AR064208A1 - DERIVATIVES OF PIRIDIN-3-IL-QUINAZOLINAS AS INHIBITORS OF B-RAF. PROCESSES OF OBTAINING AND PHARMACEUTICAL COMPOSITIONS. - Google Patents

DERIVATIVES OF PIRIDIN-3-IL-QUINAZOLINAS AS INHIBITORS OF B-RAF. PROCESSES OF OBTAINING AND PHARMACEUTICAL COMPOSITIONS.

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Publication number
AR064208A1
AR064208A1 ARP070105508A ARP070105508A AR064208A1 AR 064208 A1 AR064208 A1 AR 064208A1 AR P070105508 A ARP070105508 A AR P070105508A AR P070105508 A ARP070105508 A AR P070105508A AR 064208 A1 AR064208 A1 AR 064208A1
Authority
AR
Argentina
Prior art keywords
alkyl
carbamoyl
amino
sulfamoyl
carbocyclyl
Prior art date
Application number
ARP070105508A
Other languages
Spanish (es)
Inventor
Brian Aquila
Donald J Cook
Stephen Lee
Paul Lyne
Melissa Vasbinder
Haixia Wang
Craig Johnstone
David A Rudge
Original Assignee
Astrazeneca Ab
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=39386079&utm_source=***_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=AR064208(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab
Publication of AR064208A1 publication Critical patent/AR064208A1/en

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Classifications

    • 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
    • C07D401/04—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 directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Abstract

