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

Substituted hereroaryls as inhibitors of protein tyrosine phosphatases Download PDF

Info

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

Links

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
YFKJEAMPRZIWQW-UHFFFAOYSA-N 2-[(6-bromo-4-phenylquinazolin-2-yl)amino]-3-phenylpropanoic acid Chemical compound N=1C(C=2C=CC=CC=2)=C2C=C(Br)C=CC2=NC=1NC(C(=O)O)CC1=CC=CC=C1 YFKJEAMPRZIWQW-UHFFFAOYSA-N 0.000 claims 1
ODOVAKKLCXJGIL-UHFFFAOYSA-N 2-[4-(benzenesulfonyl)piperazin-1-yl]-6-chloro-4-phenylquinazoline Chemical compound C12=CC(Cl)=CC=C2N=C(N2CCN(CC2)S(=O)(=O)C=2C=CC=CC=2)N=C1C1=CC=CC=C1 ODOVAKKLCXJGIL-UHFFFAOYSA-N 0.000 claims 1
ZNOVKRKFMKPLMQ-UHFFFAOYSA-N 2-[[4-[(6-bromo-4-phenylquinazolin-2-yl)-(carboxymethyl)amino]phenyl]sulfonyl-methylamino]-3-phenylpropanoic acid Chemical compound C=1C=C(N(CC(O)=O)C=2N=C3C=CC(Br)=CC3=C(C=3C=CC=CC=3)N=2)C=CC=1S(=O)(=O)N(C)C(C(O)=O)CC1=CC=CC=C1 ZNOVKRKFMKPLMQ-UHFFFAOYSA-N 0.000 claims 1
PCSFTJMWGDYZCX-UHFFFAOYSA-N 2-[[4-[(6-bromo-4-phenylquinazolin-2-yl)amino]phenyl]sulfonyl-methylamino]-3-phenylpropanoic acid Chemical compound C=1C=C(NC=2N=C3C=CC(Br)=CC3=C(C=3C=CC=CC=3)N=2)C=CC=1S(=O)(=O)N(C)C(C(O)=O)CC1=CC=CC=C1 PCSFTJMWGDYZCX-UHFFFAOYSA-N 0.000 claims 1
KFCFNDFRDNJNOD-UHFFFAOYSA-N 3-[5-chloro-1-(6-chloro-4-phenylquinazolin-2-yl)indol-3-yl]-2,2-difluoro-3-oxopropanoic acid Chemical compound C12=CC=C(Cl)C=C2C(C(=O)C(F)(F)C(=O)O)=CN1C(N=C1C=CC(Cl)=CC1=1)=NC=1C1=CC=CC=C1 KFCFNDFRDNJNOD-UHFFFAOYSA-N 0.000 claims 1
CDLLINFZEFTHCI-UHFFFAOYSA-N 3-[5-chloro-1-(6-chloro-4-phenylquinazolin-2-yl)indol-3-yl]-3-hydroxypropanoic acid Chemical compound C12=CC=C(Cl)C=C2C(C(CC(O)=O)O)=CN1C(N=C1C=CC(Cl)=CC1=1)=NC=1C1=CC=CC=C1 CDLLINFZEFTHCI-UHFFFAOYSA-N 0.000 claims 1
CXPRWCCFOLFODJ-UHFFFAOYSA-N 3-[5-chloro-1-(6-chloro-4-phenylquinazolin-2-yl)indol-3-yl]-3-oxopropanoic acid Chemical compound C12=CC=C(Cl)C=C2C(C(=O)CC(=O)O)=CN1C(N=C1C=CC(Cl)=CC1=1)=NC=1C1=CC=CC=C1 CXPRWCCFOLFODJ-UHFFFAOYSA-N 0.000 claims 1
ORMVACRTRBVNSK-UHFFFAOYSA-N 3-[[5-chloro-1-(6-chloro-4-phenylquinazolin-2-yl)indole-3-carbonyl]amino]propanoic acid Chemical compound C12=CC=C(Cl)C=C2C(C(=O)NCCC(=O)O)=CN1C(N=C1C=CC(Cl)=CC1=1)=NC=1C1=CC=CC=C1 ORMVACRTRBVNSK-UHFFFAOYSA-N 0.000 claims 1
125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims 1
BTBITJAXKKTZJJ-UHFFFAOYSA-N 4-(6-chloro-4-phenylquinazolin-2-yl)-1,3-dihydroquinoxalin-2-one Chemical compound C12=CC(Cl)=CC=C2N=C(N2C3=CC=CC=C3NC(=O)C2)N=C1C1=CC=CC=C1 BTBITJAXKKTZJJ-UHFFFAOYSA-N 0.000 claims 1
YUSHPPZXHQYVGQ-UHFFFAOYSA-N 4-(n-(6-bromo-4-phenylquinazolin-2-yl)-4-sulfamoylanilino)butanoic acid Chemical compound C1=CC(S(=O)(=O)N)=CC=C1N(CCCC(O)=O)C1=NC(C=2C=CC=CC=2)=C(C=C(Br)C=C2)C2=N1 YUSHPPZXHQYVGQ-UHFFFAOYSA-N 0.000 claims 1
RCUGZMJAEQVKQH-UHFFFAOYSA-N 4-[(6-bromo-4-phenylquinazolin-2-yl)amino]-n-(2,6-dimethylphenyl)benzamide Chemical compound CC1=CC=CC(C)=C1NC(=O)C(C=C1)=CC=C1NC1=NC(C=2C=CC=CC=2)=C(C=C(Br)C=C2)C2=N1 RCUGZMJAEQVKQH-UHFFFAOYSA-N 0.000 claims 1
RHNBQPJVWMGUTD-UHFFFAOYSA-N 4-[(6-bromo-4-phenylquinazolin-2-yl)amino]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1NC1=NC(C=2C=CC=CC=2)=C(C=C(Br)C=C2)C2=N1 RHNBQPJVWMGUTD-UHFFFAOYSA-N 0.000 claims 1
IXIRNSYIJPNCQM-UHFFFAOYSA-N 4-[1-(6-chloro-4-phenylquinazolin-2-yl)-6-fluoroindol-3-yl]-4-oxobutanoic acid Chemical compound C12=CC(F)=CC=C2C(C(=O)CCC(=O)O)=CN1C(N=C1C=CC(Cl)=CC1=1)=NC=1C1=CC=CC=C1 IXIRNSYIJPNCQM-UHFFFAOYSA-N 0.000 claims 1
YDWXOACJXHDAFF-UHFFFAOYSA-N 4-[1-(6-chloro-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(Cl)=CC1=1)=NC=1C1=CC=CC=C1 YDWXOACJXHDAFF-UHFFFAOYSA-N 0.000 claims 1
RRSHQMVKXDOYDS-UHFFFAOYSA-N 4-[1-[4-(4-butylphenyl)-6-(furan-2-yl)quinazolin-2-yl]indol-3-yl]-4-oxobutanoic acid Chemical compound C1=CC(CCCC)=CC=C1C1=NC(N2C3=CC=CC=C3C(C(=O)CCC(O)=O)=C2)=NC2=CC=C(C=3OC=CC=3)C=C12 RRSHQMVKXDOYDS-UHFFFAOYSA-N 0.000 claims 1
WMLUHVYNKDTXHP-UHFFFAOYSA-N 4-[1-[4-(4-tert-butylanilino)-6-morpholin-4-yl-1,3,5-triazin-2-yl]-5-chloroindol-3-yl]-4-oxobutanoic acid Chemical compound C1=CC(C(C)(C)C)=CC=C1NC1=NC(N2CCOCC2)=NC(N2C3=CC=C(Cl)C=C3C(C(=O)CCC(O)=O)=C2)=N1 WMLUHVYNKDTXHP-UHFFFAOYSA-N 0.000 claims 1
BXLOOUYSJKXNHD-UHFFFAOYSA-N 4-[1-[6-bromo-4-(2-fluorophenyl)quinazolin-2-yl]indol-3-yl]-4-oxobutanoic acid Chemical compound C12=CC=CC=C2C(C(=O)CCC(=O)O)=CN1C(N=C1C=CC(Br)=CC1=1)=NC=1C1=CC=CC=C1F BXLOOUYSJKXNHD-UHFFFAOYSA-N 0.000 claims 1
FFEWGQFONGQPBA-UHFFFAOYSA-N 4-[5-bromo-1-[4-(4-butylphenyl)-6-(furan-2-yl)quinazolin-2-yl]indol-3-yl]-4-oxobutanoic acid Chemical compound C1=CC(CCCC)=CC=C1C1=NC(N2C3=CC=C(Br)C=C3C(C(=O)CCC(O)=O)=C2)=NC2=CC=C(C=3OC=CC=3)C=C12 FFEWGQFONGQPBA-UHFFFAOYSA-N 0.000 claims 1
MHVZMCQLJWKLLE-UHFFFAOYSA-N 4-[5-bromo-1-[6-(furan-2-yl)-4-(furan-2-ylmethylamino)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=1NCC1=CC=CO1 MHVZMCQLJWKLLE-UHFFFAOYSA-N 0.000 claims 1
FQFIABWTCOUMBA-UHFFFAOYSA-N 4-[5-bromo-1-[6-(furan-2-yl)-4-[4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-yl]quinazolin-2-yl]indol-3-yl]-4-oxobutanoic acid Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=NC(N2C3=CC=C(Br)C=C3C(C(=O)CCC(O)=O)=C2)=NC2=CC=C(C=3OC=CC=3)C=C12 FQFIABWTCOUMBA-UHFFFAOYSA-N 0.000 claims 1
RINDSEWUNOCEBT-UHFFFAOYSA-N 4-[5-chloro-1-(6-chloro-4-phenylquinazolin-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(Cl)=CC1=1)=NC=1C1=CC=CC=C1 RINDSEWUNOCEBT-UHFFFAOYSA-N 0.000 claims 1
BBOXWUNPHIGXLF-UHFFFAOYSA-N 4-[5-chloro-1-(6-chloro-4-phenylquinazolin-2-yl)indol-3-yl]-n-hydroxy-4-oxobutanamide Chemical compound C12=CC=C(Cl)C=C2C(C(=O)CCC(=O)NO)=CN1C(N=C1C=CC(Cl)=CC1=1)=NC=1C1=CC=CC=C1 BBOXWUNPHIGXLF-UHFFFAOYSA-N 0.000 claims 1
FGLHGJGPZZGDHE-UHFFFAOYSA-N 4-[5-chloro-1-[(4-dibenzofuran-4-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=3OC4=CC=CC=C4C=3C=CC=2)C=C1 FGLHGJGPZZGDHE-UHFFFAOYSA-N 0.000 claims 1
WDYQHJHCQSBLKF-UHFFFAOYSA-N 4-[5-chloro-1-[2-(4-ethoxycarbonylpiperidin-1-yl)-7-(furan-2-yl)quinazolin-4-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)=C(C=CC(=C2)C=3OC=CC=3)C2=N1 WDYQHJHCQSBLKF-UHFFFAOYSA-N 0.000 claims 1
FVELWJCCDHZCPQ-UHFFFAOYSA-N 4-[5-chloro-1-[4-(3-methoxyphenyl)-6-phenylpyrimidin-2-yl]indol-3-yl]-4-oxobutanoic acid Chemical compound COC1=CC=CC(C=2N=C(N=C(C=2)C=2C=CC=CC=2)N2C3=CC=C(Cl)C=C3C(C(=O)CCC(O)=O)=C2)=C1 FVELWJCCDHZCPQ-UHFFFAOYSA-N 0.000 claims 1
RHVPRKYHTUXJAF-UHFFFAOYSA-N 4-[5-cyano-1-(4,6-diphenylpyrimidin-2-yl)indol-3-yl]-4-oxobutanoic acid Chemical compound C12=CC=C(C#N)C=C2C(C(=O)CCC(=O)O)=CN1C(N=1)=NC(C=2C=CC=CC=2)=CC=1C1=CC=CC=C1 RHVPRKYHTUXJAF-UHFFFAOYSA-N 0.000 claims 1
FMRIPRATVYGVFX-UHFFFAOYSA-N 4-[6-chloro-1-(6-chloro-4-phenylquinazolin-2-yl)indol-3-yl]-4-oxobutanoic acid Chemical compound C12=CC(Cl)=CC=C2C(C(=O)CCC(=O)O)=CN1C(N=C1C=CC(Cl)=CC1=1)=NC=1C1=CC=CC=C1 FMRIPRATVYGVFX-UHFFFAOYSA-N 0.000 claims 1
CCJFZOLVFVOZPJ-UHFFFAOYSA-N 4-[[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 CCJFZOLVFVOZPJ-UHFFFAOYSA-N 0.000 claims 1
JVNWZAPGVAKZGP-UHFFFAOYSA-N 4-[[4-(4-tert-butylphenyl)quinazolin-2-yl]amino]benzenesulfonamide Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=NC(NC=2C=CC(=CC=2)S(N)(=O)=O)=NC2=CC=CC=C12 JVNWZAPGVAKZGP-UHFFFAOYSA-N 0.000 claims 1
229940006015 4-hydroxybutyric acid Drugs 0.000 claims 1
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 1
CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 claims 1
MPQPHESJYBIQPM-UHFFFAOYSA-N 6-bromo-2-chloro-4-(4-phenylmethoxyphenyl)quinazoline Chemical compound C=12C=C(Br)C=CC2=NC(Cl)=NC=1C(C=C1)=CC=C1OCC1=CC=CC=C1 MPQPHESJYBIQPM-UHFFFAOYSA-N 0.000 claims 1
DFMQOMKAZHAEMR-UHFFFAOYSA-N 6-bromo-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(Br)C=C2)C2=N1 DFMQOMKAZHAEMR-UHFFFAOYSA-N 0.000 claims 1
BCMXUWAWOUUFPC-UHFFFAOYSA-N 6-chloro-2-(3,4-dihydro-2h-quinolin-1-yl)-4-(4-ethylphenyl)quinazoline Chemical compound C1=CC(CC)=CC=C1C1=NC(N2C3=CC=CC=C3CCC2)=NC2=CC=C(Cl)C=C12 BCMXUWAWOUUFPC-UHFFFAOYSA-N 0.000 claims 1
