SK4152003A3 - Substituted 3,4-dihydro-pyrimido[1,2-a]pyrimidines and 3,4-dihydropyrazino[1,2-a]pyrimidines, process for producing thereof, medicaments comprising same and their use - Google Patents

Substituted 3,4-dihydro-pyrimido[1,2-a]pyrimidines and 3,4-dihydropyrazino[1,2-a]pyrimidines, process for producing thereof, medicaments comprising same and their use Download PDF

Info

Publication number: SK4152003A3
Authority: SK; Slovakia
Prior art keywords: alkyl; dihydro; substituted; unsubstituted; group
Prior art date: 2000-10-13

Application number

SK415-2003A

Other languages

English (en)

Slovak (sk)

Inventor

Matthias Gerlach

Corinna Sundermann

Utz-Peter Jagusch

Original Assignee

Gruenenthal Chemie

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.)

2000-10-13

Filing date

2001-10-10

Publication date

2003-10-07

2001-10-10 Application filed by Gruenenthal Chemie filed Critical Gruenenthal Chemie

2003-10-07 Publication of SK4152003A3 publication Critical patent/SK4152003A3/sk

Links

238000000034 method Methods 0.000 title claims abstract description 32
239000003814 drug Substances 0.000 title claims abstract description 16
MECADPQDCNOAHD-UHFFFAOYSA-N 3,4-dihydro-2h-pyrazino[1,2-a]pyrimidine Chemical class C1=NC=CN2CCCN=C21 MECADPQDCNOAHD-UHFFFAOYSA-N 0.000 title claims description 15
VXXMURHWSOJZOW-UHFFFAOYSA-N 7,8-dihydro-6h-pyrimido[1,2-a]pyrimidine Chemical class N1=CC=CN2CCCN=C21 VXXMURHWSOJZOW-UHFFFAOYSA-N 0.000 title claims description 15
150000001875 compounds Chemical class 0.000 claims abstract description 65
239000000126 substance Substances 0.000 claims abstract description 13
208000002193 Pain Diseases 0.000 claims abstract description 12
238000004519 manufacturing process Methods 0.000 claims abstract description 7
206010012735 Diarrhoea Diseases 0.000 claims abstract description 6
208000009205 Tinnitus Diseases 0.000 claims abstract description 6
206010046543 Urinary incontinence Diseases 0.000 claims abstract description 6
231100000886 tinnitus Toxicity 0.000 claims abstract description 6
239000000825 pharmaceutical preparation Substances 0.000 claims abstract description 4
125000000217 alkyl group Chemical group 0.000 claims description 141
125000004432 carbon atom Chemical group C* 0.000 claims description 94
229920006395 saturated elastomer Polymers 0.000 claims description 87
-1 OR 10 Chemical class 0.000 claims description 86
125000003118 aryl group Chemical group 0.000 claims description 79
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 67
125000001072 heteroaryl group Chemical class 0.000 claims description 47
125000000753 cycloalkyl group Chemical group 0.000 claims description 39
229910052739 hydrogen Inorganic materials 0.000 claims description 39
239000001257 hydrogen Substances 0.000 claims description 38
150000003839 salts Chemical class 0.000 claims description 35
125000000623 heterocyclic group Chemical group 0.000 claims description 31
229910052799 carbon Inorganic materials 0.000 claims description 27
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 25
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 24
125000003107 substituted aryl group Chemical group 0.000 claims description 24
125000002877 alkyl aryl group Chemical class 0.000 claims description 17
229910052801 chlorine Inorganic materials 0.000 claims description 17
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 15
