公开(公告)号：US10656162B2

公开(公告)日：2020-05-19

申请号：US15986577

申请日：2018-05-22

申请人： Basilea Pharmaceutica AG

发明人： Heidi Alexandra Lane ,  Felix Bachmann

IPC分类号： A61K31/4245 ,  G01N33/50 ,  G01N33/68

摘要： Use of glu-tubulin as a biomarker for predicting the response to a compound, preferably resistance of a disease such as cancer in a subject to said compound, wherein the compound is a furazanobenzimidazole compound of general formula (I).

公开(公告)号：US20190010536A1

公开(公告)日：2019-01-10

申请号：US15992813

申请日：2018-05-30

申请人： Basilea Pharmaceutica AG

发明人： Heidi Alexandra Lane ,  Felix Bachmann

IPC分类号： C12Q1/48 ,  C07D413/14 ,  G01N33/574 ,  C07D413/04

摘要： Use of phospho-Akt as a biomarker for predicting the response, such as resistance, to a compound, wherein phospho-Akt is Akt that has been phosphorylated on one or more residues, with the proviso that fir Akt1, Akt2, and Akt3 the designation phospho-Akt is used to indicate phosphorylation at a site other than T308, T309 or T305 respectively, wherein the compound is a compound of general formula (I) wherein R represents phenyl, thienyl or pyridinyl wherein phenyl is optionally substituted by one or two substituents independently selected from alkyl, halo-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, acyloxy-lower alkyl, phenyl, hydroxy, lower alkoxy, hydroxy-lower alkoxy, lower alkoxy-lower alkoxy, phenyl-lower alkoxy, lower alkylcarbonyloxy, amino, monoalkylamino, dialkylamino, lower alkoxycarbonylamino, lower alkylcarbonylamino, substituted amino wherein the two substituents on nitrogen form together with the nitrogen heterocyclyl, lower alkylcarbonyl, carboxy, lower alkoxycarbonyl, cyano, halogen, and nitro; and wherein two adjacent substituents are methylenedioxy; and wherein pyridinyl is optionally substituted by lower alkoxy, amino or halogen; X represents a group C═Y, wherein Y stands for oxygen or nitrogen substituted by hydroxy or lower alkoxy; R1 represents hydrogen, lower alkylcarbonyl, hydroxy-lower alkyl or cyano-lower alkyl; R2, R3 and R6 represent hydrogen; R4 and R5, independently of each other, represent hydrogen, lower alkyl or lower alkoxy, or R4 and R5 together represent methylenedioxy, and pharmaceutically acceptable derivatives thereof; or wherein R represents phenyl or pyridinyl wherein phenyl is optionally substituted by one or two substituents independently selected from alkyl, halo-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, acyloxy-lower alkyl, phenyl, hydroxy, lower alkoxy, hydroxy-lower alkoxy, lower alkoxy-lower alkoxy, phenyl-lower alkoxy, lower alkylcarbonyloxy, amino, monoalkylamino, dialkylamino, lower alkoxycarbonylamino, lower alkoxycarbonylamino, substituted amino wherein the two substituents on nitrogen form together with the nitrogen heterocyclyl, lower alkylcarbonyl, carboxy, lower alkoxycarbonyl, formyl, cyano, halogen, and nitro; and wherein two adjacent substituents are methylenedioxy; and wherein pyridinyl is optionally substituted by lower alkoxy, amino or halogen; X represents oxygen; R1 represents hydrogen, lower alkylcarbonyl, hydroxy-lower alkyl or cyano-lower alkyl; R2, R3 and R6 represent hydrogen; R4 and R5, independently of each other, represent hydrogen, lower alkyl or lower alkoxy, or R4 and R5 together represent methylenedioxy; and pharmaceutically acceptable derivatives thereof. Methods of treatment of neoplastic and autoimmune diseases with these compounds we also disclosed.

