4 amino o alcoxi C1 5 carbonil amino, con un grupo cicloalquilo C3 7, aza bicicloalquilo C5 9, fenilo, piridilo, alcoxi C1 3 o di (alquil C1 3) amino, con un grupo alquilo C1 3, que está sustituido con un grupo piperidin 3 ilo o piperidin 4 ilo eventualmente sustituido en posición 1 con un grupo alquilo C1 3 o alcoxi C1 5 carbonilo, ocon un grupo amino, alquil C1 3 amino o fenil alquil C1 3 amino eventualmente sustituido en el átomo de nitrógeno de amino con un grupo alcanoílo C1 4, alcoxi C1 5 carbonilo, benzoílo, pirrolidino, piperidino, morfolino o N (alquil C1 3) piperazino, con un grupo carbonilo sustituido con un grupo pirrolidino, pirrolino, piperidino, morfolino o N (alquil C1 3) piperazino, con un grupo sulfonilo sustituido con un grupo amino, alquil C1 3 amino, di (alquil C1 3) amino, pirrolidino, piperidino, morfolino o N (alquil C1 3) piperazino, con un grupo amino o N (alquil C1 3) amino, que está sustituido en cada caso en el átomo de nitrógeno de amino con un grupo amino carbonilo, alquil C1 3 amino carbonilo, fenil alquil C1 3 amino carbonilo, fenil amino carbonilo, fenoxi fenil amino carbonilo, piridil amino carbonilo, pirrolidino carbonilo, piperidino carbonilo, morfolino carbonilo o - 3 -N (alquil C1 3) piperazino carbonilo, pudiendo un átomo de hidrógeno presente en los grupos amino carbonilo precedentemente mencionados estar sustituido adicionalmente con un grupo alquilo C1 3, con un grupo heteroarilo de 5 ó 6 miembros, con un grupo dihidro oxazolilo, dihidro imidazolilo, 2 oxo pirrolidino, 2 oxo piperidino o 2 oxo hexametilen imino, con los que puede estar condensado un anillo de fenilo a través de dos átomos de carbono contiguos, con un grupo etinilo sustituido con un grupo fenilo, hidroximetilo o dimetilamino, pudiendo los grupos fenilo mono o di sustituidos precedentemente mencionados estar sustituidos adicionalmente con otro átomo de flúor, cloro o bromo, o con uno o dos grupos alquilo C1 3 o alcoxi C1 3 adicionales y pudiendo dos grupos alcoxi C1 3 situados en posición o (= orto) estar reemplazados por un grupo metilendioxi,y los grupos heteroarilo de 6 miembros precedentemente mencionados contienen uno, dos o tres átomos de nitrógeno y los grupos heteroarilo de 5 miembros precedentemente mencionados contienen un grupo imino eventualmente sustituido con un grupo alquilo C1 3, un átomo de oxígeno o azufre o un grupo imino eventualmente sustituido con un grupo alquilo C1 3 y un átomo de oxígeno o azufre o uno o dos átomos de nitrógeno, y adicionalmente puede estar condensado con los grupos heteroarilo monocíclicos precedentemente mencionados a través de dos átomos de carbono contiguos un anillo de fenilo, que en el entramado de carbonos puede estar sustituido con un átomo de flúor, cloro o bromo, o con un grupo alquilo C1 3 o alcoxi C1 3, pudiendo los grupos heteroarilo monocíclicos de 5 miembros precedentemente mencionados estar sustituidos en el entramado de carbonos adicionalmente con un grupo alquilo C1 4, trifluorometilo, fenilo o furanilo y estar sustituidos con otro grupo alquilo C1 3, pudiendo los grupos amino e imino, mencionados con ocasión de la definición de los radicales precedentemente mencionados, estar sustituidos adicionalmente con un radical separable in vivo, sus isómeros y sus sales, especialmente sus sales fisiológicamente compatibles, para la inhibición de la telomerasa.
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