239000000460 chlorine Substances 0.000 claims description 15
125000005241 heteroarylamino group Chemical group 0.000 claims description 15
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 15
125000004093 cyano group Chemical group *C#N 0.000 claims description 14
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 12
LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 12
229910052794 bromium Inorganic materials 0.000 claims description 12
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
229910052731 fluorine Inorganic materials 0.000 claims description 12
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 11
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 11
239000011737 fluorine Substances 0.000 claims description 11
150000001336 alkenes Chemical class 0.000 claims description 10
125000001309 chloro group Chemical group Cl* 0.000 claims description 10
239000000203 mixture Substances 0.000 claims description 10
238000002360 preparation method Methods 0.000 claims description 10
ZFCHNZDUMIOWFV-UHFFFAOYSA-N pyrimidine-2-carboxylic acid Chemical compound OC(=O)C1=NC=CC=N1 ZFCHNZDUMIOWFV-UHFFFAOYSA-N 0.000 claims description 10
239000002253 acid Substances 0.000 claims description 9
238000006243 chemical reaction Methods 0.000 claims description 9
JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims description 9
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
RFPASPHXJLDWSI-UHFFFAOYSA-N 4-(4-methoxyphenyl)-3,4-dihydro-2h-pyrazino[1,2-a]pyrimidine-2-carboxylic acid Chemical compound C1=CC(OC)=CC=C1C1N2C=CN=CC2=NC(C(O)=O)C1 RFPASPHXJLDWSI-UHFFFAOYSA-N 0.000 claims description 7
125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
YVTNSQSJYKVXKF-UHFFFAOYSA-N 7-bromo-4-(4-methoxyphenyl)-3,4-dihydro-2h-pyrimido[1,2-a]pyrimidine-2-carboxylic acid Chemical compound C1=CC(OC)=CC=C1C1N2C=C(Br)C=NC2=NC(C(O)=O)C1 YVTNSQSJYKVXKF-UHFFFAOYSA-N 0.000 claims description 7
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 description 7
229910052757 nitrogen Inorganic materials 0.000 claims description 7
125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 6
125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 6
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 6
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 6
125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 6
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 6
125000001769 aryl amino group Chemical group 0.000 claims description 6
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 6
125000004986 diarylamino group Chemical group 0.000 claims description 6
125000004494 ethyl ester group Chemical group 0.000 claims description 6
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
ZEMVWNALNLEDRK-UHFFFAOYSA-N 4-phenylsulfanyl-3,4-dihydro-2h-pyrazino[1,2-a]pyrimidine-2-carboxylic acid Chemical compound N12C=CN=CC2=NC(C(=O)O)CC1SC1=CC=CC=C1 ZEMVWNALNLEDRK-UHFFFAOYSA-N 0.000 claims description 5
208000003251 Pruritus Diseases 0.000 claims description 5
125000004429 atom Chemical group 0.000 claims description 5
125000001246 bromo group Chemical group Br* 0.000 claims description 5
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
125000001153 fluoro group Chemical group F* 0.000 claims description 5
230000007803 itching Effects 0.000 claims description 5
229910052760 oxygen Inorganic materials 0.000 claims description 5
239000000546 pharmaceutical excipient Substances 0.000 claims description 5
