CA2619459A1 - Novel 4-amino-thieno[3,2-c]pyridine-7-carboxylic acid amides - Google Patents
Novel 4-amino-thieno[3,2-c]pyridine-7-carboxylic acid amides Download PDFInfo
- Publication number
- CA2619459A1 CA2619459A1 CA002619459A CA2619459A CA2619459A1 CA 2619459 A1 CA2619459 A1 CA 2619459A1 CA 002619459 A CA002619459 A CA 002619459A CA 2619459 A CA2619459 A CA 2619459A CA 2619459 A1 CA2619459 A1 CA 2619459A1
- Authority
- CA
- Canada
- Prior art keywords
- substituted
- lower alkyl
- heterocycle
- thieno
- pyridine
- Prior art date
- Legal status (The legal status 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 status listed.)
- Abandoned
Links
- HJRDTJWMWFIQBH-UHFFFAOYSA-N 4-aminothieno[3,2-c]pyridine-7-carboxamide Chemical class NC(=O)C1=CN=C(N)C2=C1SC=C2 HJRDTJWMWFIQBH-UHFFFAOYSA-N 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 214
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 30
- 150000003839 salts Chemical class 0.000 claims abstract description 27
- 238000000034 method Methods 0.000 claims abstract description 23
- 150000002148 esters Chemical class 0.000 claims abstract description 22
- 238000011282 treatment Methods 0.000 claims abstract description 21
- 201000011510 cancer Diseases 0.000 claims abstract description 13
- 210000000481 breast Anatomy 0.000 claims abstract description 12
- 210000001072 colon Anatomy 0.000 claims abstract description 10
- 210000004072 lung Anatomy 0.000 claims abstract description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- 239000003814 drug Substances 0.000 claims abstract description 5
- 230000008569 process Effects 0.000 claims abstract description 4
- 210000002307 prostate Anatomy 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 171
- 125000000623 heterocyclic group Chemical group 0.000 claims description 119
- 125000001072 heteroaryl group Chemical group 0.000 claims description 92
- 125000003118 aryl group Chemical group 0.000 claims description 73
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 58
- 125000006413 ring segment Chemical group 0.000 claims description 53
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 48
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 43
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 39
- 125000003107 substituted aryl group Chemical group 0.000 claims description 34
- 125000005842 heteroatom Chemical group 0.000 claims description 31
- 229910052757 nitrogen Inorganic materials 0.000 claims description 30
- 101100440695 Dictyostelium discoideum corB gene Proteins 0.000 claims description 24
- 125000004429 atom Chemical group 0.000 claims description 24
- -1 4-bromo-phenoxymethyl Chemical group 0.000 claims description 22
