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
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 4
229960000583 acetic acid Drugs 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
150000001299 aldehydes Chemical class 0.000 description 4
125000003342 alkenyl group Chemical group 0.000 description 4
125000000304 alkynyl group Chemical group 0.000 description 4
239000002552 dosage form Substances 0.000 description 4
235000019441 ethanol Nutrition 0.000 description 4
BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 4
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 4
239000008194 pharmaceutical composition Substances 0.000 description 4
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
208000000094 Chronic Pain Diseases 0.000 description 3
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 3
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 3
235000011054 acetic acid Nutrition 0.000 description 3
239000004480 active ingredient Substances 0.000 description 3
238000003556 assay Methods 0.000 description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
239000002775 capsule Substances 0.000 description 3
230000001684 chronic effect Effects 0.000 description 3
235000015165 citric acid Nutrition 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
235000014113 dietary fatty acids Nutrition 0.000 description 3
239000000194 fatty acid Substances 0.000 description 3
229930195729 fatty acid Natural products 0.000 description 3
150000003840 hydrochlorides Chemical class 0.000 description 3
229940098779 methanesulfonic acid Drugs 0.000 description 3
150000007524 organic acids Chemical class 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
239000001301 oxygen Substances 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
239000011593 sulfur Substances 0.000 description 3
QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 2
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 2
IXHFJRAHAASGMM-UHFFFAOYSA-N 2-[(2-cyclohexyl-3,4-dihydro-2h-pyrazino[1,2-a]pyrimidin-4-yl)oxy]ethanol Chemical compound N1=C2C=NC=CN2C(OCCO)CC1C1CCCCC1 IXHFJRAHAASGMM-UHFFFAOYSA-N 0.000 description 2
UDOJUHHNGXMMOG-UHFFFAOYSA-N 2-cyclopropyl-4-(4-methoxyphenyl)-3,4-dihydro-2h-pyrazino[1,2-a]pyrimidine Chemical compound C1=CC(OC)=CC=C1C1N2C=CN=CC2=NC(C2CC2)C1 UDOJUHHNGXMMOG-UHFFFAOYSA-N 0.000 description 2
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
SHCXBQXBOUBRBW-UHFFFAOYSA-N 4-(4-methoxyphenyl)-3-methyl-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)C1C SHCXBQXBOUBRBW-UHFFFAOYSA-N 0.000 description 2
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
206010010774 Constipation Diseases 0.000 description 2
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 2
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
238000005481 NMR spectroscopy Methods 0.000 description 2
229910019142 PO4 Inorganic materials 0.000 description 2
244000025272 Persea americana Species 0.000 description 2
235000008673 Persea americana Nutrition 0.000 description 2
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 2
206010039897 Sedation Diseases 0.000 description 2
229920001800 Shellac Polymers 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
206010047700 Vomiting Diseases 0.000 description 2
XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
XZZMQPSOSDDWQK-UHFFFAOYSA-N [4-(4-hydroxyphenyl)-3-methyl-3,4-dihydro-2h-pyrazino[1,2-a]pyrimidin-2-yl]-phenylmethanone Chemical compound CC1C(C(=O)C=2C=CC=CC=2)N=C2C=NC=CN2C1C1=CC=C(O)C=C1 XZZMQPSOSDDWQK-UHFFFAOYSA-N 0.000 description 2
FSMMCONPXPLKEP-UHFFFAOYSA-N [4-(4-methoxyphenyl)-3-methyl-3,4-dihydro-2h-pyrazino[1,2-a]pyrimidin-2-yl]-phenylmethanone Chemical compound C1=CC(OC)=CC=C1C1N2C=CN=CC2=NC(C(=O)C=2C=CC=CC=2)C1C FSMMCONPXPLKEP-UHFFFAOYSA-N 0.000 description 2
