NO300843B1 - Aryliden-l-azacykloalkaner og arylalkyl-l-azacykloalkaner, salter av disse, og legemidler som inneholder disse forbindelser - Google Patents
Aryliden-l-azacykloalkaner og arylalkyl-l-azacykloalkaner, salter av disse, og legemidler som inneholder disse forbindelser Download PDFInfo
- Publication number
- NO300843B1 NO300843B1 NO933790A NO933790A NO300843B1 NO 300843 B1 NO300843 B1 NO 300843B1 NO 933790 A NO933790 A NO 933790A NO 933790 A NO933790 A NO 933790A NO 300843 B1 NO300843 B1 NO 300843B1
- Authority
- NO
- Norway
- Prior art keywords
- group
- piperidine
- benzylidene
- oxazolin
- hydrogen atom
- Prior art date
Links
- 150000003839 salts Chemical class 0.000 title claims abstract description 18
- 150000001875 compounds Chemical class 0.000 title claims description 112
- 239000003814 drug Substances 0.000 title claims description 6
- 229940079593 drug Drugs 0.000 title claims description 5
- 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 71
- 235000012000 cholesterol Nutrition 0.000 claims abstract description 34
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 32
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 62
- 125000004432 carbon atom Chemical group C* 0.000 claims description 49
- 125000000217 alkyl group Chemical group 0.000 claims description 48
- 125000005843 halogen group Chemical group 0.000 claims description 46
- 238000011282 treatment Methods 0.000 claims description 27
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- -1 methoxy, cyano, nitro, methylsulfonyl Chemical group 0.000 claims description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
- 208000001130 gallstones Diseases 0.000 claims description 15
- JQNWPWUJMRAASQ-UHFFFAOYSA-N (4-chlorophenyl)-[4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]methanone Chemical compound C1=CC(Cl)=CC=C1C(=O)N(CC1)CCC1=CC1=CC=C(C=2OCCN=2)C=C1 JQNWPWUJMRAASQ-UHFFFAOYSA-N 0.000 claims description 14
- 229910052731 fluorine Inorganic materials 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- 229910052801 chlorine Inorganic materials 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 10
- 125000001153 fluoro group Chemical group F* 0.000 claims description 10
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 9
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 9
- MIEDZIDGNDSSOM-UHFFFAOYSA-N (4-chlorophenyl)-[4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methyl]piperidin-1-yl]methanone Chemical compound C1=CC(Cl)=CC=C1C(=O)N1CCC(CC=2C=CC(=CC=2)C=2OCCN=2)CC1 MIEDZIDGNDSSOM-UHFFFAOYSA-N 0.000 claims description 8
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
- KLNRNRKDOKSJSW-UHFFFAOYSA-N [4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]-[4-(trifluoromethyl)phenyl]methanone Chemical compound C1=CC(C(F)(F)F)=CC=C1C(=O)N(CC1)CCC1=CC1=CC=C(C=2OCCN=2)C=C1 KLNRNRKDOKSJSW-UHFFFAOYSA-N 0.000 claims description 8
- 125000002947 alkylene group Chemical group 0.000 claims description 8
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 239000011737 fluorine Substances 0.000 claims description 8
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 8
- 230000002265 prevention Effects 0.000 claims description 8
- 125000001544 thienyl group Chemical group 0.000 claims description 8
- NGIXKIZJFNNRII-UHFFFAOYSA-N (5-chlorothiophen-2-yl)-[4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]methanone Chemical compound S1C(Cl)=CC=C1C(=O)N(CC1)CCC1=CC1=CC=C(C=2OCCN=2)C=C1 NGIXKIZJFNNRII-UHFFFAOYSA-N 0.000 claims description 7
- 208000031888 Mycoses Diseases 0.000 claims description 7
- RSWURALHCSSUTE-UHFFFAOYSA-N [4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]-(4-fluorophenyl)methanone Chemical compound C1=CC(F)=CC=C1C(=O)N(CC1)CCC1=CC1=CC=C(C=2OCCN=2)C=C1 RSWURALHCSSUTE-UHFFFAOYSA-N 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- ZZPNBERPQGKKRC-UHFFFAOYSA-N (4-chloro-3-methylphenyl)-[4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]methanone Chemical compound C1=C(Cl)C(C)=CC(C(=O)N2CCC(CC2)=CC=2C=CC(=CC=2)C=2OCCN=2)=C1 ZZPNBERPQGKKRC-UHFFFAOYSA-N 0.000 claims description 6
