SK178497A3 - Azetidinone derivatives, method for producing the same, pharmaceutical composition containing same and their use - Google Patents

Azetidinone derivatives, method for producing the same, pharmaceutical composition containing same and their use Download PDF

Info

Publication number: SK178497A3
Authority: SK; Slovakia
Prior art keywords: oxoazetidin; azetidin; acetamide; diastereoisomer; oxo
Prior art date: 1995-07-01

Application number

SK1784-97A

Other languages

English (en)

Slovak (sk)

Inventor

Dashyant Dhanak

Deirdre M B Hickey

Robert J Ife

Colin A Leach

David G Tew

Original Assignee

Smithkline Beecham Plc

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.)

1995-07-01

Filing date

1996-06-20

Publication date

1998-07-08

1995-07-01 Priority claimed from GBGB9513442.5A external-priority patent/GB9513442D0/en

1995-07-22 Priority claimed from GBGB9515056.1A external-priority patent/GB9515056D0/en

1995-07-25 Priority claimed from GBGB9515206.2A external-priority patent/GB9515206D0/en

1995-08-18 Priority claimed from GBGB9516985.0A external-priority patent/GB9516985D0/en

1995-12-08 Priority claimed from GBGB9525132.8A external-priority patent/GB9525132D0/en

1996-04-26 Priority claimed from GBGB9608650.9A external-priority patent/GB9608650D0/en

1996-04-26 Priority claimed from GBGB9608651.7A external-priority patent/GB9608651D0/en

1996-06-20 Application filed by Smithkline Beecham Plc filed Critical Smithkline Beecham Plc

