IL134961A - Coltistokinin (CCK) agonist-converted thiazoles, a process for their preparation, pharmaceutical preparations containing them and their use - Google Patents

Coltistokinin (CCK) agonist-converted thiazoles, a process for their preparation, pharmaceutical preparations containing them and their use

Info

Publication number: IL134961A
Authority: IL; Israel
Prior art keywords: chloro; dimethoxyphenyl; acetic acid; ylcarbamoyl; thiazol
Prior art date: 1997-09-19

Application number

IL13496198A

Other languages

English (en)

Hebrew (he)

Other versions

IL134961A0 (en

Original Assignee

Sanofi Synthelabo

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.)

1997-09-19

Filing date

1998-09-18

Publication date

2002-07-25

1997-09-19 Priority claimed from FR9711718A external-priority patent/FR2768737B1/fr

1998-04-23 Priority claimed from FR9805106A external-priority patent/FR2777887B3/fr

1998-09-18 Application filed by Sanofi Synthelabo filed Critical Sanofi Synthelabo

2001-05-20 Publication of IL134961A0 publication Critical patent/IL134961A0/xx

2002-07-25 Publication of IL134961A publication Critical patent/IL134961A/en

Links

238000002360 preparation method Methods 0.000 title claims description 87
238000000034 method Methods 0.000 title claims description 53
230000008569 process Effects 0.000 title claims description 25
239000008194 pharmaceutical composition Substances 0.000 title claims description 7
101800001982 Cholecystokinin Proteins 0.000 title description 36
102100025841 Cholecystokinin Human genes 0.000 title description 36
229940107137 cholecystokinin Drugs 0.000 title description 36
IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 title description 36
239000000556 agonist Substances 0.000 title description 13
150000003557 thiazoles Chemical class 0.000 title description 6
150000001875 compounds Chemical class 0.000 claims abstract description 282
-1 acetyloxy, methoxy, ethoxy, methylthio Chemical group 0.000 claims abstract description 68
150000003839 salts Chemical class 0.000 claims abstract description 35
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 33
239000001257 hydrogen Substances 0.000 claims abstract description 33
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 27
239000012453 solvate Substances 0.000 claims abstract description 27
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 19
125000001424 substituent group Chemical group 0.000 claims abstract description 19
229910052736 halogen Inorganic materials 0.000 claims abstract description 14
150000002367 halogens Chemical class 0.000 claims abstract description 14
239000000460 chlorine Substances 0.000 claims abstract description 11
229910052801 chlorine Inorganic materials 0.000 claims abstract description 11
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 10
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 9
125000003277 amino group Chemical group 0.000 claims abstract description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 29
239000002253 acid Substances 0.000 claims description 29
108010089335 Cholecystokinin A Receptor Proteins 0.000 claims description 18
102100034927 Cholecystokinin receptor type A Human genes 0.000 claims description 18
238000011282 treatment Methods 0.000 claims description 17
229940079593 drug Drugs 0.000 claims description 15
239000003814 drug Substances 0.000 claims description 15
RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 claims description 11
230000002496 gastric effect Effects 0.000 claims description 11