- MIDPJHYJPFLNRP-UHFFFAOYSA-N (4-chlorophenyl)-[3-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]pyrrolidin-1-yl]methanone Chemical compound C1=CC(Cl)=CC=C1C(=O)N(CC1)CC1=CC1=CC=C(C=2OCCN=2)C=C1 MIDPJHYJPFLNRP-UHFFFAOYSA-N 0.000 claims description 6
- BCSGBGSVOMSSAM-UHFFFAOYSA-N (4-chlorophenyl)-[4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)-2-fluorophenyl]methylidene]piperidin-1-yl]methanone Chemical compound FC1=CC(C=2OCCN=2)=CC=C1C=C(CC1)CCN1C(=O)C1=CC=C(Cl)C=C1 BCSGBGSVOMSSAM-UHFFFAOYSA-N 0.000 claims description 6
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 6
- VJIRPVAYIRYZQL-UHFFFAOYSA-N [4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methyl]piperidin-1-yl]-[4-(trifluoromethyl)phenyl]methanone Chemical compound C1=CC(C(F)(F)F)=CC=C1C(=O)N1CCC(CC=2C=CC(=CC=2)C=2OCCN=2)CC1 VJIRPVAYIRYZQL-UHFFFAOYSA-N 0.000 claims description 6
- 125000004450 alkenylene group Chemical group 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- CENDSAPOSUTQHX-UHFFFAOYSA-N cyclohexyl-[4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]methanone Chemical compound C1CC(=CC=2C=CC(=CC=2)C=2OCCN=2)CCN1C(=O)C1CCCCC1 CENDSAPOSUTQHX-UHFFFAOYSA-N 0.000 claims description 6
- 235000013601 eggs Nutrition 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- GGVUEPVVIOLBRU-UHFFFAOYSA-N (4-chlorophenyl)-[4-[[4-(oxazinan-2-yl)phenyl]methylidene]piperidin-1-yl]methanone Chemical compound C1=CC(Cl)=CC=C1C(=O)N(CC1)CCC1=CC1=CC=C(N2OCCCC2)C=C1 GGVUEPVVIOLBRU-UHFFFAOYSA-N 0.000 claims description 5
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 5
- 230000004663 cell proliferation Effects 0.000 claims description 5
- YDPFQUVMHKAVQG-UHFFFAOYSA-N (4-chlorophenyl)-[4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)-3-methylphenyl]methylidene]piperidin-1-yl]methanone Chemical compound C=1C=C(C=2OCCN=2)C(C)=CC=1C=C(CC1)CCN1C(=O)C1=CC=C(Cl)C=C1 YDPFQUVMHKAVQG-UHFFFAOYSA-N 0.000 claims description 4
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
- 125000004419 alkynylene group Chemical group 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 4
- 125000005191 hydroxyalkylamino group Chemical group 0.000 claims description 3
- 150000007522 mineralic acids Chemical class 0.000 claims description 3
- 150000007524 organic acids Chemical class 0.000 claims description 3
- 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 2
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 2
- 125000006524 alkoxy alkyl amino group Chemical group 0.000 claims description 2
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 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 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 235000005985 organic acids Nutrition 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 43
- 238000002844 melting Methods 0.000 description 105
- 230000008018 melting Effects 0.000 description 105
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 67
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 54
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 43
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- MMDGEHBTHZXZLX-UHFFFAOYSA-N 2-[4-(piperidin-4-ylidenemethyl)phenyl]-4,5-dihydro-1,3-oxazole Chemical compound O1CCN=C1C(C=C1)=CC=C1C=C1CCNCC1 MMDGEHBTHZXZLX-UHFFFAOYSA-N 0.000 description 31
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
- 238000006243 chemical reaction Methods 0.000 description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 22
- ROLMZTIHUMKEAI-UHFFFAOYSA-N 4,5-difluoro-2-hydroxybenzonitrile Chemical compound OC1=CC(F)=C(F)C=C1C#N ROLMZTIHUMKEAI-UHFFFAOYSA-N 0.000 description 22
- 239000003112 inhibitor Substances 0.000 description 22
