CA1296339C - Antihyperlipidemic and antiatherosclerotic urea and carbamate compounds - Google Patents
Antihyperlipidemic and antiatherosclerotic urea and carbamate compoundsInfo
- Publication number
- CA1296339C CA1296339C CA000566283A CA566283A CA1296339C CA 1296339 C CA1296339 C CA 1296339C CA 000566283 A CA000566283 A CA 000566283A CA 566283 A CA566283 A CA 566283A CA 1296339 C CA1296339 C CA 1296339C
- Authority
- CA
- Canada
- Prior art keywords
- carbon atoms
- compound
- phenyl
- urea
- 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.)
- Expired - Fee Related
Links
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 title claims abstract description 67
- 239000004202 carbamide Substances 0.000 title claims abstract description 37
- 150000004657 carbamic acid derivatives Chemical class 0.000 title description 3
- 230000000879 anti-atherosclerotic effect Effects 0.000 title 1
- 230000001315 anti-hyperlipaemic effect Effects 0.000 title 1
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims abstract description 45
- 235000012000 cholesterol Nutrition 0.000 claims abstract description 22
- 150000001875 compounds Chemical class 0.000 claims description 92
- 125000004432 carbon atom Chemical group C* 0.000 claims description 58
- 125000000217 alkyl group Chemical group 0.000 claims description 38
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 125000003545 alkoxy group Chemical group 0.000 claims description 20
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 20
- 239000000460 chlorine Substances 0.000 claims description 20
- 239000001257 hydrogen Substances 0.000 claims description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 19
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 19
- 229910052794 bromium Inorganic materials 0.000 claims description 19
- 229910052801 chlorine Inorganic materials 0.000 claims description 19
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 19
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 19
- -1 1-phenyl-cyclohexyl Chemical group 0.000 claims description 18
- AQYSYJUIMQTRMV-UHFFFAOYSA-N hypofluorous acid Chemical compound FO AQYSYJUIMQTRMV-UHFFFAOYSA-N 0.000 claims description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- 238000006243 chemical reaction Methods 0.000 claims description 13
- 125000001624 naphthyl group Chemical group 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 125000001544 thienyl group Chemical group 0.000 claims description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
- 239000001301 oxygen Substances 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 6
- 229910052717 sulfur Chemical group 0.000 claims description 5
- VLGLPERTGITNOO-UHFFFAOYSA-N 1-(2,6-dimethylphenyl)-3-(1-phenylcyclopentyl)urea Chemical compound CC1=CC=CC(C)=C1NC(=O)NC1(C=2C=CC=CC=2)CCCC1 VLGLPERTGITNOO-UHFFFAOYSA-N 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 230000001105 regulatory effect Effects 0.000 claims description 3
- 239000011593 sulfur Chemical group 0.000 claims description 3
- RXAUORBNOOOOSA-UHFFFAOYSA-N 1-(1-phenylcyclopentyl)-3-(2,4,6-trimethoxyphenyl)urea Chemical compound COC1=CC(OC)=CC(OC)=C1NC(=O)NC1(C=2C=CC=CC=2)CCCC1 RXAUORBNOOOOSA-UHFFFAOYSA-N 0.000 claims description 2
