BG107101A - 2-фенилпиран-4-онови производни - Google Patents

2-фенилпиран-4-онови производни Download PDF

Info

Publication number: BG107101A
Authority: BG; Bulgaria
Prior art keywords: group; alkyl; methanesulfonylphenyl; formula; pyran
Prior art date: 2000-03-16

Application number

BG107101A

Other languages

Bulgarian (bg)

English (en)

Inventor

Crespo Maria Isabel Crespo

Mayorga Juan Miguel Jimenez

JULIA Josep MATALLANA

Gras Joan Feixas

Original Assignee

Almirall Prodesfarma Ag

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.)

2000-03-16

Filing date

2002-09-13

Publication date

2003-07-31

2002-09-13 Application filed by Almirall Prodesfarma Ag filed Critical Almirall Prodesfarma Ag

2003-07-31 Publication of BG107101A publication Critical patent/BG107101A/bg

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UFECLJRYNAOWOI-UHFFFAOYSA-N 2-phenylpyran-4-one Chemical class O=C1C=COC(C=2C=CC=CC=2)=C1 UFECLJRYNAOWOI-UHFFFAOYSA-N 0.000 title description 15
-1 2-(-sulphonylphenyl)pyran-4-one derivatives Chemical class 0.000 claims abstract description 106
238000000034 method Methods 0.000 claims abstract description 66
238000002360 preparation method Methods 0.000 claims abstract description 54
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
239000000460 chlorine Substances 0.000 claims description 279
125000000217 alkyl group Chemical group 0.000 claims description 121
150000001875 compounds Chemical class 0.000 claims description 119
WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic acid anhydride Natural products CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 59
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 49
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 46
239000000203 mixture Substances 0.000 claims description 44
125000005843 halogen group Chemical group 0.000 claims description 30
125000000896 monocarboxylic acid group Chemical group 0.000 claims description 29
150000003839 salts Chemical class 0.000 claims description 28
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 25
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
125000001424 substituent group Chemical group 0.000 claims description 22
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 21
125000003545 alkoxy group Chemical group 0.000 claims description 19
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 18
ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 18
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
238000006243 chemical reaction Methods 0.000 claims description 16
125000004663 dialkyl amino group Chemical group 0.000 claims description 16
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 15
229910052717 sulfur Inorganic materials 0.000 claims description 15
125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 14
229910052739 hydrogen Inorganic materials 0.000 claims description 14
239000001257 hydrogen Substances 0.000 claims description 13
229910052801 chlorine Inorganic materials 0.000 claims description 12
125000004430 oxygen atom Chemical group O* 0.000 claims description 12
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
125000004849 alkoxymethyl group Chemical group 0.000 claims description 11
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 11
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 11
150000002825 nitriles Chemical class 0.000 claims description 11
229920000137 polyphosphoric acid Polymers 0.000 claims description 11
229910052794 bromium Inorganic materials 0.000 claims description 10
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 10
150000004702 methyl esters Chemical class 0.000 claims description 10
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 10
125000001624 naphthyl group Chemical group 0.000 claims description 10
239000011593 sulfur Substances 0.000 claims description 10
125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 10
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 9
125000003342 alkenyl group Chemical group 0.000 claims description 9
125000000304 alkynyl group Chemical group 0.000 claims description 9
206010061218 Inflammation Diseases 0.000 claims description 8
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 8
125000000753 cycloalkyl group Chemical group 0.000 claims description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