- BSMZTALHTNFIKX-UHFFFAOYSA-N 4-amino-3-[(4-bromophenoxy)methyl]thieno[3,2-c]pyridine-7-carboxylic acid Chemical compound C1=2C(N)=NC=C(C(O)=O)C=2SC=C1COC1=CC=C(Br)C=C1 BSMZTALHTNFIKX-UHFFFAOYSA-N 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 208000029742 colonic neoplasm Diseases 0.000 claims description 9
- AGSBUGHXQWLWRV-UHFFFAOYSA-N ethyl 4-amino-3-[(4-bromophenoxy)methyl]thieno[3,2-c]pyridine-7-carboxylate Chemical compound C=1SC=2C(C(=O)OCC)=CN=C(N)C=2C=1COC1=CC=C(Br)C=C1 AGSBUGHXQWLWRV-UHFFFAOYSA-N 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 208000026310 Breast neoplasm Diseases 0.000 claims description 8
- LXLXFZVZXDUUSO-UHFFFAOYSA-N ethyl 3-(bromomethyl)-4-chlorothieno[3,2-c]pyridine-7-carboxylate Chemical compound CCOC(=O)C1=CN=C(Cl)C2=C1SC=C2CBr LXLXFZVZXDUUSO-UHFFFAOYSA-N 0.000 claims description 8
- YCBCHKDACLRYNZ-UHFFFAOYSA-N 3-methyl-5h-thieno[3,2-c]pyridin-4-one Chemical compound C1=CNC(=O)C2=C1SC=C2C YCBCHKDACLRYNZ-UHFFFAOYSA-N 0.000 claims description 6
- UFNMXGNTPWVJOF-UHFFFAOYSA-N 4-amino-3-[(4-bromophenoxy)methyl]-n-(2-hydroxyethyl)thieno[3,2-c]pyridine-7-carboxamide Chemical compound C1=2C(N)=NC=C(C(=O)NCCO)C=2SC=C1COC1=CC=C(Br)C=C1 UFNMXGNTPWVJOF-UHFFFAOYSA-N 0.000 claims description 6
- NHYYWHIRXTZMDE-UHFFFAOYSA-N ethyl 4-chloro-3-(phenoxymethyl)thieno[3,2-c]pyridine-7-carboxylate Chemical compound C=1SC=2C(C(=O)OCC)=CN=C(Cl)C=2C=1COC1=CC=CC=C1 NHYYWHIRXTZMDE-UHFFFAOYSA-N 0.000 claims description 6
- OZWUCKOIYBLMIT-UHFFFAOYSA-N 4-amino-3-[(4-bromophenoxy)methyl]-n-(2-morpholin-4-ylethyl)thieno[3,2-c]pyridine-7-carboxamide Chemical compound C1=2SC=C(COC=3C=CC(Br)=CC=3)C=2C(N)=NC=C1C(=O)NCCN1CCOCC1 OZWUCKOIYBLMIT-UHFFFAOYSA-N 0.000 claims description 5
- IPRSBFSQYOMSDI-UHFFFAOYSA-N 4-amino-3-[(4-bromophenoxy)methyl]-n-[2-(2-piperidin-1-ylethoxy)ethyl]thieno[3,2-c]pyridine-7-carboxamide Chemical compound C1=2SC=C(COC=3C=CC(Br)=CC=3)C=2C(N)=NC=C1C(=O)NCCOCCN1CCCCC1 IPRSBFSQYOMSDI-UHFFFAOYSA-N 0.000 claims description 5
- JADBBBSLRXQXFF-UHFFFAOYSA-N 7-iodo-3-methyl-5h-thieno[3,2-c]pyridin-4-one Chemical compound IC1=CNC(=O)C2=C1SC=C2C JADBBBSLRXQXFF-UHFFFAOYSA-N 0.000 claims description 5
- YPHSTCWMEFAYRV-UHFFFAOYSA-N ethyl 3-[(4-bromo-2,6-difluorophenoxy)methyl]-4-chlorothieno[3,2-c]pyridine-7-carboxylate Chemical compound C=1SC=2C(C(=O)OCC)=CN=C(Cl)C=2C=1COC1=C(F)C=C(Br)C=C1F YPHSTCWMEFAYRV-UHFFFAOYSA-N 0.000 claims description 5
- HWIIISIMJCDAIJ-UHFFFAOYSA-N ethyl 3-[(4-bromophenoxy)methyl]-4-chlorothieno[3,2-c]pyridine-7-carboxylate Chemical compound C=1SC=2C(C(=O)OCC)=CN=C(Cl)C=2C=1COC1=CC=C(Br)C=C1 HWIIISIMJCDAIJ-UHFFFAOYSA-N 0.000 claims description 5