FVOBUHBCAWLQTD-UHFFFAOYSA-N [7-bromo-4-(3,4-dimethoxyphenyl)-3,4-dihydro-2h-pyrimido[1,2-a]pyrimidin-2-yl]-phenylmethanone Chemical compound C1=C(OC)C(OC)=CC=C1C1N2C=C(Br)C=NC2=NC(C(=O)C=2C=CC=CC=2)C1 FVOBUHBCAWLQTD-UHFFFAOYSA-N 0.000 description 2
150000001242 acetic acid derivatives Chemical class 0.000 description 2
229910000147 aluminium phosphate Inorganic materials 0.000 description 2
235000003704 aspartic acid Nutrition 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
125000002619 bicyclic group Chemical group 0.000 description 2
FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 2
OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 2
150000004649 carbonic acid derivatives Chemical class 0.000 description 2
229960000541 cetyl alcohol Drugs 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
150000001860 citric acid derivatives Chemical class 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
125000004122 cyclic group Chemical group 0.000 description 2
235000019700 dicalcium phosphate Nutrition 0.000 description 2
229940095079 dicalcium phosphate anhydrous Drugs 0.000 description 2
201000010099 disease Diseases 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
230000000694 effects Effects 0.000 description 2
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 2
235000019253 formic acid Nutrition 0.000 description 2
150000004675 formic acid derivatives Chemical class 0.000 description 2
235000011389 fruit/vegetable juice Nutrition 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 2
239000001530 fumaric acid Substances 0.000 description 2
235000011087 fumaric acid Nutrition 0.000 description 2
125000002541 furyl group Chemical group 0.000 description 2
235000013922 glutamic acid Nutrition 0.000 description 2
239000004220 glutamic acid Substances 0.000 description 2
150000002306 glutamic acid derivatives Chemical class 0.000 description 2
239000008187 granular material Substances 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
239000004310 lactic acid Substances 0.000 description 2
235000014655 lactic acid Nutrition 0.000 description 2
239000008101 lactose Substances 0.000 description 2
229910052943 magnesium sulfate Inorganic materials 0.000 description 2
235000019341 magnesium sulphate Nutrition 0.000 description 2
229960002510 mandelic acid Drugs 0.000 description 2
239000000463 material Substances 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
229960005181 morphine Drugs 0.000 description 2
229940005483 opioid analgesics Drugs 0.000 description 2
150000003891 oxalate salts Chemical class 0.000 description 2
235000006408 oxalic acid Nutrition 0.000 description 2
UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
239000012071 phase Substances 0.000 description 2
230000005501 phase interface Effects 0.000 description 2
235000021317 phosphate Nutrition 0.000 description 2
150000003013 phosphoric acid derivatives Chemical class 0.000 description 2
239000006187 pill Substances 0.000 description 2
125000003367 polycyclic group Chemical group 0.000 description 2
229920001451 polypropylene glycol Polymers 0.000 description 2
IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
238000012216 screening Methods 0.000 description 2
230000036280 sedation Effects 0.000 description 2
ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 2
239000004208 shellac Substances 0.000 description 2
229940113147 shellac Drugs 0.000 description 2
235000013874 shellac Nutrition 0.000 description 2
239000007787 solid Substances 0.000 description 2
239000000600 sorbitol Substances 0.000 description 2
235000010356 sorbitol Nutrition 0.000 description 2
239000007921 spray Substances 0.000 description 2