230000004054 inflammatory process Effects 0.000 claims description 8
125000004076 pyridyl group Chemical group 0.000 claims description 8
125000001544 thienyl group Chemical group 0.000 claims description 8
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 8
CVQUWLDCFXOXEN-UHFFFAOYSA-N Pyran-4-one Chemical compound O=C1C=COC=C1 CVQUWLDCFXOXEN-UHFFFAOYSA-N 0.000 claims description 7
230000005764 inhibitory process Effects 0.000 claims description 7
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
208000002193 Pain Diseases 0.000 claims description 6
239000011737 fluorine Substances 0.000 claims description 6
229910052731 fluorine Inorganic materials 0.000 claims description 6
125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 claims description 6
239000007800 oxidant agent Substances 0.000 claims description 6
OETIMMSWPHDTTA-UHFFFAOYSA-N 3-(4-fluoro-2-methylphenoxy)-6-methyl-2-(4-methylsulfonylphenyl)pyran-4-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1OC(C)=CC(=O)C=1OC1=CC=C(F)C=C1C OETIMMSWPHDTTA-UHFFFAOYSA-N 0.000 claims description 5
206010009944 Colon cancer Diseases 0.000 claims description 5
208000001333 Colorectal Neoplasms Diseases 0.000 claims description 5
150000008064 anhydrides Chemical class 0.000 claims description 5
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 5
230000002265 prevention Effects 0.000 claims description 5
230000016160 smooth muscle contraction Effects 0.000 claims description 5
QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 claims description 4
KRFKBVRMCXACPL-UHFFFAOYSA-N 2-(difluoromethyl)-5-(2,4-difluorophenoxy)-3-methyl-6-(4-methylsulfonylphenyl)pyran-4-one Chemical compound C=1C=C(F)C=C(F)C=1OC=1C(=O)C(C)=C(C(F)F)OC=1C1=CC=C(S(C)(=O)=O)C=C1 KRFKBVRMCXACPL-UHFFFAOYSA-N 0.000 claims description 4
DFQHKIXVIYDTGY-UHFFFAOYSA-N 3-(2,4-difluorophenoxy)-6-(methoxymethyl)-2-(4-methylsulfonylphenyl)pyran-4-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1OC(COC)=CC(=O)C=1OC1=CC=C(F)C=C1F DFQHKIXVIYDTGY-UHFFFAOYSA-N 0.000 claims description 4
JAIOAMPOGJIYQK-UHFFFAOYSA-N 3-(2-fluoro-4-methylphenoxy)-6-methyl-2-(4-methylsulfonylphenyl)pyran-4-one Chemical compound FC1=CC(C)=CC=C1OC1=C(C=2C=CC(=CC=2)S(C)(=O)=O)OC(C)=CC1=O JAIOAMPOGJIYQK-UHFFFAOYSA-N 0.000 claims description 4
BEUSXCFVSULHCA-UHFFFAOYSA-N 3-(4-chlorophenoxy)-6-(hydroxymethyl)-2-(4-methylsulfonylphenyl)pyran-4-one Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(OC=2C=CC(Cl)=CC=2)C(=O)C=C(CO)O1 BEUSXCFVSULHCA-UHFFFAOYSA-N 0.000 claims description 4
RGBUWQFPRPMUDZ-UHFFFAOYSA-N 3-(4-fluorophenoxy)-6-(methoxymethyl)-2-(4-methylsulfonylphenyl)pyran-4-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1OC(COC)=CC(=O)C=1OC1=CC=C(F)C=C1 RGBUWQFPRPMUDZ-UHFFFAOYSA-N 0.000 claims description 4
BUVNUHAZLOLFFJ-UHFFFAOYSA-N 3-bromo-5-(4-chlorophenoxy)-2-methyl-6-(4-methylsulfonylphenyl)pyran-4-one Chemical compound C=1C=C(Cl)C=CC=1OC=1C(=O)C(Br)=C(C)OC=1C1=CC=C(S(C)(=O)=O)C=C1 BUVNUHAZLOLFFJ-UHFFFAOYSA-N 0.000 claims description 4
VRQFSFPNHQFPIE-UHFFFAOYSA-N 3-chloro-5-(2,4-difluorophenoxy)-2-methyl-6-(4-methylsulfonylphenyl)pyran-4-one Chemical compound C=1C=C(F)C=C(F)C=1OC=1C(=O)C(Cl)=C(C)OC=1C1=CC=C(S(C)(=O)=O)C=C1 VRQFSFPNHQFPIE-UHFFFAOYSA-N 0.000 claims description 4
VMYMVQUKYUNQHW-UHFFFAOYSA-N 3-chloro-5-(4-fluorophenoxy)-2-methyl-6-(4-methylsulfonylphenyl)pyran-4-one Chemical compound C=1C=C(F)C=CC=1OC=1C(=O)C(Cl)=C(C)OC=1C1=CC=C(S(C)(=O)=O)C=C1 VMYMVQUKYUNQHW-UHFFFAOYSA-N 0.000 claims description 4
ICMSGBUGGUXQQI-UHFFFAOYSA-N 5-(2,4-difluorophenoxy)-2,3-dimethyl-6-(4-methylsulfonylphenyl)pyran-4-one Chemical compound C=1C=C(F)C=C(F)C=1OC=1C(=O)C(C)=C(C)OC=1C1=CC=C(S(C)(=O)=O)C=C1 ICMSGBUGGUXQQI-UHFFFAOYSA-N 0.000 claims description 4
AQJZPWCLCJWGFK-UHFFFAOYSA-N 5-(2,4-difluorophenoxy)-2-ethyl-3-methyl-6-(4-methylsulfonylphenyl)pyran-4-one Chemical compound C=1C=C(F)C=C(F)C=1OC=1C(=O)C(C)=C(CC)OC=1C1=CC=C(S(C)(=O)=O)C=C1 AQJZPWCLCJWGFK-UHFFFAOYSA-N 0.000 claims description 4
RLGNMIDASULXKL-UHFFFAOYSA-N 5-(2,4-difluorophenoxy)-3-ethenyl-2-methyl-6-(4-methylsulfonylphenyl)pyran-4-one Chemical compound C=1C=C(F)C=C(F)C=1OC=1C(=O)C(C=C)=C(C)OC=1C1=CC=C(S(C)(=O)=O)C=C1 RLGNMIDASULXKL-UHFFFAOYSA-N 0.000 claims description 4