- LVUBZRMTVUJANP-UHFFFAOYSA-N 1-(2,4-difluorophenyl)-3-(1-thiophen-2-ylcyclohexyl)urea Chemical compound FC1=CC(F)=CC=C1NC(=O)NC1(C=2SC=CC=2)CCCCC1 LVUBZRMTVUJANP-UHFFFAOYSA-N 0.000 claims description 2
- KECPQGMVARDUMQ-UHFFFAOYSA-N 1-(2,4-difluorophenyl)-3-[(1-phenylcyclohexyl)methyl]urea Chemical compound FC1=CC(F)=CC=C1NC(=O)NCC1(C=2C=CC=CC=2)CCCCC1 KECPQGMVARDUMQ-UHFFFAOYSA-N 0.000 claims description 2
- FQNVZOOFASRHRC-UHFFFAOYSA-N 1-(2,4-difluorophenyl)-3-[(1-phenylcyclopentyl)methyl]urea Chemical compound FC1=CC(F)=CC=C1NC(=O)NCC1(C=2C=CC=CC=2)CCCC1 FQNVZOOFASRHRC-UHFFFAOYSA-N 0.000 claims description 2
- CGYVCFWTPPIHRE-UHFFFAOYSA-N 1-(2,6-dibromo-4-fluorophenyl)-3-[(1-phenylcyclohexyl)methyl]urea Chemical compound BrC1=CC(F)=CC(Br)=C1NC(=O)NCC1(C=2C=CC=CC=2)CCCCC1 CGYVCFWTPPIHRE-UHFFFAOYSA-N 0.000 claims description 2
- LGDYLYDWIHVHQU-UHFFFAOYSA-N 1-(2,6-diethylphenyl)-3-(1-phenylcyclobutyl)urea Chemical compound CCC1=CC=CC(CC)=C1NC(=O)NC1(C=2C=CC=CC=2)CCC1 LGDYLYDWIHVHQU-UHFFFAOYSA-N 0.000 claims description 2
- CJZDQJPGMSQIRC-UHFFFAOYSA-N 1-(2,6-diethylphenyl)-3-[(1-phenylcyclopentyl)methyl]urea Chemical compound CCC1=CC=CC(CC)=C1NC(=O)NCC1(C=2C=CC=CC=2)CCCC1 CJZDQJPGMSQIRC-UHFFFAOYSA-N 0.000 claims description 2
- CWXPWWUNYNBADK-UHFFFAOYSA-N 1-(2,6-diethylphenyl)-3-[(1-phenylcyclopropyl)methyl]urea Chemical compound CCC1=CC=CC(CC)=C1NC(=O)NCC1(C=2C=CC=CC=2)CC1 CWXPWWUNYNBADK-UHFFFAOYSA-N 0.000 claims description 2
- HJKWYKLOWTWHAL-UHFFFAOYSA-N 1-(2,6-dimethylphenyl)-3-(1-thiophen-2-ylcyclohexyl)urea Chemical compound CC1=CC=CC(C)=C1NC(=O)NC1(C=2SC=CC=2)CCCCC1 HJKWYKLOWTWHAL-UHFFFAOYSA-N 0.000 claims description 2
- FLABQNHKMUJTCC-UHFFFAOYSA-N 1-(2,6-dimethylphenyl)-3-[(1-phenylcyclopentyl)methyl]urea Chemical compound CC1=CC=CC(C)=C1NC(=O)NCC1(C=2C=CC=CC=2)CCCC1 FLABQNHKMUJTCC-UHFFFAOYSA-N 0.000 claims description 2
- LTPXLYHQNFPPCX-UHFFFAOYSA-N 1-(2-ethyl-6-propan-2-ylphenyl)-3-[(1-phenylcyclopentyl)methyl]urea Chemical compound CCC1=CC=CC(C(C)C)=C1NC(=O)NCC1(C=2C=CC=CC=2)CCCC1 LTPXLYHQNFPPCX-UHFFFAOYSA-N 0.000 claims description 2
- SDGLYIYTVDBENT-UHFFFAOYSA-N 1-(2-methyl-6-propan-2-ylphenyl)-3-[(1-phenylcyclohexyl)methyl]urea Chemical compound CC(C)C1=CC=CC(C)=C1NC(=O)NCC1(C=2C=CC=CC=2)CCCCC1 SDGLYIYTVDBENT-UHFFFAOYSA-N 0.000 claims description 2
- DCYJVKSJIBPVJR-UHFFFAOYSA-N 1-(2-methyl-6-propan-2-ylphenyl)-3-[(1-phenylcyclopentyl)methyl]urea Chemical compound CC(C)C1=CC=CC(C)=C1NC(=O)NCC1(C=2C=CC=CC=2)CCCC1 DCYJVKSJIBPVJR-UHFFFAOYSA-N 0.000 claims description 2
- UXYZKOZURBFQPG-UHFFFAOYSA-N 1-(2-tert-butyl-6-methylphenyl)-3-[(1-phenylcyclohexyl)methyl]urea Chemical compound CC1=CC=CC(C(C)(C)C)=C1NC(=O)NCC1(C=2C=CC=CC=2)CCCCC1 UXYZKOZURBFQPG-UHFFFAOYSA-N 0.000 claims description 2
- SBPATIATVVXAJG-UHFFFAOYSA-N 1-(2-tert-butyl-6-methylphenyl)-3-[(1-phenylcyclopentyl)methyl]urea Chemical compound CC1=CC=CC(C(C)(C)C)=C1NC(=O)NCC1(C=2C=CC=CC=2)CCCC1 SBPATIATVVXAJG-UHFFFAOYSA-N 0.000 claims description 2
- KNOVBZUETNLMFB-UHFFFAOYSA-N 1-[2,6-di(propan-2-yl)phenyl]-3-[(1-phenylcyclohexyl)methyl]urea Chemical compound CC(C)C1=CC=CC(C(C)C)=C1NC(=O)NCC1(C=2C=CC=CC=2)CCCCC1 KNOVBZUETNLMFB-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 5
- AHWOQXFLHROOLX-UHFFFAOYSA-N 1-(2,6-diethylphenyl)-3-(1-thiophen-2-ylcyclohexyl)urea Chemical compound CCC1=CC=CC(CC)=C1NC(=O)NC1(C=2SC=CC=2)CCCCC1 AHWOQXFLHROOLX-UHFFFAOYSA-N 0.000 claims 1
