SK122099A3 - Substituted 4-arylmethylene-2-imino-2,3-dihydrothiazoles and derivatives and their pharmaceutical use - Google Patents

Substituted 4-arylmethylene-2-imino-2,3-dihydrothiazoles and derivatives and their pharmaceutical use Download PDF

Info

Publication number: SK122099A3
Authority: SK; Slovakia
Prior art keywords: cyclobutyl; dihydrothiazole; optionally substituted; carbon atoms; dichlorophenyl
Prior art date: 1997-03-15

Application number

SK1220-99A

Other languages

English (en)

Slovak (sk)

Inventor

Sharon Cheetham

Frank Kerrigan

Colin Gerhart Pryce Jones

Original Assignee

Knoll 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.)

1997-03-15

Filing date

1998-03-09

Publication date

2000-05-16

1998-03-09 Application filed by Knoll Ag filed Critical Knoll Ag

2000-05-16 Publication of SK122099A3 publication Critical patent/SK122099A3/sk

Links

150000001875 compounds Chemical class 0.000 claims abstract description 157
239000000203 mixture Substances 0.000 claims abstract description 115
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 90
-1 benzo[b]thiophenyl Chemical group 0.000 claims abstract description 50
125000000217 alkyl group Chemical group 0.000 claims abstract description 45
238000000034 method Methods 0.000 claims abstract description 26
125000003118 aryl group Chemical group 0.000 claims abstract description 23
125000004429 atom Chemical group 0.000 claims abstract description 22
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 21
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 18
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract description 17
150000003839 salts Chemical class 0.000 claims abstract description 16
125000001624 naphthyl group Chemical group 0.000 claims abstract description 12
208000018737 Parkinson disease Diseases 0.000 claims abstract description 9
125000002947 alkylene group Chemical group 0.000 claims abstract description 9
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 9
208000019901 Anxiety disease Diseases 0.000 claims abstract description 7
206010010904 Convulsion Diseases 0.000 claims abstract description 7
208000012902 Nervous system disease Diseases 0.000 claims abstract description 7
208000025966 Neurological disease Diseases 0.000 claims abstract description 7
208000008589 Obesity Diseases 0.000 claims abstract description 7
230000036506 anxiety Effects 0.000 claims abstract description 7
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 7
208000010877 cognitive disease Diseases 0.000 claims abstract description 7
235000020824 obesity Nutrition 0.000 claims abstract description 7
125000003342 alkenyl group Chemical group 0.000 claims abstract description 6
125000004446 heteroarylalkyl group Chemical group 0.000 claims abstract description 6
239000004090 neuroprotective agent Substances 0.000 claims abstract description 6
208000020401 Depressive disease Diseases 0.000 claims abstract description 5
125000004183 alkoxy alkyl group Chemical group 0.000 claims abstract description 5
125000005002 aryl methyl group Chemical group 0.000 claims abstract description 5
125000004981 cycloalkylmethyl group Chemical group 0.000 claims abstract description 5
