ZA200509632B - Substituted hereroaryls as inhibitors of protein tyrosine phosphatases - Google Patents

Substituted hereroaryls as inhibitors of protein tyrosine phosphatases Download PDF

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Publication number: ZA200509632B
Authority: ZA; South Africa
Prior art keywords: alkyl; phenyl; chloro; quinazolin; oxo
Prior art date: 2003-04-30

Application number

ZA200509632A

Other languages

English (en)

Inventor

Savoy Jennifer

Geraci Leo

Parker Garrett

Zandt Michael C Van

Whitehouse Darren

Hu Shaojing

Original Assignee

Inst For Pharm Discovery Inc

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.)

2003-04-30

Filing date

2005-11-29

Publication date

2007-02-28

2005-11-29 Application filed by Inst For Pharm Discovery Inc filed Critical Inst For Pharm Discovery Inc

2007-02-28 Publication of ZA200509632B publication Critical patent/ZA200509632B/en

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102000002727 Protein Tyrosine Phosphatase Human genes 0.000 title abstract description 10
108020000494 protein-tyrosine phosphatase Proteins 0.000 title abstract description 10
239000003112 inhibitor Substances 0.000 title abstract description 8
150000001875 compounds Chemical class 0.000 claims abstract description 235
238000000034 method Methods 0.000 claims abstract description 46
150000003839 salts Chemical class 0.000 claims abstract description 31
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 15
206010012601 diabetes mellitus Diseases 0.000 claims abstract description 10
125000000217 alkyl group Chemical group 0.000 claims description 417
229910052736 halogen Inorganic materials 0.000 claims description 132
-1 NH- heteroaryl Chemical group 0.000 claims description 122
125000003545 alkoxy group Chemical group 0.000 claims description 121
150000002367 halogens Chemical class 0.000 claims description 121
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 92
125000003118 aryl group Chemical group 0.000 claims description 89
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 86
125000001072 heteroaryl group Chemical group 0.000 claims description 84
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 80
125000001589 carboacyl group Chemical group 0.000 claims description 70
229910052799 carbon Inorganic materials 0.000 claims description 68
229910052739 hydrogen Inorganic materials 0.000 claims description 58
125000001188 haloalkyl group Chemical group 0.000 claims description 48
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 36
229910052792 caesium Inorganic materials 0.000 claims description 28
DQWOQZQOSNHULS-UHFFFAOYSA-N 2-trimethylsilylethyl 4-(5-chloro-1h-indol-3-yl)-4-oxobutanoate Chemical compound C1=C(Cl)C=C2C(C(=O)CCC(=O)OCC[Si](C)(C)C)=CNC2=C1 DQWOQZQOSNHULS-UHFFFAOYSA-N 0.000 claims description 22
125000005843 halogen group Chemical group 0.000 claims description 21