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
230000008878 coupling Effects 0.000 claims description 6
238000010168 coupling process Methods 0.000 claims description 6
238000005859 coupling reaction Methods 0.000 claims description 6
208000035475 disorder Diseases 0.000 claims description 6
NFDFTMICKVDYLQ-UHFFFAOYSA-N 2-[2-[[4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)-1,3-thiazol-2-yl]carbamoyl]-5,7-dimethylindol-1-yl]acetic acid Chemical compound C1=C(Cl)C(OC)=CC(C2=C(SC(NC(=O)C=3N(C4=C(C)C=C(C)C=C4C=3)CC(O)=O)=N2)CCC2CCCCC2)=C1OC NFDFTMICKVDYLQ-UHFFFAOYSA-N 0.000 claims description 5
229910052731 fluorine Inorganic materials 0.000 claims description 5
239000011737 fluorine Substances 0.000 claims description 5
208000008589 Obesity Diseases 0.000 claims description 4
235000020824 obesity Nutrition 0.000 claims description 4
208000012661 Dyskinesia Diseases 0.000 claims description 3
230000000638 stimulation Effects 0.000 claims description 3
KNMAHODWYDYBNW-UHFFFAOYSA-N 2-[2-[[4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)-1,3-thiazol-2-yl]carbamoyl]-4,5-dimethoxyindol-1-yl]acetic acid Chemical compound C1=C(Cl)C(OC)=CC(C2=C(SC(NC(=O)C=3N(C4=CC=C(OC)C(OC)=C4C=3)CC(O)=O)=N2)CCC2CCCCC2)=C1OC KNMAHODWYDYBNW-UHFFFAOYSA-N 0.000 claims description 2
AGOJEFQTAMTJHV-UHFFFAOYSA-N 2-[2-[[4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)-1,3-thiazol-2-yl]carbamoyl]-4,5-dimethylindol-1-yl]acetic acid Chemical compound C1=C(Cl)C(OC)=CC(C2=C(SC(NC(=O)C=3N(C4=CC=C(C)C(C)=C4C=3)CC(O)=O)=N2)CCC2CCCCC2)=C1OC AGOJEFQTAMTJHV-UHFFFAOYSA-N 0.000 claims description 2
PQAPEXJKQQHFKZ-UHFFFAOYSA-N 2-[2-[[4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)-1,3-thiazol-2-yl]carbamoyl]-4,7-dimethylindol-1-yl]acetic acid Chemical compound C1=C(Cl)C(OC)=CC(C2=C(SC(NC(=O)C=3N(C4=C(C)C=CC(C)=C4C=3)CC(O)=O)=N2)CCC2CCCCC2)=C1OC PQAPEXJKQQHFKZ-UHFFFAOYSA-N 0.000 claims description 2
IXSKIUYWZMHWPS-UHFFFAOYSA-N 2-[2-[[4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)-1,3-thiazol-2-yl]carbamoyl]-4-methoxy-7-methylindol-1-yl]acetic acid Chemical compound C1=C(Cl)C(OC)=CC(C2=C(SC(NC(=O)C=3N(C4=C(C)C=CC(OC)=C4C=3)CC(O)=O)=N2)CCC2CCCCC2)=C1OC IXSKIUYWZMHWPS-UHFFFAOYSA-N 0.000 claims description 2
VZVMSBUIQNSYBC-UHFFFAOYSA-N 2-[2-[[4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)-1,3-thiazol-2-yl]carbamoyl]-4-methylindol-1-yl]acetic acid Chemical compound C1=C(Cl)C(OC)=CC(C2=C(SC(NC(=O)C=3N(C4=CC=CC(C)=C4C=3)CC(O)=O)=N2)CCC2CCCCC2)=C1OC VZVMSBUIQNSYBC-UHFFFAOYSA-N 0.000 claims description 2
ITSFURYNWBMEFN-UHFFFAOYSA-N 2-[2-[[4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)-1,3-thiazol-2-yl]carbamoyl]-5-methylindol-1-yl]acetic acid Chemical compound C1=C(Cl)C(OC)=CC(C2=C(SC(NC(=O)C=3N(C4=CC=C(C)C=C4C=3)CC(O)=O)=N2)CCC2CCCCC2)=C1OC ITSFURYNWBMEFN-UHFFFAOYSA-N 0.000 claims description 2
CUUMWIRAPXOFQO-UHFFFAOYSA-N 2-[5-chloro-2-[[4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)-1,3-thiazol-2-yl]carbamoyl]-4-methylindol-1-yl]acetic acid Chemical compound C1=C(Cl)C(OC)=CC(C2=C(SC(NC(=O)C=3N(C4=CC=C(Cl)C(C)=C4C=3)CC(O)=O)=N2)CCC2CCCCC2)=C1OC CUUMWIRAPXOFQO-UHFFFAOYSA-N 0.000 claims description 2
FYGGTVJAHJMXGR-UHFFFAOYSA-N 2-[5-chloro-2-[[4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)-1,3-thiazol-2-yl]carbamoyl]-7-fluoroindol-1-yl]acetic acid Chemical compound C1=C(Cl)C(OC)=CC(C2=C(SC(NC(=O)C=3N(C4=C(F)C=C(Cl)C=C4C=3)CC(O)=O)=N2)CCC2CCCCC2)=C1OC FYGGTVJAHJMXGR-UHFFFAOYSA-N 0.000 claims description 2