- ZQIKCKYDCDCDJE-UHFFFAOYSA-N ethyl 3-methyl-4-oxo-5h-thieno[3,2-c]pyridine-7-carboxylate Chemical compound CCOC(=O)C1=CNC(=O)C2=C1SC=C2C ZQIKCKYDCDCDJE-UHFFFAOYSA-N 0.000 claims description 5
- BLZWTSVLIALUJF-UHFFFAOYSA-N ethyl 4-amino-3-(phenoxymethyl)thieno[3,2-c]pyridine-7-carboxylate Chemical compound C=1SC=2C(C(=O)OCC)=CN=C(N)C=2C=1COC1=CC=CC=C1 BLZWTSVLIALUJF-UHFFFAOYSA-N 0.000 claims description 5
- WWEPHEQRSLWHPQ-UHFFFAOYSA-N ethyl 4-amino-3-[(2-chloro-4-methoxyphenoxy)methyl]thieno[3,2-c]pyridine-7-carboxylate Chemical compound C=1SC=2C(C(=O)OCC)=CN=C(N)C=2C=1COC1=CC=C(OC)C=C1Cl WWEPHEQRSLWHPQ-UHFFFAOYSA-N 0.000 claims description 5
- UUQWHCYHUSJNRD-UHFFFAOYSA-N ethyl 4-amino-3-[(4-bromo-2,6-difluorophenoxy)methyl]thieno[3,2-c]pyridine-7-carboxylate Chemical compound C=1SC=2C(C(=O)OCC)=CN=C(N)C=2C=1COC1=C(F)C=C(Br)C=C1F UUQWHCYHUSJNRD-UHFFFAOYSA-N 0.000 claims description 5
- HFNLITQKFVMKJR-UHFFFAOYSA-N 4-amino-3-(1,3-benzodioxol-5-yloxymethyl)-n-(2-hydroxyethyl)thieno[3,2-c]pyridine-7-carboxamide Chemical compound C1=C2OCOC2=CC(OCC2=CSC=3C(C(=O)NCCO)=CN=C(C2=3)N)=C1 HFNLITQKFVMKJR-UHFFFAOYSA-N 0.000 claims description 4
- FEOBGBMJIJPBGW-UHFFFAOYSA-N 4-amino-3-[(4-bromo-2,6-difluorophenoxy)methyl]-n-(2-hydroxyethyl)thieno[3,2-c]pyridine-7-carboxamide Chemical compound C1=2C(N)=NC=C(C(=O)NCCO)C=2SC=C1COC1=C(F)C=C(Br)C=C1F FEOBGBMJIJPBGW-UHFFFAOYSA-N 0.000 claims description 4
- XWOAIVJGPKSBML-UHFFFAOYSA-N 4-amino-3-[(4-bromophenoxy)methyl]-n-(1-hydroxy-2-methylpropan-2-yl)thieno[3,2-c]pyridine-7-carboxamide Chemical compound C=1SC=2C(C(=O)NC(C)(CO)C)=CN=C(N)C=2C=1COC1=CC=C(Br)C=C1 XWOAIVJGPKSBML-UHFFFAOYSA-N 0.000 claims description 4
- AOCDTVWJEURYGG-UHFFFAOYSA-N 4-amino-3-[(4-bromophenoxy)methyl]-n-(1-hydroxypropan-2-yl)thieno[3,2-c]pyridine-7-carboxamide Chemical compound C=1SC=2C(C(=O)NC(CO)C)=CN=C(N)C=2C=1COC1=CC=C(Br)C=C1 AOCDTVWJEURYGG-UHFFFAOYSA-N 0.000 claims description 4
- NRGXTVPPRHONIC-UHFFFAOYSA-N 4-amino-3-[(4-bromophenoxy)methyl]-n-(2,3-dihydroxypropyl)thieno[3,2-c]pyridine-7-carboxamide Chemical compound C1=2C(N)=NC=C(C(=O)NCC(O)CO)C=2SC=C1COC1=CC=C(Br)C=C1 NRGXTVPPRHONIC-UHFFFAOYSA-N 0.000 claims description 4
- NDIZYTMFKUMLIG-UHFFFAOYSA-N 4-amino-3-[(4-bromophenoxy)methyl]-n-(2-hydroxypropyl)thieno[3,2-c]pyridine-7-carboxamide Chemical compound C=1SC=2C(C(=O)NCC(O)C)=CN=C(N)C=2C=1COC1=CC=C(Br)C=C1 NDIZYTMFKUMLIG-UHFFFAOYSA-N 0.000 claims description 4
- NFPITRKPCDTNOM-UHFFFAOYSA-N 4-amino-3-[(4-bromophenoxy)methyl]-n-(4-morpholin-4-ylbutyl)thieno[3,2-c]pyridine-7-carboxamide Chemical compound C1=2SC=C(COC=3C=CC(Br)=CC=3)C=2C(N)=NC=C1C(=O)NCCCCN1CCOCC1 NFPITRKPCDTNOM-UHFFFAOYSA-N 0.000 claims description 4
