BR112013013898B1 - Compostos de pirimidinona, composição farmacêutica compreendendo ditos compostos e usos dos mesmos para o tratamento de doença de alzheimer e aterosclerose - Google Patents
Compostos de pirimidinona, composição farmacêutica compreendendo ditos compostos e usos dos mesmos para o tratamento de doença de alzheimer e aterosclerose Download PDFInfo
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- BR112013013898B1 BR112013013898B1 BR112013013898-0A BR112013013898A BR112013013898B1 BR 112013013898 B1 BR112013013898 B1 BR 112013013898B1 BR 112013013898 A BR112013013898 A BR 112013013898A BR 112013013898 B1 BR112013013898 B1 BR 112013013898B1
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- Prior art keywords
- mmol
- phenyl
- trifluoromethyl
- mixture
- added
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 402
- 208000024827 Alzheimer disease Diseases 0.000 title claims abstract description 17
- 238000011282 treatment Methods 0.000 title claims abstract description 14
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- 239000008194 pharmaceutical composition Substances 0.000 title claims description 4
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical class OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 title abstract description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 66
- 125000001424 substituent group Chemical group 0.000 claims description 54
- 229910052757 nitrogen Inorganic materials 0.000 claims description 39
- 125000005843 halogen group Chemical group 0.000 claims description 38
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 34
- 150000003839 salts Chemical class 0.000 claims description 34
- 125000001072 heteroaryl group Chemical group 0.000 claims description 28
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 20
- 125000004429 atom Chemical group 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 13
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 11
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 9
- 125000001188 haloalkyl group Chemical group 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 5
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 52
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- -1 methylethyl Chemical group 0.000 description 51
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- FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo(3.3.1)nonane Chemical compound C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 43
- 239000012071 phase Substances 0.000 description 43
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 39
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 38
- 229910000104 sodium hydride Inorganic materials 0.000 description 37
- 239000000047 product Substances 0.000 description 36
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 35
- TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical compound COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 description 34
- UXRDAJMOOGEIAQ-CKOZHMEPSA-N [(8r,9s,10r,13s,14s,17r)-17-acetyl-10,13-dimethyl-16-methylidene-3-oxo-1,2,8,9,11,12,14,15-octahydrocyclopenta[a]phenanthren-17-yl] acetate Chemical compound C1=CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC(=C)[C@](OC(=O)C)(C(C)=O)[C@@]1(C)CC2 UXRDAJMOOGEIAQ-CKOZHMEPSA-N 0.000 description 33
- 201000006417 multiple sclerosis Diseases 0.000 description 33
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 32
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 30
- 238000001816 cooling Methods 0.000 description 30
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 29
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 29
- 230000002829 reductive effect Effects 0.000 description 29
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- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 26