150000003890 succinate salts Chemical class 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
239000000725 suspension Substances 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
239000000454 talc Substances 0.000 description 2
235000012222 talc Nutrition 0.000 description 2
229910052623 talc Inorganic materials 0.000 description 2
239000011975 tartaric acid Substances 0.000 description 2
235000002906 tartaric acid Nutrition 0.000 description 2
150000003892 tartrate salts Chemical class 0.000 description 2
125000001544 thienyl group Chemical group 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
230000008673 vomiting Effects 0.000 description 2
TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 description 1
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
KOQHPPHOONVYOO-UHFFFAOYSA-N 10-pyridin-2-yl-3,6,9-triazatetracyclo[10.2.1.02,11.03,8]pentadeca-4,6,8,13-tetraene Chemical compound C1C2C=CC1C(N1C=CN=CC1=N1)C2C1C1=CC=CC=N1 KOQHPPHOONVYOO-UHFFFAOYSA-N 0.000 description 1
238000005160 1H NMR spectroscopy Methods 0.000 description 1
MUECOCSNWMLJHL-UHFFFAOYSA-N 2-bromo-6-pyridin-2-yl-6a,7,8,10a-tetrahydro-6h-pyrimido[1,2-a]quinazoline Chemical compound N1=C2N=CC(Br)=CN2C2C=CCCC2C1C1=CC=CC=N1 MUECOCSNWMLJHL-UHFFFAOYSA-N 0.000 description 1
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
NENZJBLBRUCPSQ-UHFFFAOYSA-N 4-(4-methoxyphenyl)-3-methyl-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)C1C NENZJBLBRUCPSQ-UHFFFAOYSA-N 0.000 description 1
RLWUIDQBNMPORB-UHFFFAOYSA-N 4-phenylsulfanyl-2-pyridin-2-yl-3,4-dihydro-2h-pyrazino[1,2-a]pyrimidine Chemical compound N12C=CN=CC2=NC(C=2N=CC=CC=2)CC1SC1=CC=CC=C1 RLWUIDQBNMPORB-UHFFFAOYSA-N 0.000 description 1
VFSVGRQARZMIPM-UHFFFAOYSA-N 6-amino-7-chloro-4-phenylsulfanyl-2-pyridin-2-yl-3,4-dihydro-2h-pyrazino[1,2-a]pyrimidine-9-carboxamide Chemical compound N1=C2C(C(=O)N)=NC(Cl)=C(N)N2C(SC=2C=CC=CC=2)CC1C1=CC=CC=N1 VFSVGRQARZMIPM-UHFFFAOYSA-N 0.000 description 1
UDFLURZQCCFDEY-UHFFFAOYSA-N 7-bromo-4-(4-methoxyphenyl)-3-methyl-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)C1C UDFLURZQCCFDEY-UHFFFAOYSA-N 0.000 description 1
CLGFFVMIQRQFEE-UHFFFAOYSA-N 7-chloro-10-pyridin-2-yl-3,6,9-triazatetracyclo[10.2.1.02,11.03,8]pentadeca-4,6,8,13-tetraene-4,5-dicarbonitrile Chemical compound N1=C2C(Cl)=NC(C#N)=C(C#N)N2C2C(C=C3)CC3C2C1C1=CC=CC=N1 CLGFFVMIQRQFEE-UHFFFAOYSA-N 0.000 description 1
OTLOPYFBAMCWAR-UHFFFAOYSA-N 7-phenyl-4-phenylsulfanyl-2-pyridin-2-yl-3,4-dihydro-2h-pyrazino[1,2-a]pyrimidine-9-carbonitrile Chemical compound N1=C2C(C#N)=NC(C=3C=CC=CC=3)=CN2C(SC=2C=CC=CC=2)CC1C1=CC=CC=N1 OTLOPYFBAMCWAR-UHFFFAOYSA-N 0.000 description 1
XGWFJBFNAQHLEF-UHFFFAOYSA-N 9-anthroic acid Chemical compound C1=CC=C2C(C(=O)O)=C(C=CC=C3)C3=CC2=C1 XGWFJBFNAQHLEF-UHFFFAOYSA-N 0.000 description 1
229920001817 Agar Polymers 0.000 description 1
239000005995 Aluminium silicate Substances 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
239000004604 Blowing Agent Substances 0.000 description 1
101000623895 Bos taurus Mucin-15 Proteins 0.000 description 1
125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
DGSKKBCOSQDTOZ-UHFFFAOYSA-N CCC(C(C)C1C(C=C2)=CC=C2O)(C(O)=O)N=C2N1C=CN=C2 Chemical compound CCC(C(C)C1C(C=C2)=CC=C2O)(C(O)=O)N=C2N1C=CN=C2 DGSKKBCOSQDTOZ-UHFFFAOYSA-N 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
AUGGHCOLPVUXBH-UHFFFAOYSA-N Cl.COC=1C=C(C=CC1OC)C1CC(N=C2N1C=CN=C2)C(=O)O Chemical compound Cl.COC=1C=C(C=CC1OC)C1CC(N=C2N1C=CN=C2)C(=O)O AUGGHCOLPVUXBH-UHFFFAOYSA-N 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
206010012335 Dependence Diseases 0.000 description 1
229920002307 Dextran Polymers 0.000 description 1
206010052804 Drug tolerance Diseases 0.000 description 1
206010013975 Dyspnoeas Diseases 0.000 description 1
239000001263 FEMA 3042 Substances 0.000 description 1