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 18
125000004093 cyano group Chemical group *C#N 0.000 claims description 18
229910002091 carbon monoxide Inorganic materials 0.000 claims description 17
125000005309 thioalkoxy group Chemical group 0.000 claims description 13
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
239000002904 solvent Substances 0.000 claims description 12
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 11
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 11
125000000593 indol-1-yl group Chemical group [H]C1=C([H])C([H])=C2N([*])C([H])=C([H])C2=C1[H] 0.000 claims description 11
229920000728 polyester Polymers 0.000 claims description 11
125000002252 acyl group Chemical group 0.000 claims description 10
125000001309 chloro group Chemical group Cl* 0.000 claims description 10
125000004438 haloalkoxy group Chemical group 0.000 claims description 10
125000001041 indolyl group Chemical group 0.000 claims description 10
125000001424 substituent group Chemical group 0.000 claims description 9
239000002671 adjuvant Substances 0.000 claims description 8
125000002877 alkyl aryl group Chemical group 0.000 claims description 8
125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 8
125000005044 dihydroquinolinyl group Chemical group N1(CC=CC2=CC=CC=C12)* 0.000 claims description 8
125000002541 furyl group Chemical group 0.000 claims description 8
239000000546 pharmaceutical excipient Substances 0.000 claims description 8
125000004193 piperazinyl group Chemical group 0.000 claims description 8
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 8
KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 7
125000001246 bromo group Chemical group Br* 0.000 claims description 7
125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 claims description 7
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 7
125000005045 dihydroisoquinolinyl group Chemical group C1(NC=CC2=CC=CC=C12)* 0.000 claims description 6
125000002757 morpholinyl group Chemical group 0.000 claims description 6
125000003386 piperidinyl group Chemical group 0.000 claims description 6
125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 6
QNGVEVOZKYHNGL-UHFFFAOYSA-N 2-chloro-4,6-diphenylpyrimidine Chemical compound N=1C(Cl)=NC(C=2C=CC=CC=2)=CC=1C1=CC=CC=C1 QNGVEVOZKYHNGL-UHFFFAOYSA-N 0.000 claims description 5
WOADQYKUJOCBGZ-UHFFFAOYSA-N 4-[1-[6-amino-4-(4-ethoxycarbonylpiperidin-1-yl)quinazolin-2-yl]-5-chloroindol-3-yl]-4-oxobutanoic acid Chemical compound C1CC(C(=O)OCC)CCN1C1=NC(N2C3=CC=C(Cl)C=C3C(C(=O)CCC(O)=O)=C2)=NC2=CC=C(N)C=C12 WOADQYKUJOCBGZ-UHFFFAOYSA-N 0.000 claims description 4
KWJBVSWADUDPBE-UHFFFAOYSA-N 4-[5-chloro-1-[4-[(4-fluorophenyl)methylamino]-6-(furan-2-yl)quinazolin-2-yl]indol-3-yl]-4-oxobutanoic acid Chemical compound C12=CC=C(Cl)C=C2C(C(=O)CCC(=O)O)=CN1C(N=C1C=CC(=CC1=1)C=2OC=CC=2)=NC=1NCC1=CC=C(F)C=C1 KWJBVSWADUDPBE-UHFFFAOYSA-N 0.000 claims description 4