DZSILQIXYOZOKN-UHFFFAOYSA-N 5-(2,4-difluorophenoxy)-3-ethyl-2-methyl-6-(4-methylsulfonylphenyl)pyran-4-one Chemical compound C=1C=C(F)C=C(F)C=1OC=1C(=O)C(CC)=C(C)OC=1C1=CC=C(S(C)(=O)=O)C=C1 DZSILQIXYOZOKN-UHFFFAOYSA-N 0.000 claims description 4
ISESFZQITYBRSI-UHFFFAOYSA-N 5-(2,4-difluorophenoxy)-6-(4-methylsulfonylphenyl)-4-oxopyran-2-carboxylic acid Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(OC=2C(=CC(F)=CC=2)F)C(=O)C=C(C(O)=O)O1 ISESFZQITYBRSI-UHFFFAOYSA-N 0.000 claims description 4
NYPDNQOXSBKAQW-UHFFFAOYSA-N 5-(4-chlorophenoxy)-6-(4-methylsulfonylphenyl)-4-oxopyran-2-carboxylic acid Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(OC=2C=CC(Cl)=CC=2)C(=O)C=C(C(O)=O)O1 NYPDNQOXSBKAQW-UHFFFAOYSA-N 0.000 claims description 4
QFGVWVQHHYWJKM-UHFFFAOYSA-N 6-methyl-3-(2-methylphenoxy)-2-(4-methylsulfonylphenyl)pyran-4-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1OC(C)=CC(=O)C=1OC1=CC=CC=C1C QFGVWVQHHYWJKM-UHFFFAOYSA-N 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 4
125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 claims description 4
230000004770 neurodegeneration Effects 0.000 claims description 4
208000015122 neurodegenerative disease Diseases 0.000 claims description 4
125000005767 propoxymethyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])[#8]C([H])([H])* 0.000 claims description 4
229940127293 prostanoid Drugs 0.000 claims description 4
150000003814 prostanoids Chemical class 0.000 claims description 4
PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 4
125000004434 sulfur atom Chemical group 0.000 claims description 4
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 3
WBEBBJFBRLUVMQ-UHFFFAOYSA-N 3-(2-bromophenoxy)-6-methyl-2-(4-methylsulfonylphenyl)pyran-4-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1OC(C)=CC(=O)C=1OC1=CC=CC=C1Br WBEBBJFBRLUVMQ-UHFFFAOYSA-N 0.000 claims description 3
DUSGGEPBMGVOMH-UHFFFAOYSA-N 3-(2-chloro-4-methylphenoxy)-6-methyl-2-(4-methylsulfonylphenyl)pyran-4-one Chemical compound ClC1=CC(C)=CC=C1OC1=C(C=2C=CC(=CC=2)S(C)(=O)=O)OC(C)=CC1=O DUSGGEPBMGVOMH-UHFFFAOYSA-N 0.000 claims description 3
AQKBTKCEELLTSZ-UHFFFAOYSA-N 3-(3-bromophenoxy)-6-methyl-2-(4-methylsulfonylphenyl)pyran-4-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1OC(C)=CC(=O)C=1OC1=CC=CC(Br)=C1 AQKBTKCEELLTSZ-UHFFFAOYSA-N 0.000 claims description 3
DPYLMVIJRWFZIG-UHFFFAOYSA-N 3-(4-bromo-2-chlorophenoxy)-6-methyl-2-(4-methylsulfonylphenyl)pyran-4-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1OC(C)=CC(=O)C=1OC1=CC=C(Br)C=C1Cl DPYLMVIJRWFZIG-UHFFFAOYSA-N 0.000 claims description 3
HZIMQUSOGVRMRT-UHFFFAOYSA-N 3-(4-bromo-2-fluorophenoxy)-6-(hydroxymethyl)-2-(4-methylsulfonylphenyl)pyran-4-one Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(OC=2C(=CC(Br)=CC=2)F)C(=O)C=C(CO)O1 HZIMQUSOGVRMRT-UHFFFAOYSA-N 0.000 claims description 3
SGZPDQDNNJQFNW-UHFFFAOYSA-N 3-(4-bromo-2-fluorophenoxy)-6-methyl-2-(4-methylsulfonylphenyl)pyran-4-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1OC(C)=CC(=O)C=1OC1=CC=C(Br)C=C1F SGZPDQDNNJQFNW-UHFFFAOYSA-N 0.000 claims description 3
DICHKUSVPRXKBB-UHFFFAOYSA-N 3-(4-chloro-2-methylphenoxy)-6-methyl-2-(4-methylsulfonylphenyl)pyran-4-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1OC(C)=CC(=O)C=1OC1=CC=C(Cl)C=C1C DICHKUSVPRXKBB-UHFFFAOYSA-N 0.000 claims description 3
SBRUXVDEMQJAFP-UHFFFAOYSA-N 3-(4-fluorophenoxy)-6-(hydroxymethyl)-2-(4-methylsulfonylphenyl)pyran-4-one Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(OC=2C=CC(F)=CC=2)C(=O)C=C(CO)O1 SBRUXVDEMQJAFP-UHFFFAOYSA-N 0.000 claims description 3
ODZXJBMBUAGGSS-UHFFFAOYSA-N 3-bromo-2-(difluoromethyl)-5-(2,4-difluorophenoxy)-6-(4-methylsulfonylphenyl)pyran-4-one Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(OC=2C(=CC(F)=CC=2)F)C(=O)C(Br)=C(C(F)F)O1 ODZXJBMBUAGGSS-UHFFFAOYSA-N 0.000 claims description 3
MFPZGTHLTRZKEO-UHFFFAOYSA-N 3-bromo-5-(2,4-difluorophenoxy)-2-methyl-6-(4-methylsulfonylphenyl)pyran-4-one Chemical compound C=1C=C(F)C=C(F)C=1OC=1C(=O)C(Br)=C(C)OC=1C1=CC=C(S(C)(=O)=O)C=C1 MFPZGTHLTRZKEO-UHFFFAOYSA-N 0.000 claims description 3
HWJYVVCKPDYAMV-UHFFFAOYSA-N 3-chloro-5-(4-chlorophenoxy)-2-methyl-6-(4-methylsulfonylphenyl)pyran-4-one Chemical compound C=1C=C(Cl)C=CC=1OC=1C(=O)C(Cl)=C(C)OC=1C1=CC=C(S(C)(=O)=O)C=C1 HWJYVVCKPDYAMV-UHFFFAOYSA-N 0.000 claims description 3