CFQABQGBWXICEA-UHFFFAOYSA-N 2-[5-chloro-2-[[4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)-1,3-thiazol-2-yl]carbamoyl]-7-methylindol-1-yl]acetic acid Chemical compound C1=C(Cl)C(OC)=CC(C2=C(SC(NC(=O)C=3N(C4=C(C)C=C(Cl)C=C4C=3)CC(O)=O)=N2)CCC2CCCCC2)=C1OC CFQABQGBWXICEA-UHFFFAOYSA-N 0.000 claims description 2
VBRYWAAVGGWBTI-UHFFFAOYSA-N 2-[5-chloro-2-[[4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)-1,3-thiazol-2-yl]carbamoyl]indol-1-yl]acetic acid Chemical compound C1=C(Cl)C(OC)=CC(C2=C(SC(NC(=O)C=3N(C4=CC=C(Cl)C=C4C=3)CC(O)=O)=N2)CCC2CCCCC2)=C1OC VBRYWAAVGGWBTI-UHFFFAOYSA-N 0.000 claims description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
208000030499 combat disease Diseases 0.000 claims description 2
238000010511 deprotection reaction Methods 0.000 claims description 2
150000004677 hydrates Chemical class 0.000 claims description 2
208000002551 irritable bowel syndrome Diseases 0.000 claims description 2
JPZVGJPPGUMEHC-UHFFFAOYSA-N 2-(2-ethylindol-1-yl)acetic acid Chemical compound C1=CC=C2N(CC(O)=O)C(CC)=CC2=C1 JPZVGJPPGUMEHC-UHFFFAOYSA-N 0.000 claims 1
JBGFIZSFYCETDI-UHFFFAOYSA-N 2-[2-[[4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)-1,3-thiazol-2-yl]carbamoyl]-4,7-dimethoxyindol-1-yl]acetic acid Chemical compound C1=C(Cl)C(OC)=CC(C2=C(SC(NC(=O)C=3N(C4=C(OC)C=CC(OC)=C4C=3)CC(O)=O)=N2)CCC2CCCCC2)=C1OC JBGFIZSFYCETDI-UHFFFAOYSA-N 0.000 claims 1
HYGJUCCSZDXPRF-UHFFFAOYSA-N 2-[2-[[4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)-1,3-thiazol-2-yl]carbamoyl]-5-methoxyindol-1-yl]acetic acid Chemical compound C=1C2=CC(OC)=CC=C2N(CC(O)=O)C=1C(=O)NC(S1)=NC(C=2C(=CC(Cl)=C(OC)C=2)OC)=C1CCC1CCCCC1 HYGJUCCSZDXPRF-UHFFFAOYSA-N 0.000 claims 1
AXDWNJKERZGTNC-UHFFFAOYSA-N 2-[2-[[4-(4-chloro-2,5-dimethoxyphenyl)-5-(2-cyclohexylethyl)-1,3-thiazol-2-yl]carbamoyl]-7-methoxyindol-1-yl]acetic acid Chemical compound C1=C(Cl)C(OC)=CC(C2=C(SC(NC(=O)C=3N(C4=C(OC)C=CC=C4C=3)CC(O)=O)=N2)CCC2CCCCC2)=C1OC AXDWNJKERZGTNC-UHFFFAOYSA-N 0.000 claims 1
101800001545 Cholecystokinin-5 Proteins 0.000 claims 1
102400000884 Cholecystokinin-5 Human genes 0.000 claims 1
239000000203 mixture Substances 0.000 description 180
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 158
239000000243 solution Substances 0.000 description 130
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 127
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 121
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 117
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 111
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 95
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 87
238000003756 stirring Methods 0.000 description 82
206010012812 Diffuse cutaneous mastocytosis Diseases 0.000 description 73
239000000047 product Substances 0.000 description 73
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OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 56
239000000377 silicon dioxide Substances 0.000 description 55
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 52
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 48
239000002244 precipitate Substances 0.000 description 45
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 40
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 40
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 38
239000012074 organic phase Substances 0.000 description 34
229910052943 magnesium sulfate Inorganic materials 0.000 description 32
239000002904 solvent Substances 0.000 description 31
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
235000019441 ethanol Nutrition 0.000 description 28
239000000284 extract Substances 0.000 description 28
