CA2252696A1 - Azetidinone derivatives for the treatment of atherosclerosis - Google Patents
Azetidinone derivatives for the treatment of atherosclerosis Download PDFInfo
- Publication number
- CA2252696A1 CA2252696A1 CA002252696A CA2252696A CA2252696A1 CA 2252696 A1 CA2252696 A1 CA 2252696A1 CA 002252696 A CA002252696 A CA 002252696A CA 2252696 A CA2252696 A CA 2252696A CA 2252696 A1 CA2252696 A1 CA 2252696A1
- Authority
- CA
- Canada
- Prior art keywords
- formula
- fluorophenyl
- compound
- oxoazetidin
- alkyl
- Prior art date
- Legal status (The legal status 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 status listed.)
- Abandoned
Links
- 201000001320 Atherosclerosis Diseases 0.000 title abstract description 13
- MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical class O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 145
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 38
- 150000003839 salts Chemical class 0.000 claims abstract description 26
- 102000016752 1-Alkyl-2-acetylglycerophosphocholine Esterase Human genes 0.000 claims abstract description 25
- 108010024976 Asparaginase Proteins 0.000 claims abstract description 25
- 150000002148 esters Chemical class 0.000 claims abstract description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 25
- 239000001257 hydrogen Substances 0.000 claims abstract description 24
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000003112 inhibitor Substances 0.000 claims abstract description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 10
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 4
- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims abstract 4
- 235000019256 formaldehyde Nutrition 0.000 claims abstract 4
- -1 alkenyl ester Chemical class 0.000 claims description 82
- 239000002253 acid Substances 0.000 claims description 49
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 48
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 36
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 34
- 238000006243 chemical reaction Methods 0.000 claims description 33
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 31
- 238000000034 method Methods 0.000 claims description 24
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
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- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 9
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- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 6
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 claims description 5
- 206010048554 Endothelial dysfunction Diseases 0.000 claims description 5
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- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- KMPWYEUPVWOPIM-KODHJQJWSA-N cinchonidine Chemical compound C1=CC=C2C([C@H]([C@H]3[N@]4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-KODHJQJWSA-N 0.000 claims description 4
- KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 claims description 4
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- RYCNUMLMNKHWPZ-SNVBAGLBSA-N 1-acetyl-sn-glycero-3-phosphocholine Chemical compound CC(=O)OC[C@@H](O)COP([O-])(=O)OCC[N+](C)(C)C RYCNUMLMNKHWPZ-SNVBAGLBSA-N 0.000 claims description 3
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- 208000006011 Stroke Diseases 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 150000001408 amides Chemical class 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000004185 ester group Chemical group 0.000 claims description 3
