SK80397A3 - Substituted azetidin-2-ones, preparation method thereof, farmaceutical compositions and their use - Google Patents

Substituted azetidin-2-ones, preparation method thereof, farmaceutical compositions and their use Download PDF

Info

Publication number: SK80397A3
Authority: SK; Slovakia
Prior art keywords: acetamide; oxoazetidin; hexyl; azetidin; phenyl
Prior art date: 1994-12-22

Application number

SK803-97A

Other languages

English (en)

Slovak (sk)

Inventor

Deirdre M B Hickey

Colin A Leach

Robert J Ife

David G Tew

Dashyant Dhanak

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.)

1994-12-22

Filing date

1995-12-20

Publication date

1998-01-14

1994-12-22 Priority claimed from GBGB9426020.5A external-priority patent/GB9426020D0/en

1994-12-23 Priority claimed from GBGB9426030.4A external-priority patent/GB9426030D0/en

1995-06-08 Priority claimed from GBGB9511599.4A external-priority patent/GB9511599D0/en

1995-06-08 Priority claimed from GBGB9511600.0A external-priority patent/GB9511600D0/en

1995-12-20 Application filed by Smithkline Beecham Plc filed Critical Smithkline Beecham Plc

1998-01-14 Publication of SK80397A3 publication Critical patent/SK80397A3/sk

Links

238000002360 preparation method Methods 0.000 title claims description 32
MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical class O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 title claims description 11
239000000203 mixture Substances 0.000 title description 223
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 352
150000001875 compounds Chemical class 0.000 claims abstract description 183
125000000217 alkyl group Chemical group 0.000 claims abstract description 21
201000001320 Atherosclerosis Diseases 0.000 claims abstract description 12
125000003118 aryl group Chemical group 0.000 claims abstract description 12
229910052736 halogen Inorganic materials 0.000 claims abstract description 12
150000002367 halogens Chemical class 0.000 claims abstract description 12
239000001257 hydrogen Substances 0.000 claims abstract description 9
239000003112 inhibitor Substances 0.000 claims abstract description 8
102000016752 1-Alkyl-2-acetylglycerophosphocholine Esterase Human genes 0.000 claims abstract description 7
108010024976 Asparaginase Proteins 0.000 claims abstract description 7
150000002431 hydrogen Chemical class 0.000 claims abstract description 4
125000003107 substituted aryl group Chemical group 0.000 claims abstract description 3
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 254
-1 4-carboxybenzyl Chemical group 0.000 claims description 207
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 166
229910052717 sulfur Inorganic materials 0.000 claims description 152
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 51
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 47
238000006243 chemical reaction Methods 0.000 claims description 40
238000000034 method Methods 0.000 claims description 34
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 30
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 21
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
201000010099 disease 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 11
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 9
102000004190 Enzymes Human genes 0.000 claims description 9
108090000790 Enzymes Proteins 0.000 claims description 9
239000002253 acid Substances 0.000 claims description 9
230000015572 biosynthetic process Effects 0.000 claims description 9
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
230000029936 alkylation Effects 0.000 claims description 8