JEMRYPJHPWTMQK-UHFFFAOYSA-N 6-chloro-2-[4-(4-nitrophenyl)piperazin-1-yl]-4-phenylquinazoline Chemical compound C1=CC([N+](=O)[O-])=CC=C1N1CCN(C=2N=C3C=CC(Cl)=CC3=C(C=3C=CC=CC=3)N=2)CC1 JEMRYPJHPWTMQK-UHFFFAOYSA-N 0.000 claims 1
BVPSNHKYAUJDPO-UHFFFAOYSA-N 6-chloro-4-(4-ethylphenyl)-n-(4-nitrophenyl)quinazolin-2-amine Chemical compound C1=CC(CC)=CC=C1C1=NC(NC=2C=CC(=CC=2)[N+]([O-])=O)=NC2=CC=C(Cl)C=C12 BVPSNHKYAUJDPO-UHFFFAOYSA-N 0.000 claims 1
NKIXFKRPGDKGMN-UHFFFAOYSA-N 6-chloro-n-(1,1-dioxo-1-benzothiophen-6-yl)-4-phenylquinazolin-2-amine Chemical compound C12=CC(Cl)=CC=C2N=C(NC=2C=C3S(=O)(=O)C=CC3=CC=2)N=C1C1=CC=CC=C1 NKIXFKRPGDKGMN-UHFFFAOYSA-N 0.000 claims 1
QFLKTWXUHMCZDL-UHFFFAOYSA-N 6-chloro-n-(2-nitrophenyl)-4-phenylquinazolin-2-amine Chemical compound [O-][N+](=O)C1=CC=CC=C1NC1=NC(C=2C=CC=CC=2)=C(C=C(Cl)C=C2)C2=N1 QFLKTWXUHMCZDL-UHFFFAOYSA-N 0.000 claims 1
UIUJIQZEACWQSV-UHFFFAOYSA-N succinic semialdehyde Chemical compound OC(=O)CCC=O UIUJIQZEACWQSV-UHFFFAOYSA-N 0.000 claims 1
HVHYGTZOUOSZSB-UHFFFAOYSA-N tert-butyl 4-(6-bromo-4-phenylquinazolin-2-yl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=NC(C=2C=CC=CC=2)=C(C=C(Br)C=C2)C2=N1 HVHYGTZOUOSZSB-UHFFFAOYSA-N 0.000 claims 1
102100033001 Tyrosine-protein phosphatase non-receptor type 1 Human genes 0.000 abstract description 20
108010015847 Non-Receptor Type 1 Protein Tyrosine Phosphatase Proteins 0.000 abstract description 19
208000001072 type 2 diabetes mellitus Diseases 0.000 abstract description 12
206010022489 Insulin Resistance Diseases 0.000 abstract description 8
206010028980 Neoplasm Diseases 0.000 abstract description 7
102100028516 Receptor-type tyrosine-protein phosphatase U Human genes 0.000 abstract description 7
201000011510 cancer Diseases 0.000 abstract description 7
102000016267 Leptin Human genes 0.000 abstract description 6
108010092277 Leptin Proteins 0.000 abstract description 6
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 6
NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 abstract description 6
229940039781 leptin Drugs 0.000 abstract description 6
201000010099 disease Diseases 0.000 abstract description 5
230000004770 neurodegeneration Effects 0.000 abstract description 3
208000015122 neurodegenerative disease Diseases 0.000 abstract description 3
201000001421 hyperglycemia Diseases 0.000 abstract description 2
230000001404 mediated effect Effects 0.000 abstract description 2
208000030159 metabolic disease Diseases 0.000 abstract description 2
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 132
239000007787 solid Substances 0.000 description 77
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 57
238000005481 NMR spectroscopy Methods 0.000 description 57
239000000203 mixture Substances 0.000 description 56
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 52
238000002360 preparation method Methods 0.000 description 50
235000019439 ethyl acetate Nutrition 0.000 description 37
239000000243 solution Substances 0.000 description 34
BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 28
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
235000002639 sodium chloride Nutrition 0.000 description 25
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
ZKUHYVOLOVYURV-UHFFFAOYSA-N methyl 4-(5-bromo-1h-indol-3-yl)-4-oxobutanoate Chemical compound C1=C(Br)C=C2C(C(=O)CCC(=O)OC)=CNC2=C1 ZKUHYVOLOVYURV-UHFFFAOYSA-N 0.000 description 22
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 21
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 18
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 17
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
239000000047 product Substances 0.000 description 16
239000004480 active ingredient Substances 0.000 description 15
238000009472 formulation Methods 0.000 description 15
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 14
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
238000003756 stirring Methods 0.000 description 12
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 11
102000003746 Insulin Receptor Human genes 0.000 description 10
108010001127 Insulin Receptor Proteins 0.000 description 10
239000003921 oil Substances 0.000 description 10
235000019198 oils Nutrition 0.000 description 10
239000011734 sodium Substances 0.000 description 10
DIBYEJGJCKYISG-UHFFFAOYSA-N 2,4-dichloro-6-(furan-2-yl)quinazoline Chemical compound C1=CC2=NC(Cl)=NC(Cl)=C2C=C1C1=CC=CO1 DIBYEJGJCKYISG-UHFFFAOYSA-N 0.000 description 9
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
239000003814 drug Substances 0.000 description 9
238000003818 flash chromatography Methods 0.000 description 9
239000000725 suspension Substances 0.000 description 9
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 8
239000002253 acid Substances 0.000 description 8
RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical class NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 8
238000005859 coupling reaction Methods 0.000 description 8
229910052763 palladium Inorganic materials 0.000 description 8
HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 8
ZQJYTTPJYLKTTI-UHFFFAOYSA-M zinc;2h-pyridin-2-ide;bromide Chemical compound Br[Zn+].C1=CC=N[C-]=C1 ZQJYTTPJYLKTTI-UHFFFAOYSA-M 0.000 description 8
MAOBFOXLCJIFLV-UHFFFAOYSA-N (2-aminophenyl)-phenylmethanone Chemical class NC1=CC=CC=C1C(=O)C1=CC=CC=C1 MAOBFOXLCJIFLV-UHFFFAOYSA-N 0.000 description 7
102000004877 Insulin Human genes 0.000 description 7
108090001061 Insulin Proteins 0.000 description 7
239000011575 calcium Substances 0.000 description 7
238000006243 chemical reaction Methods 0.000 description 7
239000003995 emulsifying agent Substances 0.000 description 7
150000002148 esters Chemical class 0.000 description 7
RUJPPJYDHHAEEK-UHFFFAOYSA-N ethyl piperidine-4-carboxylate Chemical compound CCOC(=O)C1CCNCC1 RUJPPJYDHHAEEK-UHFFFAOYSA-N 0.000 description 7
229940125396 insulin Drugs 0.000 description 7
OATYCBHROMXWJO-UHFFFAOYSA-N 2-amino-5-bromobenzonitrile Chemical compound NC1=CC=C(Br)C=C1C#N OATYCBHROMXWJO-UHFFFAOYSA-N 0.000 description 6
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 6
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-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
239000003153 chemical reaction reagent Substances 0.000 description 6
239000007859 condensation product Substances 0.000 description 6
230000008878 coupling Effects 0.000 description 6
238000010168 coupling process Methods 0.000 description 6
235000014113 dietary fatty acids Nutrition 0.000 description 6
239000000839 emulsion Substances 0.000 description 6
229930195729 fatty acid Natural products 0.000 description 6
239000000194 fatty acid Substances 0.000 description 6
150000004665 fatty acids Chemical class 0.000 description 6
239000000796 flavoring agent Substances 0.000 description 6
239000000463 material Substances 0.000 description 6
239000012044 organic layer Substances 0.000 description 6
239000011780 sodium chloride Substances 0.000 description 6
239000000758 substrate Substances 0.000 description 6
239000003765 sweetening agent Substances 0.000 description 6
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
WMPTYRGXBUYONY-UHFFFAOYSA-N 2-chloroquinazoline Chemical compound C1=CC=CC2=NC(Cl)=NC=C21 WMPTYRGXBUYONY-UHFFFAOYSA-N 0.000 description 5
JZDVFUAHGLJVQG-UHFFFAOYSA-N 6-bromo-1h-quinazoline-2,4-dione Chemical compound N1C(=O)NC(=O)C2=CC(Br)=CC=C21 JZDVFUAHGLJVQG-UHFFFAOYSA-N 0.000 description 5
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 5
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 5
239000006071 cream Substances 0.000 description 5
239000013058 crude material Substances 0.000 description 5
239000003085 diluting agent Substances 0.000 description 5
USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 5
229940079593 drug Drugs 0.000 description 5
230000000694 effects Effects 0.000 description 5
DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 5
239000003925 fat Substances 0.000 description 5
235000019197 fats Nutrition 0.000 description 5