229910052717 sulfur Inorganic materials 0.000 claims description 5
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 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
125000004947 alkyl aryl amino group Chemical group 0.000 claims description 4
125000005418 aryl aryl group Chemical group 0.000 claims description 4
125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 4
125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
239000003960 organic solvent Substances 0.000 claims description 4
WKOLRHSEBPKKPE-UHFFFAOYSA-N 2-cyclohexyl-4-(4-methoxyphenyl)-3,4-dihydro-2h-pyrazino[1,2-a]pyrimidine Chemical compound C1=CC(OC)=CC=C1C1N2C=CN=CC2=NC(C2CCCCC2)C1 WKOLRHSEBPKKPE-UHFFFAOYSA-N 0.000 claims description 3
ZXWRHLCAIPINLF-UHFFFAOYSA-N 2-cyclopropyl-4-(3,4-dimethoxyphenyl)-3,4-dihydro-2h-pyrazino[1,2-a]pyrimidine Chemical compound C1=C(OC)C(OC)=CC=C1C1N2C=CN=CC2=NC(C2CC2)C1 ZXWRHLCAIPINLF-UHFFFAOYSA-N 0.000 claims description 3
RIQYBJOTAWMHJO-UHFFFAOYSA-N 4-(3,4-dimethoxyphenyl)-3,4-dihydro-2h-pyrazino[1,2-a]pyrimidine-2-carboxylic acid Chemical compound C1=C(OC)C(OC)=CC=C1C1N2C=CN=CC2=NC(C(O)=O)C1 RIQYBJOTAWMHJO-UHFFFAOYSA-N 0.000 claims description 3
XRKOVTBLLFDYHR-UHFFFAOYSA-N 4-(4-methoxyphenyl)-3-methyl-2-(5-methylfuran-2-yl)-3,4-dihydro-2h-pyrazino[1,2-a]pyrimidine Chemical compound C1=CC(OC)=CC=C1C1N2C=CN=CC2=NC(C=2OC(C)=CC=2)C1C XRKOVTBLLFDYHR-UHFFFAOYSA-N 0.000 claims description 3
HOWFVKWIFBRPCW-UHFFFAOYSA-N 4-(7-bromo-2-cyclohexyl-3-methyl-3,4-dihydro-2h-pyrimido[1,2-a]pyrimidin-4-yl)phenol Chemical compound CC1C(C2CCCCC2)N=C2N=CC(Br)=CN2C1C1=CC=C(O)C=C1 HOWFVKWIFBRPCW-UHFFFAOYSA-N 0.000 claims description 3
WYRSPZVTTMUNBL-UHFFFAOYSA-N 9h-fluorene-3-carboxylic acid Chemical compound C1=CC=C2C3=CC(C(=O)O)=CC=C3CC2=C1 WYRSPZVTTMUNBL-UHFFFAOYSA-N 0.000 claims description 3
GADOQTRQMPJIPK-UHFFFAOYSA-N [4-(2-hydroxyethoxy)-3,4-dihydro-2h-pyrazino[1,2-a]pyrimidin-2-yl]-phenylmethanone Chemical compound N1=C2C=NC=CN2C(OCCO)CC1C(=O)C1=CC=CC=C1 GADOQTRQMPJIPK-UHFFFAOYSA-N 0.000 claims description 3
DXIQLNYJVNNUFP-UHFFFAOYSA-N [7-bromo-4-(4-hydroxyphenyl)-3-methyl-3,4-dihydro-2h-pyrimido[1,2-a]pyrimidin-2-yl]-phenylmethanone Chemical compound CC1C(C(=O)C=2C=CC=CC=2)N=C2N=CC(Br)=CN2C1C1=CC=C(O)C=C1 DXIQLNYJVNNUFP-UHFFFAOYSA-N 0.000 claims description 3
ITUVYXCBFLQLLX-UHFFFAOYSA-N [7-bromo-4-(4-methoxyphenyl)-3,4-dihydro-2h-pyrimido[1,2-a]pyrimidin-2-yl]-phenylmethanone Chemical compound C1=CC(OC)=CC=C1C1N2C=C(Br)C=NC2=NC(C(=O)C=2C=CC=CC=2)C1 ITUVYXCBFLQLLX-UHFFFAOYSA-N 0.000 claims description 3
LDDOSDVZPSGLFZ-UHFFFAOYSA-N ethyl cyclopropanecarboxylate Chemical compound CCOC(=O)C1CC1 LDDOSDVZPSGLFZ-UHFFFAOYSA-N 0.000 claims description 3
229910052740 iodine Inorganic materials 0.000 claims description 3
229940124531 pharmaceutical excipient Drugs 0.000 claims description 3
PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 3
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
OXJICKCEYOUAEQ-UHFFFAOYSA-N 2-chloro-6-phenylsulfanyl-8-pyridin-2-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-amine Chemical compound N12C(N)=CC(Cl)=NC2=NC(C=2N=CC=CC=2)CC1SC1=CC=CC=C1 OXJICKCEYOUAEQ-UHFFFAOYSA-N 0.000 claims description 2
DTDBWJWNKBTTEF-UHFFFAOYSA-N 2-phenylsulfanyl-3-pyridin-2-yl-2,3-dihydro-1h-pyrimido[1,2-a]quinolin-10-ol Chemical compound C1N2C=3C(O)=CC=CC=3C=CC2=NC(C=2N=CC=CC=2)C1SC1=CC=CC=C1 DTDBWJWNKBTTEF-UHFFFAOYSA-N 0.000 claims description 2