238000005804 alkylation reaction Methods 0.000 claims description 8
125000001424 substituent group Chemical group 0.000 claims description 8
150000002148 esters Chemical class 0.000 claims description 7
239000008194 pharmaceutical composition Substances 0.000 claims description 7
VFFZACOXEBIKPF-UHFFFAOYSA-N 4-benzylsulfinyl-1-(2-oxo-4-phenylbutyl)azetidin-2-one Chemical compound C=1C=CC=CC=1CS(=O)C1CC(=O)N1CC(=O)CCC1=CC=CC=C1 VFFZACOXEBIKPF-UHFFFAOYSA-N 0.000 claims description 6
206010012601 diabetes mellitus Diseases 0.000 claims description 6
230000010410 reperfusion Effects 0.000 claims description 6
238000002560 therapeutic procedure Methods 0.000 claims description 6
KANZOFLWLNQFCU-UHFFFAOYSA-N 2-(2-oxoazetidin-1-yl)acetamide Chemical compound NC(=O)CN1CCC1=O KANZOFLWLNQFCU-UHFFFAOYSA-N 0.000 claims description 5
RAMZEPLVLLSIGP-UHFFFAOYSA-N 4-benzylsulfinyl-1-(2-oxo-9-phenylnonyl)azetidin-2-one Chemical compound C=1C=CC=CC=1CS(=O)C1CC(=O)N1CC(=O)CCCCCCCC1=CC=CC=C1 RAMZEPLVLLSIGP-UHFFFAOYSA-N 0.000 claims description 5
MDZXPXOTVMIEFL-UHFFFAOYSA-N 4-benzylsulfinyl-1-(2-phenylethyl)azetidin-2-one Chemical compound O=C1CC(S(=O)CC=2C=CC=CC=2)N1CCC1=CC=CC=C1 MDZXPXOTVMIEFL-UHFFFAOYSA-N 0.000 claims description 5
206010048554 Endothelial dysfunction Diseases 0.000 claims description 5
230000000694 effects Effects 0.000 claims description 5
230000008694 endothelial dysfunction Effects 0.000 claims description 5
210000002540 macrophage Anatomy 0.000 claims description 5
JOAVKKUKYPKXFE-UHFFFAOYSA-N methyl 4-[[2-[6-(4-chlorophenyl)hexylamino]-2-oxo-1-(2-oxoazetidin-1-yl)ethyl]sulfinylmethyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CS(=O)C(C(=O)NCCCCCCC=1C=CC(Cl)=CC=1)N1C(=O)CC1 JOAVKKUKYPKXFE-UHFFFAOYSA-N 0.000 claims description 5
210000001616 monocyte Anatomy 0.000 claims description 5
ASFPYGMXZWAPHR-UHFFFAOYSA-N 1-(2-oxo-4-phenylbutyl)-4-(2-phenylethylsulfinyl)azetidin-2-one Chemical compound C=1C=CC=CC=1CCS(=O)C1CC(=O)N1CC(=O)CCC1=CC=CC=C1 ASFPYGMXZWAPHR-UHFFFAOYSA-N 0.000 claims description 4
RCAXGEQPRXSKDR-UHFFFAOYSA-N 1-(2-oxo-4-phenylbutyl)-4-(3-phenylpropylsulfinyl)azetidin-2-one Chemical compound C=1C=CC=CC=1CCCS(=O)C1CC(=O)N1CC(=O)CCC1=CC=CC=C1 RCAXGEQPRXSKDR-UHFFFAOYSA-N 0.000 claims description 4
RZMRIZFJTDRIGX-UHFFFAOYSA-N 1-(2-oxo-4-phenylbutyl)-4-phenylsulfanylazetidin-2-one Chemical compound C=1C=CC=CC=1SC1CC(=O)N1CC(=O)CCC1=CC=CC=C1 RZMRIZFJTDRIGX-UHFFFAOYSA-N 0.000 claims description 4
GVZLTIXOMWZBPQ-UHFFFAOYSA-N 2-[2-(benzenesulfonyl)-4-oxoazetidin-1-yl]-n-[6-(4-chlorophenyl)hexyl]acetamide Chemical compound C1=CC(Cl)=CC=C1CCCCCCNC(=O)CN1C(=O)CC1S(=O)(=O)C1=CC=CC=C1 GVZLTIXOMWZBPQ-UHFFFAOYSA-N 0.000 claims description 4
UWPZJMGSPBWCIV-UHFFFAOYSA-N 4-[(2-methoxyphenyl)methylsulfinyl]-1-(2-oxo-4-phenylbutyl)azetidin-2-one Chemical compound COC1=CC=CC=C1CS(=O)C1N(CC(=O)CCC=2C=CC=CC=2)C(=O)C1 UWPZJMGSPBWCIV-UHFFFAOYSA-N 0.000 claims description 4
IISFIAPVXCWWJB-UHFFFAOYSA-N 4-[(4-fluorophenyl)methylsulfinyl]-1-(2-oxo-4-phenylbutyl)azetidin-2-one Chemical compound C1=CC(F)=CC=C1CS(=O)C1N(CC(=O)CCC=2C=CC=CC=2)C(=O)C1 IISFIAPVXCWWJB-UHFFFAOYSA-N 0.000 claims description 4
UXRVWRAKQXAJHN-UHFFFAOYSA-N 4-[(4-methoxyphenyl)methylsulfinyl]-1-(2-oxo-4-phenylbutyl)azetidin-2-one Chemical compound C1=CC(OC)=CC=C1CS(=O)C1N(CC(=O)CCC=2C=CC=CC=2)C(=O)C1 UXRVWRAKQXAJHN-UHFFFAOYSA-N 0.000 claims description 4
BOBUAVSZAAASGU-UHFFFAOYSA-N 4-benzylsulfinyl-1-(9-phenylnonyl)azetidin-2-one Chemical compound O=C1CC(S(=O)CC=2C=CC=CC=2)N1CCCCCCCCCC1=CC=CC=C1 BOBUAVSZAAASGU-UHFFFAOYSA-N 0.000 claims description 4