235000003599 food sweetener Nutrition 0.000 description 5
239000000543 intermediate Substances 0.000 description 5
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 5
239000003755 preservative agent Substances 0.000 description 5
238000000746 purification Methods 0.000 description 5
239000003826 tablet Substances 0.000 description 5
239000003981 vehicle Substances 0.000 description 5
PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 4
PLSFBSVTQIUQIM-UHFFFAOYSA-N 6-(furan-2-yl)-1h-quinazoline-2,4-dione Chemical compound C1=C2C(=O)NC(=O)NC2=CC=C1C1=CC=CO1 PLSFBSVTQIUQIM-UHFFFAOYSA-N 0.000 description 4
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
102000004190 Enzymes Human genes 0.000 description 4
108090000790 Enzymes Proteins 0.000 description 4
IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
241001465754 Metazoa Species 0.000 description 4
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
239000004809 Teflon Substances 0.000 description 4
229920006362 Teflon® Polymers 0.000 description 4
206010067584 Type 1 diabetes mellitus Diseases 0.000 description 4
239000013543 active substance Substances 0.000 description 4
239000007900 aqueous suspension Substances 0.000 description 4
239000003086 colorant Substances 0.000 description 4
239000002270 dispersing agent Substances 0.000 description 4
239000003937 drug carrier Substances 0.000 description 4
235000019441 ethanol Nutrition 0.000 description 4
235000013355 food flavoring agent Nutrition 0.000 description 4
239000011521 glass Substances 0.000 description 4
208000031169 hemorrhagic disease Diseases 0.000 description 4
230000002401 inhibitory effect Effects 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
238000004519 manufacturing process Methods 0.000 description 4
230000004048 modification Effects 0.000 description 4
238000012986 modification Methods 0.000 description 4
231100000252 nontoxic Toxicity 0.000 description 4
230000003000 nontoxic effect Effects 0.000 description 4
229910052760 oxygen Inorganic materials 0.000 description 4
239000012071 phase Substances 0.000 description 4
239000000843 powder Substances 0.000 description 4
239000000375 suspending agent Substances 0.000 description 4
LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
239000000080 wetting agent Substances 0.000 description 4
DQNACBBVZVXMGZ-UHFFFAOYSA-N (2-amino-5-bromophenyl)-(4-butylphenyl)methanone Chemical compound C1=CC(CCCC)=CC=C1C(=O)C1=CC(Br)=CC=C1N DQNACBBVZVXMGZ-UHFFFAOYSA-N 0.000 description 3
IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 description 3
GIRZVOLAMBXCAO-UHFFFAOYSA-N 2-[[6-bromo-4-(4-butylphenyl)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(Br)C=C12 GIRZVOLAMBXCAO-UHFFFAOYSA-N 0.000 description 3
ZLCIALUBLCAXPL-UHFFFAOYSA-N 2-amino-5-(trifluoromethyl)benzonitrile Chemical compound NC1=CC=C(C(F)(F)F)C=C1C#N ZLCIALUBLCAXPL-UHFFFAOYSA-N 0.000 description 3
MGCGMYPNXAFGFA-UHFFFAOYSA-N 2-amino-5-nitrobenzonitrile Chemical compound NC1=CC=C([N+]([O-])=O)C=C1C#N MGCGMYPNXAFGFA-UHFFFAOYSA-N 0.000 description 3
ZCLSECNUJOLWPR-UHFFFAOYSA-N 2-chloro-6-(furan-2-yl)-4-pyridin-2-ylquinazoline Chemical compound C=12C=C(C=3OC=CC=3)C=CC2=NC(Cl)=NC=1C1=CC=CC=N1 ZCLSECNUJOLWPR-UHFFFAOYSA-N 0.000 description 3
XZEFCXYDALFADU-UHFFFAOYSA-N 2-trimethylsilylethyl 4-[5-chloro-1-[6-(furan-2-yl)-4-pyridin-2-ylquinazolin-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=C1C=CC(=CC1=1)C=2OC=CC=2)=NC=1C1=CC=CC=N1 XZEFCXYDALFADU-UHFFFAOYSA-N 0.000 description 3
125000004080 3-carboxypropanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C(O[H])=O 0.000 description 3
MPQFKGNFXASODT-UHFFFAOYSA-N 4-[1-(4-anilino-6-phenylpyrimidin-2-yl)-5-chloroindol-3-yl]-4-oxobutanoic acid Chemical compound C12=CC=C(Cl)C=C2C(C(=O)CCC(=O)O)=CN1C(N=C(C=1)C=2C=CC=CC=2)=NC=1NC1=CC=CC=C1 MPQFKGNFXASODT-UHFFFAOYSA-N 0.000 description 3
RGTRNYPIJDRLIC-UHFFFAOYSA-N 4-[5-chloro-1-[4-(4-ethoxycarbonylpiperidin-1-yl)-6-(2-oxopyrrolidin-1-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(N3C(CCC3)=O)C=C12 RGTRNYPIJDRLIC-UHFFFAOYSA-N 0.000 description 3
AIGSTAWQGQXHAI-UHFFFAOYSA-N 4-[5-chloro-1-[4-(furan-2-ylmethylamino)-6,7-dimethoxyquinazolin-2-yl]indol-3-yl]-4-oxobutanoic acid Chemical compound C=12C=C(OC)C(OC)=CC2=NC(N2C3=CC=C(Cl)C=C3C(C(=O)CCC(O)=O)=C2)=NC=1NCC1=CC=CO1 AIGSTAWQGQXHAI-UHFFFAOYSA-N 0.000 description 3
HHEDKZUQAHRTNP-UHFFFAOYSA-N 6-bromo-4-(4-butylphenyl)-2-chloroquinazoline Chemical compound C1=CC(CCCC)=CC=C1C1=NC(Cl)=NC2=CC=C(Br)C=C12 HHEDKZUQAHRTNP-UHFFFAOYSA-N 0.000 description 3
208000024172 Cardiovascular disease Diseases 0.000 description 3
229920000084 Gum arabic Polymers 0.000 description 3
108010015832 Non-Receptor Type 2 Protein Tyrosine Phosphatase Proteins 0.000 description 3
208000008589 Obesity Diseases 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
229930006000 Sucrose Natural products 0.000 description 3
235000010489 acacia gum Nutrition 0.000 description 3
239000004202 carbamide Substances 0.000 description 3
238000001816 cooling Methods 0.000 description 3
239000003651 drinking water Substances 0.000 description 3
235000020188 drinking water Nutrition 0.000 description 3
125000004494 ethyl ester group Chemical group 0.000 description 3
PZJSZBJLOWMDRG-UHFFFAOYSA-N furan-2-ylboronic acid Chemical compound OB(O)C1=CC=CO1 PZJSZBJLOWMDRG-UHFFFAOYSA-N 0.000 description 3
239000008187 granular material Substances 0.000 description 3
239000001257 hydrogen Substances 0.000 description 3
208000026278 immune system disease Diseases 0.000 description 3
239000007788 liquid Substances 0.000 description 3
229940057995 liquid paraffin Drugs 0.000 description 3
GMDVPPVFTDVJOF-UHFFFAOYSA-M magnesium;butylbenzene;bromide Chemical compound [Mg+2].[Br-].CCCCC1=CC=[C-]C=C1 GMDVPPVFTDVJOF-UHFFFAOYSA-M 0.000 description 3
239000012528 membrane Substances 0.000 description 3
MDOZKZXLGXCFQP-UHFFFAOYSA-N methyl 4-[5-bromo-1-[6-(furan-2-yl)-4-pyridin-2-ylquinazolin-2-yl]indol-3-yl]-4-oxobutanoate Chemical compound C12=CC=C(Br)C=C2C(C(=O)CCC(=O)OC)=CN1C(N=C1C=CC(=CC1=1)C=2OC=CC=2)=NC=1C1=CC=CC=N1 MDOZKZXLGXCFQP-UHFFFAOYSA-N 0.000 description 3
239000002480 mineral oil Substances 0.000 description 3
235000020824 obesity Nutrition 0.000 description 3
RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 3
229920001223 polyethylene glycol Polymers 0.000 description 3
102000004169 proteins and genes Human genes 0.000 description 3
108090000623 proteins and genes Proteins 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
102000005962 receptors Human genes 0.000 description 3
108020003175 receptors Proteins 0.000 description 3
230000009467 reduction Effects 0.000 description 3
238000010992 reflux Methods 0.000 description 3
229910052938 sodium sulfate Inorganic materials 0.000 description 3
235000011152 sodium sulphate Nutrition 0.000 description 3
239000003381 stabilizer Substances 0.000 description 3
239000005720 sucrose Substances 0.000 description 3
208000011580 syndromic disease Diseases 0.000 description 3
229910052723 transition metal Inorganic materials 0.000 description 3
150000003624 transition metals Chemical class 0.000 description 3
ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 2
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
238000005160 1H NMR spectroscopy Methods 0.000 description 2
SDQJTWBNWQABLE-UHFFFAOYSA-N 1h-quinazoline-2,4-dione Chemical compound C1=CC=C2C(=O)NC(=O)NC2=C1 SDQJTWBNWQABLE-UHFFFAOYSA-N 0.000 description 2
DPVIABCMTHHTGB-UHFFFAOYSA-N 2,4,6-trichloropyrimidine Chemical compound ClC1=CC(Cl)=NC(Cl)=N1 DPVIABCMTHHTGB-UHFFFAOYSA-N 0.000 description 2
DGHKCBSVAZXEPP-UHFFFAOYSA-N 2,4-dichloro-6,7-dimethoxyquinazoline Chemical compound ClC1=NC(Cl)=C2C=C(OC)C(OC)=CC2=N1 DGHKCBSVAZXEPP-UHFFFAOYSA-N 0.000 description 2
FLNFBCBVUGRDIZ-UHFFFAOYSA-N 2-chloro-6-(furan-2-yl)-n-(4-methoxyphenyl)quinazolin-4-amine Chemical compound C1=CC(OC)=CC=C1NC1=NC(Cl)=NC2=CC=C(C=3OC=CC=3)C=C12 FLNFBCBVUGRDIZ-UHFFFAOYSA-N 0.000 description 2
IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
TYEYBOSBBBHJIV-UHFFFAOYSA-N 2-oxobutanoic acid Chemical compound CCC(=O)C(O)=O TYEYBOSBBBHJIV-UHFFFAOYSA-N 0.000 description 2
XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 2
BMEYONHIJOENOQ-UHFFFAOYSA-N 4-[1-(6-amino-4-morpholin-4-ylquinazolin-2-yl)-5-chloroindol-3-yl]-4-oxobutanoic acid Chemical compound C12=CC(N)=CC=C2N=C(N2C3=CC=C(Cl)C=C3C(C(=O)CCC(O)=O)=C2)N=C1N1CCOCC1 BMEYONHIJOENOQ-UHFFFAOYSA-N 0.000 description 2
QRNIEADTXKWBRD-UHFFFAOYSA-N 4-[1-[4-(1-carboxypropylamino)-6-(furan-2-yl)quinazolin-2-yl]-5-chloroindol-3-yl]-4-oxobutanoic acid Chemical compound C1=C2C(NC(CC)C(O)=O)=NC(N3C4=CC=C(Cl)C=C4C(C(=O)CCC(O)=O)=C3)=NC2=CC=C1C1=CC=CO1 QRNIEADTXKWBRD-UHFFFAOYSA-N 0.000 description 2
YZCAIQOXVWWOSZ-UHFFFAOYSA-N 4-[5-chloro-1-[4-(4-ethoxycarbonylpiperidin-1-yl)-6-nitroquinazolin-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([N+]([O-])=O)C=C12 YZCAIQOXVWWOSZ-UHFFFAOYSA-N 0.000 description 2
JVVRCYWZTJLJSG-UHFFFAOYSA-N 4-dimethylaminophenol Chemical compound CN(C)C1=CC=C(O)C=C1 JVVRCYWZTJLJSG-UHFFFAOYSA-N 0.000 description 2
229960000549 4-dimethylaminophenol Drugs 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
JCRULBKTDUOWMP-UHFFFAOYSA-N 6-bromo-2-methyl-3,1-benzoxazin-4-one Chemical compound C1=C(Br)C=C2C(=O)OC(C)=NC2=C1 JCRULBKTDUOWMP-UHFFFAOYSA-N 0.000 description 2
244000215068 Acacia senegal Species 0.000 description 2
235000006491 Acacia senegal Nutrition 0.000 description 2
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
241000416162 Astragalus gummifer Species 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
108010010803 Gelatin Proteins 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
102000005720 Glutathione transferase Human genes 0.000 description 2
108010070675 Glutathione transferase Proteins 0.000 description 2
101001087394 Homo sapiens Tyrosine-protein phosphatase non-receptor type 1 Proteins 0.000 description 2
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
235000019483 Peanut oil Nutrition 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
235000021355 Stearic acid Nutrition 0.000 description 2
229920001615 Tragacanth Polymers 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
102100033141 Tyrosine-protein phosphatase non-receptor type 2 Human genes 0.000 description 2
238000010521 absorption reaction Methods 0.000 description 2
NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
230000004913 activation Effects 0.000 description 2
239000000853 adhesive Substances 0.000 description 2
230000001070 adhesive effect Effects 0.000 description 2
125000005907 alkyl ester group Chemical group 0.000 description 2
150000008064 anhydrides Chemical class 0.000 description 2
150000004982 aromatic amines Chemical class 0.000 description 2
239000012298 atmosphere Substances 0.000 description 2
230000035578 autophosphorylation Effects 0.000 description 2
230000009286 beneficial effect Effects 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
230000037396 body weight Effects 0.000 description 2
235000019437 butane-1,3-diol Nutrition 0.000 description 2
229910000019 calcium carbonate Inorganic materials 0.000 description 2
235000010216 calcium carbonate Nutrition 0.000 description 2
239000001506 calcium phosphate Substances 0.000 description 2
229910000389 calcium phosphate Inorganic materials 0.000 description 2
235000011010 calcium phosphates Nutrition 0.000 description 2
239000001569 carbon dioxide Substances 0.000 description 2
229910002092 carbon dioxide Inorganic materials 0.000 description 2
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
238000006555 catalytic reaction Methods 0.000 description 2
229920002678 cellulose Polymers 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
WBLIXGSTEMXDSM-UHFFFAOYSA-N chloromethane Chemical compound Cl[CH2] WBLIXGSTEMXDSM-UHFFFAOYSA-N 0.000 description 2
230000001276 controlling effect Effects 0.000 description 2
125000004122 cyclic group Chemical group 0.000 description 2
235000005911 diet Nutrition 0.000 description 2
230000037213 diet Effects 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
238000006073 displacement reaction Methods 0.000 description 2
238000004821 distillation Methods 0.000 description 2
238000001035 drying Methods 0.000 description 2
239000012467 final product Substances 0.000 description 2
230000037406 food intake Effects 0.000 description 2
235000012631 food intake Nutrition 0.000 description 2
DDRPCXLAQZKBJP-UHFFFAOYSA-N furfurylamine Chemical compound NCC1=CC=CO1 DDRPCXLAQZKBJP-UHFFFAOYSA-N 0.000 description 2
108020001507 fusion proteins Proteins 0.000 description 2
102000037865 fusion proteins Human genes 0.000 description 2
239000008273 gelatin Substances 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
239000007903 gelatin capsule Substances 0.000 description 2
235000019322 gelatine Nutrition 0.000 description 2
235000011852 gelatine desserts Nutrition 0.000 description 2
239000008103 glucose Substances 0.000 description 2
235000011187 glycerol Nutrition 0.000 description 2
125000005842 heteroatom Chemical group 0.000 description 2
BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
FBPFZTCFMRRESA-UHFFFAOYSA-N hexane-1,2,3,4,5,6-hexol Chemical compound OCC(O)C(O)C(O)C(O)CO FBPFZTCFMRRESA-UHFFFAOYSA-N 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 description 2
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
230000003834 intracellular effect Effects 0.000 description 2
239000008101 lactose Substances 0.000 description 2
239000000787 lecithin Substances 0.000 description 2
235000010445 lecithin Nutrition 0.000 description 2
229940067606 lecithin Drugs 0.000 description 2
AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
239000007937 lozenge Substances 0.000 description 2
235000019359 magnesium stearate Nutrition 0.000 description 2
KZRAAPTWXAMZHQ-UHFFFAOYSA-N methoxymethanamine Chemical group COCN KZRAAPTWXAMZHQ-UHFFFAOYSA-N 0.000 description 2
ZZWPOYPWQTUZDY-UHFFFAOYSA-N methyl 2-aminobutanoate Chemical compound CCC(N)C(=O)OC ZZWPOYPWQTUZDY-UHFFFAOYSA-N 0.000 description 2
DWAIOVAHORFQQZ-UHFFFAOYSA-N methyl 4-(1h-indol-3-yl)-4-oxobutanoate Chemical compound C1=CC=C2C(C(=O)CCC(=O)OC)=CNC2=C1 DWAIOVAHORFQQZ-UHFFFAOYSA-N 0.000 description 2
IIQQSKLUIOOFCH-UHFFFAOYSA-N methyl 4-(5-chloro-1h-indol-3-yl)-4-oxobutanoate Chemical compound C1=C(Cl)C=C2C(C(=O)CCC(=O)OC)=CNC2=C1 IIQQSKLUIOOFCH-UHFFFAOYSA-N 0.000 description 2
229920000609 methyl cellulose Polymers 0.000 description 2
239000001923 methylcellulose Substances 0.000 description 2
239000003094 microcapsule Substances 0.000 description 2
235000010446 mineral oil Nutrition 0.000 description 2
239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
150000005181 nitrobenzenes Chemical class 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
239000000346 nonvolatile oil Substances 0.000 description 2
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
239000002674 ointment Substances 0.000 description 2
239000003883 ointment base Substances 0.000 description 2
239000012188 paraffin wax Substances 0.000 description 2
239000000312 peanut oil Substances 0.000 description 2
SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 2
ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 2
HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 2
XBXHCBLBYQEYTI-UHFFFAOYSA-N piperidin-4-ylmethanol Chemical compound OCC1CCNCC1 XBXHCBLBYQEYTI-UHFFFAOYSA-N 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
239000001267 polyvinylpyrrolidone Substances 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
229910000160 potassium phosphate Inorganic materials 0.000 description 2
235000011009 potassium phosphates Nutrition 0.000 description 2
230000008569 process Effects 0.000 description 2
235000013772 propylene glycol Nutrition 0.000 description 2
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
CZAAKPFIWJXPQT-UHFFFAOYSA-N quinazolin-2-amine Chemical compound C1=CC=CC2=NC(N)=NC=C21 CZAAKPFIWJXPQT-UHFFFAOYSA-N 0.000 description 2