公开(公告)号：US10067120B2

公开(公告)日：2018-09-04

申请号：US15294157

申请日：2016-10-14

申请人： Basilea Pharmaceutica AG

发明人： Heidi Alexandra Lane ,  Felix Bachmann

IPC分类号： A61K31/415 ,  A61K31/41 ,  G01N33/50 ,  A61K31/42 ,  A61K31/4184 ,  A61K31/4245 ,  G01N33/68

摘要： Use of acetylated tubulin as a biomarker for predicting the response to a compound, preferably resistance of a disease such as cancer in a subject to said compound, wherein the compound is a furazanobenzimidazoles compound of general formula (I).

公开(公告)号：US10724072B2

公开(公告)日：2020-07-28

申请号：US15992813

申请日：2018-05-30

申请人： Basilea Pharmaceutica AG

发明人： Heidi Alexandra Lane ,  Felix Bachmann

IPC分类号： A61K31/4245 ,  A61K31/4439 ,  C12Q1/48 ,  G01N33/574 ,  C07D413/04 ,  C07D413/14

摘要： Use of phospho-Akt as a biomarker for predicting the response, such as resistance, to a compound, wherein phospho-Akt is Akt that has been phosphorylated on one or more residues, with the proviso that fir Akt1, Akt2, and Akt3 the designation phospho-Akt is used to indicate phosphorylation at a site other than T308, T309 or T305 respectively, wherein the compound is a compound of general formula (I) wherein R represents phenyl, thienyl or pyridinyl wherein phenyl is optionally substituted by one or two substituents independently selected from alkyl, halo-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, acyloxy-lower alkyl, phenyl, hydroxy, lower alkoxy, hydroxy-lower alkoxy, lower alkoxy-lower alkoxy, phenyl-lower alkoxy, lower alkylcarbonyloxy, amino, monoalkylamino, dialkylamino, lower alkoxycarbonylamino, lower alkylcarbonylamino, substituted amino wherein the two substituents on nitrogen form together with the nitrogen heterocyclyl, lower alkylcarbonyl, carboxy, lower alkoxycarbonyl, cyano, halogen, and nitro; and wherein two adjacent substituents are methylenedioxy; and wherein pyridinyl is optionally substituted by lower alkoxy, amino or halogen; X represents a group C═Y, wherein Y stands for oxygen or nitrogen substituted by hydroxy or lower alkoxy; R1 represents hydrogen, lower alkylcarbonyl, hydroxy-lower alkyl or cyano-lower alkyl; R2, R3 and R6 represent hydrogen; R4 and R5, independently of each other, represent hydrogen, lower alkyl or lower alkoxy, or R4 and R5 together represent methylenedioxy, and pharmaceutically acceptable derivatives thereof; or wherein R represents phenyl or pyridinyl wherein phenyl is optionally substituted by one or two substituents independently selected from alkyl, halo-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, acyloxy-lower alkyl, phenyl, hydroxy, lower alkoxy, hydroxy-lower alkoxy, lower alkoxy-lower alkoxy, phenyl-lower alkoxy, lower alkylcarbonyloxy, amino, monoalkylamino, dialkylamino, lower alkoxycarbonylamino, lower alkoxycarbonylamino, substituted amino wherein the two substituents on nitrogen form together with the nitrogen heterocyclyl, lower alkylcarbonyl, carboxy, lower alkoxycarbonyl, formyl, cyano, halogen, and nitro; and wherein two adjacent substituents are methylenedioxy; and wherein pyridinyl is optionally substituted by lower alkoxy, amino or halogen; X represents oxygen; R1 represents hydrogen, lower alkylcarbonyl, hydroxy-lower alkyl or cyano-lower alkyl; R2, R3 and R6 represent hydrogen; R4 and R5, independently of each other, represent hydrogen, lower alkyl or lower alkoxy, or R4 and R5 together represent methylenedioxy; and pharmaceutically acceptable derivatives thereof. Methods of treatment of neoplastic and autoimmune diseases with these compounds we also disclosed.