- 235000021588 free fatty acids Nutrition 0.000 claims description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 230000010410 reperfusion Effects 0.000 claims description 3
- 201000000980 schizophrenia Diseases 0.000 claims description 3
- 159000000000 sodium salts Chemical class 0.000 claims description 3
- 125000002030 1,2-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([*:2])C([H])=C1[H] 0.000 claims description 2
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- MZVQCMJNVPIDEA-UHFFFAOYSA-N [CH2]CN(CC)CC Chemical group [CH2]CN(CC)CC MZVQCMJNVPIDEA-UHFFFAOYSA-N 0.000 claims description 2
- 230000003213 activating effect Effects 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 210000004556 brain Anatomy 0.000 claims description 2
- 125000006264 diethylaminomethyl group Chemical group [H]C([H])([H])C([H])([H])N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 208000028867 ischemia Diseases 0.000 claims description 2
- 125000000686 lactone group Chemical group 0.000 claims description 2
- 125000005633 phthalidyl group Chemical group 0.000 claims description 2
- 229910052701 rubidium Inorganic materials 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 12
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 2
- VZRIZUFGMIOKEH-UHFFFAOYSA-N 4-[[1-[1-[2-(2-chlorophenyl)hexoxy]ethyl]-4-oxoazetidin-2-yl]sulfinylmethyl]benzoic acid Chemical compound C=1C=CC=C(Cl)C=1C(CCCC)COC(C)N(C(C1)=O)C1S(=O)CC1=CC=C(C(O)=O)C=C1 VZRIZUFGMIOKEH-UHFFFAOYSA-N 0.000 claims 2
- PMXFDIYZZWEBRW-UHFFFAOYSA-N 4-[[1-[1-[2-(2-fluorophenyl)hexoxy]ethyl]-4-oxoazetidin-2-yl]sulfinylmethyl]benzoic acid Chemical compound C=1C=CC=C(F)C=1C(CCCC)COC(C)N(C(C1)=O)C1S(=O)CC1=CC=C(C(O)=O)C=C1 PMXFDIYZZWEBRW-UHFFFAOYSA-N 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 1
- NAYVJDOSDPXYRK-MJVKXCJRSA-N ClC1=CC=C(C=C1)CCCCCCNC(CN1C(C[C@H]1[S@@](=O)CC1=CC=C(C=C1)C(=O)OCC)=O)=O Chemical compound ClC1=CC=C(C=C1)CCCCCCNC(CN1C(C[C@H]1[S@@](=O)CC1=CC=C(C=C1)C(=O)OCC)=O)=O NAYVJDOSDPXYRK-MJVKXCJRSA-N 0.000 claims 1
- MWMRKDADHJQFQU-MJVKXCJRSA-N FC1=CC=C(C=C1)CCCCCCNC(CN1C(C[C@H]1[S@@](=O)CC1=CC=C(C=C1)C(=O)OCC)=O)=O Chemical compound FC1=CC=C(C=C1)CCCCCCNC(CN1C(C[C@H]1[S@@](=O)CC1=CC=C(C=C1)C(=O)OCC)=O)=O MWMRKDADHJQFQU-MJVKXCJRSA-N 0.000 claims 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims 1
- 208000038016 acute inflammation Diseases 0.000 claims 1
- 230000006022 acute inflammation Effects 0.000 claims 1
- 125000005041 acyloxyalkyl group Chemical group 0.000 claims 1
- 208000037976 chronic inflammation Diseases 0.000 claims 1
- 230000006020 chronic inflammation Effects 0.000 claims 1
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- 230000004968 inflammatory condition Effects 0.000 claims 1
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 150
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 73
- 239000000203 mixture Substances 0.000 description 73
- 239000000243 solution Substances 0.000 description 73
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- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 40
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 33
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- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 1
- SNVLJLYUUXKWOJ-UHFFFAOYSA-N methylidenecarbene Chemical compound C=[C] SNVLJLYUUXKWOJ-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical class [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- FYPMFJGVHOHGLL-UHFFFAOYSA-N probucol Chemical compound C=1C(C(C)(C)C)=C(O)C(C(C)(C)C)=CC=1SC(C)(C)SC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 FYPMFJGVHOHGLL-UHFFFAOYSA-N 0.000 description 1