229910052757 nitrogen Inorganic materials 0.000 description 28
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UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 26
150000002148 esters Chemical class 0.000 description 23
239000012429 reaction media Substances 0.000 description 23
239000000872 buffer Substances 0.000 description 21
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 20
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 20
229910000041 hydrogen chloride Inorganic materials 0.000 description 20
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 19
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 19
229910021653 sulphate ion Inorganic materials 0.000 description 19
238000006243 chemical reaction Methods 0.000 description 18
239000000706 filtrate Substances 0.000 description 17
UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 17
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 16
229910000104 sodium hydride Inorganic materials 0.000 description 16
238000001704 evaporation Methods 0.000 description 15
230000008020 evaporation Effects 0.000 description 15
239000012071 phase Substances 0.000 description 15
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239000007787 solid Substances 0.000 description 13
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239000013078 crystal Substances 0.000 description 12
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AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 10
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PRXNKYBFWAWBNZ-UHFFFAOYSA-N trimethylphenylammonium tribromide Chemical compound Br[Br-]Br.C[N+](C)(C)C1=CC=CC=C1 PRXNKYBFWAWBNZ-UHFFFAOYSA-N 0.000 description 9
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 8
HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical group C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 8
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ZYZXGWGQYNTGAU-UHFFFAOYSA-N dibenzyl oxalate Chemical compound C=1C=CC=CC=1COC(=O)C(=O)OCC1=CC=CC=C1 ZYZXGWGQYNTGAU-UHFFFAOYSA-N 0.000 description 6
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239000004480 active ingredient Substances 0.000 description 5
150000001412 amines Chemical class 0.000 description 5
GBVAGZMJJSANDQ-UHFFFAOYSA-N benzyl 1h-indole-2-carboxylate Chemical compound C=1C2=CC=CC=C2NC=1C(=O)OCC1=CC=CC=C1 GBVAGZMJJSANDQ-UHFFFAOYSA-N 0.000 description 5
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YZGJDVPXFMTQRZ-UHFFFAOYSA-N cyclohexylmethyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC1CCCCC1 YZGJDVPXFMTQRZ-UHFFFAOYSA-N 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
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230000003111 delayed effect Effects 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
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150000001989 diazonium salts Chemical class 0.000 description 1
230000001079 digestive effect Effects 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 description 1
208000037765 diseases and disorders Diseases 0.000 description 1
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238000005886 esterification reaction Methods 0.000 description 1
ZYBWTEQKHIADDQ-UHFFFAOYSA-N ethanol;methanol Chemical compound OC.CCO ZYBWTEQKHIADDQ-UHFFFAOYSA-N 0.000 description 1
LDLDYFCCDKENPD-UHFFFAOYSA-N ethenylcyclohexane Chemical group C=CC1CCCCC1 LDLDYFCCDKENPD-UHFFFAOYSA-N 0.000 description 1
CBIVEMGUNRNUEB-UHFFFAOYSA-N ethyl 1h-pyrrolo[2,3-b]pyridine-2-carboxylate Chemical compound C1=CN=C2NC(C(=O)OCC)=CC2=C1 CBIVEMGUNRNUEB-UHFFFAOYSA-N 0.000 description 1