- GLJARDADMVXXBJ-UHFFFAOYSA-N 1-(2,6-diethylphenyl)-3-[(1-phenylcyclohexyl)methyl]urea Chemical compound CCC1=CC=CC(CC)=C1NC(=O)NCC1(C=2C=CC=CC=2)CCCCC1 GLJARDADMVXXBJ-UHFFFAOYSA-N 0.000 claims 1
- UFKXJXQEMHWTJY-UHFFFAOYSA-N 1-(2-ethyl-6-propan-2-ylphenyl)-3-[(1-phenylcyclohexyl)methyl]urea Chemical compound CCC1=CC=CC(C(C)C)=C1NC(=O)NCC1(C=2C=CC=CC=2)CCCCC1 UFKXJXQEMHWTJY-UHFFFAOYSA-N 0.000 claims 1
- VSFATKYYJJPZMC-UHFFFAOYSA-N 1-(2-methyl-6-propan-2-ylphenyl)-3-(1-thiophen-2-ylcyclohexyl)urea Chemical compound CC(C)C1=CC=CC(C)=C1NC(=O)NC1(C=2SC=CC=2)CCCCC1 VSFATKYYJJPZMC-UHFFFAOYSA-N 0.000 claims 1
- VNGFTHHERLMMNY-UHFFFAOYSA-N 1-(2-tert-butyl-6-methylphenyl)-3-(1-thiophen-2-ylcyclohexyl)urea Chemical compound CC1=CC=CC(C(C)(C)C)=C1NC(=O)NC1(C=2SC=CC=2)CCCCC1 VNGFTHHERLMMNY-UHFFFAOYSA-N 0.000 claims 1
- 108090000790 Enzymes Proteins 0.000 abstract description 6
- 102000004190 Enzymes Human genes 0.000 abstract description 6
- 150000003672 ureas Chemical class 0.000 abstract description 6
- 239000003795 chemical substances by application Substances 0.000 abstract description 5
- 230000031891 intestinal absorption Effects 0.000 abstract description 5
- 102000001494 Sterol O-Acyltransferase Human genes 0.000 abstract description 4
- 108010054082 Sterol O-acyltransferase Proteins 0.000 abstract description 4
- 230000002401 inhibitory effect Effects 0.000 abstract description 4
- 239000003112 inhibitor Substances 0.000 abstract description 3
- 230000003389 potentiating effect Effects 0.000 abstract description 3
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical class NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 abstract description 2
- 150000003558 thiocarbamic acid derivatives Chemical class 0.000 abstract description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical class NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 abstract 2
- 210000002381 plasma Anatomy 0.000 abstract 1
- 235000013877 carbamide Nutrition 0.000 description 31
- 238000002360 preparation method Methods 0.000 description 30
- 238000002844 melting Methods 0.000 description 27
- 230000008018 melting Effects 0.000 description 26
- 238000004458 analytical method Methods 0.000 description 23
- 229940107161 cholesterol Drugs 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 12
- 239000002253 acid Substances 0.000 description 11
- 125000003118 aryl group Chemical group 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 125000004429 atom Chemical group 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 229940093499 ethyl acetate Drugs 0.000 description 4
- 235000019439 ethyl acetate Nutrition 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 230000000968 intestinal effect Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 150000003585 thioureas Chemical class 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- 108010010234 HDL Lipoproteins Proteins 0.000 description 2
- 102000015779 HDL Lipoproteins Human genes 0.000 description 2
- 238000008214 LDL Cholesterol Methods 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 238000007429 general method Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 239000012948 isocyanate Substances 0.000 description 2