- 229960003912 probucol Drugs 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229910052702 rhenium Inorganic materials 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical class [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 125000001273 sulfonato group Chemical class [O-]S(*)(=O)=O 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- DUYAAUVXQSMXQP-UHFFFAOYSA-M thioacetate Chemical compound CC([S-])=O DUYAAUVXQSMXQP-UHFFFAOYSA-M 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- 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
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
- C07D205/09—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams with a sulfur atom directly attached in position 4
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Dermatology (AREA)
- Obesity (AREA)
- Physical Education & Sports Medicine (AREA)
- Toxicology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Hematology (AREA)
- Biochemistry (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9608646.7A GB9608646D0 (en) | 1996-04-26 | 1996-04-26 | Novel compounds |
| EP9608646.7 | 1996-04-26 | ||
| GBGB9623756.5A GB9623756D0 (en) | 1996-11-15 | 1996-11-15 | Novel compounds |
| EP9623756.5 | 1996-11-15 | ||
| GBGB9625121.0A GB9625121D0 (en) | 1996-12-03 | 1996-12-03 | Novel compounds |
| EP9625121.0 | 1996-12-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2252696A1 true CA2252696A1 (en) | 1997-11-06 |
Family
ID=27268259
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002252696A Abandoned CA2252696A1 (en) | 1996-04-26 | 1997-04-15 | Azetidinone derivatives for the treatment of atherosclerosis |
Country Status (17)
| Country | Link |
|---|---|
| EP (1) | EP0915843A1 (cs) |
| JP (1) | JP2000509049A (cs) |
| AR (1) | AR006833A1 (cs) |
| AU (1) | AU2698697A (cs) |
| BR (1) | BR9709196A (cs) |
| CA (1) | CA2252696A1 (cs) |
| CZ (1) | CZ341098A3 (cs) |
| HU (1) | HUP9901359A3 (cs) |
| ID (1) | ID16660A (cs) |
| IL (1) | IL126696A0 (cs) |
| MA (1) | MA26426A1 (cs) |
| NO (1) | NO984939L (cs) |
| NZ (1) | NZ332476A (cs) |
| PE (1) | PE64398A1 (cs) |
| PL (1) | PL329530A1 (cs) |
| TR (1) | TR199802160T2 (cs) |
| WO (1) | WO1997041098A1 (cs) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE60121550T2 (de) | 2000-02-16 | 2007-06-21 | Smithkline Beecham Plc, Brentford | Pyrimidin-4-onderivat als LDL-PLA2 Inhibitor |
| US6982251B2 (en) | 2000-12-20 | 2006-01-03 | Schering Corporation | Substituted 2-azetidinones useful as hypocholesterolemic agents |
| US7071181B2 (en) | 2001-01-26 | 2006-07-04 | Schering Corporation | Methods and therapeutic combinations for the treatment of diabetes using sterol absorption inhibitors |
| HU230253B1 (hu) | 2001-01-26 | 2015-11-30 | Merck Sharp & Dohme Corp | Peroxiszóma proliferátor-aktivált receptor (PPAR) aktivátor(ok) és szterin-abszorpció inhibitor(ok) kombinációi és alkalmazásuk vaszkuláris indikációk kezelésére |
| ME00145B (me) | 2001-01-26 | 2010-10-10 | Merck Sharp & Dohme | Upotreba supstituisanih jedinjenja azetidinona za lečenje sitosterolemije |
| UA75644C2 (en) | 2001-03-28 | 2006-05-15 | Schering Corp | Enantioselective synthesis of azetidinone intermediate compounds |
| DE60216275T2 (de) * | 2001-05-25 | 2007-06-21 | Schering Corp. | Verwendung von mit azetidinon substituierten derivaten bei der behandlung der alzheimer-krankheit |
| DE60216300T2 (de) | 2001-09-21 | 2007-06-28 | Schering Corp. | Behandlung von xanthom mittels azetidinon-derivate als hemmer der sterol absorption |