1998-07-08 Publication of SK178497A3 publication Critical patent/SK178497A3/sk

Links

MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical class O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 title claims abstract description 13
239000008194 pharmaceutical composition Substances 0.000 title claims description 9
238000004519 manufacturing process Methods 0.000 title claims description 4
125000000217 alkyl group Chemical group 0.000 claims abstract description 85
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 71
125000003118 aryl group Chemical group 0.000 claims abstract description 48
239000001257 hydrogen Substances 0.000 claims abstract description 40
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 31
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 21
229910052736 halogen Inorganic materials 0.000 claims abstract description 18
150000002367 halogens Chemical class 0.000 claims abstract description 18
150000002431 hydrogen Chemical class 0.000 claims abstract description 16
201000001320 Atherosclerosis Diseases 0.000 claims abstract description 12
229910052760 oxygen Inorganic materials 0.000 claims abstract description 10
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 9
239000001301 oxygen Substances 0.000 claims abstract description 9
125000003107 substituted aryl group Chemical group 0.000 claims abstract description 6
238000002560 therapeutic procedure Methods 0.000 claims abstract description 6
125000003342 alkenyl group Chemical group 0.000 claims abstract description 4
125000005647 linker group Chemical group 0.000 claims abstract description 4
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 283
-1 2- (6- (4-Fluorophenyl) hexyloxy) ethyl Chemical group 0.000 claims description 239
150000001875 compounds Chemical class 0.000 claims description 187
WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 129
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 110
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 74
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 68
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 66
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 64
NXFFJDQHYLNEJK-UHFFFAOYSA-N 2-[4-[(4-chlorophenyl)methyl]-7-fluoro-5-methylsulfonyl-2,3-dihydro-1h-cyclopenta[b]indol-3-yl]acetic acid Chemical compound C1=2C(S(=O)(=O)C)=CC(F)=CC=2C=2CCC(CC(O)=O)C=2N1CC1=CC=C(Cl)C=C1 NXFFJDQHYLNEJK-UHFFFAOYSA-N 0.000 claims description 51
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 47
230000015572 biosynthetic process Effects 0.000 claims description 43
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 38
229940080818 propionamide Drugs 0.000 claims description 38
QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 37
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
239000002904 solvent Substances 0.000 claims description 21
125000001424 substituent group Chemical group 0.000 claims description 18
229910052799 carbon Inorganic materials 0.000 claims description 16
239000000126 substance Substances 0.000 claims description 16
238000006243 chemical reaction Methods 0.000 claims description 15
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 13
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
RKOTXQYWCBGZLP-UHFFFAOYSA-N N-[(2,4-difluorophenyl)methyl]-2-ethyl-9-hydroxy-3-methoxy-1,8-dioxospiro[3H-pyrido[1,2-a]pyrazine-4,3'-oxolane]-7-carboxamide Chemical compound CCN1C(OC)C2(CCOC2)N2C=C(C(=O)NCC3=C(F)C=C(F)C=C3)C(=O)C(O)=C2C1=O RKOTXQYWCBGZLP-UHFFFAOYSA-N 0.000 claims description 10
208000035475 disorder Diseases 0.000 claims description 10
125000002947 alkylene group Chemical group 0.000 claims description 8
239000002168 alkylating agent Substances 0.000 claims description 7
229940100198 alkylating agent Drugs 0.000 claims description 7
238000005804 alkylation reaction Methods 0.000 claims description 7
229910000104 sodium hydride Inorganic materials 0.000 claims description 7
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 6