- 150000002513 isocyanates Chemical class 0.000 description 2
- NONOKGVFTBWRLD-UHFFFAOYSA-N isocyanatosulfanylimino(oxo)methane Chemical class O=C=NSN=C=O NONOKGVFTBWRLD-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000009103 reabsorption Effects 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- AUSRFKVPUCQCCN-UHFFFAOYSA-N 1,3-diethyl-2-isocyanatobenzene Chemical compound CCC1=CC=CC(CC)=C1N=C=O AUSRFKVPUCQCCN-UHFFFAOYSA-N 0.000 description 1
- YZOZUSUTGAMGTN-UHFFFAOYSA-N 1-(2,6-diethylphenyl)-3-(1-phenylcyclopentyl)urea Chemical compound CCC1=CC=CC(CC)=C1NC(=O)NC1(C=2C=CC=CC=2)CCCC1 YZOZUSUTGAMGTN-UHFFFAOYSA-N 0.000 description 1
- CEWSPMPPZHRODM-UHFFFAOYSA-N 1-(2,6-dimethylphenyl)-3-[(1-phenylcyclohexyl)methyl]urea Chemical compound CC1=CC=CC(C)=C1NC(=O)NCC1(C=2C=CC=CC=2)CCCCC1 CEWSPMPPZHRODM-UHFFFAOYSA-N 0.000 description 1
- YXAQCAOJLDGGDZ-UHFFFAOYSA-N 1-phenylcyclopentan-1-amine Chemical compound C=1C=CC=CC=1C1(N)CCCC1 YXAQCAOJLDGGDZ-UHFFFAOYSA-N 0.000 description 1
- YQLRKXVEALTVCZ-UHFFFAOYSA-N 2-isocyanato-1,3-dimethylbenzene Chemical compound CC1=CC=CC(C)=C1N=C=O YQLRKXVEALTVCZ-UHFFFAOYSA-N 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 239000004380 Cholic acid Substances 0.000 description 1
- 108010004103 Chylomicrons Proteins 0.000 description 1
- MHZGKXUYDGKKIU-UHFFFAOYSA-N Decylamine Chemical compound CCCCCCCCCCN MHZGKXUYDGKKIU-UHFFFAOYSA-N 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 108010023302 HDL Cholesterol Proteins 0.000 description 1
- 108010028554 LDL Cholesterol Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 102100030817 Liver carboxylesterase 1 Human genes 0.000 description 1
- 101710181187 Liver carboxylesterase 1 Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- RJECHNNFRHZQKU-UHFFFAOYSA-N Oelsaeurecholesterylester Natural products C12CCC3(C)C(C(C)CCCC(C)C)CCC3C2CC=C2C1(C)CCC(OC(=O)CCCCCCCC=CCCCCCCCC)C2 RJECHNNFRHZQKU-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical class [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 230000009102 absorption Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 239000003529 anticholesteremic agent Substances 0.000 description 1
- 239000003524 antilipemic agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000007962 benzene acetonitriles Chemical class 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037058 blood plasma level Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001840 cholesterol esters Chemical class 0.000 description 1
- RJECHNNFRHZQKU-RMUVNZEASA-N cholesteryl oleate Chemical compound C([C@@H]12)C[C@]3(C)[C@@H]([C@H](C)CCCC(C)C)CC[C@H]3[C@@H]1CC=C1[C@]2(C)CC[C@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)C1 RJECHNNFRHZQKU-RMUVNZEASA-N 0.000 description 1
- 235000019416 cholic acid Nutrition 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 229960002471 cholic acid Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- UVWQYWHKTZABSO-ILADVTTDSA-N de voachalotinol Chemical compound CN1C2=CC=CC=C2C(C[C@H]2[C@@H]3CO)=C1[C@H]1N2C/C(=C/C)[C@@H]3C1 UVWQYWHKTZABSO-ILADVTTDSA-N 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- QSACPWSIIRFHHR-UHFFFAOYSA-N dimethylphenyl isocyanide Natural products CC1=CC=CC(C)=C1C#N QSACPWSIIRFHHR-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000003028 