229930091371 Fructose Natural products 0.000 description 1
239000005715 Fructose Substances 0.000 description 1
RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
239000002841 Lewis acid Substances 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
238000003820 Medium-pressure liquid chromatography Methods 0.000 description 1
FEWJPZIEWOKRBE-XIXRPRMCSA-N Mesotartaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-XIXRPRMCSA-N 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
239000004368 Modified starch Substances 0.000 description 1
229920000881 Modified starch Polymers 0.000 description 1
WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
ZQINDSJELMMRRD-UHFFFAOYSA-N N1=C2NC(=O)C(C)=C(O)N2C2C(C=C3)CC3C2C1C1=CC=CC=N1 Chemical compound N1=C2NC(=O)C(C)=C(O)N2C2C(C=C3)CC3C2C1C1=CC=CC=N1 ZQINDSJELMMRRD-UHFFFAOYSA-N 0.000 description 1
206010028813 Nausea Diseases 0.000 description 1
206010028980 Neoplasm Diseases 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 description 1
229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
210000001744 T-lymphocyte Anatomy 0.000 description 1
ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 1
229940081735 acetylcellulose Drugs 0.000 description 1
125000002015 acyclic group Chemical group 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
239000008272 agar Substances 0.000 description 1
235000010419 agar Nutrition 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
235000012211 aluminium silicate Nutrition 0.000 description 1
230000000202 analgesic effect Effects 0.000 description 1
125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
125000003710 aryl alkyl group Chemical group 0.000 description 1
150000005840 aryl radicals Chemical class 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
210000003719 b-lymphocyte Anatomy 0.000 description 1
239000000440 bentonite Substances 0.000 description 1
235000012216 bentonite Nutrition 0.000 description 1
229910000278 bentonite Inorganic materials 0.000 description 1
SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000000975 bioactive effect Effects 0.000 description 1
230000033228 biological regulation Effects 0.000 description 1
230000037396 body weight Effects 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
235000011148 calcium chloride Nutrition 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
239000008112 carboxymethyl-cellulose Substances 0.000 description 1
229940105329 carboxymethylcellulose Drugs 0.000 description 1
239000000969 carrier Substances 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
235000010980 cellulose Nutrition 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
229920002301 cellulose acetate Polymers 0.000 description 1
PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 1
238000013375 chromatographic separation Methods 0.000 description 1
238000011097 chromatography purification Methods 0.000 description 1
239000008199 coating composition Substances 0.000 description 1
239000003240 coconut oil Substances 0.000 description 1
235000019864 coconut oil Nutrition 0.000 description 1
229940125904 compound 1 Drugs 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
239000006071 cream Substances 0.000 description 1
229960000913 crospovidone Drugs 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 description 1
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 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
230000003111 delayed effect Effects 0.000 description 1
238000001514 detection method Methods 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
239000008298 dragée Substances 0.000 description 1
239000006196 drop Substances 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
239000000975 dye Substances 0.000 description 1