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 6
230000029936 alkylation Effects 0.000 claims description 6
206010012601 diabetes mellitus Diseases 0.000 claims description 6
150000004702 methyl esters Chemical class 0.000 claims description 6
125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 5
206010002383 Angina Pectoris Diseases 0.000 claims description 5
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 5
150000001412 amines Chemical class 0.000 claims description 5
150000003839 salts Chemical class 0.000 claims description 5
239000012312 sodium hydride Substances 0.000 claims description 5
FEZBOGQWUJLPFB-UHFFFAOYSA-N 4-benzylsulfinyl-1-(2-phenylmethoxyethyl)azetidin-2-one Chemical compound O=C1CC(S(=O)CC=2C=CC=CC=2)N1CCOCC1=CC=CC=C1 FEZBOGQWUJLPFB-UHFFFAOYSA-N 0.000 claims description 4
DOXLEKNWIBPKPX-UHFFFAOYSA-N 4-benzylsulfinyl-1-(3-phenoxypropyl)azetidin-2-one Chemical compound O=C1CC(S(=O)CC=2C=CC=CC=2)N1CCCOC1=CC=CC=C1 DOXLEKNWIBPKPX-UHFFFAOYSA-N 0.000 claims description 4
KJGUACXIBQJPOT-UHFFFAOYSA-N 4-methylsulfanyl-1-(3-phenoxypropyl)azetidin-2-one Chemical compound CSC1CC(=O)N1CCCOC1=CC=CC=C1 KJGUACXIBQJPOT-UHFFFAOYSA-N 0.000 claims description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
230000002152 alkylating effect Effects 0.000 claims description 4
DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 claims description 4
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 4
239000003795 chemical substances by application Substances 0.000 claims description 4
208000037976 chronic inflammation Diseases 0.000 claims description 4
230000006020 chronic inflammation Effects 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
208000010125 myocardial infarction Diseases 0.000 claims description 4
206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 4
RASIATFMUKXKLX-UHFFFAOYSA-N 2-(2-benzylsulfinyl-4-oxoazetidin-1-yl)-n-[1-(3-chlorophenyl)hex-5-yn-2-yl]acetamide Chemical compound ClC1=CC=CC(CC(CCC#C)NC(=O)CN2C(CC2S(=O)CC=2C=CC=CC=2)=O)=C1 RASIATFMUKXKLX-UHFFFAOYSA-N 0.000 claims description 3
NXMKAMIWWYMIQO-UHFFFAOYSA-N 4-benzylsulfanyl-1-[2-(6-phenylhexoxy)ethyl]azetidin-2-one Chemical compound C=1C=CC=CC=1CCCCCCOCCN1C(=O)CC1SCC1=CC=CC=C1 NXMKAMIWWYMIQO-UHFFFAOYSA-N 0.000 claims description 3
VDTQLZMGFOUHRD-UHFFFAOYSA-N 4-methylsulfinyl-1-(3-phenoxypropyl)azetidin-2-one Chemical compound CS(=O)C1CC(=O)N1CCCOC1=CC=CC=C1 VDTQLZMGFOUHRD-UHFFFAOYSA-N 0.000 claims description 3
208000024827 Alzheimer disease Diseases 0.000 claims description 3
206010020772 Hypertension Diseases 0.000 claims description 3
201000004681 Psoriasis Diseases 0.000 claims description 3
206010063837 Reperfusion injury Diseases 0.000 claims description 3
206010040047 Sepsis Diseases 0.000 claims description 3
208000006011 Stroke Diseases 0.000 claims description 3
208000038016 acute inflammation Diseases 0.000 claims description 3
230000006022 acute inflammation Effects 0.000 claims description 3
210000004556 brain Anatomy 0.000 claims description 3
FOPAFEZGHASLNW-UHFFFAOYSA-N ethyl 4-[[1-[2-[6-(4-fluorophenyl)hexoxy]ethyl]-4-oxoazetidin-2-yl]sulfinylmethyl]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1CS(=O)C1N(CCOCCCCCCC=2C=CC(F)=CC=2)C(=O)C1 FOPAFEZGHASLNW-UHFFFAOYSA-N 0.000 claims description 3
125000005843 halogen group Chemical group 0.000 claims description 3
230000004968 inflammatory condition Effects 0.000 claims description 3
230000010410 reperfusion Effects 0.000 claims description 3
201000000980 schizophrenia Diseases 0.000 claims description 3
QZPIZMCHVXMVMX-UHFFFAOYSA-N 1-(2-oxo-4-phenylbutyl)-4-phenoxyazetidin-2-one Chemical compound C=1C=CC=CC=1OC1CC(=O)N1CC(=O)CCC1=CC=CC=C1 QZPIZMCHVXMVMX-UHFFFAOYSA-N 0.000 claims description 2
XTIOUARFONFMSA-UHFFFAOYSA-N 1-(2-oxo-4-phenylbutyl)-4-phenylmethoxyazetidin-2-one Chemical compound C=1C=CC=CC=1COC1CC(=O)N1CC(=O)CCC1=CC=CC=C1 XTIOUARFONFMSA-UHFFFAOYSA-N 0.000 claims description 2
