MXPA06003607A

MXPA06003607A - Quinazolinas, quinoxalinas, quinolinas e isoquinolinas 2.6-disubstituidas como inhibidores de la cinasa raf para el tratamiento del cancer.

Quinazolinas, quinoxalinas, quinolinas e isoquinolinas 2.6-disubstituidas como inhibidores de la cinasa raf para el tratamiento del cancer.

Info

Publication number: MXPA06003607A
Authority: MX; Mexico
Prior art keywords: substituted; alkyl; compound according; heteroaryl; unsubstituted
Prior art date: 2003-10-16

Application number

MXPA06003607A

Other languages

English (en)

Spanish (es)

Inventor

Savithri Ramurthy

Original Assignee

Chiron Corp

Priority date

2003-10-16

Filing date

2004-10-15

Publication date

2006-06-05

2004-10-15 Application filed by Chiron Corp filed Critical Chiron Corp

2006-06-05 Publication of MXPA06003607A publication Critical patent/MXPA06003607A/es

Links

206010028980 Neoplasm Diseases 0.000 title claims abstract description 42
238000011282 treatment Methods 0.000 title claims abstract description 35
201000011510 cancer Diseases 0.000 title claims abstract description 29
108010077182 raf Kinases Proteins 0.000 title claims abstract description 25
102000009929 raf Kinases Human genes 0.000 title claims abstract description 25
-1 2,6-disubstituted quinazolines Chemical class 0.000 title claims description 360
239000003112 inhibitor Substances 0.000 title description 12
150000003252 quinoxalines Chemical class 0.000 title description 5
229940111121 antirheumatic drug quinolines Drugs 0.000 title description 2
150000002537 isoquinolines Chemical class 0.000 title description 2
150000003248 quinolines Chemical class 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 155
239000000203 mixture Substances 0.000 claims abstract description 50
241001465754 Metazoa Species 0.000 claims abstract description 22
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 17
230000000694 effects Effects 0.000 claims abstract description 17
125000000217 alkyl group Chemical group 0.000 claims description 128
125000003118 aryl group Chemical group 0.000 claims description 84
125000001072 heteroaryl group Chemical group 0.000 claims description 77
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 74
125000004103 aminoalkyl group Chemical group 0.000 claims description 60
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 59
229910052739 hydrogen Inorganic materials 0.000 claims description 54
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 50
239000001257 hydrogen Substances 0.000 claims description 49
125000000753 cycloalkyl group Chemical group 0.000 claims description 45
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 36
125000003545 alkoxy group Chemical group 0.000 claims description 33
150000003839 salts Chemical class 0.000 claims description 30
125000003710 aryl alkyl group Chemical group 0.000 claims description 29
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 28
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 27
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
229940002612 prodrug Drugs 0.000 claims description 27
239000000651 prodrug Substances 0.000 claims description 27
239000003795 chemical substances by application Substances 0.000 claims description 24
125000000623 heterocyclic group Chemical group 0.000 claims description 19
239000003814 drug Substances 0.000 claims description 18
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 15
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 12
125000003342 alkenyl group Chemical group 0.000 claims description 11
150000001413 amino acids Chemical class 0.000 claims description 11
230000002401 inhibitory effect Effects 0.000 claims description 11
125000004076 pyridyl group Chemical group 0.000 claims description 11
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 10
XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 claims description 10
KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 claims description 10
229910052760 oxygen Inorganic materials 0.000 claims description 10
239000005411 L01XE02 - Gefitinib Substances 0.000 claims description 9
125000002252 acyl group Chemical group 0.000 claims description 9
125000002541 furyl group Chemical group 0.000 claims description 9
125000002883 imidazolyl group Chemical group 0.000 claims description 9
125000001041 indolyl group Chemical group 0.000 claims description 9
239000005517 L01XE01 - Imatinib Substances 0.000 claims description 8
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 8
UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 claims description 8
125000001624 naphthyl group Chemical group 0.000 claims description 8
125000000714 pyrimidinyl group Chemical group 0.000 claims description 8
FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 claims description 7
125000005128 aryl amino alkyl group Chemical group 0.000 claims description 7
125000001769 aryl amino group Chemical group 0.000 claims description 7
150000005347 biaryls Chemical group 0.000 claims description 7
125000000068 chlorophenyl group Chemical group 0.000 claims description 7
125000004212 difluorophenyl group Chemical group 0.000 claims description 7
229910052736 halogen Inorganic materials 0.000 claims description 7
150000002367 halogens Chemical class 0.000 claims description 7
125000005553 heteroaryloxy group Chemical group 0.000 claims description 7
GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 6
125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 6
125000000304 alkynyl group Chemical group 0.000 claims description 6
125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 6
125000004104 aryloxy group Chemical group 0.000 claims description 6
235000010290 biphenyl Nutrition 0.000 claims description 6
229960004316 cisplatin Drugs 0.000 claims description 6
DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 6