DXZGZQQRIPQWDQ-UHFFFAOYSA-N 4-benzylsulfinyl-1-phenacylazetidin-2-one Chemical compound C=1C=CC=CC=1C(=O)CN(C(C1)=O)C1S(=O)CC1=CC=CC=C1 DXZGZQQRIPQWDQ-UHFFFAOYSA-N 0.000 claims description 4
206010002383 Angina Pectoris Diseases 0.000 claims description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
239000002168 alkylating agent Substances 0.000 claims description 4
229940100198 alkylating agent Drugs 0.000 claims description 4
150000001408 amides Chemical class 0.000 claims description 4
150000001412 amines Chemical class 0.000 claims description 4
208000037976 chronic inflammation Diseases 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
230000003859 lipid peroxidation Effects 0.000 claims description 4
210000004698 lymphocyte Anatomy 0.000 claims description 4
SLUURQLMLDPRHI-UHFFFAOYSA-N methyl 2-(2-benzylsulfanyl-4-oxoazetidin-1-yl)acetate Chemical compound C1C(=O)N(CC(=O)OC)C1SCC1=CC=CC=C1 SLUURQLMLDPRHI-UHFFFAOYSA-N 0.000 claims description 4
208000010125 myocardial infarction Diseases 0.000 claims description 4
AQNSCTFCYSIETG-UHFFFAOYSA-N n-[6-(4-chlorophenyl)hexyl]-2-[2-[(4-methoxyphenyl)methylsulfinyl]-4-oxoazetidin-1-yl]acetamide Chemical compound C1=CC(OC)=CC=C1CS(=O)C1N(CC(=O)NCCCCCCC=2C=CC(Cl)=CC=2)C(=O)C1 AQNSCTFCYSIETG-UHFFFAOYSA-N 0.000 claims description 4
FITWADUWQFLSJR-UHFFFAOYSA-N n-[6-(4-fluorophenyl)hexyl]-2-[2-[(4-methoxyphenyl)methylsulfinyl]-4-oxoazetidin-1-yl]acetamide Chemical compound C1=CC(OC)=CC=C1CS(=O)C1N(CC(=O)NCCCCCCC=2C=CC(F)=CC=2)C(=O)C1 FITWADUWQFLSJR-UHFFFAOYSA-N 0.000 claims description 4
206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
ZXEZGRFEODCZCO-UHFFFAOYSA-N 4-(2-methoxyphenyl)sulfanyl-1-(2-oxo-4-phenylbutyl)azetidin-2-one Chemical compound COC1=CC=CC=C1SC1N(CC(=O)CCC=2C=CC=CC=2)C(=O)C1 ZXEZGRFEODCZCO-UHFFFAOYSA-N 0.000 claims description 3
AAMLUPORVZYOBP-UHFFFAOYSA-N 4-(3-methoxyphenyl)sulfanyl-1-(2-oxo-4-phenylbutyl)azetidin-2-one Chemical compound COC1=CC=CC(SC2N(C(=O)C2)CC(=O)CCC=2C=CC=CC=2)=C1 AAMLUPORVZYOBP-UHFFFAOYSA-N 0.000 claims description 3
QDECEHGJQIJNEU-UHFFFAOYSA-N 4-(4-methoxyphenyl)sulfinyl-1-(2-oxo-4-phenylbutyl)azetidin-2-one Chemical compound C1=CC(OC)=CC=C1S(=O)C1N(CC(=O)CCC=2C=CC=CC=2)C(=O)C1 QDECEHGJQIJNEU-UHFFFAOYSA-N 0.000 claims description 3
UYWIWHISQDMLQK-UHFFFAOYSA-N 4-(benzenesulfinyl)-1-(2-oxo-4-phenylbutyl)azetidin-2-one Chemical compound C=1C=CC=CC=1S(=O)C1CC(=O)N1CC(=O)CCC1=CC=CC=C1 UYWIWHISQDMLQK-UHFFFAOYSA-N 0.000 claims description 3
VFGZZQKQWFXOGN-UHFFFAOYSA-N 4-benzylsulfanyl-1-(2-oxo-4-phenylbutyl)azetidin-2-one Chemical compound C=1C=CC=CC=1CSC1CC(=O)N1CC(=O)CCC1=CC=CC=C1 VFGZZQKQWFXOGN-UHFFFAOYSA-N 0.000 claims description 3
XKZIPDFKXQGHCF-UHFFFAOYSA-N 4-benzylsulfanyl-1-(2-oxo-9-phenylnonyl)azetidin-2-one Chemical compound C=1C=CC=CC=1CSC1CC(=O)N1CC(=O)CCCCCCCC1=CC=CC=C1 XKZIPDFKXQGHCF-UHFFFAOYSA-N 0.000 claims description 3
LOVVEBPOKFIOTP-UHFFFAOYSA-N 4-benzylsulfanyl-1-(4-phenylbutyl)azetidin-2-one Chemical compound C=1C=CC=CC=1CCCCN1C(=O)CC1SCC1=CC=CC=C1 LOVVEBPOKFIOTP-UHFFFAOYSA-N 0.000 claims description 3
WUNWLDRBLKMSHY-UHFFFAOYSA-N 4-benzylsulfinyl-1-(3-phenylpropyl)azetidin-2-one Chemical compound O=C1CC(S(=O)CC=2C=CC=CC=2)N1CCCC1=CC=CC=C1 WUNWLDRBLKMSHY-UHFFFAOYSA-N 0.000 claims description 3
ZRJKPKJCQHZXIN-UHFFFAOYSA-N C=1C=CC=C(Cl)C=1C(C)CCCCNC(=O)CN(C(C1)=O)C1S(=O)CC1=CC=CC=C1 Chemical compound C=1C=CC=C(Cl)C=1C(C)CCCCNC(=O)CN(C(C1)=O)C1S(=O)CC1=CC=CC=C1 ZRJKPKJCQHZXIN-UHFFFAOYSA-N 0.000 claims description 3
GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 3
206010020772 Hypertension Diseases 0.000 claims description 3
