AR068376A1 - USEFUL HETEROCICLIC AMIDAS TO INHIBIT THE VIA HEDGEHOG. - Google Patents

USEFUL HETEROCICLIC AMIDAS TO INHIBIT THE VIA HEDGEHOG.

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Publication number
AR068376A1
AR068376A1 ARP080103877A ARP080103877A AR068376A1 AR 068376 A1 AR068376 A1 AR 068376A1 AR P080103877 A ARP080103877 A AR P080103877A AR P080103877 A ARP080103877 A AR P080103877A AR 068376 A1 AR068376 A1 AR 068376A1
Authority
AR
Argentina
Prior art keywords
group
ring
6alkyl
alkyl
atoms
Prior art date
Application number
ARP080103877A
Other languages
Spanish (es)
Inventor
Alexander Hird
Daniel John Russell
Benjamin Fauber
James Janetka
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
Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab
Publication of AR068376A1 publication Critical patent/AR068376A1/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
    • C07D401/12—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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
    • 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
    • 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
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

Abstract

Compuestos de amida heterocíclica, que son utiles para inhibir la vía Hedgehog, y con su uso para tratar una enfermedad o condicion médica mediada solo por inhibicion de la vía Hedgehog o mediada en parte por inhibicion de la vía Hedgehog. También se divulgan métodos para fabricar estos compuestos, composiciones farmacéuticas que incluyen a estos compuestos, y el uso de estos compuestos en la fabricacion de medicamentos para tratar dichas enfermedades y condiciones clínicas en un sujeto. Reivindicacion 1: Un compuesto caracterizado porque responde a la formula (1) en donde R1, R2 y R3 se selecciona cada uno en forma independiente entre el grupo que consiste de hidrogeno, aIquiIo C1-6, y halogeno; R4 se selecciona entre el grupo que consiste de alquilo C1-6, haloC1-6alquilo, y halogeno; cada W se selecciona en forma independiente entre el grupo que consiste de CR5, NR5, N, O, y S, donde R5 se selecciona entre el grupo que consiste de hidrogeno, aIcoxi C1-6, alcoxi C1-6-alquilo C1-6, alcoxicarbonilo C1-6, alquilo C1-6, amidino, amido, amino, alquilcarbonilo C1-6, arilo, carboxamido, cicloalquilo C3-8, ciano, haloC1-6alquilo, halogeno, heterociclilo, heterociclilC1-6alquilo, hidroxi, hidroxiC1-6alquilo, nitro, sulfuro, sulfinilo, sulfonamido, y sulfonilo, o dos átomos W adyacentes se pueden tomar juntos con sus sustituyentes R5 para formar un segundo anillo fusionado, en donde el segundo anillo se sustituye opcionalmente con uno o más sustituyentes R5 y se selecciona entre el grupo que consiste de arilo, cicloalquilo C3-8, 5- o heteroarilo de 6 miembros, y heterociclilo de 5 o 6 miembros; al menos un W es N, q es 0 o 1, donde si q es 0 y dos átomos W adyacentes se toman junto con sus sustituyentes R5 para formar un segundo anillo fusionado, luego uno de los átomos W adyacentes es N y el segundo anillo es un heterociclilo de 6 miembros, y si q es 0, y el anillo que comprende los átomos de W es 2-imidazolilo, R5 no es un anillo fenilo insustituido; A se selecciona entre el grupo que consiste de CR6, NR6, N, O, y S; R6 se selecciona entre el grupo que consiste de hidrogeno, alcoxi C1-6, alcoxi C1-6-alquilo C1-6, alcoxicarbonilo C1-6, alquilo C1-6, amidino, amido, amino, alquilcarbonilo C1-6, arilo, carboxamido, cicloalquilo