CSOYDALHEQEMAK-UHFFFAOYSA-N 2h-pyrimidine-1-carboxylic acid Chemical compound OC(=O)N1CN=CC=C1 CSOYDALHEQEMAK-UHFFFAOYSA-N 0.000 claims description 2
XLNNLLANXOHIEJ-UHFFFAOYSA-N 4-(4-methoxyphenyl)-2-(5-nitrofuran-2-yl)-3,4-dihydro-2h-pyrazino[1,2-a]pyrimidine Chemical compound C1=CC(OC)=CC=C1C1N2C=CN=CC2=NC(C=2OC(=CC=2)[N+]([O-])=O)C1 XLNNLLANXOHIEJ-UHFFFAOYSA-N 0.000 claims description 2
INJXNCQTWHOEKE-UHFFFAOYSA-N 4-hydroxy-6-phenylsulfanyl-8-pyridin-2-yl-1,6,7,8-tetrahydropyrimido[1,2-a]pyrimidin-2-one Chemical compound N12C(O)=CC(=O)NC2=NC(C=2N=CC=CC=2)CC1SC1=CC=CC=C1 INJXNCQTWHOEKE-UHFFFAOYSA-N 0.000 claims description 2
RTHGNLWQTDNVNX-UHFFFAOYSA-N 4-methyl-2-(5-nitrofuran-2-yl)-4-phenyl-2,3-dihydropyrazino[1,2-a]pyrimidine Chemical compound N1=C2C=NC=CN2C(C)(C=2C=CC=CC=2)CC1C1=CC=C([N+]([O-])=O)O1 RTHGNLWQTDNVNX-UHFFFAOYSA-N 0.000 claims description 2
PKTNUMVRSQSZOQ-UHFFFAOYSA-N 4-phenyl-2-pyridin-2-yl-3,4-dihydro-2h-pyrazino[1,2-a]pyrimidine Chemical compound C1C(C=2N=CC=CC=2)N=C2C=NC=CN2C1C1=CC=CC=C1 PKTNUMVRSQSZOQ-UHFFFAOYSA-N 0.000 claims description 2
FAQCWPLVJMZPHU-UHFFFAOYSA-N 4-phenyl-2-pyridin-2-yl-3,4-dihydro-2h-pyrazino[1,2-a]pyrimidine-9-carboxylic acid Chemical compound N1=C2C(C(=O)O)=NC=CN2C(C=2C=CC=CC=2)CC1C1=CC=CC=N1 FAQCWPLVJMZPHU-UHFFFAOYSA-N 0.000 claims description 2
YWHLHRNQIZJASO-UHFFFAOYSA-N 7-bromo-4-(3,4-dimethoxyphenyl)-3,4-dihydro-2h-pyrimido[1,2-a]pyrimidine-2-carboxylic acid Chemical compound C1=C(OC)C(OC)=CC=C1C1N2C=C(Br)C=NC2=NC(C(O)=O)C1 YWHLHRNQIZJASO-UHFFFAOYSA-N 0.000 claims description 2
ZQIABBZOMZQAPC-UHFFFAOYSA-N 7-bromo-4-phenylsulfanyl-2-pyridin-2-yl-3,4-dihydro-2h-pyrimido[1,2-a]pyrimidine Chemical compound N1=C2N=CC(Br)=CN2C(SC=2C=CC=CC=2)CC1C1=CC=CC=N1 ZQIABBZOMZQAPC-UHFFFAOYSA-N 0.000 claims description 2
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 2
KCZDVUCDBXGKKM-UHFFFAOYSA-N [4-(4-hydroxy-3-methoxyphenyl)-3-methyl-3,4-dihydro-2h-pyrazino[1,2-a]pyrimidin-2-yl]-phenylmethanone Chemical compound C1=C(O)C(OC)=CC(C2N3C=CN=CC3=NC(C2C)C(=O)C=2C=CC=CC=2)=C1 KCZDVUCDBXGKKM-UHFFFAOYSA-N 0.000 claims description 2
BAVRFMCXDRJGHI-UHFFFAOYSA-N [7-bromo-4-(2-hydroxyethoxy)-3,4-dihydro-2h-pyrimido[1,2-a]pyrimidin-2-yl]-phenylmethanone Chemical compound N1=C2N=CC(Br)=CN2C(OCCO)CC1C(=O)C1=CC=CC=C1 BAVRFMCXDRJGHI-UHFFFAOYSA-N 0.000 claims description 2
RNYZRZAOLHRMOP-UHFFFAOYSA-N [7-bromo-4-(4-hydroxy-3-methoxyphenyl)-3-methyl-3,4-dihydro-2h-pyrimido[1,2-a]pyrimidin-2-yl]-phenylmethanone Chemical compound C1=C(O)C(OC)=CC(C2N3C=C(Br)C=NC3=NC(C2C)C(=O)C=2C=CC=CC=2)=C1 RNYZRZAOLHRMOP-UHFFFAOYSA-N 0.000 claims description 2
SFILLXWVHWBVJR-UHFFFAOYSA-N [7-bromo-4-(4-methoxyphenyl)-3-methyl-3,4-dihydro-2h-pyrimido[1,2-a]pyrimidin-2-yl]-phenylmethanone Chemical compound C1=CC(OC)=CC=C1C1N2C=C(Br)C=NC2=NC(C(=O)C=2C=CC=CC=2)C1C SFILLXWVHWBVJR-UHFFFAOYSA-N 0.000 claims description 2
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 2
PBOSXVWREMLCHS-UHFFFAOYSA-N ethyl 6-bromonaphthalene-1-carboxylate Chemical compound BrC1=CC=C2C(C(=O)OCC)=CC=CC2=C1 PBOSXVWREMLCHS-UHFFFAOYSA-N 0.000 claims description 2
BYGYIGUYLXZWPE-UHFFFAOYSA-N ethyl 9h-fluorene-3-carboxylate Chemical compound C1=CC=C2C3=CC(C(=O)OCC)=CC=C3CC2=C1 BYGYIGUYLXZWPE-UHFFFAOYSA-N 0.000 claims description 2
PYFMAAFCQDFHJX-UHFFFAOYSA-N ethyl pyrimidine-2-carboxylate Chemical compound CCOC(=O)C1=NC=CC=N1 PYFMAAFCQDFHJX-UHFFFAOYSA-N 0.000 claims description 2