elevating effect Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229940012017 ethylenediamine Drugs 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000000055 hyoplipidemic effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 210000001589 microsome Anatomy 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000004351 phenylcyclohexyl group Chemical group C1(=CC=CC=C1)C1(CCCCC1)* 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 239000011345 viscous material Substances 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C335/04—Derivatives of thiourea
- C07C335/16—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C275/32—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by singly-bound oxygen atoms
- C07C275/34—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by singly-bound oxygen atoms having nitrogen atoms of urea groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/17—Amides, e.g. hydroxamic acids having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine
-
- 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
- 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
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C273/00—Preparation of urea or its derivatives, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C273/18—Preparation of urea or its derivatives, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups of substituted ureas
- C07C273/1809—Preparation of urea or its derivatives, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups of substituted ureas with formation of the N-C(O)-N moiety
- C07C273/1818—Preparation of urea or its derivatives, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups of substituted ureas with formation of the N-C(O)-N moiety from -N=C=O and XNR'R"
- C07C273/1827—X being H
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C275/32—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by singly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Vascular Medicine (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Obesity (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US5757687A | 1987-06-02 | 1987-06-02 | |
| US057,576 | 1987-06-02 | ||
| US14703788A | 1988-02-05 | 1988-02-05 | |
| US147,037 | 1988-02-05 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1296339C true CA1296339C (en) | 1992-02-25 |
Family
ID=26736644
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000566283A Expired - Fee Related CA1296339C (en) | 1987-06-02 | 1988-05-09 | Antihyperlipidemic and antiatherosclerotic urea and carbamate compounds |
Country Status (15)
| Country | Link |
|---|---|
| EP (1) | EP0293880B1 (en, 2012) |
| JP (1) | JP2575183B2 (en, 2012) |
| KR (1) | KR890000412A (en, 2012) |
| AU (1) | AU601846B2 (en, 2012) |
| CA (1) | CA1296339C (en, 2012) |
| DE (1) | DE3873992T2 (en, 2012) |
| DK (1) | DK175791B1 (en, 2012) |
| ES (1) | ES2051797T3 (en, 2012) |
| FI (1) | FI882588A7 (en, 2012) |
| GR (1) | GR3006297T3 (en, 2012) |
| IE (1) | IE61716B1 (en, 2012) |
| NO (1) | NO167200C (en, 2012) |
| NZ (1) | NZ224670A (en, 2012) |
| PH (1) | PH24216A (en, 2012) |
| PT (1) | PT87622B (en, 2012) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5015644A (en) * | 1987-06-02 | 1991-05-14 | Warner-Lambert Company | Antihyperlipidemic and antiatherosclerotic urea and carbamate compounds |