C3-8, ciano, haloC1-6alquilo, halogeno, heterociclilo, heterociclilC1-6alquilo, heterociclilC1-6alcoxi, hidroxi, hidroxiC1-6alquilo, nitro, sulfinilo, sulfuro, sulfonamido, y sulfonilo, o dos átomos A adyacentes se pueden tomar juntos con sus sustituyentes R5 para formar un segundo anillo fusionado, en donde el segundo anillo es un heterociclilo de 5 o 6 miembros; al menos uno A se selecciona entre el grupo que consiste de NR6, N, O, y S; p es 0 o 1, donde si p es 0 y R1, R2, y R4.son cada uno metilo, luego A no es S; en donde el compuesto de formula 1 no es como se muestra en las formulas (2) donde L se selecciona entre el grupo que consiste de NH y CH, y si L es NH, luego M es CH2, y si L es CH luego M es CH y sus sales aceptables para uso farmacéutico.Heterocyclic amide compounds, which are useful for inhibiting the Hedgehog pathway, and with its use to treat a medical condition or condition mediated only by inhibition of the Hedgehog pathway or mediated in part by inhibition of the Hedgehog pathway. Methods for making these compounds, pharmaceutical compositions including these compounds, and the use of these compounds in the manufacture of medicaments for treating such diseases and clinical conditions in a subject are also disclosed. Claim 1: A compound characterized in that it responds to formula (1) wherein R1, R2 and R3 are each independently selected from the group consisting of hydrogen, C1-6, and halogen; R4 is selected from the group consisting of C1-6 alkyl, haloC1-6alkyl, and halogen; each W is independently selected from the group consisting of CR5, NR5, N, O, and S, where R5 is selected from the group consisting of hydrogen, C1-6 alkoxy, C1-6 alkoxy-C1-6 alkyl , C1-6 alkoxycarbonyl, C1-6 alkyl, amidino, amido, amino, C1-6 alkylcarbonyl, aryl, carboxamido, C3-8 cycloalkyl, cyano, haloC1-6alkyl, halogen, heterocyclyl, heterocyclylC1-6alkyl, hydroxy, hydroxyC1-6alkyl , nitro, sulfide, sulfinyl, sulfonamido, and sulfonyl, or two adjacent W atoms can be taken together with their R5 substituents to form a fused second ring, wherein the second ring is optionally substituted with one or more R5 substituents and selected from the group consisting of aryl, C 3-8 cycloalkyl, 5- or 6-membered heteroaryl, and 5- or 6-membered heterocyclyl; at least one W is N, q is 0 or 1, where if q is 0 and two adjacent W atoms are taken together with their substituents R5 to form a fused second ring, then one of the adjacent W atoms is N and the second ring it is a 6-membered heterocyclyl, and if q is 0, and the ring comprising the atoms of W is 2-imidazolyl, R5 is not an unsubstituted phenyl ring; A is selected from the group consisting of CR6, NR6, N, O, and S; R 6 is selected from the group consisting of hydrogen, C 1-6 alkoxy, C 1-6 alkoxy-C 1-6 alkyl, C 1-6 alkoxycarbonyl, C 1-6 alkyl, amidino, amido, amino, C 1-6 alkylcarbonyl, aryl, carboxamido , C3-8 cycloalkyl, cyano, haloC1-6alkyl, halogen, heterocyclyl, heterocyclylC1-6alkyl, heterocyclylC1-6alkoxy, hydroxy, hydroxyC1-6alkyl, nitro, sulfinyl, sulfide, sulfonamido, and sulfonyl, or can take two adjacent A atoms together with its substituents R5 to form a fused second ring, wherein the second ring is a 5- or 6-membered heterocyclyl; at least one A is selected from the group consisting of NR6, N, O, and S; p is 0 or 1, where if p is 0 and R1, R2, and R4. are each methyl, then A is not S; wherein the compound of formula 1 is not as shown in formulas (2) where L is selected from the group consisting of NH and CH, and if L is NH, then M is CH2, and if L is CH then M It is CH and its salts acceptable for pharmaceutical use.