ZSGDYBFTFRRKPD-UHFFFAOYSA-N 6-(difluoromethyl)-3-(4-methylphenoxy)-2-(4-methylsulfonylphenyl)pyran-4-one Chemical compound C1=CC(C)=CC=C1OC1=C(C=2C=CC(=CC=2)S(C)(=O)=O)OC(C(F)F)=CC1=O ZSGDYBFTFRRKPD-UHFFFAOYSA-N 0.000 claims description 3
RTHQRIZEGPCCGE-UHFFFAOYSA-N 6-methyl-3-(3-methylphenoxy)-2-(4-methylsulfonylphenyl)pyran-4-one Chemical compound CC1=CC=CC(OC=2C(C=C(C)OC=2C=2C=CC(=CC=2)S(C)(=O)=O)=O)=C1 RTHQRIZEGPCCGE-UHFFFAOYSA-N 0.000 claims description 3
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 3
UOXRODFUOLJMSO-UHFFFAOYSA-N 3-(2,4-difluorophenoxy)-6-(hydroxymethyl)-2-(4-methylsulfonylphenyl)pyran-4-one Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(OC=2C(=CC(F)=CC=2)F)C(=O)C=C(CO)O1 UOXRODFUOLJMSO-UHFFFAOYSA-N 0.000 claims description 2
IIKFPLIAMMXVSQ-UHFFFAOYSA-N 6-(difluoromethyl)-3-(2,4-difluorophenoxy)-2-(2-methylsulfonylphenyl)pyran-4-one Chemical compound CS(=O)(=O)C1=CC=CC=C1C1=C(OC=2C(=CC(F)=CC=2)F)C(=O)C=C(C(F)F)O1 IIKFPLIAMMXVSQ-UHFFFAOYSA-N 0.000 claims description 2
241001465754 Metazoa Species 0.000 claims description 2
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical class [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
238000006264 debenzylation reaction Methods 0.000 claims description 2
239000003814 drug Substances 0.000 claims description 2
125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 2
150000002431 hydrogen Chemical class 0.000 claims description 2
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
229920002554 vinyl polymer Polymers 0.000 claims description 2
230000003993 interaction Effects 0.000 claims 2
125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 122
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 105
239000000543 intermediate Substances 0.000 description 79
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 66
239000007787 solid Substances 0.000 description 60
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 41
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 34
239000000243 solution Substances 0.000 description 32
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
239000002904 solvent Substances 0.000 description 23
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
108010037462 Cyclooxygenase 2 Proteins 0.000 description 19
102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 18
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
238000010898 silica gel chromatography Methods 0.000 description 17
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
102000010906 Cyclooxygenase 1 Human genes 0.000 description 15
108010037464 Cyclooxygenase 1 Proteins 0.000 description 15
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 15
229910052938 sodium sulfate Inorganic materials 0.000 description 15
235000011152 sodium sulphate Nutrition 0.000 description 15
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
YSSYIJBAPDTSAY-UHFFFAOYSA-N 2-bromo-1-(4-methylsulfanylphenyl)ethanone Chemical compound CSC1=CC=C(C(=O)CBr)C=C1 YSSYIJBAPDTSAY-UHFFFAOYSA-N 0.000 description 11
150000001299 aldehydes Chemical class 0.000 description 11
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
238000000746 purification Methods 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
239000003960 organic solvent Substances 0.000 description 9
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 8
238000004440 column chromatography Methods 0.000 description 8
230000000694 effects Effects 0.000 description 8
239000000741 silica gel Substances 0.000 description 8
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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
- C07D405/02—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
- C07D405/12—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 linked by a chain containing hetero atoms as chain links
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/34—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D309/36—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms
- C07D309/38—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms one oxygen atom in position 2 or 4, e.g. pyrones
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/34—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D309/36—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms
- C07D309/40—Oxygen atoms attached in positions 3 and 4, e.g. maltol