201000004681 Psoriasis Diseases 0.000 claims description 3
208000038016 acute inflammation Diseases 0.000 claims description 3
230000006022 acute inflammation Effects 0.000 claims description 3
125000002947 alkylene group Chemical group 0.000 claims description 3
230000006020 chronic inflammation Effects 0.000 claims description 3
235000021588 free fatty acids Nutrition 0.000 claims description 3
230000004968 inflammatory condition Effects 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
201000000980 schizophrenia Diseases 0.000 claims description 3
238000005809 transesterification reaction Methods 0.000 claims description 3
HPRPQOAEOLQFKD-IERDGZPVSA-N (3r,4s)-4-benzylsulfanyl-3-methyl-1-(2-oxo-4-phenylbutyl)azetidin-2-one Chemical compound S([C@H]1[C@@H](C(N1CC(=O)CCC=1C=CC=CC=1)=O)C)CC1=CC=CC=C1 HPRPQOAEOLQFKD-IERDGZPVSA-N 0.000 claims description 2
UYWIWHISQDMLQK-DVECYGJZSA-N (4r)-1-(2-oxo-4-phenylbutyl)-4-[(s)-phenylsulfinyl]azetidin-2-one Chemical compound C([C@H]1[S@@](=O)C=2C=CC=CC=2)C(=O)N1CC(=O)CCC1=CC=CC=C1 UYWIWHISQDMLQK-DVECYGJZSA-N 0.000 claims description 2
RZMRIZFJTDRIGX-LJQANCHMSA-N (4r)-1-(2-oxo-4-phenylbutyl)-4-phenylsulfanylazetidin-2-one Chemical compound C([C@H]1SC=2C=CC=CC=2)C(=O)N1CC(=O)CCC1=CC=CC=C1 RZMRIZFJTDRIGX-LJQANCHMSA-N 0.000 claims description 2
RZMRIZFJTDRIGX-IBGZPJMESA-N (4s)-1-(2-oxo-4-phenylbutyl)-4-phenylsulfanylazetidin-2-one Chemical compound C([C@@H]1SC=2C=CC=CC=2)C(=O)N1CC(=O)CCC1=CC=CC=C1 RZMRIZFJTDRIGX-IBGZPJMESA-N 0.000 claims description 2
FCZHTDPOPISYIR-UHFFFAOYSA-N 1-(2-oxo-4-phenylbutyl)-4-(2-phenylethylsulfanyl)azetidin-2-one Chemical compound C=1C=CC=CC=1CCSC1CC(=O)N1CC(=O)CCC1=CC=CC=C1 FCZHTDPOPISYIR-UHFFFAOYSA-N 0.000 claims description 2
WBHKKSXYGZTHOM-UHFFFAOYSA-N 1-(2-oxo-4-phenylbutyl)-4-(3-phenylpropylsulfanyl)azetidin-2-one Chemical compound C=1C=CC=CC=1CCCSC1CC(=O)N1CC(=O)CCC1=CC=CC=C1 WBHKKSXYGZTHOM-UHFFFAOYSA-N 0.000 claims description 2
CDPCZUUERMHHNW-UHFFFAOYSA-N 4-(2-methoxyphenyl)sulfinyl-1-(2-oxo-4-phenylbutyl)azetidin-2-one Chemical compound COC1=CC=CC=C1S(=O)C1N(CC(=O)CCC=2C=CC=CC=2)C(=O)C1 CDPCZUUERMHHNW-UHFFFAOYSA-N 0.000 claims description 2
PAKQSFIJHSUIES-UHFFFAOYSA-N 4-(3-methoxyphenyl)sulfinyl-1-(2-oxo-4-phenylbutyl)azetidin-2-one Chemical compound COC1=CC=CC(S(=O)C2N(C(=O)C2)CC(=O)CCC=2C=CC=CC=2)=C1 PAKQSFIJHSUIES-UHFFFAOYSA-N 0.000 claims description 2
JUALINDNTHYOHN-UHFFFAOYSA-N 4-[(2-methoxyphenyl)methylsulfanyl]-1-(2-oxo-4-phenylbutyl)azetidin-2-one Chemical compound COC1=CC=CC=C1CSC1N(CC(=O)CCC=2C=CC=CC=2)C(=O)C1 JUALINDNTHYOHN-UHFFFAOYSA-N 0.000 claims description 2
BDBXJUFUFHQDEP-UHFFFAOYSA-N 4-[(4-fluorophenyl)methylsulfanyl]-1-(2-oxo-4-phenylbutyl)azetidin-2-one Chemical compound C1=CC(F)=CC=C1CSC1N(CC(=O)CCC=2C=CC=CC=2)C(=O)C1 BDBXJUFUFHQDEP-UHFFFAOYSA-N 0.000 claims description 2
HJIJJYCRUFIORL-UHFFFAOYSA-N 4-benzylsulfanyl-1-(2-phenylethyl)azetidin-2-one Chemical compound C=1C=CC=CC=1CCN1C(=O)CC1SCC1=CC=CC=C1 HJIJJYCRUFIORL-UHFFFAOYSA-N 0.000 claims description 2
PKBZWSCKACJRMJ-UHFFFAOYSA-N 4-benzylsulfanyl-1-(3-phenylpropyl)azetidin-2-one Chemical compound C=1C=CC=CC=1CCCN1C(=O)CC1SCC1=CC=CC=C1 PKBZWSCKACJRMJ-UHFFFAOYSA-N 0.000 claims description 2
RJZQWOZTPJAPPP-UHFFFAOYSA-N 4-benzylsulfanyl-1-(9-phenylnonyl)azetidin-2-one Chemical compound C=1C=CC=CC=1CCCCCCCCCN1C(=O)CC1SCC1=CC=CC=C1 RJZQWOZTPJAPPP-UHFFFAOYSA-N 0.000 claims description 2
RLITXAMLTYYMGY-UHFFFAOYSA-N 4-benzylsulfanyl-1-phenacylazetidin-2-one Chemical compound C=1C=CC=CC=1C(=O)CN(C(C1)=O)C1SCC1=CC=CC=C1 RLITXAMLTYYMGY-UHFFFAOYSA-N 0.000 claims description 2