RDEWTAHSEKSPPT-UHFFFAOYSA-N ethyl 2-(bromomethyl)benzoate Chemical compound CCOC(=O)C1=CC=CC=C1CBr RDEWTAHSEKSPPT-UHFFFAOYSA-N 0.000 description 1
NHVRUHNRPZCTHY-UHFFFAOYSA-N ethyl 2-azido-3-(2,3-dimethoxyphenyl)prop-2-enoate Chemical compound CCOC(=O)C(N=[N+]=[N-])=CC1=CC=CC(OC)=C1OC NHVRUHNRPZCTHY-UHFFFAOYSA-N 0.000 description 1
GMMVWTXZXVPBAG-UHFFFAOYSA-N ethyl 2-azido-3-(3,5-dimethylphenyl)prop-2-enoate Chemical compound CCOC(=O)C(N=[N+]=[N-])=CC1=CC(C)=CC(C)=C1 GMMVWTXZXVPBAG-UHFFFAOYSA-N 0.000 description 1
OKANYBNORCUPKZ-UHFFFAOYSA-N ethyl 2-ethyl-3-oxobutanoate Chemical compound CCOC(=O)C(CC)C(C)=O OKANYBNORCUPKZ-UHFFFAOYSA-N 0.000 description 1
FNENWZWNOPCZGK-UHFFFAOYSA-N ethyl 2-methyl-3-oxobutanoate Chemical compound CCOC(=O)C(C)C(C)=O FNENWZWNOPCZGK-UHFFFAOYSA-N 0.000 description 1
SOUAXOGPALPTTC-UHFFFAOYSA-N ethyl 2-methylbenzoate Chemical compound CCOC(=O)C1=CC=CC=C1C SOUAXOGPALPTTC-UHFFFAOYSA-N 0.000 description 1
SOBSEOUZZDHRIZ-UHFFFAOYSA-N ethyl 3,5-dimethyl-1h-indole-2-carboxylate Chemical compound C1=C(C)C=C2C(C)=C(C(=O)OCC)NC2=C1 SOBSEOUZZDHRIZ-UHFFFAOYSA-N 0.000 description 1
CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 description 1
FQTIYMRSUOADDK-UHFFFAOYSA-N ethyl 3-bromopropanoate Chemical compound CCOC(=O)CCBr FQTIYMRSUOADDK-UHFFFAOYSA-N 0.000 description 1
CZJQBZNLVGKZRX-UHFFFAOYSA-N ethyl 4,5-dimethoxy-1h-indole-2-carboxylate Chemical compound COC1=CC=C2NC(C(=O)OCC)=CC2=C1OC CZJQBZNLVGKZRX-UHFFFAOYSA-N 0.000 description 1
WOVSDROSNOFLOZ-UHFFFAOYSA-N ethyl 4-cycloheptylbutanoate Chemical compound CCOC(=O)CCCC1CCCCCC1 WOVSDROSNOFLOZ-UHFFFAOYSA-N 0.000 description 1
GTDTWFBGWFSRHW-UHFFFAOYSA-N ethyl 4-cycloheptylidenebut-2-enoate Chemical compound CCOC(=O)C=CC=C1CCCCCC1 GTDTWFBGWFSRHW-UHFFFAOYSA-N 0.000 description 1
LXLODBXSCRTXFG-UHFFFAOYSA-N ethyl 4-diethoxyphosphorylbut-2-enoate Chemical compound CCOC(=O)C=CCP(=O)(OCC)OCC LXLODBXSCRTXFG-UHFFFAOYSA-N 0.000 description 1
SPWRJLSJMFDLNF-UHFFFAOYSA-N ethyl 5,6-dimethyl-1h-indole-2-carboxylate Chemical compound CC1=C(C)C=C2NC(C(=O)OCC)=CC2=C1 SPWRJLSJMFDLNF-UHFFFAOYSA-N 0.000 description 1
BPAHRSSJFSVBFO-UHFFFAOYSA-N ethyl 5-ethyl-1h-indole-2-carboxylate Chemical compound CCC1=CC=C2NC(C(=O)OCC)=CC2=C1 BPAHRSSJFSVBFO-UHFFFAOYSA-N 0.000 description 1
KMVFKXFOPNKHEM-UHFFFAOYSA-N ethyl 5-methyl-1h-indole-2-carboxylate Chemical compound CC1=CC=C2NC(C(=O)OCC)=CC2=C1 KMVFKXFOPNKHEM-UHFFFAOYSA-N 0.000 description 1
DVFJMQCNICEPAI-UHFFFAOYSA-N ethyl 5-nitro-1h-indole-2-carboxylate Chemical compound [O-][N+](=O)C1=CC=C2NC(C(=O)OCC)=CC2=C1 DVFJMQCNICEPAI-UHFFFAOYSA-N 0.000 description 1
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XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
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UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
239000006210 lotion Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
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JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
- 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
- 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
- A61P3/04—Anorexiants; Antiobesity 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
- 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
- C07D417/12—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 linked by a chain containing hetero atoms as chain links
- 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
- C07D417/14—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 three or more hetero rings

