AR038767A1 - DERIVATIVES OF REPLACED AMINA AND METHODS OF USE - Google Patents

DERIVATIVES OF REPLACED AMINA AND METHODS OF USE

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Publication number
AR038767A1
AR038767A1 ARP020100076A ARP020100076A AR038767A1 AR 038767 A1 AR038767 A1 AR 038767A1 AR P020100076 A ARP020100076 A AR P020100076A AR P020100076 A ARP020100076 A AR P020100076A AR 038767 A1 AR038767 A1 AR 038767A1
Authority
AR
Argentina
Prior art keywords
phenyl
substituted
addition
optionally substituted
heterocyclyl
Prior art date
Application number
ARP020100076A
Other languages
Spanish (es)
Inventor
Lucian Dipietro
Daniel Elbaum
Jean Bemis
Michael Croghan
Celia Dominguez
Julie Germain
Qi Huang
Tae-Seong Kim
Xiaohu Ouyang
Leon M Smith
Andrew Tasker
Shimin Xu
Joseph L Kim
Vinod F Patel
Xin Ning
Chester Chenguang Yuan
Jeffrey Adams
Guoqing Chen
Original Assignee
Amgen Inc
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 Amgen Inc filed Critical Amgen Inc
Publication of AR038767A1 publication Critical patent/AR038767A1/en

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Classifications

    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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