JXGHZMOYXSQYRH-UHFFFAOYSA-N 4-benzylsulfonyl-1-(2-oxo-4-phenylbutyl)azetidin-2-one Chemical compound C=1C=CC=CC=1CS(=O)(=O)C1CC(=O)N1CC(=O)CCC1=CC=CC=C1 JXGHZMOYXSQYRH-UHFFFAOYSA-N 0.000 claims description 2
208000024827 Alzheimer disease Diseases 0.000 claims description 2
CHQMTBVAVBXSNS-UHFFFAOYSA-N C1=CC(Cl)=CC=C1CCCCCNC(=O)CN1C(=O)CC1S(=O)CC1=CC=CC=C1 Chemical compound C1=CC(Cl)=CC=C1CCCCCNC(=O)CN1C(=O)CC1S(=O)CC1=CC=CC=C1 CHQMTBVAVBXSNS-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
230000000879 anti-atherosclerotic 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
239000002260 anti-inflammatory agent Substances 0.000 claims description 2
230000003110 anti-inflammatory effect Effects 0.000 claims description 2
239000002220 antihypertensive agent Substances 0.000 claims description 2
229940030600 antihypertensive agent Drugs 0.000 claims description 2
208000035475 disorder Diseases 0.000 claims description 2
NSFYMAPSOHWQIL-UHFFFAOYSA-N ethyl 4-[[2-oxo-1-(2-oxoazetidin-1-yl)-2-(6-phenylhexylamino)ethyl]sulfinylmethyl]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1CS(=O)C(C(=O)NCCCCCCC=1C=CC=CC=1)N1C(=O)CC1 NSFYMAPSOHWQIL-UHFFFAOYSA-N 0.000 claims description 2
230000003557 neuropsychological effect Effects 0.000 claims description 2
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
JMJFBZWYEVUHQI-UHFFFAOYSA-N n-[6-(4-chlorophenyl)hexyl]-2-(2-oxo-4-phenylsulfanylazetidin-1-yl)acetamide;hydrate Chemical compound O.C1=CC(Cl)=CC=C1CCCCCCNC(=O)CN1C(=O)CC1SC1=CC=CC=C1 JMJFBZWYEVUHQI-UHFFFAOYSA-N 0.000 claims 3
DBNXVDUYOZBGKG-UHFFFAOYSA-N 2-[2-[(4-chlorophenyl)methylsulfinyl]-4-oxoazetidin-1-yl]-n-(6-phenylhexyl)acetamide Chemical compound C1=CC(Cl)=CC=C1CS(=O)C1N(CC(=O)NCCCCCCC=2C=CC=CC=2)C(=O)C1 DBNXVDUYOZBGKG-UHFFFAOYSA-N 0.000 claims 2
VJSZHGGKPWHISO-UHFFFAOYSA-N C=1C=CC=CC=1CCCCCCCNC(=O)CN(C(C1)=O)C1S(=O)CC1=CC=CC=C1 Chemical compound C=1C=CC=CC=1CCCCCCCNC(=O)CN(C(C1)=O)C1S(=O)CC1=CC=CC=C1 VJSZHGGKPWHISO-UHFFFAOYSA-N 0.000 claims 2
CYPODBSXUIOVKF-YGWCCBPASA-N N1([C@H]([C@@H](C1=O)C)S(=O)CC=1C=CC=CC=1)CC(=O)CCC1=CC=CC=C1 Chemical compound N1([C@H]([C@@H](C1=O)C)S(=O)CC=1C=CC=CC=1)CC(=O)CCC1=CC=CC=C1 CYPODBSXUIOVKF-YGWCCBPASA-N 0.000 claims 2
239000003814 drug Substances 0.000 claims 2
WCMXBKCPFOYGIK-UHFFFAOYSA-N 1-(4-phenylbutyl)azetidin-2-one Chemical compound O=C1CCN1CCCCC1=CC=CC=C1 WCMXBKCPFOYGIK-UHFFFAOYSA-N 0.000 claims 1
GRKLKNJTWNSRTJ-UHFFFAOYSA-N 2-(2-benzylsulfanyl-4-oxoazetidin-1-yl)-n-[6-(4-fluorophenyl)hexyl]acetamide Chemical compound C1=CC(F)=CC=C1CCCCCCNC(=O)CN1C(=O)CC1SCC1=CC=CC=C1 GRKLKNJTWNSRTJ-UHFFFAOYSA-N 0.000 claims 1
SITOYKPUWLCZDC-UHFFFAOYSA-N 2-(2-benzylsulfinyl-4-oxoazetidin-1-yl)-n-(6-phenylhexyl)acetamide Chemical compound C=1C=CC=CC=1CCCCCCNC(=O)CN(C(C1)=O)C1S(=O)CC1=CC=CC=C1 SITOYKPUWLCZDC-UHFFFAOYSA-N 0.000 claims 1
CRBAXJZXZTWQFN-UHFFFAOYSA-N 2-(2-benzylsulfinyl-4-oxoazetidin-1-yl)-n-[6-(4-fluorophenyl)hexyl]acetamide Chemical compound C1=CC(F)=CC=C1CCCCCCNC(=O)CN1C(=O)CC1S(=O)CC1=CC=CC=C1 CRBAXJZXZTWQFN-UHFFFAOYSA-N 0.000 claims 1
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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
- 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
- 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
- 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
- A61P3/06—Antihyperlipidemics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
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- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- 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
- 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
- A61P9/12—Antihypertensives