125000004546 quinazolin-4-yl group Chemical group N1=CN=C(C2=CC=CC=C12)* 0.000 description 2
230000001105 regulatory effect Effects 0.000 description 2
239000008159 sesame oil Substances 0.000 description 2
235000011803 sesame oil Nutrition 0.000 description 2
230000019491 signal transduction Effects 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
235000010413 sodium alginate Nutrition 0.000 description 2
239000000661 sodium alginate Substances 0.000 description 2
229940005550 sodium alginate Drugs 0.000 description 2
239000001593 sorbitan monooleate Substances 0.000 description 2
235000011069 sorbitan monooleate Nutrition 0.000 description 2
229940035049 sorbitan monooleate Drugs 0.000 description 2
239000000600 sorbitol Substances 0.000 description 2
235000010356 sorbitol Nutrition 0.000 description 2
239000007921 spray Substances 0.000 description 2
239000008107 starch Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
239000008117 stearic acid Substances 0.000 description 2
239000000829 suppository Substances 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
239000000454 talc Substances 0.000 description 2
229910052623 talc Inorganic materials 0.000 description 2
FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 2
HLZKNKRTKFSKGZ-UHFFFAOYSA-N tetradecan-1-ol Chemical compound CCCCCCCCCCCCCCO HLZKNKRTKFSKGZ-UHFFFAOYSA-N 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
239000011135 tin Substances 0.000 description 2
210000001519 tissue Anatomy 0.000 description 2
238000011200 topical administration Methods 0.000 description 2
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
229940086542 triethylamine Drugs 0.000 description 2
235000015112 vegetable and seed oil Nutrition 0.000 description 2
239000008158 vegetable oil Substances 0.000 description 2
CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 2
IIFVWLUQBAIPMJ-UHFFFAOYSA-N (4-fluorophenyl)methanamine Chemical compound NCC1=CC=C(F)C=C1 IIFVWLUQBAIPMJ-UHFFFAOYSA-N 0.000 description 1
WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
QMMJWQMCMRUYTG-UHFFFAOYSA-N 1,2,4,5-tetrachloro-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=C(Cl)C(Cl)=CC(Cl)=C1Cl QMMJWQMCMRUYTG-UHFFFAOYSA-N 0.000 description 1
AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 1
MFMMQMQMBGYCIL-UHFFFAOYSA-N 1-(2-bromo-4-butylphenyl)quinazolin-2-one Chemical compound BrC1=CC(CCCC)=CC=C1N1C(=O)N=CC2=CC=CC=C21 MFMMQMQMBGYCIL-UHFFFAOYSA-N 0.000 description 1
LGEZTMRIZWCDLW-UHFFFAOYSA-N 14-methylpentadecyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCC(C)C LGEZTMRIZWCDLW-UHFFFAOYSA-N 0.000 description 1
AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical compound C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 description 1
TUQSVSYUEBNNKQ-UHFFFAOYSA-N 2,4-dichloroquinazoline Chemical compound C1=CC=CC2=NC(Cl)=NC(Cl)=C21 TUQSVSYUEBNNKQ-UHFFFAOYSA-N 0.000 description 1
SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
NIXRNOMOGUPDOR-UHFFFAOYSA-N 2-[[5-chloro-1-(6-chloro-4-phenylquinazolin-2-yl)indole-3-carbonyl]amino]acetic acid Chemical compound C12=CC=C(Cl)C=C2C(C(=O)NCC(=O)O)=CN1C(N=C1C=CC(Cl)=CC1=1)=NC=1C1=CC=CC=C1 NIXRNOMOGUPDOR-UHFFFAOYSA-N 0.000 description 1
JVIVLOMOMIXJPB-UHFFFAOYSA-N 2-[[6-(furan-2-yl)-4-phenylquinazolin-2-yl]amino]benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1NC1=NC(C=2C=CC=CC=2)=C(C=C(C=C2)C=3OC=CC=3)C2=N1 JVIVLOMOMIXJPB-UHFFFAOYSA-N 0.000 description 1
GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
CUKXRHLWPSBCTI-UHFFFAOYSA-N 2-amino-5-bromobenzoic acid Chemical compound NC1=CC=C(Br)C=C1C(O)=O CUKXRHLWPSBCTI-UHFFFAOYSA-N 0.000 description 1
KLRQTZHBYODVTH-UHFFFAOYSA-N 2-chloro-4,6-diphenylpyridine-3-carbonitrile Chemical compound N#CC=1C(Cl)=NC(C=2C=CC=CC=2)=CC=1C1=CC=CC=C1 KLRQTZHBYODVTH-UHFFFAOYSA-N 0.000 description 1
BQEPTIIJSKEJMX-UHFFFAOYSA-N 2-chloro-5-(4-chlorophenyl)pyrimidine Chemical compound C1=CC(Cl)=CC=C1C1=CN=C(Cl)N=C1 BQEPTIIJSKEJMX-UHFFFAOYSA-N 0.000 description 1
SFAAOBGYWOUHLU-UHFFFAOYSA-N 2-ethylhexyl hexadecanoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(CC)CCCC SFAAOBGYWOUHLU-UHFFFAOYSA-N 0.000 description 1
SDNXQWUJWNTDCC-UHFFFAOYSA-N 2-methylsulfonylethanamine Chemical compound CS(=O)(=O)CCN SDNXQWUJWNTDCC-UHFFFAOYSA-N 0.000 description 1
DPJCXCZTLWNFOH-UHFFFAOYSA-N 2-nitroaniline Chemical compound NC1=CC=CC=C1[N+]([O-])=O DPJCXCZTLWNFOH-UHFFFAOYSA-N 0.000 description 1
VDDAVZWCRBHDLQ-UHFFFAOYSA-N 2-phenylquinazoline Chemical compound C1=CC=CC=C1C1=NC=C(C=CC=C2)C2=N1 VDDAVZWCRBHDLQ-UHFFFAOYSA-N 0.000 description 1
ZNGINKJHQQQORD-UHFFFAOYSA-N 2-trimethylsilylethanol Chemical compound C[Si](C)(C)CCO ZNGINKJHQQQORD-UHFFFAOYSA-N 0.000 description 1
JGDNFTUJBOLEBT-UHFFFAOYSA-N 2-trimethylsilylethyl 4-oxobutanoate Chemical compound C[Si](C)(C)CCOC(=O)CCC=O JGDNFTUJBOLEBT-UHFFFAOYSA-N 0.000 description 1
LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
VNCYWBFVRYCKQF-UHFFFAOYSA-N 3-[(6-bromo-4-phenylquinazolin-2-yl)amino]benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC(NC=2N=C3C=CC(Br)=CC3=C(C=3C=CC=CC=3)N=2)=C1 VNCYWBFVRYCKQF-UHFFFAOYSA-N 0.000 description 1
KARIAORLDGQWHQ-UHFFFAOYSA-N 4-(5-bromo-1h-indol-3-yl)-4-oxobutanoic acid Chemical compound C1=C(Br)C=C2C(C(=O)CCC(=O)O)=CNC2=C1 KARIAORLDGQWHQ-UHFFFAOYSA-N 0.000 description 1
XYTRNHVKBNXQQU-UHFFFAOYSA-N 4-(5-chloro-1h-indol-3-yl)-4-oxobutanoic acid Chemical compound C1=C(Cl)C=C2C(C(=O)CCC(=O)O)=CNC2=C1 XYTRNHVKBNXQQU-UHFFFAOYSA-N 0.000 description 1
PHXWODZSAXVMQV-UHFFFAOYSA-N 4-[5-bromo-1-(6-chloro-4-phenylquinolin-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(Cl)=CC1=1)=CC=1C1=CC=CC=C1 PHXWODZSAXVMQV-UHFFFAOYSA-N 0.000 description 1
NNLXEJIYWOQZDW-UHFFFAOYSA-N 4-[5-bromo-1-(6-fluoro-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(F)=CC1=1)=NC=1C1=CC=CC=C1 NNLXEJIYWOQZDW-UHFFFAOYSA-N 0.000 description 1
ZQMJOLKLQNPKPB-UHFFFAOYSA-N 4-[5-bromo-1-[4-[(1-carboxy-2-phenylethyl)amino]-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=1NC(C(O)=O)CC1=CC=CC=C1 ZQMJOLKLQNPKPB-UHFFFAOYSA-N 0.000 description 1
DVVGIEXFNYPMPC-UHFFFAOYSA-N 4-[5-bromo-1-[6-(furan-2-yl)-4-(4-methoxyphenyl)quinazolin-2-yl]indol-3-yl]-4-oxobutanoic acid Chemical compound C1=CC(OC)=CC=C1C1=NC(N2C3=CC=C(Br)C=C3C(C(=O)CCC(O)=O)=C2)=NC2=CC=C(C=3OC=CC=3)C=C12 DVVGIEXFNYPMPC-UHFFFAOYSA-N 0.000 description 1
SNCHPRLPXUPMST-UHFFFAOYSA-N 4-[5-chloro-1-(2,6-diphenylpyrimidin-4-yl)indol-3-yl]-4-oxobutanoic acid Chemical compound C12=CC=C(Cl)C=C2C(C(=O)CCC(=O)O)=CN1C(N=1)=CC(C=2C=CC=CC=2)=NC=1C1=CC=CC=C1 SNCHPRLPXUPMST-UHFFFAOYSA-N 0.000 description 1
VGCFUWVVDHTVDE-UHFFFAOYSA-N 4-[5-chloro-1-[2-(5-chloro-3-methyl-1-benzothiophen-2-yl)-2-oxoethyl]indol-3-yl]-4-oxobutanoic acid Chemical compound C1=C(C(=O)CCC(O)=O)C2=CC(Cl)=CC=C2N1CC(=O)C1=C(C)C2=CC(Cl)=CC=C2S1 VGCFUWVVDHTVDE-UHFFFAOYSA-N 0.000 description 1
CRRNOTLUVRUJNB-UHFFFAOYSA-N 4-[5-chloro-1-[4-(4-hydroxypiperidin-1-yl)-6-(trifluoromethyl)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(F)(F)F)C=C12 CRRNOTLUVRUJNB-UHFFFAOYSA-N 0.000 description 1
TYWNLGLKXROTQN-UHFFFAOYSA-N 4-[5-chloro-1-[6-(furan-2-yl)-4-[4-(hydroxymethyl)piperidin-1-yl]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=3OC=CC=3)C=C12 TYWNLGLKXROTQN-UHFFFAOYSA-N 0.000 description 1
QPKXLOVHOLDSCL-UHFFFAOYSA-N 4-[5-chloro-1-[[4-[(2-methoxydibenzofuran-3-yl)amino]phenyl]methyl]indol-3-yl]-4-oxobutanoic acid Chemical compound O1C2=CC=CC=C2C2=C1C=C(NC=1C=CC(CN3C4=CC=C(Cl)C=C4C(C(=O)CCC(O)=O)=C3)=CC=1)C(OC)=C2 QPKXLOVHOLDSCL-UHFFFAOYSA-N 0.000 description 1
CLJYQJBXRKOFEH-UHFFFAOYSA-N 4-amino-2-(2-aminophenyl)benzenesulfonamide Chemical compound NC1=CC=C(S(N)(=O)=O)C(C=2C(=CC=CC=2)N)=C1 CLJYQJBXRKOFEH-UHFFFAOYSA-N 0.000 description 1
VOHRKOUWQPDOQQ-UHFFFAOYSA-N 4-bromo-2-chloroquinazoline Chemical compound BrC1=NC(=NC2=CC=CC=C12)Cl VOHRKOUWQPDOQQ-UHFFFAOYSA-N 0.000 description 1