YPABZAQKCLORCR-UHFFFAOYSA-N 4-[5-chloro-1-[4-[4-(hydroxymethyl)piperidin-1-yl]-6-(trifluoromethyl)quinazolin-2-yl]indol-3-yl]-4-oxobutanoic acid Chemical compound C1CC(CO)CCN1C1=NC(N2C3=CC=C(Cl)C=C3C(C(=O)CCC(O)=O)=C2)=NC2=CC=C(C(F)(F)F)C=C12 YPABZAQKCLORCR-UHFFFAOYSA-N 0.000 claims description 4
CTOVSUBYQUUXAI-UHFFFAOYSA-N 4-[5-chloro-1-[5-(4-chlorophenyl)pyrimidin-2-yl]indol-3-yl]-4-oxobutanoic acid Chemical compound C12=CC=C(Cl)C=C2C(C(=O)CCC(=O)O)=CN1C(N=C1)=NC=C1C1=CC=C(Cl)C=C1 CTOVSUBYQUUXAI-UHFFFAOYSA-N 0.000 claims description 4
XTIVKDGRXMZNPU-UHFFFAOYSA-N 4-[5-chloro-1-[6-(furan-2-yl)-4-(2-methylsulfonylethylamino)quinazolin-2-yl]indol-3-yl]-4-oxobutanoic acid Chemical compound C1=C2C(NCCS(=O)(=O)C)=NC(N3C4=CC=C(Cl)C=C4C(C(=O)CCC(O)=O)=C3)=NC2=CC=C1C1=CC=CO1 XTIVKDGRXMZNPU-UHFFFAOYSA-N 0.000 claims description 4
HMKBHXQQWBJZKY-UHFFFAOYSA-N 4-[5-chloro-1-[6-(furan-2-yl)-4-(4-hydroxypiperidin-1-yl)quinazolin-2-yl]indol-3-yl]-4-oxobutanoic acid Chemical compound C1CC(O)CCN1C1=NC(N2C3=CC=C(Cl)C=C3C(C(=O)CCC(O)=O)=C2)=NC2=CC=C(C=3OC=CC=3)C=C12 HMKBHXQQWBJZKY-UHFFFAOYSA-N 0.000 claims description 4
229910052684 Cerium Inorganic materials 0.000 claims description 4
125000004432 carbon atom Chemical group C* 0.000 claims description 4
125000000753 cycloalkyl group Chemical group 0.000 claims description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
125000004260 quinazolin-2-yl group Chemical group [H]C1=NC(*)=NC2=C1C([H])=C([H])C([H])=C2[H] 0.000 claims description 4
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 4
125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 4
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
GUVXCXLPPWXJBF-UHFFFAOYSA-N 4-[1-[6-(furan-2-yl)-4-phenylquinazolin-2-yl]indol-3-yl]-4-oxobutanoic acid Chemical compound C12=CC=CC=C2C(C(=O)CCC(=O)O)=CN1C(N=C1C=CC(=CC1=1)C=2OC=CC=2)=NC=1C1=CC=CC=C1 GUVXCXLPPWXJBF-UHFFFAOYSA-N 0.000 claims description 3
SAHDIPXFQREICJ-UHFFFAOYSA-N 4-[5-bromo-1-[4-(1-carboxypropylamino)-6-(furan-2-yl)quinazolin-2-yl]indol-3-yl]-4-oxobutanoic acid Chemical compound C1=C2C(NC(CC)C(O)=O)=NC(N3C4=CC=C(Br)C=C4C(C(=O)CCC(O)=O)=C3)=NC2=CC=C1C1=CC=CO1 SAHDIPXFQREICJ-UHFFFAOYSA-N 0.000 claims description 3
SGHZNGZYLATRLO-UHFFFAOYSA-N 4-[5-bromo-1-[6-(furan-2-yl)-4-(4-methoxyanilino)quinazolin-2-yl]indol-3-yl]-4-oxobutanoic acid Chemical compound C1=CC(OC)=CC=C1NC1=NC(N2C3=CC=C(Br)C=C3C(C(=O)CCC(O)=O)=C2)=NC2=CC=C(C=3OC=CC=3)C=C12 SGHZNGZYLATRLO-UHFFFAOYSA-N 0.000 claims description 3
KAJHLUGBJNOKIN-UHFFFAOYSA-N 4-[5-bromo-1-[6-(furan-2-yl)-4-pyridin-2-ylquinazolin-2-yl]indol-3-yl]-4-oxobutanoic acid Chemical compound C12=CC=C(Br)C=C2C(C(=O)CCC(=O)O)=CN1C(N=C1C=CC(=CC1=1)C=2OC=CC=2)=NC=1C1=CC=CC=N1 KAJHLUGBJNOKIN-UHFFFAOYSA-N 0.000 claims description 3