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SK803-97A 1994-12-22 1995-12-20 Substituted azetidin-2-ones, preparation method thereof, farmaceutical compositions and their use SK80397A3 (en)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
GBGB9426020.5A GB9426020D0 (en)	1994-12-22	1994-12-22	Novel compounds
GBGB9426030.4A GB9426030D0 (en)	1994-12-23	1994-12-23	Novel compounds
GBGB9511599.4A GB9511599D0 (en)	1995-06-08	1995-06-08	Novel compounds
GBGB9511600.0A GB9511600D0 (en)	1995-06-08	1995-06-08	Novel compounds
PCT/EP1995/005130 WO1996019451A1 (fr)	1994-12-22	1995-12-20	Azetidin-2-ones substituees, destinees au traitement de l'atherosclerose

Publications (1)

Publication Number	Publication Date
SK80397A3 true SK80397A3 (en)	1998-01-14

Family

ID=27451242

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK803-97A SK80397A3 (en)	1994-12-22	1995-12-20	Substituted azetidin-2-ones, preparation method thereof, farmaceutical compositions and their use

Country Status (24)

Country	Link
US (1)	US5990102A (fr)
EP (1)	EP0799200A1 (fr)
JP (1)	JPH11500415A (fr)
CN (1)	CN1175246A (fr)
AP (1)	AP9701007A0 (fr)
AR (1)	AR002012A1 (fr)
AU (1)	AU704407B2 (fr)
BG (1)	BG101687A (fr)
BR (1)	BR9510420A (fr)
CA (1)	CA2208530A1 (fr)
CZ (1)	CZ192297A3 (fr)
DZ (1)	DZ1958A1 (fr)
FI (1)	FI972584L (fr)
HU (1)	HUT77089A (fr)
IL (1)	IL116485A0 (fr)
MA (1)	MA23834A1 (fr)
MX (1)	MX9704736A (fr)
NO (1)	NO972909L (fr)
NZ (1)	NZ298416A (fr)
OA (1)	OA10737A (fr)
PL (1)	PL320937A1 (fr)
SK (1)	SK80397A3 (fr)
TR (1)	TR199501655A2 (fr)
WO (1)	WO1996019451A1 (fr)