公开(公告)号：US20170122934A1

公开(公告)日：2017-05-04

申请号：US15294157

申请日：2016-10-14

申请人： Basilea Pharmaceutica AG

发明人： Heidi Alexandra Lane ,  Felix Bachmann

IPC分类号： G01N33/50

CPC分类号： G01N33/5026 ,  A61K31/4184 ,  A61K31/42 ,  A61K31/4245 ,  A61K38/00 ,  G01N33/5011 ,  G01N33/68 ,  G01N33/6893 ,  G01N2800/44 ,  G01N2800/52

摘要： Use of acetylated tubulin as a biomarker for predicting the response to a compound, preferably resistance of a disease such as cancer in a subject to said compound, wherein the compound is a furazanobenzimidazoles compound of general formula (1).

公开(公告)号：US20180364254A1

公开(公告)日：2018-12-20

申请号：US15986577

申请日：2018-05-22

申请人： Basilea Pharmaceutica AG

发明人： Heidi Alexandra Lane ,  Felix Bachmann

IPC分类号： G01N33/68 ,  A61K31/4245 ,  G01N33/50

摘要： Use of glu-tubulin as a biomarker for predicting the response to a compound, preferably resistance of a disease such as cancer in a subject to said compound, wherein the compound is a furazanobenzimidazole compound of general formula (I).

公开(公告)号：US09970938B2

公开(公告)日：2018-05-15

申请号：US15060998

申请日：2016-03-04

申请人： Basilea Pharmaceutica AG

发明人： Heidi Alexandra Lane ,  Felix Bachmann ,  Madlaina Breuleux ,  Michael Boutros ,  Daniel Gilbert ,  Xian Zhang

IPC分类号： G01N33/574 ,  A61K31/4245 ,  G01N33/50 ,  A61K31/4439 ,  C12Q1/68

CPC分类号： G01N33/57484 ,  A61K31/4245 ,  A61K31/4439 ,  C12Q1/6886 ,  C12Q2600/158 ,  G01N33/5011 ,  G01N33/5026 ,  G01N33/57496 ,  G01N2333/91205 ,  G01N2800/44 ,  G01N2800/52

摘要： Use of BUBR1 as a biomarker for predicting the response to a compound, preferably resistance of a disease such as cancer in a subject, wherein the compound is a compound of general formula I wherein R represents phenyl, thienyl or pyridinyl wherein phenyl is optionally substituted by one or two substituents independently selected from alkyl, halo-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, acyloxy-lower alkyl, phenyl, hydroxy, lower alkoxy, hydroxy-lower alkoxy, lower alkoxy-lower alkoxy, phenyl-lower alkoxy, lower alkylcarbonyloxy, amino, monoalkylamino, dialkylamino, lower alkoxycarbonylamino, lower alkylcarbonylamino, substituted amino wherein the two substituents on nitrogen form together with the nitrogen heterocyclyl, lower alkylcarbonyl, carboxy, lower alkoxycarbonyl, cyano, halogen, and nitro; and wherein two adjacent substituents are methylenedioxy; and wherein pyridinyl is optionally substituted by lower alkoxy, amino or halogen; X represents a group C═Y, wherein Y stands for oxygen or nitrogen substituted by hydroxy or lower alkoxy; R1 represents hydrogen, lower alkylcarbonyl, hydroxy-lower alkyl or cyano-lower alkyl; R2, R3 and R6 represent hydrogen; R4 and R5, independently of each other, represent hydrogen, lower alkyl or lower alkoxy; or R4 and R5 together represent methylenedioxy; and pharmaceutically acceptable derivatives thereof; or wherein R represents phenyl or pyridinyl wherein phenyl is optionally substituted by one or two substituents independently selected from alkyl, halo-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, acyloxy-lower alkyl, phenyl, hydroxy, lower alkoxy, hydroxy-lower alkoxy, lower alkoxy-lower alkoxy, phenyl-lower alkoxy, lower alkylcarbonyloxy, amino, monoalkylamino, dialkylamino, lower alkoxycarbonylamino, lower alkylcarbonylamino, substituted amino wherein the two substituents on nitrogen form together with the nitrogen heterocyclyl, lower alkylcarbonyl, carboxy, lower alkoxycarbonyl, formyl, cyano, halogen, and nitro; and wherein two adjacent substituents are methylenedioxy; and wherein pyridinyl is optionally substituted by lower alkoxy, amino or halogen; X represents oxygen; R1 represents hydrogen, lower alkylcarbonyl, hydroxy-lower alkyl or cyano-lower alkyl; R2, R3 and R6 represent hydrogen; R4 and R5, independently of each other, represent hydrogen, lower alkyl or lower alkoxy; or R4 and R5 together represent methylenedioxy; and pharmaceutically acceptable derivatives thereof. Methods of treatment of neoplastic and autoimmune diseases with these compounds are also disclosed.