Procesos para la elaboracion de dichos compuestos químicos, con composiciones farmacéuticas que los contienen y con su uso en la elaboracion de medicamentos para la produccion de un efecto anticanceroso en un animal de sangre caliente, tal como el hombre. Reivindicacion 1: Un compuesto caracterizado porque tiene la formula (1), en donde: R1 se selecciona entre halo, nitro, ciano, hidroxi, trifluorometoxi, amino, carboxi, carbamoílo, mercapto, sulfamoílo, ureido, alquilo C1-6, alquenilo C2- 6, alquinilo C2-6, aIcoxi C1-6, alcanoílo C1-6, alcanoiloxi C1-6, N-(C1-6 alquil)amino, N,N-(C1-6 alquil)2amino, N'-(C1-6 alquil)ureido, N',N'-(C1-6 aIquil)2ureido, N'-(C1-6 alquil)-N-(C1-6 aIquil)ureido, N',N'-(C1-6 aIquil)2-N-(C1-6 aIquil)ureido, alcanoilamino C1-6, N-(C1-6 alquil)C1-6alcanoilamino, N-(C1-6 alquiI)carbamoilo, N,N-(C1-6 aIquil)2carbamoilo, alquiI C1-6S(O)a en donde a es entre 0 y 2, alcoxicarbonilo C1-6, N-(C1-6 alquil)sulfamoilo, N,N-(C1-6 alquiI)2sulfamoilo, alquilsulfonilamino C1-6, (R20)(R21)P(O)-, (R27)(R28)P(O)NH-, (R29)(R30)P(O)(C1-6 aIquil)N-, (R24)(R25)(R26)Si-, carbociclil-R3- y heterociclil-R4-; en donde R1 puede estar opcionalmente sustituido sobre carbono con uno o más R5; y en donde si dicho heterociclilo contiene una porcion -NH- dicho nitrogeno puede estar opcionalmente sustituido con un grupo seleccionado entre R6; n se selecciona entre 0-4; en donde los valores de R1 pueden ser iguales o diferentes; R2 se selecciona entre halo, nitro, ciano, hidroxi, trifluorometoxi, amino, carboxi, carbamoilo, mercapto, sulfamoilo, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, aIcoxi C1-6, alcanoílo C1-6, alcanoiloxi C1-6, N-(C1-6 alquil)amino, N,N-(C1-6 alquil)2amino, alcanoilamino C1-6, N-(C1-6 alquiI)carbamoilo, N,N-(C1-6 aIquil)2carbamoilo, alquiI C1-6S(O)a en donde a es entre 0 y 2, alcoxicarbonilo C1-6, N-(C1-6 alquil)sulfamoilo, N,N-(C1-6 alquiI)2sulfamoilo, alquilsulfonilamino C1-6, carbociclil-R7- y heterociclil-R8-; en donde R2 puede estar opcionalmente sustituido sobre carbono con uno o más R9; y en donde si dicho heterociclilo contiene una porcion -NH- dicho nitrogeno puede estar opcionalmente sustituido con un grupo seleccionado entre R10; m se selecciona entre 0-4; en donde los valores de R2 pueden ser iguales o diferentes; R5 y R9 se seleccionan en forma independiente entre halo, nitro, ciano. hidroxi, amino, carboxi, carbamoilo, mercapto, sulfamoilo, alquilo C1-6, alquenilo C2-6, alquinilo C2-6, aIcoxi C1-6, alcanoílo C1-6, alcanoiloxi C1-6, N-(C1-6 alquil)amino, N,N-(C1-6 alquil)2amino, alcanoilamino C1-6, N-(C1-6 alquil)C1-6 alcanoilamino, N-(C1-6 alquiI)carbamoilo, N,N-(C1-6 aIquil)2carbamoilo, alquiI C1-6S(O)a en donde a es entre 0 y 2, alcoxicarbonilo C1-6, alcoxicarbonilamino C1-6, N-(C1-6 alquil)sulfamoilo, N,N-(C1-6 alquiI)2sulfamoilo, alquilsulfonilamino C1-6, (R22)(R23)P(O)-, (R32)(R32)P(O)NH-, (R33)(R34)P(O)(C1-6 alquil)N-, carbociclil-R11- y heterociclil-R12-; en donde R5 y R9 en forma independiente entre sí pueden estar sustituidos opcionalmente sobre carbono con uno o más R13; y en donde si dicho heterociclilo contiene una porcion -NH- dicho nitrogeno puede estar opcionalmente sustituido con un grupo seleccionado entre R14; R3, R4, R7, R8, R11 y R12 se seleccionan en forma independiente entre un enlace directo, -O-, -N(R15)-, -C(O)-, -N(R16)C(O)-, -C(O)N(R17)-, -S(O)s-, -SO2N(R18)- y -N(R19)SO2-; en donde R15, R16, R17, R18 y R19 es hidrogeno, alcoxicarbonilo C1-6 o alquilo C1-6 y s es 0-2; R6, R10 y R14 se seleccionan en forma independiente entre alquilo C1-6, alcanoilo C1-6, alquilsulfonilo C1-6, alcoxicarbonilo C1-6, carbamoilo, N-(C1-6alquil)carbamoilo, N,N-(C1-6 alquil)carbamoilo, bencilo, benciloxicarbonilo, benzoilo y fenilsulfonilo; R20, R21, R22, R23, R27, R28, R29, R30, R31, R32, R33, y R34 se seleccionan en forma independiente entre amino, alquilo C1-6, alcoxi C1-6 y carbociclilo; R24, R25 y R26 se seleccionan en forma independiente entre hidroxi, alquilo C1-6, alcoxi C1-6 y carbociclilo; o R24 y R25 junto con el silicio al cual se encuentran unidos forman un anillo; en donde R24, R25 y R26 se pueden sustituir opcionalmente en forma independiente sobre carbono con uno o más R35; R13 y R35 se seleccionan en forma independiente entre halo, nitro, ciano, hidroxi, trifluorometoxi, trifluorometilo, amino, carboxi, carbamoilo, mercapto, sulfamoilo, metilo, etilo, metoxi, etoxi, acetilo, acetoxi, metilamino, etilamino, dimetilamino, dietilamino, N-metil-N-etilamino, acetilamino, N-metilcarbamoilo, N-etilcarbamoilo, N,N-dimetilcarbamoilo, N,N-dietilcarbamoilo, N-metil-N-etilcarbamoilo, metiltio, etiltio, metilsulfinilo, etilsulfinilo, mesilo, etilsulfonilo, metoxicarbonilo, etoxicarbonilo, N-metilsulfamoilo, N-etilsulfamoilo, N,N-dimetilsulfamoilo, NN-dietilsulfamoilo