- XGTCGHXGXAOLGU-UHFFFAOYSA-N 4-amino-3-[(4-bromophenoxy)methyl]-n-(4-pyrrolidin-1-ylbutyl)thieno[3,2-c]pyridine-7-carboxamide Chemical compound C1=2SC=C(COC=3C=CC(Br)=CC=3)C=2C(N)=NC=C1C(=O)NCCCCN1CCCC1 XGTCGHXGXAOLGU-UHFFFAOYSA-N 0.000 claims description 4
- GOVWOCDUJOEDBN-UHFFFAOYSA-N 4-amino-3-[(4-bromophenoxy)methyl]-n-[2-(diethylamino)ethyl]thieno[3,2-c]pyridine-7-carboxamide Chemical compound C=1SC=2C(C(=O)NCCN(CC)CC)=CN=C(N)C=2C=1COC1=CC=C(Br)C=C1 GOVWOCDUJOEDBN-UHFFFAOYSA-N 0.000 claims description 4
- ZQHBRAMGPUWSIA-UHFFFAOYSA-N 4-amino-3-[(4-bromophenoxy)methyl]-n-[3-(2,3-dihydroxypropoxy)propyl]thieno[3,2-c]pyridine-7-carboxamide Chemical compound C1=2C(N)=NC=C(C(=O)NCCCOCC(O)CO)C=2SC=C1COC1=CC=C(Br)C=C1 ZQHBRAMGPUWSIA-UHFFFAOYSA-N 0.000 claims description 4
- KNSLOQAHCTWHGH-UHFFFAOYSA-N 4-amino-3-[(4-bromophenoxy)methyl]-n-[3-(dimethylamino)-2,2-dimethylpropyl]thieno[3,2-c]pyridine-7-carboxamide Chemical compound C=1SC=2C(C(=O)NCC(C)(C)CN(C)C)=CN=C(N)C=2C=1COC1=CC=C(Br)C=C1 KNSLOQAHCTWHGH-UHFFFAOYSA-N 0.000 claims description 4
- PPSCDLNYOKXAAY-UHFFFAOYSA-N 4-amino-3-[(4-bromophenoxy)methyl]thieno[3,2-c]pyridine-7-carboxamide Chemical compound C=1SC=2C(C(=O)N)=CN=C(N)C=2C=1COC1=CC=C(Br)C=C1 PPSCDLNYOKXAAY-UHFFFAOYSA-N 0.000 claims description 4
- SMPPPDHNASMREP-UHFFFAOYSA-N 4-amino-n-(2-hydroxyethyl)-3-(phenoxymethyl)thieno[3,2-c]pyridine-7-carboxamide Chemical compound C1=2C(N)=NC=C(C(=O)NCCO)C=2SC=C1COC1=CC=CC=C1 SMPPPDHNASMREP-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- OGGMPOZTPMKXCG-UHFFFAOYSA-N ethyl 4-chloro-3-methylthieno[3,2-c]pyridine-7-carboxylate Chemical compound CCOC(=O)C1=CN=C(Cl)C2=C1SC=C2C OGGMPOZTPMKXCG-UHFFFAOYSA-N 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- ZHUOXDNPKVSAJE-UHFFFAOYSA-N 4-amino-3-[(2-chloro-4-methoxyphenoxy)methyl]-n-(2-hydroxyethyl)thieno[3,2-c]pyridine-7-carboxamide Chemical compound ClC1=CC(OC)=CC=C1OCC1=CSC2=C(C(=O)NCCO)C=NC(N)=C12 ZHUOXDNPKVSAJE-UHFFFAOYSA-N 0.000 claims description 3
- XPIJPMXHHBYPSO-UHFFFAOYSA-N 4-amino-3-[(4-bromophenoxy)methyl]-n-(1,3-dihydroxypropan-2-yl)thieno[3,2-c]pyridine-7-carboxamide Chemical compound C1=2C(N)=NC=C(C(=O)NC(CO)CO)C=2SC=C1COC1=CC=C(Br)C=C1 XPIJPMXHHBYPSO-UHFFFAOYSA-N 0.000 claims description 3
- ZRIGIERYMLJQNB-UHFFFAOYSA-N 4-amino-3-[(4-bromophenoxy)methyl]-n-(2-morpholin-4-ylethyl)thieno[3,2-c]pyridine-7-carboxamide;hydrochloride Chemical compound Cl.C1=2SC=C(COC=3C=CC(Br)=CC=3)C=2C(N)=NC=C1C(=O)NCCN1CCOCC1 ZRIGIERYMLJQNB-UHFFFAOYSA-N 0.000 claims description 3
- BEHGCGMOEUTSOG-UHFFFAOYSA-N 4-amino-3-[(4-bromophenoxy)methyl]-n-(4-piperidin-1-ylbutyl)thieno[3,2-c]pyridine-7-carboxamide Chemical compound C1=2SC=C(COC=3C=CC(Br)=CC=3)C=2C(N)=NC=C1C(=O)NCCCCN1CCCCC1 BEHGCGMOEUTSOG-UHFFFAOYSA-N 0.000 claims description 3