DQAZPZIYEOGZAF-UHFFFAOYSA-N 4-ethyl-n-[4-(3-ethynylanilino)-7-methoxyquinazolin-6-yl]piperazine-1-carboxamide Chemical compound C1CN(CC)CCN1C(=O)NC(C(=CC1=NC=N2)OC)=CC1=C2NC1=CC=CC(C#C)=C1 DQAZPZIYEOGZAF-UHFFFAOYSA-N 0.000 description 1
HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
DXSMYDSFWCOSFM-UHFFFAOYSA-N 6-bromo-1h-3,1-benzoxazine-2,4-dione Chemical compound N1C(=O)OC(=O)C2=CC(Br)=CC=C21 DXSMYDSFWCOSFM-UHFFFAOYSA-N 0.000 description 1
LBAYOWRVZAKPLS-UHFFFAOYSA-N 6-bromo-2,4-dichloroquinazoline Chemical compound C1=C(Br)C=CC2=NC(Cl)=NC(Cl)=C21 LBAYOWRVZAKPLS-UHFFFAOYSA-N 0.000 description 1
SFXQAXIAWKLFPT-UHFFFAOYSA-N 6-bromo-4-(4-butylphenyl)-1h-quinazolin-2-one Chemical compound C1=CC(CCCC)=CC=C1C1=NC(=O)NC2=CC=C(Br)C=C12 SFXQAXIAWKLFPT-UHFFFAOYSA-N 0.000 description 1
HCCNBKFJYUWLEX-UHFFFAOYSA-N 7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)-3-(pyrazin-2-ylmethylamino)pyrido[3,4-b]pyrazin-2-one Chemical compound O=C1N(CCOCCC)C2=CC(C=3C=NC(OC)=CC=3)=NC=C2N=C1NCC1=CN=CC=N1 HCCNBKFJYUWLEX-UHFFFAOYSA-N 0.000 description 1
BBPLRENRRYYWPO-UHFFFAOYSA-N 8-fluoronaphthalen-2-ol Chemical compound C1=CC=C(F)C2=CC(O)=CC=C21 BBPLRENRRYYWPO-UHFFFAOYSA-N 0.000 description 1
QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
239000005995 Aluminium silicate Substances 0.000 description 1
235000003911 Arachis Nutrition 0.000 description 1
244000105624 Arachis hypogaea Species 0.000 description 1
239000004358 Butane-1, 3-diol Substances 0.000 description 1
CFRJWLSNXCMWEE-UHFFFAOYSA-N C1=CC=CC2=[N+]([O-])C(N)=NC=C21 Chemical compound C1=CC=CC2=[N+]([O-])C(N)=NC=C21 CFRJWLSNXCMWEE-UHFFFAOYSA-N 0.000 description 1
244000060011 Cocos nucifera Species 0.000 description 1
235000013162 Cocos nucifera Nutrition 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
230000006820 DNA synthesis Effects 0.000 description 1
208000032928 Dyslipidaemia Diseases 0.000 description 1
NRFQZTCQAYEXEE-UHFFFAOYSA-N Fenclorim Chemical compound ClC1=CC(Cl)=NC(C=2C=CC=CC=2)=N1 NRFQZTCQAYEXEE-UHFFFAOYSA-N 0.000 description 1
244000068988 Glycine max Species 0.000 description 1
235000010469 Glycine max Nutrition 0.000 description 1
239000007818 Grignard reagent Substances 0.000 description 1
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
241000257303 Hymenoptera Species 0.000 description 1
206010020608 Hypercoagulation Diseases 0.000 description 1
206010020772 Hypertension Diseases 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
108010034219 Insulin Receptor Substrate Proteins Proteins 0.000 description 1
102100025087 Insulin receptor substrate 1 Human genes 0.000 description 1
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
208000017170 Lipid metabolism disease Diseases 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
240000007817 Olea europaea Species 0.000 description 1
239000005642 Oleic acid Substances 0.000 description 1
ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
235000019502 Orange oil Nutrition 0.000 description 1
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
108010001441 Phosphopeptides Proteins 0.000 description 1
108091000080 Phosphotransferase Proteins 0.000 description 1
229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
239000004698 Polyethylene Substances 0.000 description 1
229920001214 Polysorbate 60 Polymers 0.000 description 1
239000004372 Polyvinyl alcohol Substances 0.000 description 1
229910008338 Si—(CH3) Inorganic materials 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 description 1
229940100389 Sulfonylurea Drugs 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
BZHJMEDXRYGGRV-UHFFFAOYSA-N Vinyl chloride Chemical compound ClC=C BZHJMEDXRYGGRV-UHFFFAOYSA-N 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
WERKSKAQRVDLDW-ANOHMWSOSA-N [(2s,3r,4r,5r)-2,3,4,5,6-pentahydroxyhexyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO WERKSKAQRVDLDW-ANOHMWSOSA-N 0.000 description 1
LQZSXVWAYWHCRB-UHFFFAOYSA-N [3-[(6-bromo-4-phenylquinazolin-2-yl)amino]phenyl]-morpholin-4-ylmethanone Chemical compound N1=C(C=2C=CC=CC=2)C2=CC(Br)=CC=C2N=C1NC(C=1)=CC=CC=1C(=O)N1CCOCC1 LQZSXVWAYWHCRB-UHFFFAOYSA-N 0.000 description 1
MVFMOCPJJLMYDP-UHFFFAOYSA-N [4-[(6-bromo-4-phenylquinazolin-2-yl)amino]phenyl]-piperidin-1-ylmethanone Chemical compound N1=C(C=2C=CC=CC=2)C2=CC(Br)=CC=C2N=C1NC(C=C1)=CC=C1C(=O)N1CCCCC1 MVFMOCPJJLMYDP-UHFFFAOYSA-N 0.000 description 1
230000005856 abnormality Effects 0.000 description 1
230000037374 absorbed through the skin Effects 0.000 description 1
239000000205 acacia gum Substances 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
239000011149 active material Substances 0.000 description 1
125000002015 acyclic group Chemical group 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
125000002947 alkylene group Chemical group 0.000 description 1
235000012211 aluminium silicate Nutrition 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
125000005219 aminonitrile group Chemical group 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
239000011609 ammonium molybdate Substances 0.000 description 1
235000018660 ammonium molybdate Nutrition 0.000 description 1
229940010552 ammonium molybdate Drugs 0.000 description 1
230000003110 anti-inflammatory effect Effects 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
230000003078 antioxidant effect Effects 0.000 description 1
235000006708 antioxidants Nutrition 0.000 description 1
238000013459 approach Methods 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
239000003125 aqueous solvent Substances 0.000 description 1
125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
235000013871 bee wax Nutrition 0.000 description 1
239000012166 beeswax Substances 0.000 description 1
230000008901 benefit Effects 0.000 description 1
RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
239000012965 benzophenone Substances 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
230000000740 bleeding effect Effects 0.000 description 1
230000006583 body weight regulation Effects 0.000 description 1
239000012267 brine Substances 0.000 description 1
239000000872 buffer Substances 0.000 description 1
239000006172 buffering agent Substances 0.000 description 1
159000000007 calcium salts Chemical class 0.000 description 1
239000002775 capsule Substances 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
239000000969 carrier Substances 0.000 description 1
239000012876 carrier material Substances 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
230000007248 cellular mechanism Effects 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229940082500 cetostearyl alcohol Drugs 0.000 description 1
229960000541 cetyl alcohol Drugs 0.000 description 1
238000012822 chemical development Methods 0.000 description 1
238000000576 coating method Methods 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
239000003240 coconut oil Substances 0.000 description 1
235000019864 coconut oil Nutrition 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
238000002648 combination therapy Methods 0.000 description 1
229940126545 compound 53 Drugs 0.000 description 1
238000013270 controlled release Methods 0.000 description 1
239000002285 corn oil Substances 0.000 description 1
235000005687 corn oil Nutrition 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
239000002537 cosmetic Substances 0.000 description 1
235000012343 cottonseed oil Nutrition 0.000 description 1
239000002385 cottonseed oil Substances 0.000 description 1
SASYSVUEVMOWPL-NXVVXOECSA-N decyl oleate Chemical compound CCCCCCCCCCOC(=O)CCCCCCC\C=C/CCCCCCCC SASYSVUEVMOWPL-NXVVXOECSA-N 0.000 description 1
230000007547 defect Effects 0.000 description 1
230000002950 deficient Effects 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
231100000223 dermal penetration Toxicity 0.000 description 1
238000003113 dilution method Methods 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
239000000890 drug combination Substances 0.000 description 1
239000003974 emollient agent Substances 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