Abstract

Las aminas seleccionadas resultan eficaces para la profilaxis y el tratamiento de enfermedades, tales como las enfermedades mediadas por angiogénesis. Se incluyen novedosos compuestos, análogos, profármacos y sus sales farmacéuticamente aceptables, composiciones farmacéuticas y métodos destinados a la profilaxis y el tratamiento de enfermedades y demás dolencias o estados que se relacionan con el cáncer y otras patologías similares. Se refiere, asimismo, a los procedimientos para la elaboración de dichos compuestos y también a los productos intermedios que resultan de utilidad en dichos procedimientos. Reivindicación 1: Un compuesto de la fórmula (1) donde cada uno de A1 y A2 se selecciona independientemente de C, CH, o N; donde el anillo A se selecciona de a) heterociclilo parcialmente saturado de 5 ó 6 miembros, b) heteroarilo de 5 ó 6 miembros, c) heterociclilo parcialmente saturado, fusionado, de 9, 10 u 11 miembros, d) heteroarilo fusionado de 9, 10, u 11 miembros, e) arilo, y f) cicloalquenilo de 4, 5 ó 6 miembros; donde X es como se muestra en la estructura (2), donde Z es O ó S; donde R se selecciona de a) heterociclilo sustituido o instituido de 4-6 miembros, b) arilo sustituido, y c) heterociclilo bicíclico o tricíclico, sustituido o insustituido, fusionado de 9-14 miembros donde R sustituido es sustituido con uno o más sustituyentes que se seleccionan independientemente de halo, -OR3, -SR3, -SO2R3, -CO2R3, -CONR3R3, -COR3, -NR3R3, -SO2NR3R3,-NR3C(O)OR3, -NR3C(O)R3, cicloalquilo, heterociclilo opcionalmente sustituido de 3-6 miembros, fenilo opcionalmente sustituido, nitro, alquilaminoalcoxialcoxi, ciano, alquilaminoalcoxi, alquilo inferior sustituido con R2, alquenilo inferior sustituido con R2 y alquinilo inferior sustituido con R2; donde R1 se selecciona de a) arilo sustituido o insustituido de 6-10 miembros, b) heterociclilo sustituido o insustituido de 4-6 miembros, c) heterociclilo bicíclico o tricíclico, sustituido o insustituido, de 9-14 miembros, d) cicloalquilo, y e) cicloalquenilo, donde R1 sustituido es sustituido con uno o más sustituyentes que se seleccionan independientemente de halo, -OR3, -SR3, -CO2R3, -CONR3R3, -COR3, -NR3R3, -NH(alquilenilo C1-4R14), -SO2R3, -SO2NR3R3, -NR3C(O)OR3, -NR3C(O)R3, cicloalquilo opcionalmente sustituido, heterociclilo opcionalmente sustituido de 4-6 miembros, fenilo opcionalmente sustituido, halosulfonilo, ciano, alquilaminoalcoxi, alquilaminoalcoxialcoxi, nitro, alquilo inferior sustituido con R2, alquenilo inferior sustituido con R2 y alquinilo inferior sustituido con R2; donde R2 es uno o más sustituyentes que se seleccionan independientemente de H, halo, -OR3, oxo, -SR3, -CO2R3, -COR3, -CONR3R3, -NR3R3, -SO2NR3R3, -NR3C(O)OR3, -NR3C(O)R3, cicloalquilo, fenilalquilenilo opcionalmente sustituido, heterociclilo opcionalmente sustituido de 4-6 miembros, heteroarilalquilenilo opcionalmente sustituido, fenilo opcionalmente sustituido, alquilo inferior, ciano, hidroxialquilo inferior, carboxialquilo inferior, nitro, alcoxi C1-6-alcoxi C1-6, alcoxi C1-6-alcoxi C1-6-alcoxi C1-6, alquenilo inferior, alquinilo inferior, aminoalquilo inferior, alquilaminoalquilo inferior y haloalquilo inferior; donde R3 se selecciona independientemente de H, alquilo inferior, fenilo, heterociclilo de 3-6 miembros, cicloalquilo C3-6, fenilalquilo, heterociclilalquilo de 3-6 miembros, cicloalquilalquilo C3-6 y haloalquilo inferior; donde R4 se selecciona de un enlace directo, alquilenilo C2-4, alquenilenilo C2-4 y alquinilenilo C2-4, donde uno de los grupos CH2 puede ser sustituido con un átomo de O ó un -NH-, donde R4 es opcionalmente sustituido con hidroxi, donde R5 se selecciona de H, alquilo inferior, fenilo y aralquilo inferior; donde R14 se selecciona de H, fenilo, heterociclilo de 4-6 miembros y cicloalquilo C3-6; y sus derivados farmacéuticamente aceptables; siempre que A no sea piridilo cuando X es -C(O)NH- y cuando R1 es 4-[3,5-bis(trifluorometil)-1H-pirazol-1-il]fenilo cuando R5 es metilo y cuando R es 