XKKKNWRPLVSJBE-UHFFFAOYSA-N l021387 Chemical compound C12C(C=C3)CC3C2N2C(O)=CC(=O)NC2=NC1C1=CC=CC=N1 XKKKNWRPLVSJBE-UHFFFAOYSA-N 0.000 claims description 2
125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 2
125000006239 protecting group Chemical group 0.000 claims description 2
230000035484 reaction time Effects 0.000 claims description 2
241000124008 Mammalia Species 0.000 claims 2
YOQIFFKUWYFLPZ-UHFFFAOYSA-N 4-phenylsulfanyl-2-pyridin-2-yl-3,4-dihydro-2h-pyrazino[1,2-a]pyrimidine-9-carboxylic acid Chemical compound N1=C2C(C(=O)O)=NC=CN2C(SC=2C=CC=CC=2)CC1C1=CC=CC=N1 YOQIFFKUWYFLPZ-UHFFFAOYSA-N 0.000 claims 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims 1
101150062830 NIFK gene Proteins 0.000 claims 1
OBASDBHRXUCXKQ-UHFFFAOYSA-N [F].[Br] Chemical group [F].[Br] OBASDBHRXUCXKQ-UHFFFAOYSA-N 0.000 claims 1
150000001408 amides Chemical class 0.000 claims 1
125000003277 amino group Chemical group 0.000 claims 1
150000001732 carboxylic acid derivatives Chemical class 0.000 claims 1
YMGUBTXCNDTFJI-UHFFFAOYSA-M cyclopropanecarboxylate Chemical compound [O-]C(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-M 0.000 claims 1
238000005580 one pot reaction Methods 0.000 claims 1
QPILZZVXGUNELN-UHFFFAOYSA-M sodium;4-amino-5-hydroxynaphthalene-2,7-disulfonate;hydron Chemical compound [Na+].OS(=O)(=O)C1=CC(O)=C2C(N)=CC(S([O-])(=O)=O)=CC2=C1 QPILZZVXGUNELN-UHFFFAOYSA-M 0.000 claims 1
150000003230 pyrimidines Chemical class 0.000 abstract description 7
239000004743 Polypropylene Substances 0.000 description 36
150000003254 radicals Chemical class 0.000 description 23
125000004076 pyridyl group Chemical group 0.000 description 13
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
239000000243 solution Substances 0.000 description 7
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
125000005842 heteroatom Chemical group 0.000 description 6
235000019359 magnesium stearate Nutrition 0.000 description 6
239000003826 tablet Substances 0.000 description 6
239000002904 solvent Substances 0.000 description 5
125000001424 substituent group Chemical group 0.000 description 5
238000006467 substitution reaction Methods 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
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125000000335 thiazolyl group Chemical group 0.000 description 1
239000004408 titanium dioxide Substances 0.000 description 1
OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
150000004670 unsaturated fatty acids Chemical class 0.000 description 1
235000021122 unsaturated fatty acids Nutrition 0.000 description 1
229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
239000001993 wax Substances 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1
239000011787 zinc oxide Substances 0.000 description 1
235000014692 zinc oxide Nutrition 0.000 description 1
NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
229910000368 zinc sulfate Inorganic materials 0.000 description 1
229960001763 zinc sulfate Drugs 0.000 description 1
108020001612 μ-opioid receptors Proteins 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—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
- A61P1/12—Antidiarrhoeals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
- 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]
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B40/00—Libraries per se, e.g. arrays, mixtures