y N-metil-N-etilsulfamoilo; o una sal aceptable para uso farmacéutico del mismo.Processes for the elaboration of said chemical compounds, with pharmaceutical compositions that contain them and with their use in the elaboration of medicines for the production of an anticancer effect in a warm-blooded animal, such as man. Claim 1: A compound characterized in that it has the formula (1), wherein: R1 is selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulfamoyl, ureido, C1-6 alkyl, C2 alkenyl - 6, C2-6 alkynyl, C1-6 alkoxy, C1-6 alkanoyl, C1-6 alkanoyloxy, N- (C1-6 alkyl) amino, N, N- (C1-6 alkyl) 2amino, N '- (C1 -6 alkyl) ureido, N ', N' - (C1-6 alkyl) 2ureido, N '- (C1-6 alkyl) -N- (C1-6 alkyl) ureido, N', N '- (C1-6 alkyl) 2-N- (C1-6 alkyl) ureido, C1-6 alkanoylamino, N- (C1-6 alkyl) C1-6 alkanoylamino, N- (C1-6 alkyl) carbamoyl, N, N- (C1-6 alkyl) ) 2carbamoyl, C1-6S alkyl (O) a where a is between 0 and 2, C1-6 alkoxycarbonyl, N- (C1-6 alkyl) sulfamoyl, N, N- (C1-6 alkyl) 2sulfamoyl, C1- alkylsulfonylamino 6, (R20) (R21) P (O) -, (R27) (R28) P (O) NH-, (R29) (R30) P (O) (C1-6 alkyl) N-, (R24) ( R25) (R26) Si-, carbocyclyl-R3- and heterocyclyl-R4-; wherein R1 may be optionally substituted on carbon with one or more R5; and wherein if said heterocyclyl contains a portion -NH- said nitrogen may be optionally substituted with a group selected from R6; n is selected from 0-4; where the values of R1 can be the same or different; R2 is selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, amino, carboxy, carbamoyl, mercapto, sulfamoyl, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C1-6 alkanoyl, alkanoyloxy C1-6, N- (C1-6 alkyl) amino, N, N- (C1-6 alkyl) 2amino, C1-6 alkanoylamino, N- (C1-6 alkyl) carbamoyl, N, N- (C1-6 alkyl) ) 2carbamoyl, C1-6S alkyl (O) a where a is between 0 and 2, C1-6 alkoxycarbonyl, N- (C1-6 alkyl) sulfamoyl, N, N- (C1-6 alkyl) 2sulfamoyl, C1- alkylsulfonylamino 6, carbocyclyl-R7- and heterocyclyl-R8-; wherein R2 may be optionally substituted on carbon with one or more R9; and wherein if said heterocyclyl contains a portion -NH- said nitrogen may be optionally substituted with a group selected from R10; m is selected from 0-4; where R2 values may be the same or different; R5 and R9 are independently selected from halo, nitro, cyano. hydroxy, amino, carboxy, carbamoyl, mercapto, sulfamoyl, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkanoyl, C 1-6 alkanoyloxy, N- (C 1-6 alkyl) amino, N, N- (C1-6 alkyl) 2amino, C1-6 alkanoylamino, N- (C1-6 alkyl) C1-6 alkanoylamino, N- (C1-6 alkyl) carbamoyl, N, N- (C1-6 alkyl) 2carbamoyl, C1-6S alkyl (O) a where a is between 0 and 2, C1-6 alkoxycarbonyl, C1-6 alkoxycarbonylamino, N- (C1-6 alkyl) sulfamoyl, N, N- (C1-6 alkyl ) 2sulfamoyl, C1-6 alkylsulfonylamino, (R22) (R23) P (O) -, (R32) (R32) P (O) NH-, (R33) (R34) P (O) (C1-6 alkyl) N -, carbocyclyl-R11- and heterocyclyl-R12-; wherein R5 and R9 independently of each other may optionally be substituted on carbon with one or more R13; and wherein if said heterocyclyl contains a portion -NH- said nitrogen may be optionally substituted with a group selected from R14; R3, R4, R7, R8, R11 and R12 are independently selected from a direct link, -O-, -N (R15) -, -C (O) -, -N (R16) C (O) -, -C (O) N (R17) -, -S (O) s-, -SO2N (R18) - and -N (R19) SO2-; wherein R15, R16, R17, R18 and R19 is hydrogen, C1-6 alkoxycarbonyl or C1-6 alkyl and s is 0-2; R6, R10 and R14 are independently selected from C1-6 alkyl, C1-6 alkanoyl, C1-6 alkylsulfonyl, C1-6 alkoxycarbonyl, carbamoyl, N- (C1-6 alkyl) carbamoyl, N, N- (C1-6 alkyl) carbamoyl, benzyl, benzyloxycarbonyl, benzoyl and phenylsulfonyl; R20, R21, R22, R23, R27, R28, R29, R30, R31, R32, R33, and R34 are independently selected from amino, C1-6 alkyl, C1-6 alkoxy and carbocyclyl; R24, R25 and R26 are independently selected from hydroxy, C1-6 alkyl, C1-6 alkoxy and carbocyclyl; or R24 and R25 together with the silicon to which they are attached form a ring; wherein R24, R25 and R26 can optionally be independently substituted on carbon with one or more R35; R13 and R35 are independently selected from halo, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino , N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N, N-dimethylcarbamoyl, N, N-diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, mesyl , methoxycarbonyl, ethoxycarbonyl, N-methylsulfamoyl, N-ethylsulfamoyl, N, N-dimethylsulfamoyl, NN-diethylsulfamoyl and N-methyl-N-ethylsulfamoyl; or a salt acceptable for pharmaceutical use thereof.