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Engineering & Computer Science (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Neurosurgery (AREA)
Diabetes (AREA)
Obesity (AREA)
Hematology (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Child & Adolescent Psychology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Thiazole And Isothizaole Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Indole Compounds (AREA)

IL13496198A 1997-09-19 1998-09-18 Coltistokinin (CCK) agonist-converted thiazoles, a process for their preparation, pharmaceutical preparations containing them and their use IL134961A (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
FR9711718A FR2768737B1 (fr)	1997-09-19	1997-09-19	Derives de carboxamidothiazoles, leur preparation, les compositions pharmaceutiques en contenant
FR9805106A FR2777887B3 (fr)	1998-04-23	1998-04-23	Derives de carboxamidothiazoles, leur preparation, les compositions pharmaceutiques en contenant
PCT/FR1998/002007 WO1999015525A1 (fr)	1997-09-19	1998-09-18	Derives de carboxamidothiazoles, leur preparation, les compositions pharmaceutiques en contenant

Publications (2)

Publication Number	Publication Date
IL134961A0 IL134961A0 (en)	2001-05-20
IL134961A true IL134961A (en)	2002-07-25

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ID=26233812

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL13496198A IL134961A (en)	1997-09-19	1998-09-18	Coltistokinin (CCK) agonist-converted thiazoles, a process for their preparation, pharmaceutical preparations containing them and their use

Country Status (27)

Country	Link
US (1)	US6380230B1 (fr)
EP (1)	EP1017693A1 (fr)
JP (1)	JP3456970B2 (fr)
KR (1)	KR20010030629A (fr)
CN (1)	CN1276790A (fr)
AR (1)	AR013494A1 (fr)
AU (1)	AU746707B2 (fr)
BG (1)	BG104254A (fr)
BR (1)	BR9812653A (fr)
CA (1)	CA2304397A1 (fr)
CO (1)	CO4970713A1 (fr)
EA (1)	EA003093B1 (fr)
EE (1)	EE200000168A (fr)
HR (1)	HRP20000153A2 (fr)
HU (1)	HUP0100225A3 (fr)
ID (1)	ID25528A (fr)
IL (1)	IL134961A (fr)
IS (1)	IS5409A (fr)
MY (1)	MY141444A (fr)
NO (1)	NO314455B1 (fr)
NZ (1)	NZ503339A (fr)
PL (1)	PL339292A1 (fr)
SK (1)	SK4052000A3 (fr)
TR (1)	TR200001218T2 (fr)
TW (1)	TW430664B (fr)
UY (1)	UY25180A1 (fr)
WO (1)	WO1999015525A1 (fr)