- 239000000243 solution Substances 0.000 description 22
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 22
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 238000000034 method Methods 0.000 description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- 239000000741 silica gel Substances 0.000 description 16
- 229910002027 silica gel Inorganic materials 0.000 description 16
- IQQZQHHFNQQONM-UHFFFAOYSA-N 2-[4-(piperidin-4-ylmethyl)phenyl]-4,5-dihydro-1,3-oxazole Chemical compound C=1C=C(C=2OCCN=2)C=CC=1CC1CCNCC1 IQQZQHHFNQQONM-UHFFFAOYSA-N 0.000 description 14
- YSHOWEKUVWPFNR-UHFFFAOYSA-N Burgess reagent Substances CC[N+](CC)(CC)S(=O)(=O)N=C([O-])OC YSHOWEKUVWPFNR-UHFFFAOYSA-N 0.000 description 14
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- 102100032011 Lanosterol synthase Human genes 0.000 description 11
- 108010059597 Lanosterol synthase Proteins 0.000 description 11
- 239000013543 active substance Substances 0.000 description 11
- 239000012230 colorless oil Substances 0.000 description 11
- AOBXGZHWDJSPRW-UHFFFAOYSA-N 2-[4-(diethoxyphosphorylmethyl)phenyl]-4,5-dihydro-1,3-oxazole Chemical compound C1=CC(CP(=O)(OCC)OCC)=CC=C1C1=NCCO1 AOBXGZHWDJSPRW-UHFFFAOYSA-N 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 10
- SXWRTZOXMUOJER-UHFFFAOYSA-N hydron;piperidin-4-one;chloride;hydrate Chemical compound O.Cl.O=C1CCNCC1 SXWRTZOXMUOJER-UHFFFAOYSA-N 0.000 description 10
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 10
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- VVTSPGAEYDBBSQ-UHFFFAOYSA-N 1-(4-chlorobenzoyl)piperidin-4-one Chemical compound C1=CC(Cl)=CC=C1C(=O)N1CCC(=O)CC1 VVTSPGAEYDBBSQ-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 208000035475 disorder Diseases 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- 239000003208 petroleum Substances 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
- 229960004844 lovastatin Drugs 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000011347 resin Substances 0.000 description 8
- 229920005989 resin Polymers 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 239000013078 crystal Substances 0.000 description 7
- 238000005984 hydrogenation reaction Methods 0.000 description 7
- 210000003491 skin Anatomy 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 7
- QYIMSPSDBYKPPY-BANQPHDMSA-N 2,3-epoxysqualene Chemical compound CC(C)=CCC\C(C)=C\CC\C(C)=C\CC\C=C(/C)CC\C=C(/C)CCC1OC1(C)C QYIMSPSDBYKPPY-BANQPHDMSA-N 0.000 description 6
- MFXWOYIWKNJHPC-UHFFFAOYSA-N 4-(diethoxyphosphorylmethyl)benzonitrile Chemical compound CCOP(=O)(OCC)CC1=CC=C(C#N)C=C1 MFXWOYIWKNJHPC-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 241000699800 Cricetinae Species 0.000 description 6
- 208000035150 Hypercholesterolemia Diseases 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
- 230000003463 hyperproliferative effect Effects 0.000 description 6
- 230000000927 lithogenic effect Effects 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 208000017520 skin disease Diseases 0.000 description 6
- 239000000829 suppository Substances 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- RKIDDEGICSMIJA-UHFFFAOYSA-N 4-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)C=C1 RKIDDEGICSMIJA-UHFFFAOYSA-N 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- 229930182558 Sterol Natural products 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 5
- 210000000941 bile Anatomy 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 230000008686 ergosterol biosynthesis Effects 0.000 description 5
- 230000002538 fungal effect Effects 0.000 description 5
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 5
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 150000003431 steroids Chemical class 0.000 description 5
- 235000003702 sterols Nutrition 0.000 description 5
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound 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 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 4