239000008387 emulsifying waxe Substances 0.000 description 1
239000008393 encapsulating agent Substances 0.000 description 1
239000003623 enhancer Substances 0.000 description 1
238000006911 enzymatic reaction Methods 0.000 description 1
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
230000029142 excretion Effects 0.000 description 1
239000003889 eye drop Substances 0.000 description 1
229940012356 eye drops Drugs 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
238000007429 general method Methods 0.000 description 1
229940074045 glyceryl distearate Drugs 0.000 description 1
125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 description 1
229940075507 glyceryl monostearate Drugs 0.000 description 1
BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical compound NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 description 1
150000004795 grignard reagents Chemical class 0.000 description 1
239000007902 hard capsule Substances 0.000 description 1
230000036541 health Effects 0.000 description 1
208000019622 heart disease Diseases 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
206010073071 hepatocellular carcinoma Diseases 0.000 description 1
JYGYEBCBALMPDC-UHFFFAOYSA-N heptane;propan-2-one Chemical compound CC(C)=O.CCCCCCC JYGYEBCBALMPDC-UHFFFAOYSA-N 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
UBHWBODXJBSFLH-UHFFFAOYSA-N hexadecan-1-ol;octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO.CCCCCCCCCCCCCCCCCCO UBHWBODXJBSFLH-UHFFFAOYSA-N 0.000 description 1
102000049286 human PTPN1 Human genes 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
239000008309 hydrophilic cream Substances 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
230000003027 hypercoagulation Effects 0.000 description 1
239000005457 ice water Substances 0.000 description 1
230000036737 immune function Effects 0.000 description 1
230000028993 immune response Effects 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
239000003701 inert diluent Substances 0.000 description 1
238000001802 infusion Methods 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
229940102223 injectable solution Drugs 0.000 description 1
229940102213 injectable suspension Drugs 0.000 description 1
229910052816 inorganic phosphate Inorganic materials 0.000 description 1
108010042209 insulin receptor tyrosine kinase Proteins 0.000 description 1
230000003914 insulin secretion Effects 0.000 description 1
230000004155 insulin signaling pathway Effects 0.000 description 1
230000003993 interaction Effects 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000007913 intrathecal administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
229910052742 iron Inorganic materials 0.000 description 1
229940078545 isocetyl stearate Drugs 0.000 description 1
SRJOCJYGOFTFLH-UHFFFAOYSA-N isonipecotic acid Chemical compound OC(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-N 0.000 description 1
QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 1
150000002540 isothiocyanates Chemical group 0.000 description 1
NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
239000004816 latex Substances 0.000 description 1
229920000126 latex Polymers 0.000 description 1
150000002632 lipids Chemical class 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
238000011068 loading method Methods 0.000 description 1
239000003589 local anesthetic agent Substances 0.000 description 1
229960005015 local anesthetics Drugs 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
239000000395 magnesium oxide Substances 0.000 description 1
CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
RBWRWAUAVRMBAC-UHFFFAOYSA-M magnesium;methoxybenzene;bromide Chemical compound [Mg+2].[Br-].COC1=CC=[C-]C=C1 RBWRWAUAVRMBAC-UHFFFAOYSA-M 0.000 description 1
AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
FDZZZRQASAIRJF-UHFFFAOYSA-M malachite green Chemical compound [Cl-].C1=CC(N(C)C)=CC=C1C(C=1C=CC=CC=1)=C1C=CC(=[N+](C)C)C=C1 FDZZZRQASAIRJF-UHFFFAOYSA-M 0.000 description 1
229940107698 malachite green Drugs 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
239000011159 matrix material Substances 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
ROEPVXYBUCIGKS-UHFFFAOYSA-N methyl 4-[5-bromo-1-[6-(furan-2-yl)-4-(4-methoxyanilino)quinazolin-2-yl]indol-3-yl]-4-oxobutanoate Chemical compound C12=CC=C(Br)C=C2C(C(=O)CCC(=O)OC)=CN1C(N=C1C=CC(=CC1=1)C=2OC=CC=2)=NC=1NC1=CC=C(OC)C=C1 ROEPVXYBUCIGKS-UHFFFAOYSA-N 0.000 description 1
VSDUZFOSJDMAFZ-VIFPVBQESA-N methyl L-phenylalaninate Chemical compound COC(=O)[C@@H](N)CC1=CC=CC=C1 VSDUZFOSJDMAFZ-VIFPVBQESA-N 0.000 description 1
238000002156 mixing Methods 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
210000004877 mucosa Anatomy 0.000 description 1
230000035772 mutation Effects 0.000 description 1
229940043348 myristyl alcohol Drugs 0.000 description 1
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
230000003472 neutralizing effect Effects 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
125000006501 nitrophenyl group Chemical group 0.000 description 1
125000006574 non-aromatic ring group Chemical group 0.000 description 1
231100000344 non-irritating Toxicity 0.000 description 1
239000012038 nucleophile Substances 0.000 description 1
GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
WYURNTSHIVDZCO-SVYQBANQSA-N oxolane-d8 Chemical compound [2H]C1([2H])OC([2H])([2H])C([2H])([2H])C1([2H])[2H] WYURNTSHIVDZCO-SVYQBANQSA-N 0.000 description 1
239000001301 oxygen Chemical group 0.000 description 1
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
230000035515 penetration Effects 0.000 description 1
239000008251 pharmaceutical emulsion Substances 0.000 description 1
WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
230000026731 phosphorylation Effects 0.000 description 1
238000006366 phosphorylation reaction Methods 0.000 description 1
102000020233 phosphotransferase Human genes 0.000 description 1
RFIOZSIHFNEKFF-UHFFFAOYSA-N piperazine-1-carboxylic acid Chemical compound OC(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-N 0.000 description 1
229920000573 polyethylene Polymers 0.000 description 1
239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
229920000053 polysorbate 80 Polymers 0.000 description 1
229920002451 polyvinyl alcohol Polymers 0.000 description 1
GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
239000003801 protein tyrosine phosphatase 1B inhibitor Substances 0.000 description 1
125000003072 pyrazolidinyl group Chemical group 0.000 description 1
TXQWFIVRZNOPCK-UHFFFAOYSA-N pyridin-4-ylmethanamine Chemical compound NCC1=CC=NC=C1 TXQWFIVRZNOPCK-UHFFFAOYSA-N 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
210000000664 rectum Anatomy 0.000 description 1
230000007363 regulatory process Effects 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
229940081974 saccharin Drugs 0.000 description 1
235000019204 saccharin Nutrition 0.000 description 1
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
230000011664 signaling Effects 0.000 description 1
230000007781 signaling event Effects 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000007901 soft capsule Substances 0.000 description 1
208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
238000010186 staining Methods 0.000 description 1
230000007847 structural defect Effects 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
150000005846 sugar alcohols Polymers 0.000 description 1
FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 1
229940124530 sulfonamide Drugs 0.000 description 1
229910052717 sulfur Chemical group 0.000 description 1
239000011593 sulfur Chemical group 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
230000002194 synthesizing effect Effects 0.000 description 1
CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
238000012360 testing method Methods 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
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)