239000008157 edible vegetable oil Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
239000003623 enhancer Substances 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
RLJSRSAHCGLFBE-UHFFFAOYSA-N ethyl 2-[7-bromo-4-(2,4-dimethylphenyl)-3,4-dihydro-2h-pyrimido[1,2-a]pyrimidin-2-yl]cyclopropane-1-carboxylate Chemical compound CCOC(=O)C1CC1C1N=C2N=CC(Br)=CN2C(C=2C(=CC(C)=CC=2)C)C1 RLJSRSAHCGLFBE-UHFFFAOYSA-N 0.000 description 1
HBEXVADWMNJCFO-UHFFFAOYSA-N ethyl 6-phenylsulfanyl-8-pyridin-2-yl-2-(trifluoromethyl)-7,8-dihydro-6H-pyrimido[1,2-a]pyrimidine-3-carboxylate Chemical compound C(C)OC(=O)C=1C(=NC=2N(C=1)C(CC(N=2)C1=NC=CC=C1)SC1=CC=CC=C1)C(F)(F)F HBEXVADWMNJCFO-UHFFFAOYSA-N 0.000 description 1
CGUKSIKADBHHRL-UHFFFAOYSA-N ethyl 7-bromo-4-(3-methylphenyl)-3,4-dihydro-2h-pyrimido[1,2-a]pyrimidine-2-carboxylate Chemical compound N12C=C(Br)C=NC2=NC(C(=O)OCC)CC1C1=CC=CC(C)=C1 CGUKSIKADBHHRL-UHFFFAOYSA-N 0.000 description 1
HWFCXDCVFJGBRE-UHFFFAOYSA-N ethyl 7-bromo-4-(4-hydroxyphenyl)-3-methyl-3,4-dihydro-2h-pyrimido[1,2-a]pyrimidine-2-carboxylate Chemical compound CC1C(C(=O)OCC)N=C2N=CC(Br)=CN2C1C1=CC=C(O)C=C1 HWFCXDCVFJGBRE-UHFFFAOYSA-N 0.000 description 1
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
150000004665 fatty acids Chemical class 0.000 description 1
239000000945 filler Substances 0.000 description 1
238000009472 formulation Methods 0.000 description 1
LRBQNJMCXXYXIU-QWKBTXIPSA-N gallotannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@H]2[C@@H]([C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-QWKBTXIPSA-N 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000011521 glass Substances 0.000 description 1
239000008103 glucose Substances 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
125000006038 hexenyl group Chemical group 0.000 description 1
238000013537 high throughput screening Methods 0.000 description 1
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
229960000367 inositol Drugs 0.000 description 1
230000007794 irritation Effects 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
239000000644 isotonic solution Substances 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
235000015110 jellies Nutrition 0.000 description 1
NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
239000000787 lecithin Substances 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
229940067606 lecithin Drugs 0.000 description 1
150000007517 lewis acids Chemical class 0.000 description 1
238000004811 liquid chromatography Methods 0.000 description 1
239000008297 liquid dosage form Substances 0.000 description 1
239000006210 lotion Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
125000004401 m-toluyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])[H])C(*)=O 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
235000011147 magnesium chloride Nutrition 0.000 description 1
239000000395 magnesium oxide Substances 0.000 description 1
CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
235000012245 magnesium oxide Nutrition 0.000 description 1
AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
229960002900 methylcellulose Drugs 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
238000002156 mixing Methods 0.000 description 1
235000019426 modified starch Nutrition 0.000 description 1
235000013379 molasses Nutrition 0.000 description 1
125000002757 morpholinyl group Chemical group 0.000 description 1
102000051367 mu Opioid Receptors Human genes 0.000 description 1
210000004400 mucous membrane Anatomy 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
230000008693 nausea Effects 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
208000004296 neuralgia Diseases 0.000 description 1
230000002981 neuropathic effect Effects 0.000 description 1