Landscapes

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)
Urology & Nephrology (AREA)
Rheumatology (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Dermatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

SK415-2003A 2000-10-13 2001-10-10 Substituted 3,4-dihydro-pyrimido[1,2-a]pyrimidines and 3,4-dihydropyrazino[1,2-a]pyrimidines, process for producing thereof, medicaments comprising same and their use SK4152003A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE10050661A DE10050661A1 (de)	2000-10-13	2000-10-13	Substituierte 3,4-Dihydro-pyrimido[1,2-a]pyrimidine und 3,4-Dihydro-pyrazino[1,2-a]pyrimidine
PCT/EP2001/011702 WO2002030934A1 (de)	2000-10-13	2001-10-10	Substituierte 3,4-dihydro-pyrimido[1,2-a]pyrimidine und 3,4-dihydropyrazino[1,2-a]pyrimidine

Publications (1)

Publication Number	Publication Date
SK4152003A3 true SK4152003A3 (en)	2003-10-07

Family

ID=7659596

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK415-2003A SK4152003A3 (en)	2000-10-13	2001-10-10	Substituted 3,4-dihydro-pyrimido[1,2-a]pyrimidines and 3,4-dihydropyrazino[1,2-a]pyrimidines, process for producing thereof, medicaments comprising same and their use

Country Status (25)

Country	Link
US (1)	US7226924B2 (es)
EP (1)	EP1325010B1 (es)
JP (1)	JP2004511485A (es)
KR (1)	KR20030036923A (es)
CN (1)	CN1243753C (es)
AR (1)	AR035496A1 (es)
AT (1)	ATE294180T1 (es)
AU (1)	AU2002214007A1 (es)
BR (1)	BR0114735A (es)
CA (1)	CA2425685A1 (es)
DE (2)	DE10050661A1 (es)
EC (1)	ECSP034554A (es)
ES (1)	ES2239168T3 (es)
HU (1)	HUP0302606A3 (es)
IL (1)	IL155379A0 (es)
MX (1)	MXPA03003199A (es)
NO (1)	NO20031588L (es)
NZ (1)	NZ525651A (es)
PE (1)	PE20020477A1 (es)
PL (1)	PL361777A1 (es)
PT (1)	PT1325010E (es)
RU (1)	RU2003113965A (es)
SK (1)	SK4152003A3 (es)
WO (1)	WO2002030934A1 (es)
ZA (1)	ZA200303634B (es)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AU2005316668B2 (en)	2004-12-13	2012-09-06	Millennium Pharmaceuticals, Inc.	Pyrido pyrimidinones, dihydro pyrimido pyrimidinones and pteridinones useful as RAF kinase inhibitors
US20070155738A1 (en)	2005-05-20	2007-07-05	Alantos Pharmaceuticals, Inc.	Heterobicyclic metalloprotease inhibitors

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3558618A (en) *	1968-04-01	1971-01-26	Dow Chemical Co	Novel 4h-pyrazino(1,2-a)pyrimidine-4-ones
GB1347493A (en) *	1971-02-11	1974-02-27	Aspro Nicholas Ltd	Benzazine derivatives
HU178910B (en) *	1977-08-19	1982-07-28	Chinoin Gyogyszer Es Vegyeszet	Process for preparing 2,3-disubstituted-4-oxo-4h-pyrido/1,2-a/-pyrimidines
JP2668259B2 (ja) *	1988-02-18	1997-10-27	塩野義製薬株式会社	複素環化合物および抗潰瘍剤
FI94531C (fi) *	1990-03-13	1995-09-25	Ime Intermed Enterpris Sa	Menetelmä farmaseuttisesti aktiivisen 1,3,4,6,7,8-heksahydro-2H-pyrimido-(1,2-a)-pyrimidiinijohdannaisen valmistamiseksi
IT1263804B (it) *	1993-01-22	1996-09-03	Luso Farmaco Inst	Derivati pirimidinonici fusi con eterocicli azotati ad attivita' a ii antagonista
CN1169149A (zh) *	1995-09-28	1997-12-31	株式会社大制药工场	止痛组合物