- SXQIRRYUEWXRLE-UHFFFAOYSA-N 4-amino-3-[(4-bromophenoxy)methyl]-n-(4-pyrrolidin-1-ylbutyl)thieno[3,2-c]pyridine-7-carboxamide;hydrochloride Chemical compound Cl.C1=2SC=C(COC=3C=CC(Br)=CC=3)C=2C(N)=NC=C1C(=O)NCCCCN1CCCC1 SXQIRRYUEWXRLE-UHFFFAOYSA-N 0.000 claims description 3
- KBTNGDFSTJJYFX-UHFFFAOYSA-N 4-amino-3-[(4-bromophenoxy)methyl]-n-(4-pyrrolidin-1-ylbutyl)thieno[3,2-c]pyridine-7-carboxamide;methanesulfonic acid Chemical compound CS(O)(=O)=O.C1=2SC=C(COC=3C=CC(Br)=CC=3)C=2C(N)=NC=C1C(=O)NCCCCN1CCCC1 KBTNGDFSTJJYFX-UHFFFAOYSA-N 0.000 claims description 3
- XDRUVIZPBVLFKJ-UHFFFAOYSA-N 4-amino-3-[(4-bromophenoxy)methyl]-n-[2-(2-morpholin-4-ylethoxy)ethyl]thieno[3,2-c]pyridine-7-carboxamide Chemical compound C1=2SC=C(COC=3C=CC(Br)=CC=3)C=2C(N)=NC=C1C(=O)NCCOCCN1CCOCC1 XDRUVIZPBVLFKJ-UHFFFAOYSA-N 0.000 claims description 3
- RRVOYYABKPUINM-UHFFFAOYSA-N 4-amino-3-[(4-bromophenoxy)methyl]-n-[2-(2-pyrrolidin-1-ylethoxy)ethyl]thieno[3,2-c]pyridine-7-carboxamide Chemical compound C1=2SC=C(COC=3C=CC(Br)=CC=3)C=2C(N)=NC=C1C(=O)NCCOCCN1CCCC1 RRVOYYABKPUINM-UHFFFAOYSA-N 0.000 claims description 3
- YEDSCRQJUMZMHX-UHFFFAOYSA-N 4-amino-3-[(4-bromophenoxy)methyl]-n-[4-(3-methoxypiperidin-1-yl)butyl]thieno[3,2-c]pyridine-7-carboxamide Chemical compound C1C(OC)CCCN1CCCCNC(=O)C1=CN=C(N)C2=C1SC=C2COC1=CC=C(Br)C=C1 YEDSCRQJUMZMHX-UHFFFAOYSA-N 0.000 claims description 3
- KRGAPJSEZRYCLI-UHFFFAOYSA-N 4-amino-3-[(4-bromophenoxy)methyl]-n-[4-(3-methoxypyrrolidin-1-yl)butyl]thieno[3,2-c]pyridine-7-carboxamide Chemical compound C1C(OC)CCN1CCCCNC(=O)C1=CN=C(N)C2=C1SC=C2COC1=CC=C(Br)C=C1 KRGAPJSEZRYCLI-UHFFFAOYSA-N 0.000 claims description 3
- KQPVCSLDJLLKII-UHFFFAOYSA-N 4-amino-3-[(4-bromophenoxy)methyl]-n-[4-(4-methoxypiperidin-1-yl)butyl]thieno[3,2-c]pyridine-7-carboxamide Chemical compound C1CC(OC)CCN1CCCCNC(=O)C1=CN=C(N)C2=C1SC=C2COC1=CC=C(Br)C=C1 KQPVCSLDJLLKII-UHFFFAOYSA-N 0.000 claims description 3
- XUGNPVWQKUCTBT-UHFFFAOYSA-N 4-amino-3-[(4-bromophenoxy)methyl]-n-[6-(diethylamino)hexan-2-yl]thieno[3,2-c]pyridine-7-carboxamide Chemical compound C=1SC=2C(C(=O)NC(C)CCCCN(CC)CC)=CN=C(N)C=2C=1COC1=CC=C(Br)C=C1 XUGNPVWQKUCTBT-UHFFFAOYSA-N 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 206010009944 Colon cancer Diseases 0.000 claims 4
- 206010006187 Breast cancer Diseases 0.000 claims 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 3
- 206010060862 Prostate cancer Diseases 0.000 claims 3
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 3
- 201000005202 lung cancer Diseases 0.000 claims 3
- 208000020816 lung neoplasm Diseases 0.000 claims 3
- 239000002671 adjuvant Substances 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 230000001131 transforming effect Effects 0.000 claims 1