208000021722 neuropathic pain Diseases 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
125000004365 octenyl group Chemical group C(=CCCCCCC)* 0.000 description 1
239000002674 ointment Substances 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
239000001814 pectin Substances 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
239000008188 pellet Substances 0.000 description 1
230000035515 penetration Effects 0.000 description 1
125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
125000006194 pentinyl group Chemical group 0.000 description 1
239000008024 pharmaceutical diluent Substances 0.000 description 1
WNNAVCMAKKZWPG-UHFFFAOYSA-N phenanthrene-3,4-dicarbonitrile Chemical compound C1=CC(=C(C=2C3=CC=CC=C3C=CC1=2)C#N)C#N WNNAVCMAKKZWPG-UHFFFAOYSA-N 0.000 description 1
125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
LEVJVKGPFAQPOI-UHFFFAOYSA-N phenylmethanone Chemical compound O=[C]C1=CC=CC=C1 LEVJVKGPFAQPOI-UHFFFAOYSA-N 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
239000002574 poison Substances 0.000 description 1
231100000614 poison Toxicity 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
229940072033 potash Drugs 0.000 description 1
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
235000015320 potassium carbonate Nutrition 0.000 description 1
239000001103 potassium chloride Substances 0.000 description 1
235000011164 potassium chloride Nutrition 0.000 description 1
235000007715 potassium iodide Nutrition 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
238000012545 processing Methods 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
239000000376 reactant Substances 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
230000029058 respiratory gaseous exchange Effects 0.000 description 1
238000004007 reversed phase HPLC Methods 0.000 description 1
150000004671 saturated fatty acids Chemical class 0.000 description 1
235000003441 saturated fatty acids Nutrition 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000008299 semisolid dosage form Substances 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
206010040872 skin infection Diseases 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
235000015424 sodium Nutrition 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000001540 sodium lactate Substances 0.000 description 1
235000011088 sodium lactate Nutrition 0.000 description 1
229940005581 sodium lactate Drugs 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
239000003549 soybean oil Substances 0.000 description 1
235000012424 soybean oil Nutrition 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000001384 succinic acid Substances 0.000 description 1
235000011044 succinic acid Nutrition 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
235000015523 tannic acid Nutrition 0.000 description 1
229920002258 tannic acid Polymers 0.000 description 1
229940033123 tannic acid Drugs 0.000 description 1
238000012360 testing method Methods 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
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)
Veterinary Medicine (AREA)
Life Sciences & Earth Sciences (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Pain & Pain Management (AREA)
Urology & Nephrology (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Rheumatology (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 (fr)	2000-10-13	2001-10-10	3,4-dihydro-pyrimido[1,2-a]pyrimidines substituees et 3,4-dihydropyrazino[1,2-a]pyrimidines substituees

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

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP1828186A1 (fr)	2004-12-13	2007-09-05	Sunesis Pharmaceuticals, Inc.	Pyridopyrimidinones, dihydropyrimidopyrimidinones et pteridinones utiles en tant qu'inhibiteurs des kinases raf