UMTFEBAPLMQJJZ-UHFFFAOYSA-N 4-[5-chloro-1-(3-cyano-4,6-diphenylpyridin-2-yl)indol-3-yl]-4-oxobutanoic acid Chemical compound C12=CC=C(Cl)C=C2C(C(=O)CCC(=O)O)=CN1C(C=1C#N)=NC(C=2C=CC=CC=2)=CC=1C1=CC=CC=C1 UMTFEBAPLMQJJZ-UHFFFAOYSA-N 0.000 claims description 3
FTCPXJINPQQHOP-UHFFFAOYSA-N 4-[5-chloro-1-[4-(4-methoxyanilino)-6-(trifluoromethyl)quinazolin-2-yl]indol-3-yl]-4-oxobutanoic acid Chemical compound C1=CC(OC)=CC=C1NC1=NC(N2C3=CC=C(Cl)C=C3C(C(=O)CCC(O)=O)=C2)=NC2=CC=C(C(F)(F)F)C=C12 FTCPXJINPQQHOP-UHFFFAOYSA-N 0.000 claims description 3
PCPHJNWHOLBJQA-UHFFFAOYSA-N 4-[5-chloro-1-[4-[(4-methoxyphenyl)methylamino]-6-(trifluoromethyl)quinazolin-2-yl]indol-3-yl]-4-oxobutanoic acid Chemical compound C1=CC(OC)=CC=C1CNC1=NC(N2C3=CC=C(Cl)C=C3C(C(=O)CCC(O)=O)=C2)=NC2=CC=C(C(F)(F)F)C=C12 PCPHJNWHOLBJQA-UHFFFAOYSA-N 0.000 claims description 3
HQPCKILBNARRFW-UHFFFAOYSA-N 4-[5-chloro-1-[6-(furan-2-yl)-4-(pyridin-4-ylmethylamino)quinazolin-2-yl]indol-3-yl]-4-oxobutanoic acid Chemical compound C12=CC=C(Cl)C=C2C(C(=O)CCC(=O)O)=CN1C(N=C1C=CC(=CC1=1)C=2OC=CC=2)=NC=1NCC1=CC=NC=C1 HQPCKILBNARRFW-UHFFFAOYSA-N 0.000 claims description 3
ACTMTCRGMULBQQ-UHFFFAOYSA-N 4-[5-chloro-1-[6-(furan-2-yl)-4-morpholin-4-ylquinazolin-2-yl]indol-3-yl]-4-oxobutanoic acid Chemical compound C12=CC=C(Cl)C=C2C(C(=O)CCC(=O)O)=CN1C(N=C1C=CC(=CC1=1)C=2OC=CC=2)=NC=1N1CCOCC1 ACTMTCRGMULBQQ-UHFFFAOYSA-N 0.000 claims description 3
OAMFJGPHEAHSKA-UHFFFAOYSA-N 4-[5-chloro-1-[6-(furan-2-yl)-4-pyridin-2-ylquinazolin-2-yl]indol-3-yl]-4-oxobutanoic acid Chemical compound C12=CC=C(Cl)C=C2C(C(=O)CCC(=O)O)=CN1C(N=C1C=CC(=CC1=1)C=2OC=CC=2)=NC=1C1=CC=CC=N1 OAMFJGPHEAHSKA-UHFFFAOYSA-N 0.000 claims description 3
229910014585 C2-Ce Inorganic materials 0.000 claims description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 3
YLYFAXIBLFYMDR-UHFFFAOYSA-N 1-[2-[3-(3-carboxypropanoyl)-5-chloroindol-1-yl]-6-(furan-2-yl)quinazolin-4-yl]piperidine-4-carboxylic acid Chemical compound C12=CC=C(Cl)C=C2C(C(=O)CCC(=O)O)=CN1C(N=C1C=CC(=CC1=1)C=2OC=CC=2)=NC=1N1CCC(C(O)=O)CC1 YLYFAXIBLFYMDR-UHFFFAOYSA-N 0.000 claims description 2
ZELDTDQTTPGSML-UHFFFAOYSA-N 1-[2-[5-bromo-3-(3-carboxypropanoyl)indol-1-yl]-6-(furan-2-yl)quinazolin-4-yl]piperidine-4-carboxylic acid Chemical compound C12=CC=C(Br)C=C2C(C(=O)CCC(=O)O)=CN1C(N=C1C=CC(=CC1=1)C=2OC=CC=2)=NC=1N1CCC(C(O)=O)CC1 ZELDTDQTTPGSML-UHFFFAOYSA-N 0.000 claims description 2
GDGVQQCQYLNXQB-UHFFFAOYSA-N 2-(n-(6-bromo-4-phenylquinazolin-2-yl)-4-sulfamoylanilino)acetic acid Chemical compound C1=CC(S(=O)(=O)N)=CC=C1N(CC(O)=O)C1=NC(C=2C=CC=CC=2)=C(C=C(Br)C=C2)C2=N1 GDGVQQCQYLNXQB-UHFFFAOYSA-N 0.000 claims description 2
SOBGBWIWMSGECQ-UHFFFAOYSA-N 2-[[4-(4-butylphenyl)-6-(furan-2-yl)quinazolin-2-yl]amino]benzenesulfonamide Chemical compound C1=CC(CCCC)=CC=C1C1=NC(NC=2C(=CC=CC=2)S(N)(=O)=O)=NC2=CC=C(C=3OC=CC=3)C=C12 SOBGBWIWMSGECQ-UHFFFAOYSA-N 0.000 claims description 2