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 72
125000005843 halogen group Chemical group 0.000 claims description 55
125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 34
229910052736 halogen Inorganic materials 0.000 claims description 29
150000002367 halogens Chemical class 0.000 claims description 28
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 26
125000001424 substituent group Chemical group 0.000 claims description 24
125000003545 alkoxy group Chemical group 0.000 claims description 21
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 20
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 17
125000004414 alkyl thio group Chemical group 0.000 claims description 17
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 14
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
125000005605 benzo group Chemical group 0.000 claims description 10
239000008194 pharmaceutical composition Substances 0.000 claims description 9
238000002360 preparation method Methods 0.000 claims description 8
239000002253 acid Substances 0.000 claims description 6
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 5
125000001544 thienyl group Chemical group 0.000 claims description 5
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 4
RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 4
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 3
XSJMTOGUYJUHOZ-UHFFFAOYSA-N 4-(1-naphthalen-2-ylcyclobutyl)-n,3-bis(2-phenylethyl)-1,3-thiazol-2-imine;hydrobromide Chemical compound Br.S1C=C(C2(CCC2)C=2C=C3C=CC=CC3=CC=2)N(CCC=2C=CC=CC=2)C1=NCCC1=CC=CC=C1 XSJMTOGUYJUHOZ-UHFFFAOYSA-N 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims description 2
IMQGPVYEWRJWIC-UHFFFAOYSA-N 3-(1-naphthalen-2-ylcyclobutyl)-5,6-dihydroimidazo[2,1-b][1,3]thiazole Chemical compound C1CCC1(C=1C=C2C=CC=CC2=CC=1)C1=CSC2=NCCN12 IMQGPVYEWRJWIC-UHFFFAOYSA-N 0.000 claims description 2
PXUUKOHHLWOYSK-UHFFFAOYSA-N 3-[1-(1-benzothiophen-2-yl)cyclobutyl]-5,6-dihydroimidazo[2,1-b][1,3]thiazole Chemical compound C1CCC1(C=1SC2=CC=CC=C2C=1)C1=CSC2=NCCN12 PXUUKOHHLWOYSK-UHFFFAOYSA-N 0.000 claims description 2
FJAAZBLQWSUTDT-UHFFFAOYSA-N 3-[1-(4-chlorophenyl)cyclobutyl]-5,6-dihydroimidazo[2,1-b][1,3]thiazole Chemical compound C1=CC(Cl)=CC=C1C1(C=2N3CCN=C3SC=2)CCC1 FJAAZBLQWSUTDT-UHFFFAOYSA-N 0.000 claims description 2
IFBZTJGMQIDPEE-UHFFFAOYSA-N 3-[1-(4-chlorophenyl)cyclobutyl]-6,7-dihydro-5h-[1,3]thiazolo[3,2-a]pyrimidine Chemical compound C1=CC(Cl)=CC=C1C1(C=2N3CCCN=C3SC=2)CCC1 IFBZTJGMQIDPEE-UHFFFAOYSA-N 0.000 claims description 2
RNVGATJASLYQQY-UHFFFAOYSA-N 4-(1-naphthalen-2-ylcyclobutyl)-n,3-di(propan-2-yl)-1,3-thiazol-2-imine Chemical compound CC(C)N1C(=NC(C)C)SC=C1C1(C=2C=C3C=CC=CC3=CC=2)CCC1 RNVGATJASLYQQY-UHFFFAOYSA-N 0.000 claims description 2
WGBOGKTXQZWLLF-UHFFFAOYSA-N 4-(1-naphthalen-2-ylcyclobutyl)-n,3-diphenyl-1,3-thiazol-2-imine Chemical compound C1CCC1(C=1C=C2C=CC=CC2=CC=1)C(N1C=2C=CC=CC=2)=CSC1=NC1=CC=CC=C1 WGBOGKTXQZWLLF-UHFFFAOYSA-N 0.000 claims description 2
CDWVJCIZYWAEEA-UHFFFAOYSA-N 4-(1-naphthalen-2-ylcyclobutyl)-n,3-dipropyl-1,3-thiazol-2-imine Chemical compound CCCN1C(=NCCC)SC=C1C1(C=2C=C3C=CC=CC3=CC=2)CCC1 CDWVJCIZYWAEEA-UHFFFAOYSA-N 0.000 claims description 2