4-metilpiperidilo; siempre que A, además, no sea piridilo cuando X es -C(O)NH-, cuando R5 es H, cuando R2 es 6-metilo y cuando R es indazolilo; siempre que A, además, no sea fenilo cuando X es -C(O)NH-, cuando R1 es fenilo, 4-bromofenilo, 2-metilfenilo, 4-metoxifenilo, cuando R5 es H y cuando R es 4-piridilo; siempre que A, además, no sea fenilo cuando X es -C(O)NH-, cuando R1 es fenilo, cuando R5 es H y cuando R es 2-oxobenzopian-4-ilo, siempre que A, además, no sea fenilo cuando X es -C(O)NH-, cuando R1 es fenilo, 4-clorofenilo, 3-nitrofenilo, 4-metoxifenilo, cuando R5 es H y cuando R es 4-imidazolinilo; siempre que A, además, no sea fenilo cuando X es -C(O)NH-, cuando R5 es H, cuando R5a es bencilo sustituido y cuando R es triazinilo sustituido; siempre que A, además, no sea fenilo cuando X es -C(O)NH-, cuando R1 es fenilo o 2-clorofenilo, cuando R5 es H y cuando R es 4-quinazolinilo; siempre que A, además, no sea fenilo cuando X es -C(O)NH-, cuando R1 es fenilo, cuando R5 es H y cuando R es isoquinolin-1-ilo; siempre que A, además, no sea fenilo cuando X es -C(O)NH-, cuando R1 es 2-clorofenilo o 4-clorofenilo, cuando R5 es H y cuando R es 3-cloroisoquinolin-1-ilo; siempre que A, además, no sea fenilo cuando X es -C(O)NH-, cuando R1 es 1-etilpiperid-3-ilo o 1-etilpiperid-4-ilo, cuando R5 es H y cuando R es 8-trifluorometilquinolin-4-ilo; siempre que A, además, no sea fenilo cuando X es -C(O)NH-, cuando R1 es 1-etilpiperid-3-ilo, cuando R5 es H y cuando R es 8-cloroquinolin-4-ilo; siempre que A, además, no sea fenilo cuando X es -C(O)NH-; cuando R1 es halo fenilo sustituido, 1-butilpiperid-4-ilo, 1-etilpiperid-3-ilo o 1-etilpiperid-4-ilo, cuando R5 es H y cuando R es 7-cloroquinolin-4-ilo; y siempre que, además, R no sea 2-tienilo insustituido, 2-piridilo insustituido o 3-piridilo insustituido.The selected amines are effective for the prophylaxis and treatment of diseases, such as angiogenesis-mediated diseases. Novel compounds, analogs, prodrugs and their pharmaceutically acceptable salts, pharmaceutical compositions and methods for the prophylaxis and treatment of diseases and other conditions or conditions that are related to cancer and other similar pathologies are included. It also refers to the procedures for the preparation of said compounds and also to the intermediate products that are useful in said procedures. Claim 1: A compound of the formula (1) wherein each of A1 and A2 is independently selected from C, CH, or N; wherein ring A is selected from a) partially saturated 5 or 6 membered heterocyclyl, b) 5 or 6 membered heteroaryl, c) partially saturated, fused, 9, 10 or 11 membered heterocyclyl, d) fused 9 heteroaryl, 10, or 11 members, e) aryl, and f) cycloalkenyl of 4, 5 or 6 members; where X is as shown in structure (2), where Z is O or S; where R is selected from a) 4-6 membered substituted or instituted heterocyclyl, b) substituted aryl, and c) bicyclic or tricyclic heterocyclyl, substituted or unsubstituted, fused from 9-14 members where R substituted is substituted with one or more substituents that are independently selected from halo, -OR3, -SR3, -SO2R3, -CO2R3, -CONR3R3, -COR3, -NR3R3, -SO2NR3R3, -NR3C (O) OR3, -NR3C (O) R3, cycloalkyl, optionally substituted heterocyclyl 3-6 members, optionally substituted phenyl, nitro, alkylaminoalkoxyalkoxy, cyano, alkylaminoalkoxy, lower alkyl substituted with R2, lower alkenyl substituted with R2 and lower alkynyl substituted with R2; where R1 is selected from a) substituted or unsubstituted aryl of 6-10 members, b) substituted or unsubstituted heterocyclyl of 4-6 members, c) bicyclic or tricyclic heterocyclyl, substituted or unsubstituted, of 9-14 members, d) cycloalkyl, and e) cycloalkenyl, where substituted R1 is substituted with one or more substituents that are independently selected from halo, -OR3, -SR3, -CO2R3, -CONR3R3, -COR3, -NR3R3, -NH (C1-4R14 alkylenyl), -SO2R3 , -SO2NR3R3, -NR3C (O) OR3, -NR3C (O) R3, optionally substituted cycloalkyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted phenyl, halosulfonyl, cyano, alkylaminoalkoxy, alkylaminoalkoxyalkoxy, nitro, lower alkyl substituted with R2 , lower alkenyl substituted with R2 and lower alkynyl substituted with R2; where R2 is one or more substituents that are independently selected from H, halo, -OR3, oxo, -SR3, -CO2R3, -COR3, -CONR3R3, -NR3R3, -SO2NR3R3, -NR3C (O) OR3, -NR3C (O ) R3, cycloalkyl, optionally substituted phenylalkylenyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted heteroarylalkylene, optionally substituted phenyl, lower alkyl, cyano, lower hydroxyalkyl, lower carboxyalkyl, nitro, C1-6 alkoxy-C1-6 alkoxy, alkoxy C1-6-C1-6 alkoxy-C1-6 alkoxy, lower alkenyl, lower alkynyl, lower aminoalkyl, lower alkylaminoalkyl and lower haloalkyl; wherein R3 is independently selected from H, lower alkyl, phenyl, 3-6 membered heterocyclyl, C3-6 cycloalkyl, phenylalkyl, 3-6 membered heterocyclyl alkyl, C3-6 cycloalkylalkyl and lower haloalkyl; where R4 is selected from a direct bond, C2-4 alkylenyl, C2-4 alkenylenyl and C2-4 alkynyl, where one of the CH2 groups can be substituted with an O atom or an -NH-, where R4 is optionally substituted with hydroxy, where R5 is selected from H, lower alkyl, phenyl and lower aralkyl; where R14 is selected from H, phenyl, 4-6 membered heterocyclyl and C3-6 cycloalkyl; and its pharmaceutically acceptable derivatives; provided that A is not pyridyl when X is -C (O) NH- and when R1 is 4- [3,5-bis (trifluoromethyl) -1H-pyrazol-1-yl] phenyl when R5 is methyl and when R is 4 -methylpiperidyl; provided that A, in addition, is not pyridyl when X is -C (O) NH-, when R5 is H, when R2 is 6-methyl and when R is indazolyl; provided that A, in addition, is not phenyl when X is -C (O) NH-, when R1 is phenyl, 4-bromophenyl, 2-methylphenyl, 4-methoxyphenyl, when R5 is H and when R is 4-pyridyl; provided that A, in addition, is not phenyl when X is -C (O) NH-, when R1 is phenyl, when R5 is H and when R is 2-oxobenzopian-4-yl, provided that A, in addition, is not phenyl when X is -C (O) NH-, when R1 is phenyl, 4-chlorophenyl, 3-nitrophenyl, 4-methoxyphenyl, when R5 is H and when R is 4-imidazolinyl; provided that A, in addition, is not phenyl when X is -C (O) NH-, when R5 is H, when R5a is substituted benzyl and when R is substituted triazinyl; provided that A, in addition, is not phenyl when X is -C (O) NH-, when R1 is phenyl or 2-chlorophenyl, when R5 is H and when R is 4-quinazolinyl; provided that A, in addition, is not phenyl when X is -C (O) NH-, when R1 is phenyl, when R5 is H and when R is isoquinolin-1-yl; provided that A, in addition, is not phenyl when X is -C (O) NH-, when R1 is 2-chlorophenyl or 4-chlorophenyl, when R5 is H and when R is 3-chloroisoquinolin-1-yl; provided that A, in addition, is not phenyl when X is -C (O) NH-, when R1 is 1-ethylpiperid-3-yl or 1-ethylpiperid-4-yl, when R5 is H and when R is 8-trifluoromethylquinolin -4-yl; provided that A, in addition, is not phenyl when X is -C (O) NH-, when R1 is 1-ethylpiperid-3-yl, when R5 is H and when R is 8-chloroquinolin-4-yl; provided that A, in addition, is not phenyl when X is -C (O) NH-; when R1 is halo substituted phenyl, 1-butylpiperid-4-yl, 1-ethylpiperid-3-yl or 1-ethylpiperid-4-yl, when R5 is H and when R is 7-chloroquinolin-4-yl; and provided that, in addition, R is not unsubstituted 2-thienyl, unsubstituted 2-pyridyl or unsubstituted 3-pyridyl.

ARP020100076A 2001-01-12 2002-01-11 DERIVATIVES OF REPLACED AMINA AND METHODS OF USE AR038767A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US26188201P 2001-01-12 2001-01-12
US32380801P 2001-09-19 2001-09-19

Publications (1)

Publication Number Publication Date
AR038767A1 true AR038767A1 (en) 2005-01-26

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Application Number Title Priority Date Filing Date
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AR (1) AR038767A1 (en)
TW (1) TWI297010B (en)

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TWI297010B (en) 2008-05-21

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