FISQIYYHXXWBJD-UHFFFAOYSA-N 2-(2-benzylsulfanyl-4-oxoazetidin-1-yl)-n-(5-phenoxypentyl)acetamide Chemical compound C=1C=CC=CC=1OCCCCCNC(=O)CN(C(C1)=O)C1SCC1=CC=CC=C1 FISQIYYHXXWBJD-UHFFFAOYSA-N 0.000 claims description 2
FWIXKNHMKBRIGY-UHFFFAOYSA-N 2-(2-benzylsulfanyl-4-oxoazetidin-1-yl)-n-[2-(2-phenoxyethoxy)ethyl]acetamide Chemical compound C=1C=CC=CC=1OCCOCCNC(=O)CN(C(C1)=O)C1SCC1=CC=CC=C1 FWIXKNHMKBRIGY-UHFFFAOYSA-N 0.000 claims description 2
HTHODRWFKQYIHK-UHFFFAOYSA-N 2-(2-benzylsulfanyl-4-oxoazetidin-1-yl)-n-[2-(3-phenylpropoxy)ethyl]acetamide Chemical compound C=1C=CC=CC=1CCCOCCNC(=O)CN(C(C1)=O)C1SCC1=CC=CC=C1 HTHODRWFKQYIHK-UHFFFAOYSA-N 0.000 claims description 2
LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 claims description 2
JOQKOLDUSMQXCT-UHFFFAOYSA-N 4-benzylsulfanyl-1-(2-phenylmethoxyethyl)azetidin-2-one Chemical compound C=1C=CC=CC=1COCCN1C(=O)CC1SCC1=CC=CC=C1 JOQKOLDUSMQXCT-UHFFFAOYSA-N 0.000 claims description 2
RIPGJEJWSWOPTJ-UHFFFAOYSA-N 4-benzylsulfinyl-1-[2-(6-phenylhexoxy)ethyl]azetidin-2-one Chemical compound O=C1CC(S(=O)CC=2C=CC=CC=2)N1CCOCCCCCCC1=CC=CC=C1 RIPGJEJWSWOPTJ-UHFFFAOYSA-N 0.000 claims description 2
XSRCOEXDDABEKK-UHFFFAOYSA-N ClC1=C(CC(CCC#C)NC(=O)CN2C(CC2=O)S(=O)(=O)CC2=CC=CC=C2)C=CC=C1 Chemical compound ClC1=C(CC(CCC#C)NC(=O)CN2C(CC2=O)S(=O)(=O)CC2=CC=CC=C2)C=CC=C1 XSRCOEXDDABEKK-UHFFFAOYSA-N 0.000 claims description 2
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 2
CBXNYKLIVLKQMR-UHFFFAOYSA-N O=C1[CH-]N=C1 Chemical compound O=C1[CH-]N=C1 CBXNYKLIVLKQMR-UHFFFAOYSA-N 0.000 claims description 2
230000003213 activating effect Effects 0.000 claims description 2
150000001336 alkenes Chemical class 0.000 claims description 2
150000001345 alkine derivatives Chemical class 0.000 claims description 2
230000000879 anti-atherosclerotic effect Effects 0.000 claims description 2
230000003178 anti-diabetic effect Effects 0.000 claims description 2
230000001315 anti-hyperlipaemic effect Effects 0.000 claims description 2
229940121363 anti-inflammatory agent Drugs 0.000 claims description 2
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239000002220 antihypertensive agent Substances 0.000 claims description 2
230000003197 catalytic effect Effects 0.000 claims description 2
125000001033 ether group Chemical group 0.000 claims description 2
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 claims description 2
238000010438 heat treatment Methods 0.000 claims description 2
125000000335 thiazolyl group Chemical group 0.000 claims description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 2
238000005809 transesterification reaction Methods 0.000 claims description 2
WZYXDLRGEUUJAT-UHFFFAOYSA-N 2-(2-benzylsulfinyl-4-oxoazetidin-1-yl)-n-[1-(2-chlorophenyl)hex-5-yn-2-yl]acetamide Chemical compound ClC1=CC=CC=C1CC(CCC#C)NC(=O)CN1C(=O)CC1S(=O)CC1=CC=CC=C1 WZYXDLRGEUUJAT-UHFFFAOYSA-N 0.000 claims 2
OQEWSXNIJVEQBK-UHFFFAOYSA-N 2-(2-benzylsulfonyl-4-oxoazetidin-1-yl)-n-[1-(3-chlorophenyl)hex-5-yn-2-yl]acetamide Chemical compound ClC1=CC=CC(CC(CCC#C)NC(=O)CN2C(CC2S(=O)(=O)CC=2C=CC=CC=2)=O)=C1 OQEWSXNIJVEQBK-UHFFFAOYSA-N 0.000 claims 1
HFBWTLKCADPXEI-UHFFFAOYSA-N 4-benzylsulfanyl-1-[2-[6-(4-chlorophenyl)hexoxy]ethyl]azetidin-2-one Chemical compound C1=CC(Cl)=CC=C1CCCCCCOCCN1C(=O)CC1SCC1=CC=CC=C1 HFBWTLKCADPXEI-UHFFFAOYSA-N 0.000 claims 1
SWWVYTLFKQNHSQ-UHFFFAOYSA-N 4-benzylsulfanyl-1-[2-[6-(4-fluorophenyl)hexoxy]ethyl]azetidin-2-one Chemical compound C1=CC(F)=CC=C1CCCCCCOCCN1C(=O)CC1SCC1=CC=CC=C1 SWWVYTLFKQNHSQ-UHFFFAOYSA-N 0.000 claims 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
239000013543 active substance Substances 0.000 claims 1
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150000003254 radicals Chemical class 0.000 claims 1
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238000005481 NMR spectroscopy Methods 0.000 description 165
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NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 20
238000000034 method Methods 0.000 description 20
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Classifications