125000000000 cycloalkoxy group Chemical group 0.000 claims description 6
125000004858 cycloalkoxyalkyl group Chemical group 0.000 claims description 6
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 6
125000006310 cycloalkyl amino group Chemical group 0.000 claims description 6
125000004367 cycloalkylaryl group Chemical group 0.000 claims description 6
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
229960003901 dacarbazine Drugs 0.000 claims description 6
125000004188 dichlorophenyl group Chemical group 0.000 claims description 6
239000003937 drug carrier Substances 0.000 claims description 6
229960002949 fluorouracil Drugs 0.000 claims description 6
125000005241 heteroarylamino group Chemical group 0.000 claims description 6
125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 6
229940088597 hormone Drugs 0.000 claims description 6
239000005556 hormone Substances 0.000 claims description 6
229960002411 imatinib Drugs 0.000 claims description 6
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 6
229960004768 irinotecan Drugs 0.000 claims description 6
125000000842 isoxazolyl group Chemical group 0.000 claims description 6
125000002757 morpholinyl group Chemical group 0.000 claims description 6
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 6
229960004641 rituximab Drugs 0.000 claims description 6
YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 5
VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 claims description 5
GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 claims description 5
GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 claims description 5
229940123237 Taxane Drugs 0.000 claims description 5
229940122803 Vinca alkaloid Drugs 0.000 claims description 5
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 5
125000005036 alkoxyphenyl group Chemical group 0.000 claims description 5
125000005037 alkyl phenyl group Chemical group 0.000 claims description 5
229940045799 anthracyclines and related substance Drugs 0.000 claims description 5
VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 claims description 5
RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 claims description 5
239000004305 biphenyl Substances 0.000 claims description 5
125000004799 bromophenyl group Chemical group 0.000 claims description 5
229960004117 capecitabine Drugs 0.000 claims description 5
229960004562 carboplatin Drugs 0.000 claims description 5
125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 5
125000004986 diarylamino group Chemical group 0.000 claims description 5
125000005240 diheteroarylamino group Chemical group 0.000 claims description 5
DLAHAXOYRFRPFQ-UHFFFAOYSA-N dodecyl benzoate Chemical compound CCCCCCCCCCCCOC(=O)C1=CC=CC=C1 DLAHAXOYRFRPFQ-UHFFFAOYSA-N 0.000 claims description 5
VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 claims description 5
235000008191 folinic acid Nutrition 0.000 claims description 5
239000011672 folinic acid Substances 0.000 claims description 5
229960002584 gefitinib Drugs 0.000 claims description 5
229960005277 gemcitabine Drugs 0.000 claims description 5
SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims description 5
125000006485 halo alkoxy phenyl group Chemical group 0.000 claims description 5
125000005059 halophenyl group Chemical group 0.000 claims description 5
125000005326 heteroaryloxy alkyl group Chemical group 0.000 claims description 5
125000004464 hydroxyphenyl group Chemical group 0.000 claims description 5
125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 5
125000006303 iodophenyl group Chemical group 0.000 claims description 5
229940084651 iressa Drugs 0.000 claims description 5
229960001691 leucovorin Drugs 0.000 claims description 5
125000006501 nitrophenyl group Chemical group 0.000 claims description 5
125000003884 phenylalkyl group Chemical group 0.000 claims description 5
125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 claims description 5
125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 5
229950006410 tezacitabine Drugs 0.000 claims description 5
GFFXZLZWLOBBLO-ASKVSEFXSA-N tezacitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(=C/F)/[C@H](O)[C@@H](CO)O1 GFFXZLZWLOBBLO-ASKVSEFXSA-N 0.000 claims description 5
229930192474 thiophene Natural products 0.000 claims description 5
QERYCTSHXKAMIS-UHFFFAOYSA-M thiophene-2-carboxylate Chemical compound [O-]C(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-M 0.000 claims description 5
229960000303 topotecan Drugs 0.000 claims description 5
UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 claims description 5
229960000575 trastuzumab Drugs 0.000 claims description 5
206010006187 Breast cancer Diseases 0.000 claims description 4
208000026310 Breast neoplasm Diseases 0.000 claims description 4
CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 4
HSMPSHPWCOOUJH-UHFFFAOYSA-N anilinyl Chemical group [NH]C1=CC=CC=C1 HSMPSHPWCOOUJH-UHFFFAOYSA-N 0.000 claims description 4
239000012965 benzophenone Substances 0.000 claims description 4
WVIIMZNLDWSIRH-UHFFFAOYSA-N cyclohexylcyclohexane Chemical group C1CCCCC1C1CCCCC1 WVIIMZNLDWSIRH-UHFFFAOYSA-N 0.000 claims description 4
229960004397 cyclophosphamide Drugs 0.000 claims description 4
125000001207 fluorophenyl group Chemical group 0.000 claims description 4
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
230000001419 dependent effect Effects 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
150000002431 hydrogen Chemical class 0.000 claims 16
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 4
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims 2
208000019838 Blood disease Diseases 0.000 claims 1
206010060862 Prostate cancer Diseases 0.000 claims 1
125000005081 alkoxyalkoxyalkyl group Chemical group 0.000 claims 1
238000000034 method Methods 0.000 abstract description 30
125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 abstract description 17