IFVCMBOIYOAZHT-UHFFFAOYSA-N 2-trimethylsilylethyl 4-[5-chloro-1-(4,6-diphenylpyrimidin-2-yl)indol-3-yl]-4-oxobutanoate Chemical compound C12=CC=C(Cl)C=C2C(C(=O)CCC(=O)OCC[Si](C)(C)C)=CN1C(N=1)=NC(C=2C=CC=CC=2)=CC=1C1=CC=CC=C1 IFVCMBOIYOAZHT-UHFFFAOYSA-N 0.000 claims description 2
FBSILPISGYMMPF-UHFFFAOYSA-N 4-[1-(6-chloro-4-phenylquinazolin-2-yl)-5-methoxycarbonylindol-3-yl]-4-oxobutanoic acid Chemical compound C1=C(C(=O)CCC(O)=O)C2=CC(C(=O)OC)=CC=C2N1C(N=C1C=CC(Cl)=CC1=1)=NC=1C1=CC=CC=C1 FBSILPISGYMMPF-UHFFFAOYSA-N 0.000 claims description 2
UCGBYBMPZQJQEQ-UHFFFAOYSA-N 4-[1-[4-[(2-amino-2-oxoethyl)amino]-6-(furan-2-yl)quinazolin-2-yl]-5-chloroindol-3-yl]-4-oxobutanoic acid Chemical compound C1=C2C(NCC(=O)N)=NC(N3C4=CC=C(Cl)C=C4C(C(=O)CCC(O)=O)=C3)=NC2=CC=C1C1=CC=CO1 UCGBYBMPZQJQEQ-UHFFFAOYSA-N 0.000 claims description 2
OJJLMRUFDZBUOF-UHFFFAOYSA-N 4-[5-bromo-1-[4-(4-cyanophenyl)-6-(furan-2-yl)quinazolin-2-yl]indol-3-yl]-4-oxobutanoic acid Chemical compound C12=CC=C(Br)C=C2C(C(=O)CCC(=O)O)=CN1C(N=C1C=CC(=CC1=1)C=2OC=CC=2)=NC=1C1=CC=C(C#N)C=C1 OJJLMRUFDZBUOF-UHFFFAOYSA-N 0.000 claims description 2
RPRBZKLFLWBFOM-UHFFFAOYSA-N 4-[5-bromo-1-[4-(4-ethoxycarbonylpiperidin-1-yl)-6-(furan-2-yl)quinazolin-2-yl]indol-3-yl]-4-oxobutanoic acid Chemical compound C1CC(C(=O)OCC)CCN1C1=NC(N2C3=CC=C(Br)C=C3C(C(=O)CCC(O)=O)=C2)=NC2=CC=C(C=3OC=CC=3)C=C12 RPRBZKLFLWBFOM-UHFFFAOYSA-N 0.000 claims description 2
CFFWUAHKOHYYOW-UHFFFAOYSA-N 4-[5-bromo-1-[4-(4-fluorophenyl)-6-(furan-2-yl)quinazolin-2-yl]indol-3-yl]-4-oxobutanoic acid Chemical compound C12=CC=C(Br)C=C2C(C(=O)CCC(=O)O)=CN1C(N=C1C=CC(=CC1=1)C=2OC=CC=2)=NC=1C1=CC=C(F)C=C1 CFFWUAHKOHYYOW-UHFFFAOYSA-N 0.000 claims description 2
LEJSRYBMFJXPHU-UHFFFAOYSA-N 4-[5-bromo-1-[6-(furan-2-yl)-4-morpholin-4-ylquinazolin-2-yl]indol-3-yl]-4-oxobutanoic acid Chemical compound C12=CC=C(Br)C=C2C(C(=O)CCC(=O)O)=CN1C(N=C1C=CC(=CC1=1)C=2OC=CC=2)=NC=1N1CCOCC1 LEJSRYBMFJXPHU-UHFFFAOYSA-N 0.000 claims description 2
FHRYNCIOPHYYOD-UHFFFAOYSA-N 4-[5-bromo-1-[6-(furan-2-yl)-4-phenylquinazolin-2-yl]indol-3-yl]-4-oxobutanoic acid Chemical compound C12=CC=C(Br)C=C2C(C(=O)CCC(=O)O)=CN1C(N=C1C=CC(=CC1=1)C=2OC=CC=2)=NC=1C1=CC=CC=C1 FHRYNCIOPHYYOD-UHFFFAOYSA-N 0.000 claims description 2
GWLOOGDQVLRGGS-UHFFFAOYSA-N 4-[5-chloro-1-[(4-thianthren-1-ylphenyl)methyl]indol-3-yl]-4-oxobutanoic acid Chemical compound C12=CC=C(Cl)C=C2C(C(=O)CCC(=O)O)=CN1CC1=CC=C(C=2C=3SC4=CC=CC=C4SC=3C=CC=2)C=C1 GWLOOGDQVLRGGS-UHFFFAOYSA-N 0.000 claims description 2
URIFWWVHMSIKCZ-UHFFFAOYSA-N 4-[5-chloro-1-[4-(4-ethoxycarbonylpiperidin-1-yl)-6-(furan-2-yl)quinazolin-2-yl]indol-3-yl]-4-oxobutanoic acid Chemical compound C1CC(C(=O)OCC)CCN1C1=NC(N2C3=CC=C(Cl)C=C3C(C(=O)CCC(O)=O)=C2)=NC2=CC=C(C=3OC=CC=3)C=C12 URIFWWVHMSIKCZ-UHFFFAOYSA-N 0.000 claims description 2