- 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
- 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
- C07D401/02—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
- 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
- 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
- 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
- C07D205/085—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 nitrogen atom directly attached in position 3
- 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
- C07D205/095—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 and with a nitrogen atom directly attached in position 3
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Chemical Kinetics & Catalysis (AREA)
Urology & Nephrology (AREA)
Medicinal Chemistry (AREA)
Vascular Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

SK1784-97A 1995-07-01 1996-06-20 Azetidinone derivatives, method for producing the same, pharmaceutical composition containing same and their use SK178497A3 (en)

Applications Claiming Priority (8)

Application Number	Priority Date	Filing Date	Title
GBGB9513442.5A GB9513442D0 (en)	1995-07-01	1995-07-01	Novel compounds
GBGB9515056.1A GB9515056D0 (en)	1995-07-22	1995-07-22	Novel compounds
GBGB9515206.2A GB9515206D0 (en)	1995-07-25	1995-07-25	Novel compounds
GBGB9516985.0A GB9516985D0 (en)	1995-08-18	1995-08-18	Novel compounds
GBGB9525132.8A GB9525132D0 (en)	1995-12-08	1995-12-08	Novel compounds
GBGB9608650.9A GB9608650D0 (en)	1996-04-26	1996-04-26	Novel compounds
GBGB9608651.7A GB9608651D0 (en)	1996-04-26	1996-04-26	Novel compounds
PCT/EP1996/002765 WO1997002242A1 (en)	1995-07-01	1996-06-20	Azetidinone derivatives for the treatment of atherosclerosis

Publications (1)

Publication Number	Publication Date
SK178497A3 true SK178497A3 (en)	1998-07-08

Family

ID=27562921

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1784-97A SK178497A3 (en)	1995-07-01	1996-06-20	Azetidinone derivatives, method for producing the same, pharmaceutical composition containing same and their use

Country Status (23)

Country	Link
EP (1)	EP0840725A1 (cs)
JP (1)	JP2002515852A (cs)
KR (1)	KR19990028630A (cs)
CN (1)	CN1197452A (cs)
AP (1)	AP728A (cs)
AU (1)	AU708032B2 (cs)
BG (1)	BG102214A (cs)
BR (1)	BR9609445A (cs)
CA (1)	CA2225627A1 (cs)
CZ (1)	CZ422197A3 (cs)
EA (1)	EA199800109A1 (cs)
HU (1)	HUP9901153A3 (cs)
IL (1)	IL122650A0 (cs)
MA (1)	MA23922A1 (cs)
MX (1)	MX9800186A (cs)
NO (1)	NO976158L (cs)
NZ (1)	NZ311684A (cs)
OA (1)	OA10648A (cs)
PE (1)	PE8998A1 (cs)
PL (1)	PL324240A1 (cs)
SK (1)	SK178497A3 (cs)
TR (1)	TR199701762T1 (cs)
WO (1)	WO1997002242A1 (cs)