- 230000000326 anti-hypercholesterolaemic effect Effects 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 239000006260 foam Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 4
- 229920001592 potato starch Polymers 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 150000003432 sterols Chemical class 0.000 description 4
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- OHJYFSWUYYTNEE-UHFFFAOYSA-N 4-[[1-(4-chlorobenzoyl)piperidin-4-ylidene]methyl]benzonitrile Chemical compound C1=CC(Cl)=CC=C1C(=O)N(CC1)CCC1=CC1=CC=C(C#N)C=C1 OHJYFSWUYYTNEE-UHFFFAOYSA-N 0.000 description 3
- 206010004146 Basal cell carcinoma Diseases 0.000 description 3
- 239000004342 Benzoyl peroxide Substances 0.000 description 3
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 3
- 229940126062 Compound A Drugs 0.000 description 3
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 3
- 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 3
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 3
- 206010020649 Hyperkeratosis Diseases 0.000 description 3
- 208000001126 Keratosis Diseases 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 3
- 201000004681 Psoriasis Diseases 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 3
- 102000005782 Squalene Monooxygenase Human genes 0.000 description 3
- 108020003891 Squalene monooxygenase Proteins 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 229940121375 antifungal agent Drugs 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 230000003143 atherosclerotic effect Effects 0.000 description 3
- 235000019400 benzoyl peroxide Nutrition 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 229950005499 carbon tetrachloride Drugs 0.000 description 3
- 201000001883 cholelithiasis Diseases 0.000 description 3
- 208000029078 coronary artery disease Diseases 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 3
- 230000037213 diet Effects 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 239000008298 dragée Substances 0.000 description 3
- 210000002615 epidermis Anatomy 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 3
- 238000009374 poultry farming Methods 0.000 description 3
- 229960002965 pravastatin Drugs 0.000 description 3
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- 238000007127 saponification reaction Methods 0.000 description 3
- 229960002855 simvastatin Drugs 0.000 description 3
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 3
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 3
- 235000011121 sodium hydroxide Nutrition 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 3
- 229910052721 tungsten Inorganic materials 0.000 description 3
- 239000010937 tungsten Substances 0.000 description 3
- 230000002792 vascular Effects 0.000 description 3
- 208000019553 vascular disease Diseases 0.000 description 3
- 229910052727 yttrium Inorganic materials 0.000 description 3
- BQPPJGMMIYJVBR-UHFFFAOYSA-N (10S)-3c-Acetoxy-4.4.10r.13c.14t-pentamethyl-17c-((R)-1.5-dimethyl-hexen-(4)-yl)-(5tH)-Delta8-tetradecahydro-1H-cyclopenta[a]phenanthren Natural products CC12CCC(OC(C)=O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C BQPPJGMMIYJVBR-UHFFFAOYSA-N 0.000 description 2
- HXKKHQJGJAFBHI-GSVOUGTGSA-N (2R)-1-aminopropan-2-ol Chemical compound C[C@@H](O)CN HXKKHQJGJAFBHI-GSVOUGTGSA-N 0.000 description 2
- XMAYWYJOQHXEEK-OZXSUGGESA-N (2R,4S)-ketoconazole Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2C=NC=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 XMAYWYJOQHXEEK-OZXSUGGESA-N 0.000 description 2
- HXKKHQJGJAFBHI-VKHMYHEASA-N (2s)-1-aminopropan-2-ol Chemical compound C[C@H](O)CN HXKKHQJGJAFBHI-VKHMYHEASA-N 0.000 description 2
- CHGIKSSZNBCNDW-UHFFFAOYSA-N (3beta,5alpha)-4,4-Dimethylcholesta-8,24-dien-3-ol Natural products CC12CCC(O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21 CHGIKSSZNBCNDW-UHFFFAOYSA-N 0.000 description 2