| US7056906B2 (en) | 2001-09-21 | 2006-06-06 | Schering Corporation | Combinations of hormone replacement therapy composition(s) and sterol absorption inhibitor(s) and treatments for vascular conditions in post-menopausal women |
| US7053080B2 (en) | 2001-09-21 | 2006-05-30 | Schering Corporation | Methods and therapeutic combinations for the treatment of obesity using sterol absorption inhibitors |
| WO2004043457A1 (en) | 2002-11-06 | 2004-05-27 | Schering Corporation | Cholesterol absorptions inhibitors for the treatment of autoimmune disorders |
| CA2517573C (en) | 2003-03-07 | 2011-12-06 | Schering Corporation | Substituted azetidinone compounds, formulations and uses thereof for the treatment of hypercholesterolemia |
| ATE406364T1 (de) | 2003-03-07 | 2008-09-15 | Schering Corp | Substituierte azetidinon-derivate, deren pharmazeutische formulierungen und deren verwendung zur behandlung von hypercholesterolemia |
| US7459442B2 (en) | 2003-03-07 | 2008-12-02 | Schering Corporation | Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof |
| WO2004081003A1 (en) | 2003-03-07 | 2004-09-23 | Schering Corporation | Substituted azetidinone compounds, formulations and uses thereof for the treatment of hypercholeterolemia |
| US8962633B2 (en) | 2007-05-11 | 2015-02-24 | Thomas Jefferson University | Methods of treatment and prevention of metabolic bone diseases and disorders |
| US9029383B2 (en) | 2007-05-11 | 2015-05-12 | The Trustees Of The University Of Pennsylvania | Methods of treatment of skin ulcers |
| EA200971050A1 (ru) | 2007-05-11 | 2010-06-30 | Томас Джефферсон Юниверсити | Способы лечения и предупреждения нейродегенеративных заболеваний и нарушений |
| EA023796B1 (ru) | 2010-12-06 | 2016-07-29 | Глэксо Груп Лимитед | ПИРИМИДИНОНОВЫЕ СОЕДИНЕНИЯ ДЛЯ ПРИМЕНЕНИЯ В ЛЕЧЕНИИ ЗАБОЛЕВАНИЙ ИЛИ СОСТОЯНИЙ, ОПОСРЕДОВАННЫХ Lp-PLA |
| JP2013545792A (ja) | 2010-12-17 | 2013-12-26 | グラクソ グループ リミテッド | 眼疾患の処置および防止方法 |
| EP2725024A4 (en) | 2011-06-27 | 2014-12-03 | Shanghai Inst Materia Medica | HETEROCYCLIC AZOL COMPOUND, METHOD OF MANUFACTURING THEREOF, PHARMACEUTICAL COMPOSITION AND USE THEREOF |
| KR20140059204A (ko) | 2011-07-27 | 2014-05-15 | 글락소 그룹 리미티드 | 비시클릭 피리미돈 화합물 |
| WO2013013503A1 (en) | 2011-07-27 | 2013-01-31 | Glaxo Group Limited | 2,3-dihydroimidazo[1,2-c] pyrimidin-5(1h)-one compounds use as lp-pla2 inhibitors |
| WO2014114249A1 (en) | 2013-01-25 | 2014-07-31 | Glaxosmithkline Intellectual Property Development Limited | Bicyclic pyrimidone compounds as inhibitors of lp-pla2 |
| CN105008368B (zh) | 2013-01-25 | 2017-02-01 | 葛兰素史密斯克莱知识产权发展有限公司 | 基于2,3‑二氢咪唑并[1,2‑c]嘧啶‑5(1H)‑酮的脂蛋白相关磷脂酶A2(Lp‑PLA2)抑制剂 |
| WO2014114248A1 (en) | 2013-01-25 | 2014-07-31 | Glaxosmithkline Intellectual Property Development Limited | Compounds |
| 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 |
| 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 |
| CA3156783A1 (en) | 2019-11-09 | 2021-05-14 | Yun Jin | Tricycle dihydroimidazopyrimidone derivative, preparation method thereof, pharmaceutical composition and use thereof |
| CN115304620A (zh) | 2021-05-07 | 2022-11-08 | 上海赛默罗生物科技有限公司 | 嘧啶酮衍生物、其制备方法、药物组合物和用途 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4680391A (en) * | 1983-12-01 | 1987-07-14 | Merck & Co., Inc. | Substituted azetidinones as anti-inflammatory and antidegenerative agents |
| IL89835A0 (en) * | 1988-04-11 | 1989-12-15 | Merck & Co Inc | Substituted azetidinones,their preparation and pharmaceutical compositions containing them |