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EP0869943A1 (en) *	1995-12-08	1998-10-14	Smithkline Beecham Plc	Monocyclic beta-lactame derivatives for treatment of atherosclerosis
GB9608649D0 (en) *	1996-04-26	1996-07-03	Smithkline Beecham Plc	Novel compounds
IL126696A0 (en) *	1996-04-26	1999-08-17	Smithkline Beecham Plc	Azetidinone derivatives for the treatment of atherosclerosis
DK1263740T3 (da)	2000-02-16	2006-11-13	Smithkline Beecham Plc	Pyrimidin-4-on-derivat som LDL-PLA2-inhibitor
GB0024808D0 (en)	2000-10-10	2000-11-22	Smithkline Beecham Plc	Novel compounds
KR101730290B1 (ko)	2007-05-11	2017-04-25	토마스 제퍼슨 유니버시티	신경변성 질환 및 장애의 치료 및 예방 방법
CN101687009A (zh)	2007-05-11	2010-03-31	宾夕法尼亚大学理事会	治疗皮肤溃疡的方法
US8962633B2 (en)	2007-05-11	2015-02-24	Thomas Jefferson University	Methods of treatment and prevention of metabolic bone diseases and disorders
KR101861883B1 (ko)	2010-12-06	2018-05-28	글락소 그룹 리미티드	Lp-PLA₂에 의해 매개되는 질환 또는 상태의 치료에 사용하기 위한 피리미디논 화합물
ES2847883T3 (es)	2010-12-17	2021-08-04	Glaxo Group Ltd	Uso de inhibidores de LP-PLA2 en el tratamiento y prevención de enfermedades oculares
CN103619831B (zh)	2011-06-27	2016-05-04	中国科学院上海药物研究所	唑类杂环化合物、其制备方法、药物组合物和用途
CA2842965A1 (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
AR087309A1 (es)	2011-07-27	2014-03-12	Glaxo Group Ltd	Compuesto heterociclico de anillos condensados sustituido, composicion farmaceutica que lo comprende y su uso para la fabricacion de un medicamento para el tratamiento de enfermedades neurogenerativas y aterosclerosis
EP2948456A4 (en)	2013-01-25	2016-09-14	Glaxosmithkline Ip Dev Ltd	BICYCLIC PYRIMIDONE COMPOUNDS AS LP-PLA2 INHIBITORS
MX2015009633A (es)	2013-01-25	2015-11-30	Glaxosmithkline Ip Dev Ltd	Inhibidores de fosfolipasa a2 asociada con lipoproteinas basados en 2,3-dihidroimidazol[1,2-c] pirimidin-5(1h)-ona.
US9296755B2 (en)	2013-01-25	2016-03-29	Glaxosmithkline Intellectual Property Development Limited	3,4-dihydro-1H-pyrimido[1,6-a]pyrimidin-6(2H)-one compounds and their therapeutic applications
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
EP4056571A4 (en)	2019-11-09	2024-01-24	Shanghai Simr Biotechnology Co., Ltd.	Tricyclic dihydroimidazopyrimidone derivative, preparation method therefor, 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
WO2025015951A1 (zh)	2023-07-17	2025-01-23	上海枢境生物科技有限公司	双环[5,6]咪唑嘧啶酮类衍生物、其制备方法和应用

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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
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

1996
- 1996-06-20 CN CN96196661A patent/CN1197452A/zh active Pending
- 1996-06-20 KR KR1019970709952A patent/KR19990028630A/ko not_active Withdrawn
- 1996-06-20 JP JP50477297A patent/JP2002515852A/ja active Pending
- 1996-06-20 EP EP96922030A patent/EP0840725A1/en not_active Withdrawn
- 1996-06-20 WO PCT/EP1996/002765 patent/WO1997002242A1/en not_active Ceased
- 1996-06-20 AU AU63050/96A patent/AU708032B2/en not_active Ceased
- 1996-06-20 AP APAP/P/1997/001161A patent/AP728A/en active
- 1996-06-20 IL IL12265096A patent/IL122650A0/xx unknown
- 1996-06-20 CA CA002225627A patent/CA2225627A1/en not_active Abandoned
- 1996-06-20 PL PL96324240A patent/PL324240A1/xx unknown
- 1996-06-20 NZ NZ311684A patent/NZ311684A/xx unknown
- 1996-06-20 EA EA199800109A patent/EA199800109A1/ru unknown
- 1996-06-20 HU HU9901153A patent/HUP9901153A3/hu unknown
- 1996-06-20 BR BR9609445A patent/BR9609445A/pt unknown
- 1996-06-20 SK SK1784-97A patent/SK178497A3/sk unknown
- 1996-06-20 TR TR97/01762T patent/TR199701762T1/xx unknown
- 1996-06-20 CZ CZ974221A patent/CZ422197A3/cs unknown
- 1996-06-28 PE PE1996000496A patent/PE8998A1/es not_active Application Discontinuation
- 1996-06-28 MA MA24298A patent/MA23922A1/fr unknown
1997
- 1997-12-30 NO NO976158A patent/NO976158L/no unknown
- 1997-12-31 OA OA70172A patent/OA10648A/en unknown
1998
- 1998-01-07 MX MX9800186A patent/MX9800186A/es unknown
- 1998-01-28 BG BG102214A patent/BG102214A/xx unknown