- RUDATBOHQWOJDD-UHFFFAOYSA-N (3beta,5beta,7alpha)-3,7-Dihydroxycholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 RUDATBOHQWOJDD-UHFFFAOYSA-N 0.000 description 2
- XFVVPAFOKRTDIL-UHFFFAOYSA-N (4-bromophenyl)-[4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]methanone Chemical compound C1=CC(Br)=CC=C1C(=O)N(CC1)CCC1=CC1=CC=C(C=2OCCN=2)C=C1 XFVVPAFOKRTDIL-UHFFFAOYSA-N 0.000 description 2
- NFJBSWYEUWBJSE-UHFFFAOYSA-N (4-chlorophenyl)-[3-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]methanone Chemical compound C1=CC(Cl)=CC=C1C(=O)N(CCC1)CC1=CC1=CC=C(C=2OCCN=2)C=C1 NFJBSWYEUWBJSE-UHFFFAOYSA-N 0.000 description 2
- SHVMDJRPQSJXKI-UHFFFAOYSA-N (4-chlorophenyl)-[4-[1-[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]ethylidene]piperidin-1-yl]methanone Chemical group C=1C=C(C=2OCCN=2)C=CC=1C(C)=C(CC1)CCN1C(=O)C1=CC=C(Cl)C=C1 SHVMDJRPQSJXKI-UHFFFAOYSA-N 0.000 description 2
- JCZWHCSNHNFMHY-UHFFFAOYSA-N (4-chlorophenyl)-[4-[[4-(4,5-dihydro-1,3-thiazol-2-yl)phenyl]methyl]piperidin-1-yl]methanone Chemical compound C1=CC(Cl)=CC=C1C(=O)N1CCC(CC=2C=CC(=CC=2)C=2SCCN=2)CC1 JCZWHCSNHNFMHY-UHFFFAOYSA-N 0.000 description 2
- WXLAMGVZTQDOCI-UHFFFAOYSA-N (4-chlorophenyl)-[4-[[4-(5-phenyl-4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]methanone Chemical compound C1=CC(Cl)=CC=C1C(=O)N(CC1)CCC1=CC1=CC=C(C=2OC(CN=2)C=2C=CC=CC=2)C=C1 WXLAMGVZTQDOCI-UHFFFAOYSA-N 0.000 description 2
- AGFWPKXAVVLFQV-MRXNPFEDSA-N (4-chlorophenyl)-[4-[[4-[(4r)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl]phenyl]methylidene]piperidin-1-yl]methanone Chemical group C[C@@H]1COC(C=2C=CC(C=C3CCN(CC3)C(=O)C=3C=CC(Cl)=CC=3)=CC=2)=N1 AGFWPKXAVVLFQV-MRXNPFEDSA-N 0.000 description 2
- FXUWKHOFWXKFBP-UHFFFAOYSA-N (4-chlorophenyl)-[4-[[4-[4-(hydroxymethyl)-4,5-dihydro-1,3-oxazol-2-yl]phenyl]methylidene]piperidin-1-yl]methanone Chemical group OCC1COC(C=2C=CC(C=C3CCN(CC3)C(=O)C=3C=CC(Cl)=CC=3)=CC=2)=N1 FXUWKHOFWXKFBP-UHFFFAOYSA-N 0.000 description 2
- MNWXZHHJKAHJFH-UHFFFAOYSA-N (4-chlorophenyl)-[4-[[4-[5-(diethylaminomethyl)-4,5-dihydro-1,3-oxazol-2-yl]phenyl]methylidene]piperidin-1-yl]methanone Chemical group O1C(CN(CC)CC)CN=C1C(C=C1)=CC=C1C=C1CCN(C(=O)C=2C=CC(Cl)=CC=2)CC1 MNWXZHHJKAHJFH-UHFFFAOYSA-N 0.000 description 2
- AHZGEYJLRDXCFQ-UHFFFAOYSA-N (4-tert-butylphenyl)-[4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]methanone Chemical group C1=CC(C(C)(C)C)=CC=C1C(=O)N(CC1)CCC1=CC1=CC=C(C=2OCCN=2)C=C1 AHZGEYJLRDXCFQ-UHFFFAOYSA-N 0.000 description 2
- KJTLQQUUPVSXIM-ZCFIWIBFSA-N (R)-mevalonic acid Chemical compound OCC[C@](O)(C)CC(O)=O KJTLQQUUPVSXIM-ZCFIWIBFSA-N 0.000 description 2
- BKMMTJMQCTUHRP-VKHMYHEASA-N (S)-2-aminopropan-1-ol Chemical compound C[C@H](N)CO BKMMTJMQCTUHRP-VKHMYHEASA-N 0.000 description 2
- KIRGLCXNEVICOG-SOFGYWHQSA-N (e)-n-ethyl-6,6-dimethyl-n-[[3-[(4-thiophen-3-ylthiophen-2-yl)methoxy]phenyl]methyl]hept-2-en-4-yn-1-amine Chemical compound CC(C)(C)C#C/C=C/CN(CC)CC1=CC=CC(OCC=2SC=C(C=2)C2=CSC=C2)=C1 KIRGLCXNEVICOG-SOFGYWHQSA-N 0.000 description 2
- GAKRFXBXTBSAOJ-UHFFFAOYSA-N 1-(2,2-dimethylpropanoyl)piperidin-4-one Chemical compound CC(C)(C)C(=O)N1CCC(=O)CC1 GAKRFXBXTBSAOJ-UHFFFAOYSA-N 0.000 description 2
- SGPVWOVMGWACSW-UHFFFAOYSA-N 1-(4-chlorophenyl)sulfonyl-4-[[4-(4,5-dihydro-1h-imidazol-2-yl)phenyl]methylidene]piperidine Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N(CC1)CCC1=CC1=CC=C(C=2NCCN=2)C=C1 SGPVWOVMGWACSW-UHFFFAOYSA-N 0.000 description 2
- MBFQWKZGVWXLGM-UHFFFAOYSA-N 1-(4-chlorophenyl)sulfonylpiperidin-4-one Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1CCC(=O)CC1 MBFQWKZGVWXLGM-UHFFFAOYSA-N 0.000 description 2
- SYWXLNAOEXIDMG-UHFFFAOYSA-N 1-(4-methylbenzoyl)piperidin-4-one Chemical compound C1=CC(C)=CC=C1C(=O)N1CCC(=O)CC1 SYWXLNAOEXIDMG-UHFFFAOYSA-N 0.000 description 2