Publication Number	Publication Date
ZA200509632B true ZA200509632B (en)	2007-02-28

Family

ID=33434990

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
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 (es)
EP (1)	EP1618094B1 (es)
JP (1)	JP2006525357A (es)
AT (1)	ATE372324T1 (es)
AU (1)	AU2004236239A1 (es)
CA (1)	CA2524221A1 (es)
DE (1)	DE602004008762T2 (es)
ES (1)	ES2290743T3 (es)
MX (1)	MXPA05011523A (es)
WO (1)	WO2004099159A1 (es)
ZA (1)	ZA200509632B (es)

Families Citing this family (44)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
TWI329105B (en)	2002-02-01	2010-08-21	Rigel Pharmaceuticals Inc	2,4-pyrimidinediamine compounds and their uses
ATE451104T1 (de)	2002-07-29	2009-12-15	Rigel Pharmaceuticals Inc	Verfahren zur behandlung oder pruvention von autoimmunkrankheiten mit 2,4-pyrimidindiamin- verbindungen
CN1849318B (zh)	2003-07-30	2011-10-12	里格尔药品股份有限公司	用2,4-嘧啶二胺化合物预防和治疗自体免疫疾病的方法
TWI344364B (en) *	2003-11-10	2011-07-01	Synta Pharmaceuticals Corp	Fused heterocyclic compounds
BRPI0517559A (pt) *	2004-11-09	2008-10-14	Hoffmann La Roche	composto, processo para a sua preparação, método para o tratamento terapêutico e/ou profilático de enfermidades que são moduladas por inibidores de ptb-1b e utilização dos compostos
AU2005307718A1 (en) *	2004-11-18	2006-05-26	The Institutes For Pharmaceutical Discovery, Llc	Heterocycle substituted carboxylic acids for the treatment of diabetes
BRPI0606318B8 (pt)	2005-01-19	2021-05-25	Rigel Pharmaceuticals Inc	composto, composição, e, uso de um composto
NZ560712A (en)	2005-02-17	2010-12-24	Synta Pharmaceuticals Corp	(3,4,5-trisubstituted-phenyl)isoxazole combretastin derivatives for the treatment of disorders
AU2006236557A1 (en) *	2005-04-14	2006-10-26	Novartis Vaccines And Diagnostics Inc.	2-amino-quinazolin-5-ones as HSP90 inhibitors useful in treating proliferation diseases
KR101312225B1 (ko)	2005-06-08	2013-09-26	리겔 파마슈티칼스, 인크.	Ｊａｋ 경로의 억제를 위한 조성물 및 방법
US20070203161A1 (en)	2006-02-24	2007-08-30	Rigel Pharmaceuticals, Inc.	Compositions and methods for inhibition of the jak pathway
EP1917245A1 (de)	2005-08-21	2008-05-07	Abbott GmbH & Co. KG	Heterocyclische verbindungen und ihre verwendung als bindungspartner für 5-ht5-rezeptoren
JP5113752B2 (ja)	2005-08-22	2013-01-09	メリオール・ファーマスーティカルズ・ワン・インコーポレイテッド	Ｌｙｎキナーゼの活性を調節し、関連する疾患を治療するための方法および製剤
JP2009528295A (ja)	2006-02-24	2009-08-06	ライジェルファーマシューティカルズ，インコーポレイテッド	Ｊａｋ経路の阻害のための組成物および方法
TW200813018A (en)	2006-06-09	2008-03-16	Astrazeneca Ab	Novel compounds
CA2657200A1 (en) *	2006-07-28	2008-01-31	Novartis Ag	2,4-substituted quinazolines as lipid kinase inhibitors
KR101438245B1 (ko)	2006-08-23	2014-09-04	쿠도스 파마슈티칼스 리미티드	Ｍｔｏｒ 억제제로서의 2-메틸모르폴린 피리도-, 피라조- 및 피리미도-피리미딘 유도체
WO2008072850A1 (en) *	2006-12-11	2008-06-19	Amorepacific Corporation	Triazine derivatives having inhibitory activity against acetyl-coa carboxylase
CN101686686A (zh) *	2007-02-20	2010-03-31	梅里奥尔医药I公司	鉴别Lyn激酶激活剂的方法
NZ598251A (en) *	2007-03-14	2013-06-28	Exelixis Patent Co Llc	2-Arylamino-pyridopyrimidines and their uses, particularly in the treatment of cancer
MX2009009693A (es) *	2007-07-23	2009-10-07	Melior Discovery Inc	Metodos para activar irs-1 y akt.
US8119661B2 (en)	2007-09-11	2012-02-21	Astrazeneca Ab	Piperidine derivatives and their use as muscarinic receptor modulators
CN101531638B (zh) *	2008-03-13	2011-12-28	中国科学院广州生物医药与健康研究院	用作***相关受体调节剂的化合物及其应用
CA2728183C (en)	2008-06-20	2016-10-25	Astrazeneca Ab	Compositions with and process for methylmorpholin-substituted pyrido [2,3-d] pryimidines
US8552184B2 (en) *	2008-07-03	2013-10-08	Melior Pharmaceuticals I, Inc.	Compounds and methods for treating disorders related to glucose metabolism
ES2575215T3 (es)	2009-12-11	2016-06-27	Autifony Therapeutics Limited	Derivados de imidazolidindiona
PT2550269E (pt) *	2010-03-23	2016-06-20	Scinopharm Taiwan Ltd	Processo e intermediários para a preparação de lapatinib
RS55856B1 (sr)	2010-07-14	2017-08-31	Novartis Ag	Heterociklična jedinjenja agonisti ip receptora
BR112013013914B1 (pt)	2010-12-06	2021-10-26	Autifony Therapeutics Limited	Compostos derivados de hidantoína úteis como inibidores de kv3, usos dos referidos compostos e composição farmacêutica compreendendo os mesmos
CN103596943B (zh)	2011-06-07	2016-10-12	奥蒂福尼疗法有限公司	用作kv3抑制剂的乙内酰脲衍生物
US20140309184A1 (en) *	2011-09-21	2014-10-16	University Of South Alabama	Methods and compositions for the treatment of ovarian cancer
AR089698A1 (es)	2012-01-13	2014-09-10	Novartis Ag	Compuestos heterociclicos antagonistas del receptor ip
WO2013175211A1 (en)	2012-05-22	2013-11-28	Autifony Therapeutics Limited	Hydantoin derivatives as kv3 inhibitors
BR112014028991A2 (pt)	2012-05-22	2017-06-27	Autifony Therapeutics Ltd	triazóis como inibidores de kv3
JO3407B1 (ar)	2012-05-31	2019-10-20	Eisai R&D Man Co Ltd	مركبات رباعي هيدرو بيرازولو بيريميدين
WO2014015291A1 (en) *	2012-07-20	2014-01-23	Han-Jie Zhou	FUSED PYRIMIDINES AS INHIBITORS OF p97 COMPLEX
CN105189500A (zh)	2013-02-13	2015-12-23	诺华股份有限公司	Ip受体激动剂杂环化合物
KR101658111B1 (ko) *	2013-05-13	2016-09-20	제일모직 주식회사	유기광전자소자용 화합물, 이를 포함하는 유기발광소자 및 상기 유기발광소자를 포함하는 표시장치
AR099134A1 (es)	2014-01-24	2016-06-29	Hoffmann La Roche	Procedimiento para la preparación de n-[(3-aminooxetán-3-il)metil]-2-(1,1-dioxo-3,5-dihidro-1,4-benzotiazepín-4-il)-6-metil-quinazolín-4-amina
CN105153048B (zh) *	2015-07-31	2017-10-24	苏州大学	一种2,4‑喹唑啉二酮类化合物的制备方法
IL291017B2 (en)	2015-10-21	2023-11-01	Otsuka Pharma Co Ltd	Benzolactam compounds as protein kinase inhibitors
CA3059432A1 (en)	2017-04-10	2018-10-18	Melior Pharmaceuticals I, Inc.	Compositions comprising a lyn kinase activator and a trpms agonist
GB201706327D0 (en)	2017-04-20	2017-06-07	Otsuka Pharma Co Ltd	A pharmaceutical compound
CN113416181B (zh) *	2021-08-02	2022-05-03	四川大学	喹唑啉类衍生物及其用途

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3515724A (en) *	1966-12-12	1970-06-02	Hoffmann La Roche	Process for the preparation of substituted 4-phenyl or 4-pyridyl-1,2-dihydro-quinazoline compounds and novel substituted 4 - pyridyl-1,2-dihydroquinazoline products
US4012513A (en) *	1971-11-03	1977-03-15	Imperial Chemical Industries Limited	Indole derivatives for providing analgesic and anti-inflammatory effects
BE790679A (fr) *	1971-11-03	1973-04-27	Ici Ltd	Derives de l'indole
DE2826526A1 (de) *	1977-06-17	1979-01-04	Gist Brocades Nv	Kupferkomplexe von phenanthrolin-, isochinolin- und chinazolinderivaten, verfahren zu ihrer herstellung und ihre verwendung bei der bekaempfung von mykoplasmainfektionen
FR2514765A1 (fr) *	1981-10-21	1983-04-22	Sanofi Sa	Nouveaux derives de la phenyl-4 quinazoline actifs sur le systeme nerveux central
FR2521144A1 (fr) *	1982-02-08	1983-08-12	Sanofi Sa	Nouveaux derives de la piperazinyl-2 phenyl-4 quinazoline possedant des proprietes antidepressives, methode de preparation desdits composes et medicaments en contenant
EP0664128A4 (en) *	1992-10-07	1997-12-17	Sumitomo Pharma	PHARMACEUTICAL AGENT FOR INHIBITING TUMORNESCROSE FACTOR PRODUCTION.
NO306992B1 (no) *	1993-01-28	2000-01-24	Takeda Chemical Industries Ltd	Quinolinderivater, farmasoeytiske preparater inneholdende forbindelsene og anvendelsen av forbindelsene
JPH11209350A (ja) *	1998-01-26	1999-08-03	Eisai Co Ltd	含窒素複素環誘導体およびその医薬
AU6985200A (en) *	1999-09-10	2001-04-17	Novo Nordisk A/S	Modulators of protein tyrosine phosphatases (ptpases)

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

Also Published As

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

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
CN101128452B (zh)	2012-11-21	新颖的苯并咪唑衍生物和包含它们的药物组合物
KR101152162B1 (ko)	2012-07-10	치환된 피리미딘 및 ｊｎｋ 조절제로서 그의 용도
ES2477878T3 (es)	2014-07-18	Compuestos y composiciones de 5-(4-(aloalcoxi)fenil)pirimidin-2-amina como inhibidores de quinasas
USRE37650E1 (en)	2002-04-09	Aryl and heteroaryl quinazoline compounds which inhibit CSF-1R receptor tyrosine kinase
CA2517844A1 (en)	2004-09-16	Quinazolines useful as modulators of ion channels
JP2008519762A (ja)	2008-06-12	タンパク質キナーゼ阻害剤としての化合物および組成物
US6610695B1 (en)	2003-08-26	Aryloxy substituted pyrimidine imidazole compounds
JP2014525937A (ja)	2014-10-02	キナーゼ阻害剤としてのアミノキナゾリン
AU2013339167A1 (en)	2015-05-14	Novel amine derivative or salt thereof
JP2008266295A (ja)	2008-11-06	キナーセ゛阻害活性を有する新規チアシ゛アソ゛ール誘導体
JP2010512405A (ja)	2010-04-22	キナーゼ阻害剤としての化合物および組成物
WO2021078023A1 (zh)	2021-04-29	一种小分子化合物
JP2013533316A (ja)	2013-08-22	キナーゼ阻害剤としてのキノリルアミン
AU2004212957A1 (en)	2004-09-02	Novel compounds
WO2019242689A1 (zh)	2019-12-26	一种氰基取代吡啶及氰基取代嘧啶类化合物、制备方法及其应用
CN101273033A (zh)	2008-09-24	作为治疗癌症的erbb受体酪氨酸激酶抑制剂的4-（1h-吲哚-5-基-氨基）-喹唑啉化合物