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Pain & Pain Management (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Rheumatology (AREA)
Hospice & Palliative Care (AREA)
Psychiatry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pyrane Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

BG107101A 2000-03-16 2002-09-13 2-фенилпиран-4-онови производни BG107101A (bg)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
ES200000637		2000-03-16
PCT/EP2001/003042 WO2001068633A1 (en)	2000-03-16	2001-03-16	2-phenylpyran-4-one derivatives

Publications (1)

Publication Number	Publication Date
BG107101A true BG107101A (bg)	2003-07-31

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ID=8492732

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BG107101A BG107101A (bg)	2000-03-16	2002-09-13	2-фенилпиран-4-онови производни

Country Status (27)

Country	Link
US (1)	US7354936B2 (cs)
EP (1)	EP1263751B1 (cs)
JP (1)	JP2003527389A (cs)
KR (1)	KR20030005221A (cs)
CN (1)	CN1429221A (cs)
AR (1)	AR030410A1 (cs)
AT (1)	ATE269316T1 (cs)
AU (1)	AU2001254692A1 (cs)
BG (1)	BG107101A (cs)
BR (1)	BR0109252A (cs)
CA (1)	CA2403149A1 (cs)
CZ (1)	CZ20023058A3 (cs)
DE (1)	DE60103859T2 (cs)
EE (1)	EE200200528A (cs)
ES (1)	ES2223830T3 (cs)
HK (1)	HK1048117A1 (cs)
HU (1)	HUP0301696A2 (cs)
IL (1)	IL151598A0 (cs)
MX (1)	MXPA02009016A (cs)
NO (1)	NO20024393L (cs)
NZ (1)	NZ521187A (cs)
PE (1)	PE20011333A1 (cs)
PL (1)	PL358062A1 (cs)
RU (1)	RU2002127728A (cs)
SK (1)	SK12832002A3 (cs)
WO (1)	WO2001068633A1 (cs)
ZA (1)	ZA200207184B (cs)