PGEVDNVKEOUNHS-UHFFFAOYSA-N 4-[5-chloro-1-[[4-(dibenzofuran-4-ylamino)phenyl]methyl]indol-3-yl]-4-oxobutanoic acid Chemical compound C12=CC=C(Cl)C=C2C(C(=O)CCC(=O)O)=CN1CC(C=C1)=CC=C1NC1=CC=CC2=C1OC1=CC=CC=C21 PGEVDNVKEOUNHS-UHFFFAOYSA-N 0.000 claims description 2
QUSKEWBKMCQFTC-UHFFFAOYSA-N 6-chloro-n-(4-nitrophenyl)-4-phenylquinazolin-2-amine Chemical compound C1=CC([N+](=O)[O-])=CC=C1NC1=NC(C=2C=CC=CC=2)=C(C=C(Cl)C=C2)C2=N1 QUSKEWBKMCQFTC-UHFFFAOYSA-N 0.000 claims description 2
125000001153 fluoro group Chemical group F* 0.000 claims description 2
125000000262 haloalkenyl group Chemical group 0.000 claims description 2
125000004252 isoindol-1-yl group Chemical group [H]N1C([H])=C2C([H])=C([H])C([H])=C([H])C2=C1* 0.000 claims description 2
ADCYPIUUQPXJJB-UHFFFAOYSA-N methyl 1-(6-chloro-4-phenylquinazolin-2-yl)indole-5-carboxylate Chemical compound C1=CC2=CC(C(=O)OC)=CC=C2N1C(N=C1C=CC(Cl)=CC1=1)=NC=1C1=CC=CC=C1 ADCYPIUUQPXJJB-UHFFFAOYSA-N 0.000 claims description 2
ZXKXJTNHGMZMPJ-UHFFFAOYSA-N methyl 4-[(6-chloro-4-phenylquinazolin-2-yl)amino]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1NC1=NC(C=2C=CC=CC=2)=C(C=C(Cl)C=C2)C2=N1 ZXKXJTNHGMZMPJ-UHFFFAOYSA-N 0.000 claims description 2
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
KLAWDIPKUBSYAN-UHFFFAOYSA-N n-(2,4-dimethylphenyl)-4-[(6-methyl-4-phenylquinazolin-2-yl)amino]benzamide Chemical compound CC1=CC(C)=CC=C1NC(=O)C(C=C1)=CC=C1NC1=NC(C=2C=CC=CC=2)=C(C=C(C)C=C2)C2=N1 KLAWDIPKUBSYAN-UHFFFAOYSA-N 0.000 claims description 2
CMRDRASZUBQEPF-UHFFFAOYSA-N n-[4-[(6-bromo-4-phenylquinazolin-2-yl)amino]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1NC1=NC(C=2C=CC=CC=2)=C(C=C(Br)C=C2)C2=N1 CMRDRASZUBQEPF-UHFFFAOYSA-N 0.000 claims description 2
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
125000004568 thiomorpholinyl group Chemical group 0.000 claims description 2
125000000714 pyrimidinyl group Chemical group 0.000 claims 2
QIRHVOSFSHISSV-UHFFFAOYSA-N 1-[4-[(6-bromo-4-phenylquinazolin-2-yl)amino]phenyl]ethanone Chemical compound C1=CC(C(=O)C)=CC=C1NC1=NC(C=2C=CC=CC=2)=C(C=C(Br)C=C2)C2=N1 QIRHVOSFSHISSV-UHFFFAOYSA-N 0.000 claims 1
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HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
229940100611 topical cream Drugs 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
229940042129 topical gel Drugs 0.000 description 1
229940100615 topical ointment Drugs 0.000 description 1
239000012049 topical pharmaceutical composition Substances 0.000 description 1
229940041677 topical spray Drugs 0.000 description 1
238000007832 transition metal-catalyzed coupling reaction Methods 0.000 description 1
UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
239000001993 wax Substances 0.000 description 1
239000012130 whole-cell lysate Substances 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
HEOMKTNNZDZMJZ-UHFFFAOYSA-M zinc;benzonitrile;bromide Chemical compound Br[Zn+].N#CC1=CC=[C-]C=C1 HEOMKTNNZDZMJZ-UHFFFAOYSA-M 0.000 description 1