- 108091008794 FGF receptors Proteins 0.000 abstract description 20
- 239000003795 chemical substances by application Substances 0.000 abstract description 5
- 230000001028 anti-proliverative effect Effects 0.000 abstract description 4
- 229940124639 Selective inhibitor Drugs 0.000 abstract 1
- 102000052178 fibroblast growth factor receptor activity proteins Human genes 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 149
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 96
- 239000000203 mixture Substances 0.000 description 85
- 239000000243 solution Substances 0.000 description 84
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 83
- 239000000543 intermediate Substances 0.000 description 82
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 64
- 229910001868 water Inorganic materials 0.000 description 61
- 239000007787 solid Substances 0.000 description 40
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 38
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 37
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 36
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 35
- 239000011541 reaction mixture Substances 0.000 description 31
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 29
- 238000006243 chemical reaction Methods 0.000 description 27
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 238000003756 stirring Methods 0.000 description 21
- 239000012267 brine Substances 0.000 description 20
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 20
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
- 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 19
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 19
- 229910052938 sodium sulfate Inorganic materials 0.000 description 19
- 235000011152 sodium sulphate Nutrition 0.000 description 19
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
- 238000004587 chromatography analysis Methods 0.000 description 17
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 238000003818 flash chromatography Methods 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- 238000003556 assay Methods 0.000 description 14
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/EP2005/054022 WO2007019884A1 (en) | 2005-08-16 | 2005-08-16 | Novel 4-amino-thieno[3,2-c]pyridine-7-carboxylic acid amides |
Publications (1)
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|---|---|
| CA2619459A1 true CA2619459A1 (en) | 2007-02-22 |
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| CA002619459A Abandoned CA2619459A1 (en) | 2005-08-16 | 2005-08-16 | Novel 4-amino-thieno[3,2-c]pyridine-7-carboxylic acid amides |