125000001424 substituent group Chemical group 0.000 abstract description 16
XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical class N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 abstract description 13
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical class N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 abstract description 12
125000002183 isoquinolinyl group Chemical class C1(=NC=CC2=CC=CC=C12)* 0.000 abstract description 11
230000005764 inhibitory process Effects 0.000 abstract description 9
230000001404 mediated effect Effects 0.000 abstract description 3
125000004547 quinazolin-6-yl group Chemical group N1=CN=CC2=CC(=CC=C12)* 0.000 description 57
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 47
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
230000015572 biosynthetic process Effects 0.000 description 26
238000003786 synthesis reaction Methods 0.000 description 25
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 23
IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 description 22
238000006243 chemical reaction Methods 0.000 description 21
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
235000019439 ethyl acetate Nutrition 0.000 description 16
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
239000012267 brine Substances 0.000 description 13
239000000047 product Substances 0.000 description 13
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
108091000080 Phosphotransferase Proteins 0.000 description 12
125000004432 carbon atom Chemical group C* 0.000 description 12
102000020233 phosphotransferase Human genes 0.000 description 12
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
125000005843 halogen group Chemical group 0.000 description 11
229910052757 nitrogen Inorganic materials 0.000 description 11
102000016914 ras Proteins Human genes 0.000 description 11
108010014186 ras Proteins Proteins 0.000 description 11
239000000243 solution Substances 0.000 description 11
238000012360 testing method Methods 0.000 description 11
125000005842 heteroatom Chemical group 0.000 description 10
239000012044 organic layer Substances 0.000 description 10
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
102000043136 MAP kinase family Human genes 0.000 description 9
108091054455 MAP kinase family Proteins 0.000 description 9
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 9
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
239000002253 acid Substances 0.000 description 8
239000002246 antineoplastic agent Substances 0.000 description 8
208000035475 disorder Diseases 0.000 description 8
150000002148 esters Chemical class 0.000 description 8
238000000746 purification Methods 0.000 description 8
239000011541 reaction mixture Substances 0.000 description 8
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 7
210000004027 cell Anatomy 0.000 description 7
238000001914 filtration Methods 0.000 description 7
GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 7
239000007787 solid Substances 0.000 description 7
229910052717 sulfur Inorganic materials 0.000 description 7
NKHDIWOWDNCSLS-UHFFFAOYSA-N 2-chloro-6-methoxyquinazoline Chemical compound N1=C(Cl)N=CC2=CC(OC)=CC=C21 NKHDIWOWDNCSLS-UHFFFAOYSA-N 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
150000001412 amines Chemical class 0.000 description 6
229940079593 drug Drugs 0.000 description 6
125000001188 haloalkyl group Chemical group 0.000 description 6
239000002502 liposome Substances 0.000 description 6
ATHHXGZTWNVVOU-UHFFFAOYSA-N monomethyl-formamide Natural products CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 description 6
229910000027 potassium carbonate Inorganic materials 0.000 description 6
KKVYYGGCHJGEFJ-UHFFFAOYSA-N 1-n-(4-chlorophenyl)-6-methyl-5-n-[3-(7h-purin-6-yl)pyridin-2-yl]isoquinoline-1,5-diamine Chemical compound N=1C=CC2=C(NC=3C(=CC=CN=3)C=3C=4N=CNC=4N=CN=3)C(C)=CC=C2C=1NC1=CC=C(Cl)C=C1 KKVYYGGCHJGEFJ-UHFFFAOYSA-N 0.000 description 5
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 5
BGVBBMZMEKXUTR-UHFFFAOYSA-N 4-chloro-n-methylpyridine-2-carboxamide Chemical compound CNC(=O)C1=CC(Cl)=CC=N1 BGVBBMZMEKXUTR-UHFFFAOYSA-N 0.000 description 5
IUQPNHYCLQPISC-UHFFFAOYSA-N 6-methoxy-1h-quinazolin-2-one Chemical compound N1C(=O)N=CC2=CC(OC)=CC=C21 IUQPNHYCLQPISC-UHFFFAOYSA-N 0.000 description 5
208000003200 Adenoma Diseases 0.000 description 5
208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 5
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 5
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
101100381978 Mus musculus Braf gene Proteins 0.000 description 5
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
125000003282 alkyl amino group Chemical group 0.000 description 5
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 5
125000004429 atom Chemical group 0.000 description 5
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 5
229910052799 carbon Inorganic materials 0.000 description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
210000001072 colon Anatomy 0.000 description 5
201000010099 disease Diseases 0.000 description 5
125000004438 haloalkoxy group Chemical group 0.000 description 5
239000000543 intermediate Substances 0.000 description 5
229940043355 kinase inhibitor Drugs 0.000 description 5
230000035772 mutation Effects 0.000 description 5
231100000252 nontoxic Toxicity 0.000 description 5
230000003000 nontoxic effect Effects 0.000 description 5
239000000546 pharmaceutical excipient Substances 0.000 description 5
239000003757 phosphotransferase inhibitor Substances 0.000 description 5
IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 5
230000008569 process Effects 0.000 description 5
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 5
238000006467 substitution reaction Methods 0.000 description 5
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