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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
JP2000502079A (ja) *	1995-12-08	2000-02-22	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単環β―ラクタム誘導体
GB9608649D0 (en) *	1996-04-26	1996-07-03	Smithkline Beecham Plc	Novel compounds
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
EP1099690A4 (fr) *	1998-07-23	2001-10-17	Shionogi & Co	Composes de beta-lactame monocycliques et inhibiteurs de la chymase les renfermant
NZ520752A (en)	2000-02-16	2004-03-26	Smithkline Beecham P	Pyrimidine-4-one derivatives as LDL-PLA2 inhibitors
GB0024808D0 (en)	2000-10-10	2000-11-22	Smithkline Beecham Plc	Novel compounds
US6982251B2 (en) *	2000-12-20	2006-01-03	Schering Corporation	Substituted 2-azetidinones useful as hypocholesterolemic agents
DK1355644T3 (da)	2001-01-26	2006-10-23	Schering Corp	Anvendelse af substituerede azetidinonforbindelser til behandling af sitosterolæmi
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
US7071181B2 (en)	2001-01-26	2006-07-04	Schering Corporation	Methods and therapeutic combinations for the treatment of diabetes using sterol absorption inhibitors
US7053080B2 (en)	2001-09-21	2006-05-30	Schering Corporation	Methods and therapeutic combinations for the treatment of obesity using sterol absorption inhibitors
JP2005504091A (ja)	2001-09-21	2005-02-10	シェーリング　コーポレイション	ステロール吸収阻害剤としてアゼチジノンを用いる黄色腫の処置
WO2004043457A1 (fr)	2002-11-06	2004-05-27	Schering Corporation	Inhibiteurs d'absorption de cholesterol pour le traitement de troubles auto-immuns
US7459442B2 (en)	2003-03-07	2008-12-02	Schering Corporation	Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof
JP2006519869A (ja) *	2003-03-07	2006-08-31	シェーリング　コーポレイション	置換アゼチジノン化合物、置換アゼチジノン化合物を調製するためのプロセス、それらの処方物および使用
JP4589919B2 (ja)	2003-03-07	2010-12-01	シェーリングコーポレイション	高コレステロール血症の処置のための、置換アゼチジノン化合物、これらの処方物および使用
CA2517571C (fr)	2003-03-07	2011-07-05	Schering Corporation	Azetidinones substituees , procedes pour leur preparation, formulations et utilisations de celles-ci
EP1747014A4 (fr) *	2004-05-03	2007-09-12	Ilypsa Inc	Modulation de la lysophosphatidylcholine et traitement des etats induits par un regime alimentaire
EP2977452A3 (fr)	2007-05-11	2016-05-25	Thomas Jefferson University	Procédés de traitement et de prévention de maladies et de troubles neurodégénératifs
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
EP2725024A4 (fr)	2011-06-27	2014-12-03	Shanghai Inst Materia Medica	Composé hétérocyclique azole, procédé de préparation, composition pharmaceutique et utilisation
EP2736908A1 (fr)	2011-07-27	2014-06-04	Glaxo Group Limited	Composés pyrimidones bicycliques
EP2739627A4 (fr)	2011-07-27	2015-01-21	Glaxo Group Ltd	Composés 2,3-dihydroimidazo[1,2-c]pyrimidin-5(1h)-one et utilisation en tant qu'inhibiteurs de lp-pla2
CA2899124A1 (fr)	2013-01-25	2014-07-31	Glaxosmithkline Intellectual Property Development Limited	Composes
BR112015017397A2 (pt)	2013-01-25	2017-07-11	Glaxosmithkline Ip Dev Ltd	compostos pirimidona bicíclica como inibidores de lp-pla2
UY35276A (es)	2013-01-25	2014-08-29	Glaxosmithkline Ip Dev Ltd	Nuevos compuestos que inhiben la actividad de Lp-PLA2
WO2015179293A1 (fr) *	2014-05-18	2015-11-26	The United States Of America, As Represented By The Secretary, Department Of Health And Human Services	Activateurs et inhibiteurs de petites molécules de lécithine-cholestérol acyltransférase
WO2016012916A1 (fr)	2014-07-22	2016-01-28	Glaxosmithkline Intellectual Property Development Limited	Dérivés 1,2,3,5-tétrahydro-imidazo [1,2-c]pyrimidine utiles pour le traitement de maladies et de troubles médiés par la lp-pla2
WO2016012917A1 (fr)	2014-07-22	2016-01-28	Glaxosmithkline Intellectual Property Development Limited	Dérivés 1,2,3,5-tétrahydro-imidazo [1,2-c]pyrimidine utiles pour le traitement de maladies et de troubles médiés par la lp-pla2
CN114805389B (zh)	2019-11-09	2023-08-29	上海赛默罗生物科技有限公司	三环二氢咪唑并嘧啶酮衍生物、其制备方法、药物组合物和用途
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
TWI896037B (zh)	2023-07-17	2025-09-01	大陸商上海樞境生物科技有限公司	雙環[5,6]咪唑嘧啶酮類衍生物、其製備方法和應用

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EP0010358A1 (fr) *	1978-09-20	1980-04-30	Glaxo Group Limited	Composés de bêta-lactame, procédés pour leur préparation, compositions les contenant, intermédiaires utilisables dans leur préparation et méthodes pour leur production
US4680391A (en) *	1983-12-01	1987-07-14	Merck & Co., Inc.	Substituted azetidinones as anti-inflammatory and antidegenerative agents
IL99658A0 (en) *	1990-10-15	1992-08-18	Merck & Co Inc	Substituted azetidinones and pharmaceutical compositions containing them