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1998
- 1998-09-09 CO CO98051671A patent/CO4970713A1/es unknown
- 1998-09-12 MY MYPI98004185A patent/MY141444A/en unknown
- 1998-09-14 UY UY25180A patent/UY25180A1/es unknown
- 1998-09-16 AR ARP980104588A patent/AR013494A1/es not_active Application Discontinuation
- 1998-09-18 PL PL98339292A patent/PL339292A1/xx unknown
- 1998-09-18 BR BR9812653-9A patent/BR9812653A/pt not_active IP Right Cessation
- 1998-09-18 NZ NZ503339A patent/NZ503339A/en unknown
- 1998-09-18 CA CA002304397A patent/CA2304397A1/fr not_active Abandoned
- 1998-09-18 CN CN98810341A patent/CN1276790A/zh active Pending
- 1998-09-18 AU AU91705/98A patent/AU746707B2/en not_active Ceased
- 1998-09-18 EA EA200000334A patent/EA003093B1/ru not_active IP Right Cessation
- 1998-09-18 IL IL13496198A patent/IL134961A/en not_active IP Right Cessation
- 1998-09-18 JP JP2000512830A patent/JP3456970B2/ja not_active Expired - Fee Related
- 1998-09-18 EP EP98944024A patent/EP1017693A1/fr not_active Withdrawn
- 1998-09-18 TW TW087115602A patent/TW430664B/zh active
- 1998-09-18 HR HR20000153A patent/HRP20000153A2/hr not_active Application Discontinuation
- 1998-09-18 US US09/508,830 patent/US6380230B1/en not_active Expired - Fee Related
- 1998-09-18 TR TR2000/01218T patent/TR200001218T2/xx unknown
- 1998-09-18 KR KR1020007002905A patent/KR20010030629A/ko not_active Ceased
- 1998-09-18 SK SK405-2000A patent/SK4052000A3/sk unknown
- 1998-09-18 ID IDW20000504A patent/ID25528A/id unknown
- 1998-09-18 WO PCT/FR1998/002007 patent/WO1999015525A1/fr not_active Ceased
- 1998-09-18 HU HU0100225A patent/HUP0100225A3/hu unknown
- 1998-09-18 EE EEP200000168A patent/EE200000168A/xx unknown
2000
- 2000-03-16 IS IS5409A patent/IS5409A/is unknown
- 2000-03-17 BG BG104254A patent/BG104254A/xx unknown
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Also Published As

Publication number	Publication date
KR20010030629A (ko)	2001-04-16
EP1017693A1 (fr)	2000-07-12
NO20001409L (no)	2000-05-16
PL339292A1 (en)	2000-12-04
TR200001218T2 (tr)	2001-05-21
HUP0100225A3 (en)	2003-05-28
IL134961A0 (en)	2001-05-20
CA2304397A1 (fr)	1999-04-01
JP2001517667A (ja)	2001-10-09
CO4970713A1 (es)	2000-11-07
US6380230B1 (en)	2002-04-30
CN1276790A (zh)	2000-12-13
NO20001409D0 (no)	2000-03-17
WO1999015525A1 (fr)	1999-04-01
NZ503339A (en)	2002-03-28
AU9170598A (en)	1999-04-12
SK4052000A3 (en)	2001-03-12
ID25528A (id)	2000-10-12
EE200000168A (et)	2001-04-16
BG104254A (en)	2001-08-31
HRP20000153A2 (en)	2001-04-30
IS5409A (is)	2000-03-16
MY141444A (en)	2010-04-30
UY25180A1 (es)	2001-06-29
HUP0100225A2 (hu)	2001-09-28
EA200000334A1 (ru)	2000-10-30
BR9812653A (pt)	2000-08-22
AU746707B2 (en)	2002-05-02
NO314455B1 (no)	2003-03-24
JP3456970B2 (ja)	2003-10-14
AR013494A1 (es)	2000-12-27
TW430664B (en)	2001-04-21
EA003093B1 (ru)	2002-12-26

Legal Events

Date	Code	Title
2003-01-12	FF	Patent granted
2003-01-12	KB	Patent renewed
2005-07-25	MM9K	Patent not in force due to non-payment of renewal fees

Publication	Publication Date	Title
US6380230B1 (en)	2002-04-30	Carboxamidothiazole derivatives, preparation, pharmaceutical compositions containing them
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