2000
- 2000-10-13 DE DE10050661A patent/DE10050661A1/de not_active Withdrawn
2001
- 2001-10-09 AR ARP010104730A patent/AR035496A1/es not_active Application Discontinuation
- 2001-10-10 ES ES01982417T patent/ES2239168T3/es not_active Expired - Lifetime
- 2001-10-10 NZ NZ525651A patent/NZ525651A/en unknown
- 2001-10-10 PL PL01361777A patent/PL361777A1/xx not_active Application Discontinuation
- 2001-10-10 MX MXPA03003199A patent/MXPA03003199A/es active IP Right Grant
- 2001-10-10 JP JP2002534320A patent/JP2004511485A/ja not_active Withdrawn
- 2001-10-10 DE DE50106048T patent/DE50106048D1/de not_active Expired - Lifetime
- 2001-10-10 RU RU2003113965/04A patent/RU2003113965A/ru not_active Application Discontinuation
- 2001-10-10 EP EP01982417A patent/EP1325010B1/de not_active Expired - Lifetime
- 2001-10-10 HU HU0302606A patent/HUP0302606A3/hu unknown
- 2001-10-10 KR KR10-2003-7005149A patent/KR20030036923A/ko not_active Withdrawn
- 2001-10-10 IL IL15537901A patent/IL155379A0/xx unknown
- 2001-10-10 CN CNB018171591A patent/CN1243753C/zh not_active Expired - Fee Related
- 2001-10-10 CA CA002425685A patent/CA2425685A1/en not_active Abandoned
- 2001-10-10 PT PT01982417T patent/PT1325010E/pt unknown
- 2001-10-10 AU AU2002214007A patent/AU2002214007A1/en not_active Abandoned
- 2001-10-10 AT AT01982417T patent/ATE294180T1/de active
- 2001-10-10 SK SK415-2003A patent/SK4152003A3/sk unknown
- 2001-10-10 BR BR0114735-8A patent/BR0114735A/pt not_active IP Right Cessation
- 2001-10-10 WO PCT/EP2001/011702 patent/WO2002030934A1/de not_active Ceased
- 2001-10-12 PE PE2001001013A patent/PE20020477A1/es not_active Application Discontinuation
2003
- 2003-04-08 NO NO20031588A patent/NO20031588L/no unknown
- 2003-04-09 US US10/409,614 patent/US7226924B2/en not_active Expired - Fee Related
- 2003-04-11 EC EC2003004554A patent/ECSP034554A/es unknown
- 2003-05-12 ZA ZA200303634A patent/ZA200303634B/en unknown

Also Published As

Publication number	Publication date
ATE294180T1 (de)	2005-05-15
ZA200303634B (en)	2004-08-12
DE50106048D1 (de)	2005-06-02
EP1325010A1 (de)	2003-07-09
BR0114735A (pt)	2003-10-14
KR20030036923A (ko)	2003-05-09
JP2004511485A (ja)	2004-04-15
MXPA03003199A (es)	2004-03-18
NO20031588D0 (no)	2003-04-08
PL361777A1 (en)	2004-10-04
NO20031588L (no)	2003-04-08
HUP0302606A3 (en)	2007-03-28
CN1243753C (zh)	2006-03-01
AU2002214007A1 (en)	2002-04-22
IL155379A0 (en)	2003-11-23
CA2425685A1 (en)	2003-04-11
US20030220322A1 (en)	2003-11-27
US7226924B2 (en)	2007-06-05
AR035496A1 (es)	2004-06-02
PE20020477A1 (es)	2002-06-29
ES2239168T3 (es)	2005-09-16
WO2002030934A1 (de)	2002-04-18
ECSP034554A (es)	2003-05-26
CN1469879A (zh)	2004-01-21
HK1056558A1 (en)	2004-02-20
PT1325010E (pt)	2005-08-31
DE10050661A1 (de)	2002-04-18
NZ525651A (en)	2004-10-29
RU2003113965A (ru)	2004-12-10
HUP0302606A2 (hu)	2004-07-28
EP1325010B1 (de)	2005-04-27

Legal Events

Date	Code	Title	Description
2010-05-07	FB9A	Suspension of patent application procedure

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