| US4868210A (en) * | 1988-03-30 | 1989-09-19 | Warner-Lambert Company | Antihyperlipidemic and antiatherosclerotic compounds and compositions |
| US4994465A (en) * | 1989-02-17 | 1991-02-19 | Warner-Lambert Company | Antihyperlipidemic and antiatherosclerotic trisubstituted urea compounds |
| JPH0395153A (ja) * | 1989-06-15 | 1991-04-19 | Mitsubishi Kasei Corp | ジフェニル尿素誘導体 |
| AU629376B2 (en) * | 1989-08-04 | 1992-10-01 | Mitsubishi Chemical Corporation | 1-phenylalkyl-3-phenylurea derivatives |
| US5153226A (en) * | 1989-08-31 | 1992-10-06 | Warner-Lambert Company | Acat inhibitors for treating hypocholesterolemia |
| EP0546177B1 (en) * | 1990-07-25 | 1998-01-07 | Teijin Limited | Benzopyran derivative, production thereof, and pharmaceutical composition containing the same |
| IL100915A (en) * | 1991-02-19 | 1996-03-31 | Erba Carlo Spa | Disubstituted ureas and thioureas their preparation and pharmaceutical compositions containing them |
| US5420164A (en) * | 1991-04-04 | 1995-05-30 | Yoshitomi Pharmaceutical Industries, Ltd. | Cycloalkylurea compounds |
| KR950701621A (ko) * | 1992-05-28 | 1995-04-28 | 알렌 제이. 스피겔 | 아실 조효소a : 콜레스테롤 아실 전이효소(acat)의 억제제로서 신규한 n- 아릴 및 n- 헤테로아릴우레아 유도체(new n-aryl and n-heteroarylurea derivatives as inhibitors of acyl coenzyme a : cholesterol acyl transferase(acat) |
| CA2107196A1 (en) * | 1992-09-29 | 1994-03-30 | Mitsubishi Chemical Corporation | Carboxamide derivatives |
| US5534529A (en) * | 1993-06-30 | 1996-07-09 | Sankyo Company, Limited | Substituted aromatic amides and ureas derivatives having anti-hypercholesteremic activity, their preparation and their therapeutic uses |
| DE4401893A1 (de) * | 1994-01-24 | 1995-07-27 | Bayer Ag | Substituierte Arylharnstoffe |
| US6133326A (en) | 1994-08-31 | 2000-10-17 | Pfizer Inc | Compositions and methods for decreasing sebum production |
| DE4443891A1 (de) * | 1994-12-09 | 1996-06-13 | Bayer Ag | Heterocyclisch substituierte Oxy-phenyl-(phenyl)glycinolamide |
| US6605623B1 (en) | 1998-12-18 | 2003-08-12 | Bristol-Myers Squibb Pharma Co. | N-ureidoalkyl-piperidines as modulators of chemokine receptor activity |
| MXPA02007309A (es) | 2000-02-02 | 2002-11-29 | Warner Lambert Co | Inhibidores duales de la sintesis de los esteres de la cera y los esteres del colesterol para las enfermedades de las glandulas sebaceas. |
| DE10308356A1 (de) * | 2003-02-27 | 2004-09-09 | Aventis Pharma Deutschland Gmbh | Cycloalkyl substituierte Alkansäurederivate, Verfahren zu ihrer Herstellung und ihre Anwendung als Arzneimittel |
| DE10308352A1 (de) * | 2003-02-27 | 2004-09-09 | Aventis Pharma Deutschland Gmbh | Arylcycloalkylderivate mit verzweigten Seitenketten, Verfahren zu ihrer Herstellung und ihre Anwendung als Arzneimittel |
| US8604244B2 (en) | 2010-07-02 | 2013-12-10 | Reviva Pharmaceuticals, Inc. | Compositions, synthesis, and methods of using cycloalkylmethylamine derivatives |
| WO2008034142A2 (en) | 2006-09-15 | 2008-03-20 | Reviva Pharmaceuticals, Inc. | Synthesis, methods of using, and compositions of cycloalkylmethylamines |
| FR2946346B1 (fr) | 2009-06-05 | 2011-05-20 | Galderma Res & Dev | Nouveaux derives dioxo-imidazolidine, inhibiteurs de l'enzyme soat-1, compositions pharmaceutiques et cosmetiques les contenant. |