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| Country | Link |
|---|---|
| EP (1) | EP1917015A1 (es) |
| JP (1) | JP2009504692A (es) |
| KR (1) | KR100995790B1 (es) |
| AU (1) | AU2005335661A1 (es) |
| BR (1) | BRPI0520482A2 (es) |
| CA (1) | CA2619459A1 (es) |
| IL (1) | IL189181A0 (es) |
| MX (1) | MX2008002060A (es) |
| WO (1) | WO2007019884A1 (es) |
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| CN101263145B (zh) * | 2005-09-15 | 2015-02-25 | 霍夫曼-拉罗奇有限公司 | 4-氨基-噻吩并[3,2-c]吡啶-7-羧酸衍生物 |
| AR070317A1 (es) * | 2008-02-06 | 2010-03-31 | Osi Pharm Inc | Furo (3,2-c) piridina y tieno (3,2-c) piridinas |
| US20120189641A1 (en) | 2009-02-25 | 2012-07-26 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
| WO2010099138A2 (en) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
| JP2012519281A (ja) | 2009-02-27 | 2012-08-23 | オーエスアイ・ファーマシューティカルズ，エルエルシー | 間葉様腫瘍細胞またはその生成を阻害する薬剤を同定するための方法 |
| US9896730B2 (en) | 2011-04-25 | 2018-02-20 | OSI Pharmaceuticals, LLC | Use of EMT gene signatures in cancer drug discovery, diagnostics, and treatment |
| WO2013152252A1 (en) | 2012-04-06 | 2013-10-10 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
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| WO2004100947A2 (en) * | 2003-05-06 | 2004-11-25 | Smithkline Beecham Corporation | Novel chemical compounds |
| US20050026944A1 (en) * | 2003-07-24 | 2005-02-03 | Patrick Betschmann | Thienopyridine and furopyridine kinase inhibitors |
| US20050020619A1 (en) * | 2003-07-24 | 2005-01-27 | Patrick Betschmann | Thienopyridine kinase inhibitors |
-
2005
- 2005-08-16 BR BRPI0520482-8A patent/BRPI0520482A2/pt not_active IP Right Cessation
- 2005-08-16 MX MX2008002060A patent/MX2008002060A/es not_active Application Discontinuation
- 2005-08-16 KR KR1020087003603A patent/KR100995790B1/ko not_active IP Right Cessation
- 2005-08-16 AU AU2005335661A patent/AU2005335661A1/en not_active Abandoned
- 2005-08-16 JP JP2008526383A patent/JP2009504692A/ja not_active Withdrawn
- 2005-08-16 CA CA002619459A patent/CA2619459A1/en not_active Abandoned
- 2005-08-16 WO PCT/EP2005/054022 patent/WO2007019884A1/en active Application Filing
- 2005-08-16 EP EP05792209A patent/EP1917015A1/en not_active Withdrawn
-
2008
- 2008-02-03 IL IL189181A patent/IL189181A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IL189181A0 (en) | 2008-06-05 |
| KR100995790B1 (ko) | 2010-11-22 |
| MX2008002060A (es) | 2008-04-16 |
| BRPI0520482A2 (pt) | 2009-05-12 |
| KR20080027945A (ko) | 2008-03-28 |
| AU2005335661A1 (en) | 2007-02-22 |
| WO2007019884A1 (en) | 2007-02-22 |
| JP2009504692A (ja) | 2009-02-05 |
| EP1917015A1 (en) | 2008-05-07 |
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