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Publication number	Priority date	Publication date	Assignee	Title
US6465509B2 (en)	2000-06-30	2002-10-15	Merck Frosst Canada & Co.	Pyrones as inhibitors of cyclooxygenase-2
ES2213485B1 (es) *	2003-02-13	2005-12-16	Almirall Prodesfarma, S.A.	Derivados de la 2-fenilpiran-4-ona.
CN102731456B (zh) *	2011-04-01	2014-07-09	华中科技大学	一种抗肿瘤化合物及其制备方法和应用

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CH524614A (de)	1969-12-31	1972-06-30	Ciba Geigy Ag	Verfahren zur Herstellung von neuen Imidazolderivaten
US3901908A (en)	1970-12-28	1975-08-26	Ciba Geigy Corp	2-alkyl- and 2-cycloalkyl-4,5-bis-phenyl-imidazoles
US4304728A (en)	1979-04-05	1981-12-08	Lilly Industries Limited	6-Substituted pyranone compounds and their use as pharmaceuticals
IL59748A (en)	1979-04-05	1983-11-30	Lilly Industries Ltd	5-substituted pyranone derivatives,their production and pharmaceutical compositions containing them
US6048850A (en)	1992-09-22	2000-04-11	Young; Donald A.	Method of inhibiting prostaglandin synthesis in a human host
EE9600044A (et) *	1993-11-19	1996-10-15	Parke, Davis & Company	Püranooni derivaadid kui proteaasi inhibiitorid ja viirusevastased toimeained
US5521213A (en)	1994-08-29	1996-05-28	Merck Frosst Canada, Inc.	Diaryl bicyclic heterocycles as inhibitors of cyclooxygenase-2
US5541204A (en)	1994-12-02	1996-07-30	Bristol-Myers Squibb Company	Aryloxypropanolamine β 3 adrenergic agonists
NZ304886A (en)	1995-04-04	1998-11-25	Glaxo Group Ltd	Imidazo [1,2a] pyridine derivatives, preparation and pharmaceutical compositions thereof
BR9813998A (pt)	1997-11-19	2000-09-26	Kowa Co	Novos derivados de piridazina e produtos medicinais contendo os mesmos como ingredientes efetivos
TW587079B (en) *	1998-09-25	2004-05-11	Almirall Prodesfarma Ag	2-phenylpyran-4-one derivatives