- YPJLJUYIXVELMP-UHFFFAOYSA-N 1-(cyclohexanecarbonyl)piperidin-4-one Chemical compound C1CC(=O)CCN1C(=O)C1CCCCC1 YPJLJUYIXVELMP-UHFFFAOYSA-N 0.000 description 2
- XNQQHFAOMVVKLL-UHFFFAOYSA-N 1-[3-(4-chlorophenyl)prop-2-enoyl]piperidin-4-one Chemical compound C1=CC(Cl)=CC=C1C=CC(=O)N1CCC(=O)CC1 XNQQHFAOMVVKLL-UHFFFAOYSA-N 0.000 description 2
- OKFOMVUJXRVXKT-UHFFFAOYSA-N 1-hexanoylpiperidin-4-one Chemical compound CCCCCC(=O)N1CCC(=O)CC1 OKFOMVUJXRVXKT-UHFFFAOYSA-N 0.000 description 2
- XYTLYKGXLMKYMV-UHFFFAOYSA-N 14alpha-methylzymosterol Natural products CC12CCC(O)CC1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C XYTLYKGXLMKYMV-UHFFFAOYSA-N 0.000 description 2
- DCXHJGKFDUCLFN-UHFFFAOYSA-N 2-(4-chlorophenyl)-1-[4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]ethanone Chemical compound C1=CC(Cl)=CC=C1CC(=O)N(CC1)CCC1=CC1=CC=C(C=2OCCN=2)C=C1 DCXHJGKFDUCLFN-UHFFFAOYSA-N 0.000 description 2
- UIEDZUKCXHRVOA-UHFFFAOYSA-N 2-[4-(azepan-4-ylidenemethyl)phenyl]-4,5-dihydro-1,3-oxazole Chemical compound O1CCN=C1C(C=C1)=CC=C1C=C1CCNCCC1 UIEDZUKCXHRVOA-UHFFFAOYSA-N 0.000 description 2
- JQVVKESCKMKHNO-UHFFFAOYSA-N 2-[4-[(1-tritylazepan-4-ylidene)methyl]phenyl]-4,5-dihydro-1,3-oxazole Chemical compound O1CCN=C1C(C=C1)=CC=C1C=C1CCN(C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)CCC1 JQVVKESCKMKHNO-UHFFFAOYSA-N 0.000 description 2
- KMFZBIDLKORZFY-UHFFFAOYSA-N 2-[4-[(1-tritylpiperidin-4-ylidene)methyl]phenyl]-4,5-dihydro-1,3-oxazole Chemical compound O1CCN=C1C(C=C1)=CC=C1C=C1CCN(C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 KMFZBIDLKORZFY-UHFFFAOYSA-N 0.000 description 2
- PMCPUVUCNRWQFZ-UHFFFAOYSA-N 2-[4-[[1-(4-chlorophenyl)sulfonylpiperidin-4-ylidene]methyl]phenyl]-4,5-dihydro-1,3-oxazole Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N(CC1)CCC1=CC1=CC=C(C=2OCCN=2)C=C1 PMCPUVUCNRWQFZ-UHFFFAOYSA-N 0.000 description 2
- ZPUYDPWWJCNLFT-UHFFFAOYSA-N 3-(diethoxyphosphorylmethyl)benzonitrile Chemical compound CCOP(=O)(OCC)CC1=CC=CC(C#N)=C1 ZPUYDPWWJCNLFT-UHFFFAOYSA-N 0.000 description 2
- DZEVNTXRKRZJAH-UHFFFAOYSA-N 3-[[1-(4-chlorobenzoyl)piperidin-4-ylidene]methyl]benzonitrile Chemical compound C1=CC(Cl)=CC=C1C(=O)N(CC1)CCC1=CC1=CC=CC(C#N)=C1 DZEVNTXRKRZJAH-UHFFFAOYSA-N 0.000 description 2
- RWSFTZLGMGVCQW-UHFFFAOYSA-N 3-bromo-4-[[1-(4-chlorobenzoyl)piperidin-4-ylidene]methyl]-n-(2-hydroxyethyl)benzamide Chemical compound BrC1=CC(C(=O)NCCO)=CC=C1C=C1CCN(C(=O)C=2C=CC(Cl)=CC=2)CC1 RWSFTZLGMGVCQW-UHFFFAOYSA-N 0.000 description 2
- WHIHIKVIWVIIER-UHFFFAOYSA-N 3-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC(Cl)=C1 WHIHIKVIWVIIER-UHFFFAOYSA-N 0.000 description 2
- FPTJELQXIUUCEY-UHFFFAOYSA-N 3beta-Hydroxy-lanostan Natural products C1CC2C(C)(C)C(O)CCC2(C)C2C1C1(C)CCC(C(C)CCCC(C)C)C1(C)CC2 FPTJELQXIUUCEY-UHFFFAOYSA-N 0.000 description 2
- ILVPJQJMEHTPAU-UHFFFAOYSA-N 4-(1-diethoxyphosphorylethyl)benzonitrile Chemical compound CCOP(=O)(OCC)C(C)C1=CC=C(C#N)C=C1 ILVPJQJMEHTPAU-UHFFFAOYSA-N 0.000 description 2
- FMAUUDCCCFDYNW-UHFFFAOYSA-N 4-[(1-benzylpiperidin-3-ylidene)methyl]benzonitrile Chemical compound C1=CC(C#N)=CC=C1C=C1CN(CC=2C=CC=CC=2)CCC1 FMAUUDCCCFDYNW-UHFFFAOYSA-N 0.000 description 2
- IKCNXAZOERQIST-UHFFFAOYSA-N 4-[1-[1-(4-chlorobenzoyl)piperidin-4-ylidene]ethyl]benzonitrile Chemical compound C=1C=C(C#N)C=CC=1C(C)=C(CC1)CCN1C(=O)C1=CC=C(Cl)C=C1 IKCNXAZOERQIST-UHFFFAOYSA-N 0.000 description 2
- KZUVDSMISYKGPQ-UHFFFAOYSA-N 4-[4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidine-1-carbonyl]benzonitrile Chemical group C=1C=C(C#N)C=CC=1C(=O)N(CC1)CCC1=CC(C=C1)=CC=C1C1=NCCO1 KZUVDSMISYKGPQ-UHFFFAOYSA-N 0.000 description 2
- XIHNYSZNFSAEFS-UHFFFAOYSA-N 4-[[1-(4-chlorobenzoyl)piperidin-3-ylidene]methyl]benzonitrile Chemical compound C1=CC(Cl)=CC=C1C(=O)N(CCC1)CC1=CC1=CC=C(C#N)C=C1 XIHNYSZNFSAEFS-UHFFFAOYSA-N 0.000 description 2
- MUONSSYIIKRISA-UHFFFAOYSA-N 4-[[1-(4-chlorobenzoyl)piperidin-4-yl]methyl]benzonitrile Chemical compound C1=CC(Cl)=CC=C1C(=O)N1CCC(CC=2C=CC(=CC=2)C#N)CC1 MUONSSYIIKRISA-UHFFFAOYSA-N 0.000 description 2
