AR062900A1 - Derivados de isoquinolina y de quinazolina utiles como inhibidores de quinasa rho - Google Patents

Derivados de isoquinolina y de quinazolina utiles como inhibidores de quinasa rho

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Publication number
AR062900A1
AR062900A1 ARP070104139A ARP070104139A AR062900A1 AR 062900 A1 AR062900 A1 AR 062900A1 AR P070104139 A ARP070104139 A AR P070104139A AR P070104139 A ARP070104139 A AR P070104139A AR 062900 A1 AR062900 A1 AR 062900A1
Authority
AR
Argentina
Prior art keywords
alkyl
aryl
heteroaryl
cycloalkyl
heterocyclyl
Prior art date
Application number
ARP070104139A
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English (en)
Inventor
Thomas Martin Kirrane
Chuan Liu
Anthony S Prokopowicz
Cheng-Kon Shih
Eugene Richard Hickey
Erick Richard Roush Young
Michael Robert Turner
John David Ginn
Todd Bosanac
John Snow
Frank Wu
Original Assignee
Boehringer Ingelheim Int
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.)
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Publication date
Application filed by Boehringer Ingelheim Int filed Critical Boehringer Ingelheim Int
Publication of AR062900A1 publication Critical patent/AR062900A1/es

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    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/541—Non-condensed thiazines containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
    • C07D217/24—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
    • C07D239/88—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
    • C07D239/88—Oxygen atoms
    • C07D239/90—Oxygen atoms with acyclic radicals attached in position 2 or 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/08—Bridged systems

Abstract

Para tratar diversas enfermedades y trastornos en los que intervenga o sean mantenidos por la actividad de cinasa Rho, entre ellos enfermedades cardiovasculares, composiciones farmacéuticas que comprenden tales compuestos, métodos para emplear tales compuestos y procedimientos para preparar tales compuestos. Reivindicacion 5: Un compuesto de formula (1) en donde R1 se elige entre cicloalquilo C3-8, cicloalquil C3-8-alquilo C1-6 , haloalquilo C1-6, aminoalquilo C1-6, hidroxialquilo C1-6, arilo, aril-alquilo C1-6, heteroarilo, heteroaril-alquilo C1-6, heterociclilo, -alquilo C1-3-O-arilo, -C(H)0-1-(alquil C1-6)1-2-arilo, -CH(OH)-arilo, -C(OH)(CH3)-arilo, -CH[OC(O)-(alquil C1-6)]-arilo, -CH2OCH2-arilo, -CH2OC(O)-(alquilo C1-6), - (CH2)1-3S(O)0-2-arilo, -(CH2)1-2S(O)0-2-(alquilo C1-6, -(CH2)1-3CO2-(alquilo C1-6, -(CH2)1-3NH(alquilo C1-6, -(CH2)1-3NH(alquil C1-6)-(cicloalquilo C3-8), -(CH2)1-2-CN y -CH(R3)N(R4)(R5) en donde: R3 se elige entre H, arilo, alquilo C1-6, -(CH2)1-3- arilo y - (CH2)1-3 heteroarilo; R4 se elige entre H, alquilo C1-6, cicloalquilo C3-12, (cicloalquil C3-7)-(alquilo C1-6), arilo, aril-(CH2)1-3, heteroaril-(CH2)1-3, (alquil C1-3)-O(CH2)1-3, tetrahidropiran-4-ilmetilo y (alquil C1-3)2N(CH2)2-4-; y R5 se elige entre H y alquilo C1-6 o bien R4 y R5 junto con el átomo de nitrogeno al cual están conectados pueden formar un grupo heterociclilo; en donde cada grupo arilo, arilalquilo, heteroarilo, heteroarilalquilo, cicloalquilalquilo, cicloalquilo y heterociclilo está opcionalmente sustituido con 1-3 grupos seleccionados entre halogeno, alcoxi C1-6, cicloalquilo C3-8, alquilo C1-6, -CN, NO2, -OH, oxo, -CF3, -OCF3, -(alquil C0-3)-CO2H, (alquil C1-6-CO2-, (alquil C1-6)-sulfonil-(alquilo C0-3)-, - SO2-(alquil C1-6)-NR6R7, -(alquil C0-3)-SO2NR6R7, -(alquil C0-3)-C(O)NR6R7, arilo, heteroarilo, heteroaril-(alquilo C1-3), heterociclilo, heterociclil-SO2-, aril-(alquilo C1-3), ariloxi, ariltio y C0-3NR6R7; en donde cada grupo arilo y heteroarilo está opcionalmente sustituido con 1-3 grupos seleccionados entre halogeno, alcoxi C1-6, alquilo C1-6, -CN, -NO2, -OH, -CF3, -OCF3, -C(O)NR8R9, -SO2NR8R9, -SO2Me y amino opcionalmente sustituido con uno o dos grupos alquilo C1-6 o un grupo C(O)(alquilo C1-6); R2 se elige entre H, halogeno, alcoxi C1-6, -CN, -CF3 y alquilo C1-6; R6 y R7 se seleccionan, de manera independiente, entre H, alquilo C1-6, -C(O)-(alquilo C1-6) y -(alquil C1-6)NH2; o bien R6 y R7, junto con el átomo de nitrogeno al cual están conectados, pueden formar un anillo de piperazina, piperidina o pirrolidina; R8 y R9 se seleccionan, de manera independiente, entre H y metilo; R10 se selecciona entre H, Cl y F; X se elige entre C y N; e Y se elige entre - NHC(O)-, -NHC(O)NH- y -NHC(O)O-; o un tautomero o una sal del compuesto de formula (1).
ARP070104139A 2006-09-20 2007-09-19 Derivados de isoquinolina y de quinazolina utiles como inhibidores de quinasa rho AR062900A1 (es)

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US82628406P 2006-09-20 2006-09-20
US86448406P 2006-11-06 2006-11-06

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US (5) US8809326B2 (es)
EP (2) EP2526948A1 (es)
JP (1) JP5235887B2 (es)
AR (1) AR062900A1 (es)
CA (1) CA2664335C (es)
CL (1) CL2007002686A1 (es)
ES (1) ES2729424T3 (es)
TW (1) TW200819133A (es)
WO (1) WO2008036540A2 (es)

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