公开(公告)号：US20160320397A1

公开(公告)日：2016-11-03

申请号：US15060998

申请日：2016-03-04

申请人： Basilea Pharmaceutica AG

发明人： Heidi Alexandra Lane ,  Felix Bachmann ,  Madlaina Breuleux ,  Michael Boutros ,  Daniel Gilbert ,  Xian Zhang

IPC分类号： G01N33/574 ,  A61K31/4439 ,  C12Q1/68 ,  A61K31/4245

CPC分类号： G01N33/57484 ,  A61K31/4245 ,  A61K31/4439 ,  C12Q1/6886 ,  C12Q2600/158 ,  G01N33/5011 ,  G01N33/5026 ,  G01N33/57496 ,  G01N2333/91205 ,  G01N2800/44 ,  G01N2800/52

摘要： Use of BUBR1 as a biomarker for predicting the response to a compound, preferably resistance of a disease such as cancer in a subject, wherein the compound is a compound of general formula I wherein R represents phenyl, thienyl or pyridinyl wherein phenyl is optionally substituted by one or two substituents independently selected from alkyl, halo-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, acyloxy-lower alkyl, phenyl, hydroxy, lower alkoxy, hydroxy-lower alkoxy, lower alkoxy-lower alkoxy, phenyl-lower alkoxy, lower alkylcarbonyloxy, amino, monoalkylamino, dialkylamino, lower alkoxycarbonylamino, lower alkylcarbonylamino, substituted amino wherein the two substituents on nitrogen form together with the nitrogen heterocyclyl, lower alkylcarbonyl, carboxy, lower alkoxycarbonyl, cyano, halogen, and nitro; and wherein two adjacent substituents are methylenedioxy; and wherein pyridinyl is optionally substituted by lower alkoxy, amino or halogen; X represents a group C═Y, wherein Y stands for oxygen or nitrogen substituted by hydroxy or lower alkoxy; R1 represents hydrogen, lower alkylcarbonyl, hydroxy-lower alkyl or cyano-lower alkyl; R2, R3 and R6 represent hydrogen; R4 and R5, independently of each other, represent hydrogen, lower alkyl or lower alkoxy; or R4 and R5 together represent methylenedioxy; and pharmaceutically acceptable derivatives thereof; or wherein R represents phenyl or pyridinyl wherein phenyl is optionally substituted by one or two substituents independently selected from alkyl, halo-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, acyloxy-lower alkyl, phenyl, hydroxy, lower alkoxy, hydroxy-lower alkoxy, lower alkoxy-lower alkoxy, phenyl-lower alkoxy, lower alkylcarbonyloxy, amino, monoalkylamino, dialkylamino, lower alkoxycarbonylamino, lower alkylcarbonylamino, substituted amino wherein the two substituents on nitrogen form together with the nitrogen heterocyclyl, lower alkylcarbonyl, carboxy, lower alkoxycarbonyl, formyl, cyano, halogen, and nitro; and wherein two adjacent substituents are methylenedioxy; and wherein pyridinyl is optionally substituted by lower alkoxy, amino or halogen; X represents oxygen; R1 represents hydrogen, lower alkylcarbonyl, hydroxy-lower alkyl or cyano-lower alkyl; R2, R3 and R6 represent hydrogen; R4 and R5, independently of each other, represent hydrogen, lower alkyl or lower alkoxy; or R4 and R5 together represent methylenedioxy; and pharmaceutically acceptable derivatives thereof. Methods of treatment of neoplastic and autoimmune diseases with these compounds are also disclosed.