RXGDHIWZZQULHE-UHFFFAOYSA-N 4-[1-(3,4-dichlorophenyl)cyclobutyl]-n,3-dimethyl-1,3-thiazol-2-imine Chemical compound CN1C(=NC)SC=C1C1(C=2C=C(Cl)C(Cl)=CC=2)CCC1 RXGDHIWZZQULHE-UHFFFAOYSA-N 0.000 claims description 2
SAYNFWNERVXDAS-UHFFFAOYSA-N 4-[1-(4-chlorophenyl)cyclobutyl]-n,3-bis(2-phenylethyl)-1,3-thiazol-2-imine Chemical compound C1=CC(Cl)=CC=C1C1(C=2N(C(=NCCC=3C=CC=CC=3)SC=2)CCC=2C=CC=CC=2)CCC1 SAYNFWNERVXDAS-UHFFFAOYSA-N 0.000 claims description 2
PXKXCQKMJZYMHQ-UHFFFAOYSA-N 4-[1-(4-chlorophenyl)cyclobutyl]-n,3-bis[2-(3,4-dimethoxyphenyl)ethyl]-1,3-thiazol-2-imine Chemical compound C1=C(OC)C(OC)=CC=C1CCN=C1N(CCC=2C=C(OC)C(OC)=CC=2)C(C2(CCC2)C=2C=CC(Cl)=CC=2)=CS1 PXKXCQKMJZYMHQ-UHFFFAOYSA-N 0.000 claims description 2
XPOSGVNDXZZZCC-UHFFFAOYSA-N 4-[1-(4-chlorophenyl)cyclopentyl]-n,3-bis[2-(3,4-dimethoxyphenyl)ethyl]-1,3-thiazol-2-imine Chemical compound C1=C(OC)C(OC)=CC=C1CCN=C1N(CCC=2C=C(OC)C(OC)=CC=2)C(C2(CCCC2)C=2C=CC(Cl)=CC=2)=CS1 XPOSGVNDXZZZCC-UHFFFAOYSA-N 0.000 claims description 2
125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 2
PMPVIKIVABFJJI-UHFFFAOYSA-N Cyclobutane Chemical compound C1CCC1 PMPVIKIVABFJJI-UHFFFAOYSA-N 0.000 claims description 2
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims description 2
KWRRHLASKBQPDJ-UHFFFAOYSA-N n,3-bis(2-methylphenyl)-4-(1-naphthalen-2-ylcyclobutyl)-1,3-thiazol-2-imine Chemical compound CC1=CC=CC=C1N=C1N(C=2C(=CC=CC=2)C)C(C2(CCC2)C=2C=C3C=CC=CC3=CC=2)=CS1 KWRRHLASKBQPDJ-UHFFFAOYSA-N 0.000 claims description 2
CSPXAVBPGIWJHG-UHFFFAOYSA-N n,3-bis(2-methylpropyl)-4-(1-naphthalen-2-ylcyclobutyl)-1,3-thiazol-2-imine Chemical compound CC(C)CN1C(=NCC(C)C)SC=C1C1(C=2C=C3C=CC=CC3=CC=2)CCC1 CSPXAVBPGIWJHG-UHFFFAOYSA-N 0.000 claims description 2
QKPGGSNTODJGDR-UHFFFAOYSA-N n,3-bis[2-(3,4-dimethoxyphenyl)ethyl]-4-(1-phenylcyclohexyl)-1,3-thiazol-2-imine Chemical compound C1=C(OC)C(OC)=CC=C1CCN=C1N(CCC=2C=C(OC)C(OC)=CC=2)C(C2(CCCCC2)C=2C=CC=CC=2)=CS1 QKPGGSNTODJGDR-UHFFFAOYSA-N 0.000 claims description 2
NVDZFNJLGAUSAP-UHFFFAOYSA-N n,3-dibenzyl-4-(1-naphthalen-2-ylcyclobutyl)-1,3-thiazol-2-imine Chemical compound C=1C=CC=CC=1CN=C1SC=C(C2(CCC2)C=2C=C3C=CC=CC3=CC=2)N1CC1=CC=CC=C1 NVDZFNJLGAUSAP-UHFFFAOYSA-N 0.000 claims description 2
FRCKIPCJLBMWSC-UHFFFAOYSA-N n,3-dibenzyl-4-[1-(3,4-dichlorophenyl)cyclobutyl]-1,3-thiazol-2-imine Chemical compound C1=C(Cl)C(Cl)=CC=C1C1(C=2N(C(=NCC=3C=CC=CC=3)SC=2)CC=2C=CC=CC=2)CCC1 FRCKIPCJLBMWSC-UHFFFAOYSA-N 0.000 claims description 2
IKCHWBKMJXOGEQ-UHFFFAOYSA-N n,3-dibutyl-4-(1-naphthalen-2-ylcyclobutyl)-1,3-thiazol-2-imine Chemical compound CCCCN1C(=NCCCC)SC=C1C1(C=2C=C3C=CC=CC3=CC=2)CCC1 IKCHWBKMJXOGEQ-UHFFFAOYSA-N 0.000 claims description 2
HBTFJAQDPFOROU-UHFFFAOYSA-N n,3-dibutyl-4-(1-phenylcyclohexyl)-1,3-thiazol-2-imine Chemical compound CCCCN1C(=NCCCC)SC=C1C1(C=2C=CC=CC=2)CCCCC1 HBTFJAQDPFOROU-UHFFFAOYSA-N 0.000 claims description 2
IAJLHNUYVOHYLL-UHFFFAOYSA-N n,3-dibutyl-4-[1-(3,4-dichlorophenyl)cyclobutyl]-1,3-thiazol-2-imine Chemical compound CCCCN1C(=NCCCC)SC=C1C1(C=2C=C(Cl)C(Cl)=CC=2)CCC1 IAJLHNUYVOHYLL-UHFFFAOYSA-N 0.000 claims description 2
KQRVGGHUMAMWJV-UHFFFAOYSA-N n,3-dibutyl-4-[1-(4-chlorophenyl)cyclobutyl]-1,3-thiazol-2-imine Chemical compound CCCCN1C(=NCCCC)SC=C1C1(C=2C=CC(Cl)=CC=2)CCC1 KQRVGGHUMAMWJV-UHFFFAOYSA-N 0.000 claims description 2