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 26
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 26
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- 239000010410 layer Substances 0.000 description 21
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- LSEFCHWGJNHZNT-UHFFFAOYSA-M methyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 LSEFCHWGJNHZNT-UHFFFAOYSA-M 0.000 description 20
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 19
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- 125000000217 alkyl group Chemical group 0.000 description 16
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- 239000012279 sodium borohydride Substances 0.000 description 15
- 229910000033 sodium borohydride Inorganic materials 0.000 description 15
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 13
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- 239000000126 substance Substances 0.000 description 9
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- PWFPZYCXAVJRNL-UHFFFAOYSA-N tert-butyl n-[2-[3-cyano-4-[5-(trifluoromethyl)pyridin-2-yl]oxyphenyl]ethyl]carbamate Chemical compound N#CC1=CC(CCNC(=O)OC(C)(C)C)=CC=C1OC1=CC=C(C(F)(F)F)C=N1 PWFPZYCXAVJRNL-UHFFFAOYSA-N 0.000 description 1
- YQTUHYAJGIQTTC-UHFFFAOYSA-N tert-butyl n-[2-[4-[3-(trifluoromethyl)phenoxy]phenyl]ethyl]carbamate Chemical compound C1=CC(CCNC(=O)OC(C)(C)C)=CC=C1OC1=CC=CC(C(F)(F)F)=C1 YQTUHYAJGIQTTC-UHFFFAOYSA-N 0.000 description 1
- SZMYFMBXPGEHRQ-UHFFFAOYSA-N tert-butyl n-[2-[4-[3-chloro-4-(trifluoromethyl)phenoxy]phenyl]ethyl]carbamate Chemical compound C1=CC(CCNC(=O)OC(C)(C)C)=CC=C1OC1=CC=C(C(F)(F)F)C(Cl)=C1 SZMYFMBXPGEHRQ-UHFFFAOYSA-N 0.000 description 1
- ASARNFDEBGBQPF-UHFFFAOYSA-N tert-butyl n-[2-[4-[4-chloro-3-(trifluoromethyl)phenoxy]phenyl]ethyl]-n-methylcarbamate Chemical compound C1=CC(CCN(C)C(=O)OC(C)(C)C)=CC=C1OC1=CC=C(Cl)C(C(F)(F)F)=C1 ASARNFDEBGBQPF-UHFFFAOYSA-N 0.000 description 1
- WZZZJWLLBRHDQO-UHFFFAOYSA-N tert-butyl n-methyl-n-[2-[4-[3-(trifluoromethyl)phenoxy]phenyl]ethyl]carbamate Chemical compound C1=CC(CCN(C)C(=O)OC(C)(C)C)=CC=C1OC1=CC=CC(C(F)(F)F)=C1 WZZZJWLLBRHDQO-UHFFFAOYSA-N 0.000 description 1
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- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 210000001103 thalamus Anatomy 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
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- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
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- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/20—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D239/22—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/34—One oxygen atom
- C07D239/36—One oxygen atom as doubly bound oxygen atom or as unsubstituted hydroxy radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/56—One oxygen atom and one sulfur atom
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- Engineering & Computer Science (AREA)
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- Animal Behavior & Ethology (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Neurosurgery (AREA)
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- Urology & Nephrology (AREA)
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- Heart & Thoracic Surgery (AREA)
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CNPCT/CN2010/079465 | 2010-12-06 | ||
CN2010079465 | 2010-12-06 | ||
PCT/EP2011/071690 WO2012076435A1 (en) | 2010-12-06 | 2011-12-05 | Pyrimidinone compounds for use in the treatment of diseases or conditions mediated by lp - pla2 |
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BR112013013898A2 BR112013013898A2 (pt) | 2016-07-26 |