- YYBSMBQJOZXDKF-UHFFFAOYSA-N 4-[[1-(4-chlorobenzoyl)piperidin-4-ylidene]methyl]-3-fluoro-n-(2-hydroxyethyl)benzamide Chemical compound FC1=CC(C(=O)NCCO)=CC=C1C=C1CCN(C(=O)C=2C=CC(Cl)=CC=2)CC1 YYBSMBQJOZXDKF-UHFFFAOYSA-N 0.000 description 2
- NCKKTZWXJHKUGQ-UHFFFAOYSA-N 4-[[1-(4-chlorobenzoyl)piperidin-4-ylidene]methyl]-n-(2-hydroxyethyl)-2-methylbenzamide Chemical compound C1=C(C(=O)NCCO)C(C)=CC(C=C2CCN(CC2)C(=O)C=2C=CC(Cl)=CC=2)=C1 NCKKTZWXJHKUGQ-UHFFFAOYSA-N 0.000 description 2
- OPJFKRXUCJCIBZ-UHFFFAOYSA-N 4-[[1-(4-chlorobenzoyl)piperidin-4-ylidene]methyl]-n-(2-hydroxyethyl)-3-methoxybenzamide Chemical compound COC1=CC(C(=O)NCCO)=CC=C1C=C1CCN(C(=O)C=2C=CC(Cl)=CC=2)CC1 OPJFKRXUCJCIBZ-UHFFFAOYSA-N 0.000 description 2
- USEDMAWWQDFMFY-UHFFFAOYSA-N 4-cyanobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(C#N)C=C1 USEDMAWWQDFMFY-UHFFFAOYSA-N 0.000 description 2
- CZKLEJHVLCMVQR-UHFFFAOYSA-N 4-fluorobenzoyl chloride Chemical compound FC1=CC=C(C(Cl)=O)C=C1 CZKLEJHVLCMVQR-UHFFFAOYSA-N 0.000 description 2
- NQUVCRCCRXRJCK-UHFFFAOYSA-N 4-methylbenzoyl chloride Chemical compound CC1=CC=C(C(Cl)=O)C=C1 NQUVCRCCRXRJCK-UHFFFAOYSA-N 0.000 description 2
- WNLMYNASWOULQY-UHFFFAOYSA-N 4-tert-butylbenzoyl chloride Chemical compound CC(C)(C)C1=CC=C(C(Cl)=O)C=C1 WNLMYNASWOULQY-UHFFFAOYSA-N 0.000 description 2
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 206010008120 Cerebral ischaemia Diseases 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- KJTLQQUUPVSXIM-UHFFFAOYSA-N DL-mevalonic acid Natural products OCCC(O)(C)CC(O)=O KJTLQQUUPVSXIM-UHFFFAOYSA-N 0.000 description 2
- QRLVDLBMBULFAL-UHFFFAOYSA-N Digitonin Natural products CC1CCC2(OC1)OC3C(O)C4C5CCC6CC(OC7OC(CO)C(OC8OC(CO)C(O)C(OC9OCC(O)C(O)C9OC%10OC(CO)C(O)C(OC%11OC(CO)C(O)C(O)C%11O)C%10O)C8O)C(O)C7O)C(O)CC6(C)C5CCC4(C)C3C2C QRLVDLBMBULFAL-UHFFFAOYSA-N 0.000 description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
- 206010017711 Gangrene Diseases 0.000 description 2
- BKLIAINBCQPSOV-UHFFFAOYSA-N Gluanol Natural products CC(C)CC=CC(C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(O)C(C)(C)C4CC3 BKLIAINBCQPSOV-UHFFFAOYSA-N 0.000 description 2
- 206010022562 Intermittent claudication Diseases 0.000 description 2
- LOPKHWOTGJIQLC-UHFFFAOYSA-N Lanosterol Natural products CC(CCC=C(C)C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(C)(O)C(C)(C)C4CC3 LOPKHWOTGJIQLC-UHFFFAOYSA-N 0.000 description 2
- CAHGCLMLTWQZNJ-UHFFFAOYSA-N Nerifoliol Natural products CC12CCC(O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C CAHGCLMLTWQZNJ-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical compound NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- SMCBPTINXPSTME-UHFFFAOYSA-N [4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]-(2,3,4,5,6-pentafluorophenyl)methanone Chemical compound FC1=C(F)C(F)=C(F)C(F)=C1C(=O)N(CC1)CCC1=CC1=CC=C(C=2OCCN=2)C=C1 SMCBPTINXPSTME-UHFFFAOYSA-N 0.000 description 2
- NUCGZOYEHKVDRG-UHFFFAOYSA-N [4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]-(4-methoxyphenyl)methanone Chemical compound C1=CC(OC)=CC=C1C(=O)N(CC1)CCC1=CC1=CC=C(C=2OCCN=2)C=C1 NUCGZOYEHKVDRG-UHFFFAOYSA-N 0.000 description 2
- ZUNIULHRTLIRSX-UHFFFAOYSA-N [4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]-(4-nitrophenyl)methanone Chemical group C1=CC([N+](=O)[O-])=CC=C1C(=O)N(CC1)CCC1=CC1=CC=C(C=2OCCN=2)C=C1 ZUNIULHRTLIRSX-UHFFFAOYSA-N 0.000 description 2
- BXWKAKAGLXTNES-UHFFFAOYSA-N [4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]-naphthalen-1-ylmethanone Chemical compound C=1C=CC2=CC=CC=C2C=1C(=O)N(CC1)CCC1=CC(C=C1)=CC=C1C1=NCCO1 BXWKAKAGLXTNES-UHFFFAOYSA-N 0.000 description 2
- KPJBJDQCDGBJHP-UHFFFAOYSA-N [4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]-phenylmethanone Chemical compound C=1C=CC=CC=1C(=O)N(CC1)CCC1=CC(C=C1)=CC=C1C1=NCCO1 KPJBJDQCDGBJHP-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