AEBTXXPVYTZLBI-UHFFFAOYSA-N n,3-dibutyl-4-[1-(4-chlorophenyl)cyclopentyl]-1,3-thiazol-2-imine Chemical compound CCCCN1C(=NCCCC)SC=C1C1(C=2C=CC(Cl)=CC=2)CCCC1 AEBTXXPVYTZLBI-UHFFFAOYSA-N 0.000 claims description 2
REBBPYPTMSAMAX-UHFFFAOYSA-N n,3-dibutyl-4-[1-(4-methylsulfanylphenyl)cyclobutyl]-1,3-thiazol-2-imine Chemical compound CCCCN1C(=NCCCC)SC=C1C1(C=2C=CC(SC)=CC=2)CCC1 REBBPYPTMSAMAX-UHFFFAOYSA-N 0.000 claims description 2
UVZURDAAGUIBDB-UHFFFAOYSA-N n,3-dibutyl-4-[1-(4-phenoxyphenyl)cyclobutyl]-1,3-thiazol-2-imine Chemical compound CCCCN1C(=NCCCC)SC=C1C1(C=2C=CC(OC=3C=CC=CC=3)=CC=2)CCC1 UVZURDAAGUIBDB-UHFFFAOYSA-N 0.000 claims description 2
OKQDCONLUFMRRB-UHFFFAOYSA-N n,3-dibutyl-4-[2-(3,4-dichlorophenyl)propan-2-yl]-1,3-thiazol-2-imine Chemical compound CCCCN1C(=NCCCC)SC=C1C(C)(C)C1=CC=C(Cl)C(Cl)=C1 OKQDCONLUFMRRB-UHFFFAOYSA-N 0.000 claims description 2
PCPLTHOXMONZNR-UHFFFAOYSA-N n,3-dibutyl-4-[2-(4-chlorophenyl)propan-2-yl]-1,3-thiazol-2-imine Chemical compound CCCCN1C(=NCCCC)SC=C1C(C)(C)C1=CC=C(Cl)C=C1 PCPLTHOXMONZNR-UHFFFAOYSA-N 0.000 claims description 2
CONIZJYXKKRKSS-UHFFFAOYSA-N n,3-dicyclopentyl-4-(1-naphthalen-2-ylcyclobutyl)-1,3-thiazol-2-imine Chemical compound C1CCC1(C=1C=C2C=CC=CC2=CC=1)C(N1C2CCCC2)=CSC1=NC1CCCC1 CONIZJYXKKRKSS-UHFFFAOYSA-N 0.000 claims description 2
UPPLRJUXHBGVKT-UHFFFAOYSA-N n,3-diethyl-4-(1-naphthalen-2-ylcyclobutyl)-1,3-thiazol-2-imine Chemical compound CCN1C(=NCC)SC=C1C1(C=2C=C3C=CC=CC3=CC=2)CCC1 UPPLRJUXHBGVKT-UHFFFAOYSA-N 0.000 claims description 2
DZYFSRTUKOTIRK-UHFFFAOYSA-N n,3-dimethyl-4-(1-naphthalen-2-ylcyclobutyl)-1,3-thiazol-2-imine Chemical compound CN1C(=NC)SC=C1C1(C=2C=C3C=CC=CC3=CC=2)CCC1 DZYFSRTUKOTIRK-UHFFFAOYSA-N 0.000 claims description 2
CIBLYVDBPQODMS-UHFFFAOYSA-N 2-(4-chlorophenyl)-3-[1-(3,4-dichlorophenyl)cyclobutyl]-5,6-dihydroimidazo[2,1-b][1,3]thiazole Chemical compound C1=CC(Cl)=CC=C1C(S1)=C(C2(CCC2)C=2C=C(Cl)C(Cl)=CC=2)N2C1=NCC2 CIBLYVDBPQODMS-UHFFFAOYSA-N 0.000 claims 1
VXOOZUIPGJDXFW-UHFFFAOYSA-N 3-[1-(3,4-dichlorophenyl)cyclobutyl]-5,6-dihydroimidazo[2,1-b][1,3]thiazole Chemical compound C1=C(Cl)C(Cl)=CC=C1C1(C=2N3CCN=C3SC=2)CCC1 VXOOZUIPGJDXFW-UHFFFAOYSA-N 0.000 claims 1
OPRWDOSGHNUXJJ-UHFFFAOYSA-N 3-[1-(3,4-dichlorophenyl)cyclobutyl]-6,7-dihydro-5h-[1,3]thiazolo[3,2-a]pyrimidine Chemical compound C1=C(Cl)C(Cl)=CC=C1C1(C=2N3CCCN=C3SC=2)CCC1 OPRWDOSGHNUXJJ-UHFFFAOYSA-N 0.000 claims 1
SECAURYILIOHPG-UHFFFAOYSA-N 3-[1-(3,4-dichlorophenyl)cyclopentyl]-5,6-dihydroimidazo[2,1-b][1,3]thiazole Chemical compound C1=C(Cl)C(Cl)=CC=C1C1(C=2N3CCN=C3SC=2)CCCC1 SECAURYILIOHPG-UHFFFAOYSA-N 0.000 claims 1
MZOWPOUCGQRRRL-UHFFFAOYSA-N 3-[2-(3,4-dichlorophenyl)propan-2-yl]-5,6-dihydroimidazo[2,1-b][1,3]thiazole Chemical compound C=1SC2=NCCN2C=1C(C)(C)C1=CC=C(Cl)C(Cl)=C1 MZOWPOUCGQRRRL-UHFFFAOYSA-N 0.000 claims 1
ZAOCXCZGWRLKTJ-UHFFFAOYSA-N 4-[1-(3,4-dichlorophenyl)cyclobutyl]-n,3-bis(2-methylpropyl)-1,3-thiazol-2-imine Chemical compound CC(C)CN1C(=NCC(C)C)SC=C1C1(C=2C=C(Cl)C(Cl)=CC=2)CCC1 ZAOCXCZGWRLKTJ-UHFFFAOYSA-N 0.000 claims 1