| IL99658A0 (en) * | 1990-10-15 | 1992-08-18 | Merck & Co Inc | Substituted azetidinones and pharmaceutical compositions containing them |
| WO1993000332A1 (en) * | 1991-06-25 | 1993-01-07 | Merck & Co., Inc. | Substituted azetidinones as anti-inflammatory and antidegenerative agents |
| WO1993002048A1 (en) * | 1991-07-23 | 1993-02-04 | Schering Corporation | Substituted beta-lactam compounds useful as hypocholesterolemic agents and processes for the preparation thereof |
| CA2108584C (en) * | 1992-10-27 | 1998-11-24 | James B. Doherty | Substituted azetidinones as anti-inflammatory and antidegenerative agents |
| WO1994013636A1 (en) * | 1992-12-17 | 1994-06-23 | Merck & Co., Inc. | New substituted azetidinones as anti-inflammatory and antidegenerative agents |
| EP0974663A1 (en) * | 1993-06-25 | 2000-01-26 | Smithkline Beecham Plc | Lipoprotein associated phospholipase A2, inhibitors thereof and use of same in diagnosis and therapy |
| DE69434609T2 (de) * | 1993-10-06 | 2006-09-21 | Icos Corp., Bothell | Acethylhydrolase des Plättchen aktivierenden Faktors |
| GB9421816D0 (en) * | 1994-10-29 | 1994-12-14 | Smithkline Beecham Plc | Novel compounds |
| HUT77089A (hu) * | 1994-12-22 | 1998-03-02 | Smithkline Beecham Plc. | Atherosclerosis kezelésére alkalmas szubsztituált 2-oxo-azetidinek, eljárás előállításukra és ezeket tartalmazó gyógyszerkészítmények |
| AU5014496A (en) * | 1995-03-23 | 1996-10-08 | Japan Tobacco Inc. | Diphenylmethyl-azetidinone compounds and elastase inhibitor |
| BR9609445A (pt) * | 1995-07-01 | 1999-04-06 | Smithkline Beecham Plc | Derivados de azetidinona no tratamento de aterosclerose |
| WO1997021676A1 (en) * | 1995-12-08 | 1997-06-19 | Smithkline Beecham Plc | Azetidinone compounds for the treatment of atherosclerosis |
-
1997
- 1997-04-15 NZ NZ332476A patent/NZ332476A/en unknown
- 1997-04-15 HU HU9901359A patent/HUP9901359A3/hu unknown
- 1997-04-15 CA CA002252696A patent/CA2252696A1/en not_active Abandoned
- 1997-04-15 EP EP97920699A patent/EP0915843A1/en not_active Withdrawn
- 1997-04-15 JP JP9538507A patent/JP2000509049A/ja active Pending
- 1997-04-15 PL PL97329530A patent/PL329530A1/xx unknown
- 1997-04-15 WO PCT/EP1997/001898 patent/WO1997041098A1/en not_active Ceased
- 1997-04-15 IL IL12669697A patent/IL126696A0/xx unknown
- 1997-04-15 AU AU26986/97A patent/AU2698697A/en not_active Abandoned
- 1997-04-15 CZ CZ983410A patent/CZ341098A3/cs unknown
- 1997-04-15 TR TR1998/02160T patent/TR199802160T2/xx unknown
- 1997-04-15 BR BR9709196A patent/BR9709196A/pt not_active Application Discontinuation
- 1997-04-24 AR ARP970101682A patent/AR006833A1/es unknown
- 1997-04-24 MA MA24565A patent/MA26426A1/fr unknown
- 1997-04-24 PE PE1997000311A patent/PE64398A1/es not_active Application Discontinuation
- 1997-04-25 ID IDP971394A patent/ID16660A/id unknown
-
1998
- 1998-10-23 NO NO984939A patent/NO984939L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| TR199802160T2 (xx) | 1999-04-21 |
| HUP9901359A3 (en) | 2000-03-28 |
| EP0915843A1 (en) | 1999-05-19 |
| AU2698697A (en) | 1997-11-19 |
| IL126696A0 (en) | 1999-08-17 |
| MA26426A1 (fr) | 2004-12-20 |
| PE64398A1 (es) | 1999-01-06 |
| JP2000509049A (ja) | 2000-07-18 |
| NO984939L (no) | 1998-12-23 |
| PL329530A1 (en) | 1999-03-29 |
| CZ341098A3 (cs) | 1999-03-17 |
| NO984939D0 (no) | 1998-10-23 |
| AR006833A1 (es) | 1999-09-29 |
| ID16660A (id) | 1997-10-30 |
| BR9709196A (pt) | 1999-05-25 |
| WO1997041098A1 (en) | 1997-11-06 |
| HUP9901359A2 (hu) | 1999-08-30 |
| NZ332476A (en) | 2000-06-23 |
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