Also Published As

Publication number	Publication date
MX9800186A (es)	1998-07-31
OA10648A (en)	2002-09-25
HUP9901153A2 (hu)	1999-08-30
NZ311684A (en)	2000-04-28
PE8998A1 (es)	1998-03-20
TR199701762T1 (xx)	1998-05-21
KR19990028630A (ko)	1999-04-15
PL324240A1 (en)	1998-05-11
IL122650A0 (en)	1998-08-16
CA2225627A1 (en)	1997-01-23
WO1997002242A1 (en)	1997-01-23
AU708032B2 (en)	1999-07-29
NO976158D0 (no)	1997-12-30
BR9609445A (pt)	1999-04-06
JP2002515852A (ja)	2002-05-28
AU6305096A (en)	1997-02-05
BG102214A (en)	1998-08-31
HUP9901153A3 (en)	1999-11-29
AP728A (en)	1999-01-29
EA199800109A1 (ru)	1998-10-29
MA23922A1 (fr)	1996-12-31
EP0840725A1 (en)	1998-05-13
NO976158L (no)	1998-02-25
CZ422197A3 (cs)	1998-06-17
AP9701161A0 (en)	1998-01-31
CN1197452A (zh)	1998-10-28

Publication	Publication Date	Title
AU708032B2 (en)	1999-07-29	Azetidinone derivatives for the treatment of atherosclerosis
US5990102A (en)	1999-11-23	Substituted azetidin-2-ones for treatment of atherosclerosis
US6071899A (en)	2000-06-06	Azetidinone derivatives for the treatment of atherosclerosis
AU760181B2 (en)	2003-05-08	Aminobutanoic acid derivatives
CZ341098A3 (cs)	1999-03-17	Azetidinonové deriváty pro ošetřování aterosklerózy
JP2000505063A (ja)	2000-04-25	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
EP0472449B1 (fr)	1994-09-14	Nouveaux sulfonamides substitués procédés de préparation et médicaments les contenant
FR2495613A1 (fr)	1982-06-11	Derives 1-sulfo-2-oxoazetidine, leur procede de preparation et leur utilisation dans des compositions antimicrobiennes
FR2511678A1 (fr)	1983-02-25	Derives de carbapeneme, leur procede de preparation et leur application en therapeutique
HUP0201654A2 (en)	2002-09-28	Substituted phenylpropionic acid derivatives as agonists to human peroxisome proliferator-activated receptor (ppar) alpha, their preparation and pharmaceutical composition containing the same
EP3088385A1 (en)	2016-11-02	Aryl urea derivatives as n-formyl peptide receptor like-1 (fprl-1) receptor modulators
HU227672B1 (en)	2011-11-28	Sulfur-substituted azetidinone compounds useful as hypocholesterolemic agents preparation thereof and pharmaceutical compositions containing the same
MC1513A1 (fr)	1984-02-10	Derives de 1-sulfo-2-azetidinone,leur production et leur utilisation
EP0373423A1 (de)	1990-06-20	Substituierte 2-Pyridone und Pyrid-2-thione, Verfahren zu ihrer Herstellung und ihre Verwendung in Arzneimitteln
JP2000509063A (ja)	2000-07-18	アテローム性動脈硬化症の治療用アゼチジノン誘導体
LU84947A1 (fr)	1984-03-23	Composes d'azetidine
FR2495612A1 (fr)	1982-06-11	Derives de la 2-oxoazetidine, leur preparation et leur utilisation
FR2477547A1 (fr)	1981-09-11	Derives de l'acide 2-peneme-3-carboxylique, leur preparation et leur application therapeutique
FR2524890A1 (fr)	1983-10-14	Nouveaux derives de carbapenem, compositions pharmaceutiques les contenant, composes intermediaires pour leur preparation, et leurs procedes de production
FR2526798A1 (fr)	1983-11-18	Derives de peneme, leur procede de preparation et compositions therapeutiques les contenant
JPS58134074A (ja)	1983-08-10	抗菌剤、その製法及びそれを含む医薬組成物
JPH0386882A (ja)	1991-04-11	ピロロキノリン化合物
FR2745570A1 (fr)	1997-09-05	Nouveaux derives soufres comportant une liaison retroamide, leur procede et intermediaires de preparation, leur application a titre de medicaments, et les compositions pharmaceutiques les renfermant
FR2552763A1 (fr)	1985-04-05	Nouveaux derives du carbapeneme, leur preparation et leur utilisation comme medicaments
JPH0321542B2 (cs)	1991-03-22