DNGZPFFIMISZDC-UHFFFAOYSA-N 4-[1-(3,4-dichlorophenyl)cyclobutyl]-n,3-bis(furan-2-ylmethyl)-1,3-thiazol-2-imine Chemical compound C1=C(Cl)C(Cl)=CC=C1C1(C=2N(C(=NCC=3OC=CC=3)SC=2)CC=2OC=CC=2)CCC1 DNGZPFFIMISZDC-UHFFFAOYSA-N 0.000 claims 1
MNJCSWIOOMKMOW-UHFFFAOYSA-N 4-[1-(3,4-dichlorophenyl)cyclobutyl]-n,3-di(propan-2-yl)-1,3-thiazol-2-imine Chemical compound CC(C)N1C(=NC(C)C)SC=C1C1(C=2C=C(Cl)C(Cl)=CC=2)CCC1 MNJCSWIOOMKMOW-UHFFFAOYSA-N 0.000 claims 1
MWNINNMHDQJBCZ-UHFFFAOYSA-N 4-[1-(3,4-dichlorophenyl)cyclobutyl]-n,3-diethyl-1,3-thiazol-2-imine Chemical compound CCN1C(=NCC)SC=C1C1(C=2C=C(Cl)C(Cl)=CC=2)CCC1 MWNINNMHDQJBCZ-UHFFFAOYSA-N 0.000 claims 1
YMGYOLFMBMYUFX-UHFFFAOYSA-N 4-[1-(4-bromophenyl)cyclobutyl]-n,3-dibutyl-1,3-thiazol-2-imine Chemical compound CCCCN1C(=NCCCC)SC=C1C1(C=2C=CC(Br)=CC=2)CCC1 YMGYOLFMBMYUFX-UHFFFAOYSA-N 0.000 claims 1
WMZFWNCXRDJSJY-UHFFFAOYSA-N n,3-bis(furan-2-ylmethyl)-4-(1-naphthalen-2-ylcyclobutyl)-1,3-thiazol-2-imine Chemical compound C=1C=COC=1CN=C1SC=C(C2(CCC2)C=2C=C3C=CC=CC3=CC=2)N1CC1=CC=CO1 WMZFWNCXRDJSJY-UHFFFAOYSA-N 0.000 claims 1
DINXQSYNWHLKSS-UHFFFAOYSA-N n,3-bis[2-(3,4-dimethoxyphenyl)ethyl]-4-(1-naphthalen-2-ylcyclobutyl)-1,3-thiazol-2-imine Chemical compound C1=C(OC)C(OC)=CC=C1CCN=C1N(CCC=2C=C(OC)C(OC)=CC=2)C(C2(CCC2)C=2C=C3C=CC=CC3=CC=2)=CS1 DINXQSYNWHLKSS-UHFFFAOYSA-N 0.000 claims 1
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 1
229910052739 hydrogen Inorganic materials 0.000 abstract description 5
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 120
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 92
238000004128 high performance liquid chromatography Methods 0.000 description 66
239000000243 solution Substances 0.000 description 61
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 58
239000002904 solvent Substances 0.000 description 52
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 51
239000007787 solid Substances 0.000 description 45
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
230000009102 absorption Effects 0.000 description 34
238000010521 absorption reaction Methods 0.000 description 34
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 34
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
238000001914 filtration Methods 0.000 description 33
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 28
238000003756 stirring Methods 0.000 description 28
238000010992 reflux Methods 0.000 description 26
239000000047 product Substances 0.000 description 25
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
239000003921 oil Substances 0.000 description 22
235000019198 oils Nutrition 0.000 description 22
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/10—Spiro-condensed systems
- 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
- 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
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- A61P25/08—Antiepileptics; Anticonvulsants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
- 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
- A61P25/22—Anxiolytics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- 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
- 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
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/42—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems

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Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
Psychology (AREA)
Diabetes (AREA)
Obesity (AREA)
Hospice & Palliative Care (AREA)
Child & Adolescent Psychology (AREA)
Hematology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Thiazole And Isothizaole Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Steroid Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Plural Heterocyclic Compounds (AREA)

SK1220-99A 1997-03-15 1998-03-09 Substituted 4-arylmethylene-2-imino-2,3-dihydrothiazoles and derivatives and their pharmaceutical use SK122099A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB9705428.2A GB9705428D0 (en)	1997-03-15	1997-03-15	Therapeutic agents
PCT/EP1998/001358 WO1998041528A1 (en)	1997-03-15	1998-03-09	Substituted 4-arylmethylene-2-imino-2,3-dihydrothiazoles and derivatives and their pharmaceutical use

Publications (1)

Publication Number	Publication Date
SK122099A3 true SK122099A3 (en)	2000-05-16

Family

ID=10809320

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1220-99A SK122099A3 (en)	1997-03-15	1998-03-09	Substituted 4-arylmethylene-2-imino-2,3-dihydrothiazoles and derivatives and their pharmaceutical use

Country Status (22)

Country	Link
US (1)	US6187802B1 (de)
EP (1)	EP0970090B1 (de)
JP (1)	JP2001515501A (de)
KR (1)	KR20000076190A (de)
CN (1)	CN1255136A (de)
AT (1)	ATE218573T1 (de)
AU (1)	AU6728898A (de)
BG (1)	BG103754A (de)
BR (1)	BR9808254A (de)
CA (1)	CA2283438A1 (de)
DE (1)	DE69805781D1 (de)
GB (1)	GB9705428D0 (de)
HU (1)	HUP0001508A3 (de)
ID (1)	ID22636A (de)
IL (1)	IL131515A0 (de)
NO (1)	NO994452D0 (de)
NZ (1)	NZ337378A (de)
PL (1)	PL335696A1 (de)
SK (1)	SK122099A3 (de)
TR (1)	TR199902291T2 (de)
WO (1)	WO1998041528A1 (de)
ZA (1)	ZA982134B (de)