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
WO1997011946A1 (fr) *	1995-09-28	1997-04-03	Otsuka Pharmaceutical Factory, Inc.	Analgesiques

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 EP EP01982417A patent/EP1325010B1/fr not_active Expired - Lifetime
- 2001-10-10 DE DE50106048T patent/DE50106048D1/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 ES ES01982417T patent/ES2239168T3/es not_active Expired - Lifetime
- 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 PL PL01361777A patent/PL361777A1/xx not_active Application Discontinuation
- 2001-10-10 SK SK415-2003A patent/SK4152003A3/sk unknown
- 2001-10-10 NZ NZ525651A patent/NZ525651A/en unknown
- 2001-10-10 PT PT01982417T patent/PT1325010E/pt unknown
- 2001-10-10 BR BR0114735-8A patent/BR0114735A/pt not_active IP Right Cessation
- 2001-10-10 IL IL15537901A patent/IL155379A0/xx unknown
- 2001-10-10 RU RU2003113965/04A patent/RU2003113965A/ru not_active Application Discontinuation
- 2001-10-10 CN CNB018171591A patent/CN1243753C/zh not_active Expired - Fee Related
- 2001-10-10 CA CA002425685A patent/CA2425685A1/fr not_active Abandoned
- 2001-10-10 AU AU2002214007A patent/AU2002214007A1/en not_active Abandoned
- 2001-10-10 AT AT01982417T patent/ATE294180T1/de active
- 2001-10-10 WO PCT/EP2001/011702 patent/WO2002030934A1/fr 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
CN1243753C (zh)	2006-03-01
MXPA03003199A (es)	2004-03-18
NZ525651A (en)	2004-10-29
JP2004511485A (ja)	2004-04-15
HK1056558A1 (en)	2004-02-20
WO2002030934A1 (fr)	2002-04-18
US7226924B2 (en)	2007-06-05
KR20030036923A (ko)	2003-05-09
HUP0302606A3 (en)	2007-03-28
PL361777A1 (en)	2004-10-04
BR0114735A (pt)	2003-10-14
EP1325010A1 (fr)	2003-07-09
DE10050661A1 (de)	2002-04-18
US20030220322A1 (en)	2003-11-27
NO20031588D0 (no)	2003-04-08
AR035496A1 (es)	2004-06-02
ATE294180T1 (de)	2005-05-15
DE50106048D1 (de)	2005-06-02
ZA200303634B (en)	2004-08-12
IL155379A0 (en)	2003-11-23
ECSP034554A (es)	2003-05-26
CA2425685A1 (fr)	2003-04-11
PE20020477A1 (es)	2002-06-29
ES2239168T3 (es)	2005-09-16
NO20031588L (no)	2003-04-08
CN1469879A (zh)	2004-01-21
EP1325010B1 (fr)	2005-04-27
AU2002214007A1 (en)	2002-04-22
RU2003113965A (ru)	2004-12-10
HUP0302606A2 (hu)	2004-07-28
PT1325010E (pt)	2005-08-31

Legal Events

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

Publication	Publication Date	Title
EP0846118B1 (fr)	2002-05-02	Inhibiteurs de phosphodiesterase specifiques de gmp cyclique
CN104884458B (zh)	2017-04-12	作为蛋白质激酶抑制剂的稠合杂环化合物
MXPA98000411A (en)	1998-04-01	Quimi compounds
WO2007117180A1 (fr)	2007-10-18	Bibliothèques combinatoire et focalisée d'azahétérocycles, composition pharmaceutique et procédés de leur fabrication
SK11542003A3 (sk)	2004-07-07	Substituované pyrazolopyrimidíny a tiazolopyrimidíny, spôsob ich výroby, liečivá tieto látky obsahujúce a ich použitie
WO2020156437A1 (fr)	2020-08-06	Inhibiteur d'akt
ES2751642T3 (es)	2020-04-01	Compuestos inhibidores de bromodominios y composición farmacéutica que los comprende para prevenir o tratar un cáncer
SK4152003A3 (en)	2003-10-07	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
WO2021228223A1 (fr)	2021-11-18	Inhibiteur de kinase akt deutéré
TW202535869A (zh)	2025-09-16	一種含有噻唑基的哌啶并嘧啶類衍生物、其製備方法及其醫藥上的應用
SK4142003A3 (en)	2003-10-07	Substituted 3,4-dihydro-pyrido[1,2-A]pyrimidines, process for producing thereof, medicaments comprising same and their use
WO2024088296A1 (fr)	2024-05-02	Dérivé de pipéridinopyrimidine, son procédé de préparation et son utilisation en médecine
WO2025162225A1 (fr)	2025-08-07	Composé à nouvelle structure glutarimido-isoindolinone substituée, et son utilisation
HK1056558B (en)	2005-12-16	Substituted 3.4-dihydro-pyrimido [1,2-a]pyrimidines and 3.4-dihydropyrazino [1,2-a]pyrimidines