2001
- 2001-03-13 PE PE2001000241A patent/PE20011333A1/es not_active Application Discontinuation
- 2001-03-15 AR ARP010101221A patent/AR030410A1/es not_active Application Discontinuation
- 2001-03-16 AU AU2001254692A patent/AU2001254692A1/en not_active Abandoned
- 2001-03-16 HU HU0301696A patent/HUP0301696A2/hu unknown
- 2001-03-16 IL IL15159801A patent/IL151598A0/xx unknown
- 2001-03-16 HK HK03100285.1A patent/HK1048117A1/zh unknown
- 2001-03-16 NZ NZ521187A patent/NZ521187A/en unknown
- 2001-03-16 CA CA002403149A patent/CA2403149A1/en not_active Abandoned
- 2001-03-16 EE EEP200200528A patent/EE200200528A/xx unknown
- 2001-03-16 KR KR1020027011875A patent/KR20030005221A/ko not_active Withdrawn
- 2001-03-16 MX MXPA02009016A patent/MXPA02009016A/es unknown
- 2001-03-16 BR BR0109252-9A patent/BR0109252A/pt not_active IP Right Cessation
- 2001-03-16 JP JP2001567725A patent/JP2003527389A/ja not_active Withdrawn
- 2001-03-16 DE DE60103859T patent/DE60103859T2/de not_active Expired - Lifetime
- 2001-03-16 WO PCT/EP2001/003042 patent/WO2001068633A1/en not_active Ceased
- 2001-03-16 SK SK1283-2002A patent/SK12832002A3/sk unknown
- 2001-03-16 CN CN01809447A patent/CN1429221A/zh active Pending
- 2001-03-16 CZ CZ20023058A patent/CZ20023058A3/cs unknown
- 2001-03-16 RU RU2002127728/04A patent/RU2002127728A/ru not_active Application Discontinuation
- 2001-03-16 PL PL01358062A patent/PL358062A1/xx not_active Application Discontinuation
- 2001-03-16 ES ES01927742T patent/ES2223830T3/es not_active Expired - Lifetime
- 2001-03-16 EP EP01927742A patent/EP1263751B1/en not_active Expired - Lifetime
- 2001-03-16 AT AT01927742T patent/ATE269316T1/de not_active IP Right Cessation
2002
- 2002-09-06 ZA ZA200207184A patent/ZA200207184B/en unknown
- 2002-09-13 BG BG107101A patent/BG107101A/bg unknown
- 2002-09-13 NO NO20024393A patent/NO20024393L/no not_active Application Discontinuation
- 2002-09-16 US US10/245,873 patent/US7354936B2/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
HUP0301696A2 (hu)	2003-09-29
US20030232880A1 (en)	2003-12-18
EE200200528A (et)	2004-04-15
US7354936B2 (en)	2008-04-08
ATE269316T1 (de)	2004-07-15
MXPA02009016A (es)	2004-10-15
JP2003527389A (ja)	2003-09-16
CZ20023058A3 (cs)	2004-01-14
PL358062A1 (en)	2004-08-09
CA2403149A1 (en)	2001-09-20
EP1263751A1 (en)	2002-12-11
SK12832002A3 (sk)	2003-11-04
WO2001068633A1 (en)	2001-09-20
PE20011333A1 (es)	2002-01-16
CN1429221A (zh)	2003-07-09
DE60103859D1 (de)	2004-07-22
AR030410A1 (es)	2003-08-20
NZ521187A (en)	2004-03-26
HK1048117A1 (zh)	2003-03-21
DE60103859T2 (de)	2005-07-21
NO20024393D0 (no)	2002-09-13
KR20030005221A (ko)	2003-01-17
BR0109252A (pt)	2002-12-24
NO20024393L (no)	2002-11-13
IL151598A0 (en)	2003-04-10
RU2002127728A (ru)	2004-03-20
ES2223830T3 (es)	2005-03-01
EP1263751B1 (en)	2004-06-16
AU2001254692A1 (en)	2001-09-24
ZA200207184B (en)	2003-12-08

Publication	Publication Date	Title
SU1650009A3 (ru)	1991-05-15	Способ получени 5-арилалкил-4-алкокси-2(5Н)фуранонов
US5079264A (en)	1992-01-07	Chemical process
HUT77668A (hu)	1998-07-28	Vírusellenes hatású 5,6-dihidropiron-származékok és hatóanyagként azokat tartalmazó gyógyszerkészítmények
RU2012554C1 (ru)	1994-05-15	Способ получения производных бензоциклоалкенилдигидрооксиалкановых кислот
KR100806684B1 (ko)	2008-02-26	2-페닐피란-4-온 유도체
HUT75225A (en)	1997-04-28	5,6-dihydropyrone derivatives as protease inhibitors and antiviral agents
EP1263751B1 (en)	2004-06-16	2-phenylpyran-4-one derivatives
KR20000005146A (ko)	2000-01-25	퓨란 디아릴메틸리덴 유도체, 이의 제조방법 및이를 함유하는약제학적 조성물
US20060189684A1 (en)	2006-08-24	3-Phenylfuran-2-one derivatives as cox-2 inhibitor
US5149834A (en)	1992-09-22	4-hydroxytetrahydropyran-2-one derivatives
PT87927B (pt)	1995-03-01	Processo para a preparacao de acidos 3,5-dihidroxi-hepta-6-enoicos substituidos por 7-(1h-pirrol-3-ilo), das suas correspondentes delta-lactonas e sais, e de composicoes farmaceuticas que os contem
AU610528B2 (en)	1991-05-23	Leukotriene antagonists
JPS606653A (ja)	1985-01-14	抗高コレステロ−ル血症活性を有する５−チアアルカン酸誘導体
EP1592680B1 (en)	2008-05-07	2-phenylpyran-4-one derivatives as selective cox-2 inhibitors
US5843999A (en)	1998-12-01	2-phenylazulene derivatives and a manufacturing method of these compounds
WO1999033796A1 (en)	1999-07-08	5-arylpyrrole derivatives