1995
- 1995-12-20 AR ARP950100660A patent/AR002012A1/es unknown
- 1995-12-20 AP APAP/P/1997/001007A patent/AP9701007A0/en unknown
- 1995-12-20 NZ NZ298416A patent/NZ298416A/xx unknown
- 1995-12-20 JP JP8519527A patent/JPH11500415A/ja active Pending
- 1995-12-20 CN CN95197606A patent/CN1175246A/zh active Pending
- 1995-12-20 AU AU43898/96A patent/AU704407B2/en not_active Ceased
- 1995-12-20 SK SK803-97A patent/SK80397A3/sk unknown
- 1995-12-20 FI FI972584A patent/FI972584L/fi unknown
- 1995-12-20 PL PL95320937A patent/PL320937A1/xx unknown
- 1995-12-20 CZ CZ971922A patent/CZ192297A3/cs unknown
- 1995-12-20 BR BR9510420-8A patent/BR9510420A/pt unknown
- 1995-12-20 EP EP95942734A patent/EP0799200A1/fr not_active Withdrawn
- 1995-12-20 US US08/860,162 patent/US5990102A/en not_active Expired - Fee Related
- 1995-12-20 CA CA002208530A patent/CA2208530A1/fr not_active Abandoned
- 1995-12-20 DZ DZ950141A patent/DZ1958A1/fr active
- 1995-12-20 MA MA24105A patent/MA23834A1/fr unknown
- 1995-12-20 HU HU9701948A patent/HUT77089A/hu unknown
- 1995-12-20 WO PCT/EP1995/005130 patent/WO1996019451A1/fr not_active Ceased
- 1995-12-20 MX MX9704736A patent/MX9704736A/es unknown
- 1995-12-21 IL IL11648595A patent/IL116485A0/xx unknown
- 1995-12-22 TR TR95/01655A patent/TR199501655A2/xx unknown
1997
- 1997-06-20 OA OA70034A patent/OA10737A/en unknown
- 1997-06-20 NO NO972909A patent/NO972909L/no unknown
- 1997-06-26 BG BG101687A patent/BG101687A/xx unknown

Also Published As

Publication number	Publication date
IL116485A0 (en)	1996-08-04
OA10737A (en)	2002-12-10
CN1175246A (zh)	1998-03-04
AP9701007A0 (en)	1997-07-31
AU704407B2 (en)	1999-04-22
NO972909L (no)	1997-08-20
FI972584A7 (fi)	1997-08-19
PL320937A1 (en)	1997-11-10
EP0799200A1 (fr)	1997-10-08
FI972584A0 (fi)	1997-06-17
BR9510420A (pt)	2004-04-20
NZ298416A (en)	1999-03-29
AU4389896A (en)	1996-07-10
CZ192297A3 (en)	1997-11-12
HUT77089A (hu)	1998-03-02
AR002012A1 (es)	1998-01-07
MA23834A1 (fr)	1996-10-01
BG101687A (bg)	1998-02-27
FI972584L (fi)	1997-08-19
JPH11500415A (ja)	1999-01-12
DZ1958A1 (fr)	2002-02-17
US5990102A (en)	1999-11-23
WO1996019451A1 (fr)	1996-06-27
TR199501655A2 (tr)	1996-07-21
CA2208530A1 (fr)	1996-06-27
NO972909D0 (no)	1997-06-20
MX9704736A (es)	1997-10-31

Publication	Publication Date	Title
SK80397A3 (en)	1998-01-14	Substituted azetidin-2-ones, preparation method thereof, farmaceutical compositions and their use
US6071899A (en)	2000-06-06	Azetidinone derivatives for the treatment of atherosclerosis
EP0051381B1 (fr)	1985-01-30	Acides bêta-lactame hydroxamiques 0-sulfatés
AP728A (en)	1999-01-29	Azetidinone derivatives for the treatment of atherosclerosis.
JPH05208946A (ja)	1993-08-20	芳香族アミジン誘導体及びその塩
IE913612A1 (en)	1992-04-22	New substituted azetidinones as anti-inflammatory and¹antidegenerative agents
CZ346398A3 (cs)	1999-05-12	D-prolinové deriváty
WO1997041098A1 (fr)	1997-11-06	Derives azetidinones destines au traitement de l'atherosclerose
EP0336369A1 (fr)	1989-10-11	3-Acylamino-1-[[[(substituées sulfonyl)amino]carbonyl]amino]2-azétidinones
EP0900199A1 (fr)	1999-03-10	Derives d'azetidinone pour le traitement de l'atherosclerose
BE897466A (fr)	1984-02-06	Composes d'azetidine
EP0358305B1 (fr)	1993-08-25	Acides mercapto-phénylalcanoylamino, leur préparation et leur utilisation comme inhibiteur de collagénase
US20030078251A1 (en)	2003-04-24	Benzoxazepinones and their use as squalene synthase inhibitors
CA2301967C (fr)	2005-05-17	Derives d'azetidinone pour le traitement d'infections hcmv
KR900001007B1 (ko)	1990-02-24	2-옥소-1-[[(치환 술포닐)아미노]카르보닐]아제티딘
US5466686A (en)	1995-11-14	Amides of 4-oxo-azetidine-2-sulfonic acids and salts thereof, processes for their preparation and their use
FR2581062A1 (fr)	1986-10-31	Acides b-lactame hydroxamiques o-sulfates, a action therapeutique
WO1994003168A1 (fr)	1994-02-17	Derives de penem 5 s, leur preparation et utilisation
CZ20004784A3 (cs)	2001-07-11	Beta-laktamové sloučeniny a jejich použití jako inhibitory tryptasy