BR112013013898B1 true BR112013013898B1 (pt) | 2021-10-13 |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8349577B2 (en) * | 2009-04-23 | 2013-01-08 | Research Foundation For Mental Hygiene, Inc. | Method for evaluating blood-neural barrier permeability |
EP2649053B1 (en) * | 2010-12-06 | 2015-11-04 | Glaxo Group Limited | Pyrimidinone compounds for use in the treatment of diseases or conditions mediated by lp-pla2 |
US8859573B2 (en) * | 2010-12-06 | 2014-10-14 | Glaxo Group Limited | Pyrimidinone and pyridinone compounds for use in the treatment of diseases or conditions mediated by Lp-PLA2 |
MY172885A (en) | 2011-09-01 | 2019-12-13 | Glaxo Group Ltd | Novel crystal form |
JP6037277B2 (ja) * | 2012-12-19 | 2016-12-07 | 国立研究開発法人農業・食品産業技術総合研究機構 | オーキシン生合成阻害剤 |
RU2015135806A (ru) * | 2013-01-25 | 2017-03-03 | Глэксосмитклайн Интеллекчуал Проперти Дивелопмент Лимитед | Соединения |
EP2764866A1 (en) | 2013-02-07 | 2014-08-13 | IP Gesellschaft für Management mbH | Inhibitors of nedd8-activating enzyme |
EP3036222A2 (en) * | 2013-08-23 | 2016-06-29 | Virginia Commonwealth University | Ester nitrates derivatives of aromatic aldehydes with multiple pharmalogic properties to treat sickle cell disease |
GB201322602D0 (en) * | 2013-12-19 | 2014-02-05 | Almac Discovery Ltd | Pharmaceutical compounds |
CN103896906A (zh) * | 2014-02-28 | 2014-07-02 | 苏州维泰生物技术有限公司 | 一种农药咯菌腈中间体的新合成方法 |
CN110845482B (zh) * | 2014-07-04 | 2024-01-19 | 日本烟草产业株式会社 | 制备吲哚化合物的方法 |
WO2016012916A1 (en) | 2014-07-22 | 2016-01-28 | Glaxosmithkline Intellectual Property Development Limited | 1,2,3,5-tetrahydroimidazo[1,2-c]pyrimidine derivatives useful in the treatment of diseases and disorders mediated by lp-pla2 |
WO2016012917A1 (en) | 2014-07-22 | 2016-01-28 | Glaxosmithkline Intellectual Property Development Limited | 1,2,3,5-tetrahydroimidazo[1,2-c]pyrimidine derivatives useful in the treatment of diseases and disorders mediated by lp-pla2 |
CN106188063A (zh) * | 2015-05-08 | 2016-12-07 | 中国科学院上海药物研究所 | 用作Lp-PLA2抑制剂的双环类化合物、其制备方法及医药用途 |
CN106085984B (zh) * | 2016-06-02 | 2019-07-19 | 天津科技大学 | 一种新型磷脂酶d及其制备磷脂酸、磷脂酰丝氨酸的方法 |
PT3668513T (pt) | 2017-08-15 | 2022-01-21 | Agios Pharmaceuticals Inc | Ativadores da piruvato quinase para uso no tratamento de distúrbios do sangue |
CN111533699B (zh) * | 2020-05-27 | 2023-12-01 | 龙曦宁(上海)医药科技有限公司 | 一种2-(三氟甲基)嘧啶-5-醇的合成方法 |
Family Cites Families (45)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9421816D0 (en) | 1994-10-29 | 1994-12-14 | Smithkline Beecham Plc | Novel compounds |
AP9701007A0 (en) | 1994-12-22 | 1997-07-31 | Smithkline Beecham Plc | Substituted azetidin-2-ones for treatment of atherosclerosis. |
CH690264A5 (fr) | 1995-06-30 | 2000-06-30 | Symphar Sa | Dérivés aminophosphonates substitués, leur procédé de préparation et leur utilisation pour la préparation de compositions pharmaceutiques. |
CA2225627A1 (en) | 1995-07-01 | 1997-01-23 | Deirdre Mary Bernadette Hickey | Azetidinone derivatives for the treatment of atherosclerosis |
JP2002515728A (ja) | 1995-09-29 | 2002-05-28 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | 新規用途 |
JP2000505063A (ja) | 1995-12-08 | 2000-04-25 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | アテローム性動脈硬化症の治療のためのアゼチジノン化合物 |
EP0869943A1 (en) | 1995-12-08 | 1998-10-14 | Smithkline Beecham Plc | Monocyclic beta-lactame derivatives for treatment of atherosclerosis |
HUP9901359A3 (en) | 1996-04-26 | 2000-03-28 | Smithkline Beecham Plc | Azetidinone derivatives for the treatment of atherosclerosis, process for their producing and pharmaceutical compositions containing them |
GB9608649D0 (en) | 1996-04-26 | 1996-07-03 | Smithkline Beecham Plc | Novel compounds |
GB9626615D0 (en) | 1996-12-20 | 1997-02-05 | Symphar Sa | Novel compounds |
GB9626536D0 (en) | 1996-12-20 | 1997-02-05 | Symphar Sa | Novel compounds |
GB9626616D0 (en) | 1996-12-20 | 1997-02-05 | Symphar Sa | Novel compounds |