| FR2946340B1 (fr) | 2009-06-05 | 2011-06-24 | Galderma Res & Dev | Nouveaux n-phenyl acetamie, inhibiteurs de l'enzyme soat-1, compositions pharmaceutiques et cosmetiques les contenant. |
| FR2946345B1 (fr) | 2009-06-05 | 2011-05-20 | Galderma Res & Dev | Nouveaux derives dioxo-imidazolidine, inhibiteurs de l'enzyme soat-1, compositions pharmaceutiques et cosmetiques les contenant. |
| FR2946342B1 (fr) | 2009-06-05 | 2011-06-24 | Galderma Res & Dev | Nouveaux derives de dioxo-imidazolidine, inhibiteurs de l'enzyme soat-1, compositions pharmaceutiques et cosmetiques les contenant. |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0049538A3 (de) * | 1979-07-14 | 1982-10-13 | Bayer Ag | Verwendung von Thioharnstoffderivaten als Arzneimittel bei der Behandlung von Fettstoffwechselstörungen |
| DE2945530A1 (de) * | 1979-11-10 | 1981-06-04 | Chemische Werke Hüls AG, 4370 Marl | Harnstoffe mit cyclischen substituenten, ihre herstellung und verwendung als herbizide |
| US4623662A (en) * | 1985-05-23 | 1986-11-18 | American Cyanamid Company | Antiatherosclerotic ureas and thioureas |
| US4387105A (en) * | 1982-01-26 | 1983-06-07 | American Cyanamid Company | Methods of treating atherosclerosis with dialkylureas and dialkylthioureas |
-
1988
- 1988-05-06 IE IE138088A patent/IE61716B1/en unknown
- 1988-05-09 CA CA000566283A patent/CA1296339C/en not_active Expired - Fee Related
- 1988-05-17 NZ NZ224670A patent/NZ224670A/xx unknown
- 1988-05-24 AU AU16573/88A patent/AU601846B2/en not_active Ceased
- 1988-05-31 KR KR1019880006438A patent/KR890000412A/ko not_active Withdrawn
- 1988-05-31 PH PH36994A patent/PH24216A/en unknown
- 1988-05-31 PT PT87622A patent/PT87622B/pt not_active IP Right Cessation
- 1988-06-01 JP JP63132918A patent/JP2575183B2/ja not_active Expired - Fee Related
- 1988-06-01 FI FI882588A patent/FI882588A7/fi not_active Application Discontinuation
- 1988-06-01 ES ES88108816T patent/ES2051797T3/es not_active Expired - Lifetime
- 1988-06-01 DE DE8888108816T patent/DE3873992T2/de not_active Expired - Lifetime
- 1988-06-01 NO NO882406A patent/NO167200C/no unknown
- 1988-06-01 DK DK198802979A patent/DK175791B1/da not_active IP Right Cessation
- 1988-06-01 EP EP88108816A patent/EP0293880B1/en not_active Expired - Lifetime
-
1992
- 1992-11-19 GR GR920402658T patent/GR3006297T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IE61716B1 (en) | 1994-11-30 |
| NZ224670A (en) | 1989-10-27 |
| DE3873992D1 (de) | 1992-10-01 |
| FI882588A7 (fi) | 1988-12-03 |
| IE881380L (en) | 1988-12-02 |
| DK297988A (da) | 1988-12-03 |
| NO167200B (no) | 1991-07-08 |
| DE3873992T2 (de) | 1992-12-17 |
| EP0293880B1 (en) | 1992-08-26 |
| JPS63316761A (ja) | 1988-12-26 |
| JP2575183B2 (ja) | 1997-01-22 |
| DK297988D0 (da) | 1988-06-01 |
| GR3006297T3 (en, 2012) | 1993-06-21 |
| AU601846B2 (en) | 1990-09-20 |
| PH24216A (en) | 1990-04-10 |
| NO882406L (no) | 1988-12-05 |
| ES2051797T3 (es) | 1994-07-01 |
| PT87622B (pt) | 1992-09-30 |
| DK175791B1 (da) | 2005-02-21 |
| FI882588A0 (fi) | 1988-06-01 |
| EP0293880A1 (en) | 1988-12-07 |
| NO882406D0 (no) | 1988-06-01 |
| PT87622A (pt) | 1988-06-01 |
| AU1657388A (en) | 1988-12-08 |
| KR890000412A (ko) | 1989-03-14 |
| NO167200C (no) | 1991-10-16 |
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