ARP080103877A 2007-09-05 2008-09-05 USEFUL HETEROCICLIC AMIDAS TO INHIBIT THE VIA HEDGEHOG. AR068376A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US97010707P 2007-09-05 2007-09-05
US3666108P 2008-03-14 2008-03-14

Publications (1)

Publication Number Publication Date
AR068376A1 true AR068376A1 (en) 2009-11-11

Family

ID=39938463

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP080103877A AR068376A1 (en) 2007-09-05 2008-09-05 USEFUL HETEROCICLIC AMIDAS TO INHIBIT THE VIA HEDGEHOG.

Country Status (5)

Country Link
AR (1) AR068376A1 (en)
PE (1) PE20091092A1 (en)
TW (1) TW200916458A (en)
UY (1) UY31322A1 (en)
WO (1) WO2009030952A2 (en)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2440048B8 (en) 2009-06-09 2015-12-16 NantBioScience, Inc. Isoquinoline, quinoline, and quinazoline derivatives as inhibitors of hedgehog signaling
MX2012007929A (en) * 2010-01-07 2012-11-21 Selexagen Therapeutics Inc Hedgehog inhibitors.
WO2011095807A1 (en) * 2010-02-07 2011-08-11 Astrazeneca Ab Combinations of mek and hh inhibitors
CN101993415B (en) * 2010-09-15 2013-08-14 北京韩美药品有限公司 Compound as Hedgehog path inhibitor, medicine composition containing same and application thereof
CN103570625A (en) * 2012-07-19 2014-02-12 南京英派药业有限公司 N-(3-aryl-heteroaryl)-4-aryl-aryl carboxamide and analog as hedgehog pathway inhibitors and application thereof
US9242969B2 (en) 2013-03-14 2016-01-26 Novartis Ag Biaryl amide compounds as kinase inhibitors
UY36294A (en) 2014-09-12 2016-04-29 Novartis Ag COMPOUNDS AND COMPOSITIONS AS QUINASA INHIBITORS
EP3536320A4 (en) * 2016-11-04 2020-07-29 Impact Therapeutics, Inc Application of hedgehog pathway inhibitor for treatment of fibrotic diseases
CN107281214A (en) * 2017-06-06 2017-10-24 北京工业大学 Hydrogen molecule liquid/gas is preparing the application in suppressing tumor stem cell medicine
CN109369634B (en) * 2018-12-19 2021-07-27 陕西国际商贸学院 Preparation method and application of 2-methoxynicotinamide derivative with antitumor activity

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE60334651D1 (en) * 2002-02-12 2010-12-02 Glaxosmithkline Llc Nicotinamide and its use as P38 inhibitors
CA2483311A1 (en) * 2002-04-22 2003-10-30 Philip A. Beachy Modulators of hedgehog signaling pathways, compositions and uses related thereto
US8273743B2 (en) * 2004-04-30 2012-09-25 Curis, Inc. Quinoxaline inhibitors of the hedgehog signalling
EA201890903A9 (en) * 2004-09-02 2021-11-10 Дженентек, Инк. COMPOUNDS OF PYRIDYL INHIBITORS OF SIGNAL TRANSMISSION BY HEDGEHOG PROTEIN, METHOD FOR THEIR PREPARATION, COMPOSITION AND METHODS FOR TREATING CANCER AND INHIBITING ANGIOGENESIS AND SIGNAL PATH OF HEDGEHOG IN FLAGS
EP1807074B1 (en) * 2004-11-03 2013-10-23 Curis, Inc. Mediators of hedgehog signaling pathways, compositions and uses related thereto
CA2620899A1 (en) * 2005-10-12 2007-04-19 Biolipox Ab Benzoxazoles useful in the treatment of inflammation
PE20080948A1 (en) * 2006-07-25 2008-09-10 Irm Llc IMIDAZOLE DERIVATIVES AS MODULATORS OF THE HEDGEHOG PATH

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Publication number Publication date
UY31322A1 (en) 2009-04-30
WO2009030952A3 (en) 2009-05-07
WO2009030952A2 (en) 2009-03-12
PE20091092A1 (en) 2009-08-27
TW200916458A (en) 2009-04-16

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