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US6803387B1 (en)	1999-03-19	2004-10-12	Abbott Gmbh & Co. Kg	Treatment of neuropathic pain or fibromyalgia
WO2000056321A1 (en)	1999-03-19	2000-09-28	Knoll Pharmaceutical Company	Treatment of hyperactivity disorders
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FR2796643B1 (fr) *	1999-07-22	2005-04-29	Sod Conseils Rech Applic	Derives de 2-arylimino-2, 3-dihydrothiazoles, leurs procedes de preparation et leur utilisation therapeutique
GB0005789D0 (en) *	2000-03-11	2000-05-03	Knoll Ag	Therapeutic agents
US6699866B2 (en)	2001-04-17	2004-03-02	Sepracor Inc.	Thiazole and other heterocyclic ligands for mammalian dopamine, muscarinic and serotonin receptors and transporters, and methods of use thereof
US20060281797A1 (en) *	2001-12-11	2006-12-14	University Of Virginia Patent Foundation	Neurorestoration with R(+) Pramipexole
ES2432527T3 (es) *	2001-12-11	2013-12-04	University Of Virginia Patent Foundation	Uso de pramipexol para tratar la esclerosis lateral amiotrófica
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WO2007121188A2 (en) *	2006-04-10	2007-10-25	Knopp Neurosciences, Inc.	Compositions and methods of using r(+) pramipexole
ES2379117T3 (es)	2006-05-16	2012-04-20	Knopp Neurosciences, Inc.	Composiciones de R(+) y S(-) pramipexol y métodos de utilización de las mismas
US8524695B2 (en) *	2006-12-14	2013-09-03	Knopp Neurosciences, Inc.	Modified release formulations of (6R)-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazole-diamine and methods of using the same
CA2681110A1 (en) *	2007-03-14	2008-09-18	Knopp Neurosciences, Inc.	Synthesis of chirally purified substituted benzothiazole diamines
KR20110071064A (ko) *	2008-08-19	2011-06-28	크놉 뉴로사이언시스 인코포레이티드	(ｒ)-프라미펙솔을 사용하는 조성물 및 방법
KR101049935B1 (ko) *	2008-12-03	2011-07-15	한국과학기술연구원	신규한 티아졸린계 화합물 및 이를 포함하는 ｔ-형 칼슘 채널 저해제
RU2012101792A (ru) *	2009-06-19	2013-07-27	Нопп Ньюросайенсиз, Инк.	Композиции и способы для лечения бокового амиотрофического склероза
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US9468630B2 (en)	2013-07-12	2016-10-18	Knopp Biosciences Llc	Compositions and methods for treating conditions related to increased eosinophils
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1997
- 1997-03-15 GB GBGB9705428.2A patent/GB9705428D0/en active Pending
1998
- 1998-03-09 BR BR9808254-0A patent/BR9808254A/pt not_active IP Right Cessation
- 1998-03-09 AT AT98912459T patent/ATE218573T1/de not_active IP Right Cessation
- 1998-03-09 IL IL13151598A patent/IL131515A0/xx unknown
- 1998-03-09 TR TR1999/02291T patent/TR199902291T2/xx unknown
- 1998-03-09 US US09/380,967 patent/US6187802B1/en not_active Expired - Fee Related
- 1998-03-09 JP JP54009198A patent/JP2001515501A/ja active Pending
- 1998-03-09 ID IDW991023A patent/ID22636A/id unknown
- 1998-03-09 KR KR1019997008284A patent/KR20000076190A/ko not_active Withdrawn
- 1998-03-09 DE DE69805781T patent/DE69805781D1/de not_active Expired - Lifetime
- 1998-03-09 AU AU67288/98A patent/AU6728898A/en not_active Abandoned
- 1998-03-09 PL PL98335696A patent/PL335696A1/xx unknown
- 1998-03-09 CN CN98804891A patent/CN1255136A/zh active Pending
- 1998-03-09 EP EP98912459A patent/EP0970090B1/de not_active Expired - Lifetime
- 1998-03-09 NZ NZ337378A patent/NZ337378A/xx unknown
- 1998-03-09 SK SK1220-99A patent/SK122099A3/sk unknown
- 1998-03-09 WO PCT/EP1998/001358 patent/WO1998041528A1/en not_active Ceased
- 1998-03-09 HU HU0001508A patent/HUP0001508A3/hu unknown
- 1998-03-09 CA CA002283438A patent/CA2283438A1/en not_active Abandoned
- 1998-03-13 ZA ZA9802134A patent/ZA982134B/xx unknown
1999
- 1999-09-14 NO NO994452A patent/NO994452D0/no unknown
- 1999-09-24 BG BG103754A patent/BG103754A/bg unknown