JP2001526648A (ja) | 1997-04-22 | 2001-12-18 | コセンシス・インコーポレイテッド | 炭素環及びヘテロ環で置換されたセミカルバゾン及びチオセミカルバゾン、及びその使用 |
ES2203988T3 (es) * | 1997-11-06 | 2004-04-16 | Smithkline Beecham Plc | Compuestos de pirimidinona y composiciones farmaceuticas que los contienen. |
ATE251613T1 (de) | 1998-08-21 | 2003-10-15 | Smithkline Beecham Plc | Pyrimidinonderivate zur behandlung von atheroscleros |
TR200103216T2 (tr) * | 1999-05-01 | 2002-04-22 | Smithkline Beecham P.L.C. | Pirimidinon bileşimleri |
GB9910079D0 (en) | 1999-05-01 | 1999-06-30 | Smithkline Beecham Plc | Novel compounds |
GB9910378D0 (en) * | 1999-05-05 | 1999-06-30 | Smithkline Beecham Plc | Novel compounds |
JP3757703B2 (ja) | 1999-09-22 | 2006-03-22 | 凸版印刷株式会社 | 再封可能な開口維持部材付パウチ |
AU2001235466B2 (en) | 2000-02-16 | 2004-04-22 | Glaxo Group Limited | Pyrimidine-4-one derivatives as LDL-PLA2 inhibitors |
GB0024807D0 (en) | 2000-10-10 | 2000-11-22 | Smithkline Beecham Plc | Novel compounds |
GB0024808D0 (en) * | 2000-10-10 | 2000-11-22 | Smithkline Beecham Plc | Novel compounds |
AU2002228922A1 (en) * | 2000-12-12 | 2002-06-24 | Cytovia, Inc. | Substituted 2-aryl-4-arylaminopyrimidines and analogs as activators of caspases and inducers of apoptosis and the use thereof |
DE60219292T2 (de) * | 2001-04-10 | 2008-04-10 | Pfizer Inc. | Pyrazolderivate zur behandlung von hiv |
GB0119793D0 (en) | 2001-08-14 | 2001-10-03 | Smithkline Beecham Plc | Novel compounds |
GB0119795D0 (en) | 2001-08-14 | 2001-10-03 | Smithkline Beecham Plc | Novel process |
HN2002000317A (es) * | 2001-11-02 | 2003-05-21 | Pfizer | Inhibidores de pde9 para tratamiento de trastornos cardiovasculares |
GB0127143D0 (en) | 2001-11-10 | 2002-01-02 | Smithkline Beecham | Novel compounds |
GB0127141D0 (en) | 2001-11-10 | 2002-01-02 | Smithkline Beecham Plc | Novel compounds |
GB0127140D0 (en) | 2001-11-10 | 2002-01-02 | Smithkline Beecham | Novel compounds |
GB0127139D0 (en) | 2001-11-10 | 2002-01-02 | Smithkline Beecham | Novel compounds |
GB0208280D0 (en) | 2002-04-10 | 2002-05-22 | Glaxo Group Ltd | Novel compounds |
GB0208279D0 (en) | 2002-04-10 | 2002-05-22 | Glaxo Group Ltd | Novel compounds |
EP1644353A1 (de) | 2003-07-02 | 2006-04-12 | Bayer HealthCare AG | Amid-substituierte 1, 2, 4-triazin-5 (2h) - one zur behandlung von chronisch inflammatorischen krankheiten |
DE102004061008A1 (de) | 2004-12-18 | 2006-06-22 | Bayer Healthcare Ag | 3-Arylalkyl- und 3-Heteroarylalkyl-substituierte 1,2,4-Triazin-5(2H)-one |
DE102004061009A1 (de) | 2004-12-18 | 2006-06-22 | Bayer Healthcare Ag | Substituierte 1,2,4-Triazin-5(2H)-one |
US7705005B2 (en) | 2006-10-13 | 2010-04-27 | Glaxo Group Limited | Bicyclic heteroaromatic compounds |
US20080090851A1 (en) | 2006-10-13 | 2008-04-17 | Colin Andrew Leach | Bicyclic Heteroaromatic Compounds |
JP2010506852A (ja) | 2006-10-13 | 2010-03-04 | グラクソ グループ リミテッド | 二環式ヘテロ芳香族化合物 |
US20080090852A1 (en) | 2006-10-13 | 2008-04-17 | Colin Andrew Leach | Bicyclic Heteroaromatic Compounds |
US8962633B2 (en) | 2007-05-11 | 2015-02-24 | Thomas Jefferson University | Methods of treatment and prevention of metabolic bone diseases and disorders |
US20080279846A1 (en) | 2007-05-11 | 2008-11-13 | Thomas Jefferson University | Methods of treatment and prevention of neurodegenerative diseases and disorders |
CA2687079A1 (en) | 2007-05-11 | 2008-11-20 | The Trustees Of The University Of Pennsylvania | Methods of treatment of skin ulcers |
US8859573B2 (en) * | 2010-12-06 | 2014-10-14 | Glaxo Group Limited | Pyrimidinone and pyridinone compounds for use in the treatment of diseases or conditions mediated by Lp-PLA2 |
EP2649053B1 (en) * | 2010-12-06 | 2015-11-04 | Glaxo Group Limited | Pyrimidinone compounds for use in the treatment of diseases or conditions mediated by lp-pla2 |
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