ARP070105508A 2006-12-08 2007-12-07 DERIVATIVES OF PIRIDIN-3-IL-QUINAZOLINAS AS INHIBITORS OF B-RAF. PROCESSES OF OBTAINING AND PHARMACEUTICAL COMPOSITIONS. AR064208A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US86924106P 2006-12-08 2006-12-08
US98573207P 2007-11-06 2007-11-06

Publications (1)

Publication Number Publication Date
AR064208A1 true AR064208A1 (en) 2009-03-18

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Family Applications (1)

Application Number Title Priority Date Filing Date
ARP070105508A AR064208A1 (en) 2006-12-08 2007-12-07 DERIVATIVES OF PIRIDIN-3-IL-QUINAZOLINAS AS INHIBITORS OF B-RAF. PROCESSES OF OBTAINING AND PHARMACEUTICAL COMPOSITIONS.

Country Status (5)

Country Link
AR (1) AR064208A1 (en)
CL (1) CL2007003557A1 (en)
PE (1) PE20081351A1 (en)
TW (1) TW200829566A (en)
WO (1) WO2008068507A2 (en)

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JO2769B1 (en) 2005-10-26 2014-03-15 جانسين فارماسوتيكا ان. في Fast Dissociting Dopamine 2 Receptor Antagonists
KR20090092287A (en) * 2006-12-22 2009-08-31 노파르티스 아게 Quinazolines for pdk1 inhibition
JO2849B1 (en) 2007-02-13 2015-03-15 جانسين فارماسوتيكا ان. في Fast -Dissociating Dopamine 2 Receptor Antagonists
AU2008240729B2 (en) 2007-04-23 2012-08-23 Janssen Pharmaceutica N.V. Thia(dia)zoles as fast dissociating dopamine 2 receptor antagonists
JP5431305B2 (en) 2007-04-23 2014-03-05 ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ 4-Alkoxypyridazine derivatives as fast dissociating dopamine 2 receptor antagonists
DK2307374T3 (en) 2008-07-31 2017-05-01 Janssen Pharmaceutica Nv PIPERAZIN-1-YLTRIFLUORMETHYL-SUBSTITUTED PYRIDINES AS QUICK DISSOCATING DOPAMIN-2 RECEPTOR ANTAGONISTS
CA2751517A1 (en) 2009-02-13 2010-08-19 Fovea Pharmaceuticals [1, 2, 4] triazolo [1, 5 -a] pyridines as kinase inhibitors
TW201204723A (en) 2010-06-22 2012-02-01 Fovea Pharmaceuticals Heterocyclic compounds, their preparation and their therapeutic application
US10554578B2 (en) 2015-06-30 2020-02-04 British Telecommunications Public Limited Company Quality of service management in a network
WO2018045141A1 (en) 2016-09-02 2018-03-08 New England Biolabs, Inc. Analysis of chromatin using a nicking enzyme
CN111170986A (en) * 2018-11-13 2020-05-19 北京睿熙生物科技有限公司 Inhibitors of bruton's tyrosine kinase
US20220143049A1 (en) 2019-03-21 2022-05-12 Onxeo A dbait molecule in combination with kinase inhibitor for the treatment of cancer
JP2023500906A (en) 2019-11-08 2023-01-11 インサーム（インスティテュ ナシオナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシェ メディカル） Methods of treating cancers with acquired resistance to kinase inhibitors
WO2021148581A1 (en) 2020-01-22 2021-07-29 Onxeo Novel dbait molecule and its use
WO2023138412A1 (en) * 2022-01-20 2023-07-27 Insilico Medicine Ip Limited Fused pyrimidin-2-amine compounds as cdk20 inhibitors

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JP2007509059A (en) * 2003-10-16 2007-04-12 カイロン コーポレイション 2,6-disubstituted quinazolines, quinoxalines, quinolines and isoquinolines as inhibitors of Raf kinase for the treatment of cancer
US20070054916A1 (en) * 2004-10-01 2007-03-08 Amgen Inc. Aryl nitrogen-containing bicyclic compounds and methods of use

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WO2008068507A3 (en) 2008-07-31
PE20081351A1 (en) 2008-11-26
WO2008068507A2 (en) 2008-06-12
CL2007003557A1 (en) 2008-08-01
TW200829566A (en) 2008-07-16

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