Classifications

- 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
- C07D405/14—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 three or more hetero rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/84—Nitrogen atoms
- 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
- 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
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
- 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
- C07D405/04—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 directly linked by a ring-member-to-ring-member bond
- 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
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
- 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
- C07D417/04—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 directly linked by a ring-member-to-ring-member bond

ZA200509632A 2003-04-30 2005-11-29 Substituted hereroaryls as inhibitors of protein tyrosine phosphatases ZA200509632B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US46686903P	2003-04-30	2003-04-30

Publications (1)

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ZA200509632B true ZA200509632B (en)	2007-02-28

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ZA200509632A ZA200509632B (en)	2003-04-30	2005-11-29	Substituted hereroaryls as inhibitors of protein tyrosine phosphatases

Country Status (11)

Country	Link
US (1)	US20050009817A1 (ja)
EP (1)	EP1618094B1 (ja)
JP (1)	JP2006525357A (ja)
AT (1)	ATE372324T1 (ja)
AU (1)	AU2004236239A1 (ja)
CA (1)	CA2524221A1 (ja)
DE (1)	DE602004008762T2 (ja)
ES (1)	ES2290743T3 (ja)
MX (1)	MXPA05011523A (ja)
WO (1)	WO2004099159A1 (ja)
ZA (1)	ZA200509632B (ja)

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2004
- 2004-04-30 AT AT04760673T patent/ATE372324T1/de not_active IP Right Cessation
- 2004-04-30 EP EP04760673A patent/EP1618094B1/en not_active Expired - Lifetime
- 2004-04-30 AU AU2004236239A patent/AU2004236239A1/en not_active Abandoned
- 2004-04-30 MX MXPA05011523A patent/MXPA05011523A/es unknown
- 2004-04-30 CA CA002524221A patent/CA2524221A1/en not_active Abandoned
- 2004-04-30 DE DE602004008762T patent/DE602004008762T2/de not_active Expired - Fee Related
- 2004-04-30 US US10/836,371 patent/US20050009817A1/en not_active Abandoned
- 2004-04-30 ES ES04760673T patent/ES2290743T3/es not_active Expired - Lifetime
- 2004-04-30 WO PCT/US2004/013579 patent/WO2004099159A1/en active IP Right Grant
- 2004-04-30 JP JP2006514209A patent/JP2006525357A/ja active Pending
2005
- 2005-11-29 ZA ZA200509632A patent/ZA200509632B/en unknown

Also Published As

Publication number	Publication date
AU2004236239A1 (en)	2004-11-18
ATE372324T1 (de)	2007-09-15
CA2524221A1 (en)	2004-11-18
WO2004099159A1 (en)	2004-11-18
DE602004008762D1 (de)	2007-10-18
DE602004008762T2 (de)	2008-06-12
EP1618094B1 (en)	2007-09-05
JP2006525357A (ja)	2006-11-09
US20050009817A1 (en)	2005-01-13
ES2290743T3 (es)	2008-02-16
EP1618094A1 (en)	2006-01-25
MXPA05011523A (es)	2006-01-23

Publication	Publication Date	Title
ZA200509632B (en)	2007-02-28	Substituted hereroaryls as inhibitors of protein tyrosine phosphatases
JP5325783B2 (ja)	2013-10-23	ベンゾトリアゾールキナーゼモジュレーター
US5714493A (en)	1998-02-03	Aryl and heteroaryl quinazoline compounds which inhibit CSF-1R receptor tyrosine kinase
TWI488851B (zh)	2015-06-21	作為鉀離子通道抑制劑之喹唑啉
EP0871448B1 (en)	2005-03-02	Aryl and heteroaryl quinazoline compounds which inhibit csf-1r receptor tyrosine kinase
US6645969B1 (en)	2003-11-11	Aryl and heteroaryl quinazoline compounds which inhibit CSF-1R receptor tyrosine kinase
JP5063351B2 (ja)	2012-10-31	ピラゾールキナーゼモジュレーターおよび使用方法
CA2582029C (en)	2011-12-06	Aryl nitrogen-containing bicyclic compounds and methods of use
TWI430798B (zh)	2014-03-21	猬狀途徑之抑制劑，其製備方法，包含彼等之組合物及其用途
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USRE37650E1 (en)	2002-04-09	Aryl and heteroaryl quinazoline compounds which inhibit CSF-1R receptor tyrosine kinase
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