Also Published As

Publication number	Publication date
DE69805781D1 (de)	2002-07-11
WO1998041528A1 (en)	1998-09-24
CA2283438A1 (en)	1998-09-24
BR9808254A (pt)	2000-05-16
NZ337378A (en)	2001-01-26
NO994452L (no)	1999-09-14
TR199902291T2 (xx)	1999-12-21
HUP0001508A2 (hu)	2001-01-29
ID22636A (id)	1999-12-02
US6187802B1 (en)	2001-02-13
ZA982134B (en)	1999-09-13
ATE218573T1 (de)	2002-06-15
EP0970090A1 (de)	2000-01-12
KR20000076190A (ko)	2000-12-26
JP2001515501A (ja)	2001-09-18
NO994452D0 (no)	1999-09-14
EP0970090B1 (de)	2002-06-05
IL131515A0 (en)	2001-01-28
BG103754A (bg)	2000-06-30
PL335696A1 (en)	2000-05-08
HUP0001508A3 (en)	2003-01-28
GB9705428D0 (en)	1997-04-30
AU6728898A (en)	1998-10-12
CN1255136A (zh)	2000-05-31

Publication	Publication Date	Title
SK122099A3 (en)	2000-05-16	Substituted 4-arylmethylene-2-imino-2,3-dihydrothiazoles and derivatives and their pharmaceutical use
RU2593756C2 (ru)	2016-08-10	Конденсированные производные аминодигидротиазина, пригодные в качестве ингибиторов васе
SK16852001A3 (sk)	2002-05-09	Tiazolové deriváty a farmaceutické kompozície ich obsahujúce
IL266962A (en)	2019-07-31	Troyilphenoxide Benzamide Capaide Opioids Legends, Preparations Containing Them and Their Uses
PL190721B1 (pl)	2005-12-30	Pochodna alkiloaminobenzotiazolu i alkiloaminobenzoksazolu, sposób ich wytwarzania oraz kompozycja farmaceutyczna
SK16842001A3 (sk)	2002-04-04	Substituované imidazotiazoly ako antidepresívne prostriedky
JPH04234860A (ja)	1992-08-24	チアジン（又はオキサジン）誘導体、その製法及びその合成中間体
AU708789B2 (en)	1999-08-12	Condensed thiazole derivatives, having 5-HT receptor affinity
TWI376373B (en)	2012-11-11	Crystalline base of a pharmaceutical compound
SK1382001A3 (en)	2001-08-06	N-SUBSTITUTED AZABICYCLOHEPTANE DERIVATIVES, PRODUCTION AND USEì (54) THEREOF
CZ9903260A3 (cs)	2000-11-15	Terapeutická činidla
US6458821B1 (en)	2002-10-01	N-substituted azabicycloheptane derivatives, production and use thereof
CA3045242C (en)	2025-09-23	Heteroarylphenoxy benzamide kappa opioid ligands
MXPA97009509A (en)	1998-10-15	Therapeutic agents
CA2340168A1 (en)	2000-02-24	N-substituted azabicycloheptane derivatives, production and use thereof
JPS61251676A (ja)	1986-11-08	新規トリメトキシベンジルピペラジン誘導体および該化合物を有効成分とする医薬組成物