- 239000003613 bile acid Substances 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- QOPVNWQGBQYBBP-UHFFFAOYSA-N chloroethyl chloroformate Chemical compound CC(Cl)OC(Cl)=O QOPVNWQGBQYBBP-UHFFFAOYSA-N 0.000 description 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
- 239000003245 coal Substances 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 description 2
- UVYVLBIGDKGWPX-KUAJCENISA-N digitonin Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)C[C@@H](O)[C@H](O[C@H]5[C@@H]([C@@H](O)[C@@H](O[C@H]6[C@@H]([C@@H](O[C@H]7[C@@H]([C@@H](O)[C@H](O)CO7)O)[C@H](O)[C@@H](CO)O6)O[C@H]6[C@@H]([C@@H](O[C@H]7[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O7)O)[C@@H](O)[C@@H](CO)O6)O)[C@@H](CO)O5)O)C[C@@H]4CC[C@H]3[C@@H]2[C@@H]1O)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 UVYVLBIGDKGWPX-KUAJCENISA-N 0.000 description 2
- UVYVLBIGDKGWPX-UHFFFAOYSA-N digitonine Natural products CC1C(C2(CCC3C4(C)CC(O)C(OC5C(C(O)C(OC6C(C(OC7C(C(O)C(O)CO7)O)C(O)C(CO)O6)OC6C(C(OC7C(C(O)C(O)C(CO)O7)O)C(O)C(CO)O6)O)C(CO)O5)O)CC4CCC3C2C2O)C)C2OC11CCC(C)CO1 UVYVLBIGDKGWPX-UHFFFAOYSA-N 0.000 description 2
- QBSJHOGDIUQWTH-UHFFFAOYSA-N dihydrolanosterol Natural products CC(C)CCCC(C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(C)(O)C(C)(C)C4CC3 QBSJHOGDIUQWTH-UHFFFAOYSA-N 0.000 description 2
- POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical compound CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- 229940125753 fibrate Drugs 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- RFHAOTPXVQNOHP-UHFFFAOYSA-N fluconazole Chemical compound C1=NC=NN1CC(C=1C(=CC(F)=CC=1)F)(O)CN1C=NC=N1 RFHAOTPXVQNOHP-UHFFFAOYSA-N 0.000 description 2
- 229960004884 fluconazole Drugs 0.000 description 2
- 230000000855 fungicidal effect Effects 0.000 description 2
- 230000001408 fungistatic effect Effects 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 229910000039 hydrogen halide Inorganic materials 0.000 description 2
- 239000012433 hydrogen halide Substances 0.000 description 2
- 230000000871 hypocholesterolemic effect Effects 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 230000003780 keratinization Effects 0.000 description 2
- 210000002510 keratinocyte Anatomy 0.000 description 2
- 229960004125 ketoconazole Drugs 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- CAHGCLMLTWQZNJ-RGEKOYMOSA-N lanosterol Chemical compound C([C@]12C)C[C@@H](O)C(C)(C)[C@H]1CCC1=C2CC[C@]2(C)[C@H]([C@H](CCC=C(C)C)C)CC[C@@]21C CAHGCLMLTWQZNJ-RGEKOYMOSA-N 0.000 description 2
- 229940058690 lanosterol Drugs 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 229960003151 mercaptamine Drugs 0.000 description 2
- JYRMLIYMFJQZDX-UHFFFAOYSA-N methyl 3-bromo-4-(diethoxyphosphorylmethyl)benzoate Chemical compound CCOP(=O)(OCC)CC1=CC=C(C(=O)OC)C=C1Br JYRMLIYMFJQZDX-UHFFFAOYSA-N 0.000 description 2
- UETCOAOCGJDHDF-UHFFFAOYSA-N methyl 3-bromo-4-[[1-(4-chlorobenzoyl)piperidin-4-ylidene]methyl]benzoate Chemical compound BrC1=CC(C(=O)OC)=CC=C1C=C1CCN(C(=O)C=2C=CC(Cl)=CC=2)CC1 UETCOAOCGJDHDF-UHFFFAOYSA-N 0.000 description 2
- LWQYEPVYVLDPQY-UHFFFAOYSA-N methyl 4-(diethoxyphosphorylmethyl)-2-methylbenzoate Chemical compound CCOP(=O)(OCC)CC1=CC=C(C(=O)OC)C(C)=C1 LWQYEPVYVLDPQY-UHFFFAOYSA-N 0.000 description 2
- BNAFOHSNCMFBOU-UHFFFAOYSA-N methyl 4-(diethoxyphosphorylmethyl)-3-fluorobenzoate Chemical compound CCOP(=O)(OCC)CC1=CC=C(C(=O)OC)C=C1F BNAFOHSNCMFBOU-UHFFFAOYSA-N 0.000 description 2
- STRLWTVZXMRWIX-UHFFFAOYSA-N methyl 4-(diethoxyphosphorylmethyl)-3-methoxybenzoate Chemical compound CCOP(=O)(OCC)CC1=CC=C(C(=O)OC)C=C1OC STRLWTVZXMRWIX-UHFFFAOYSA-N 0.000 description 2
- KPTODDKVARZPAV-UHFFFAOYSA-N methyl 4-[[1-(4-chlorobenzoyl)piperidin-4-ylidene]methyl]-2-methylbenzoate Chemical compound C1=C(C)C(C(=O)OC)=CC=C1C=C1CCN(C(=O)C=2C=CC(Cl)=CC=2)CC1 KPTODDKVARZPAV-UHFFFAOYSA-N 0.000 description 2
- JYINJWRZBDFMGH-UHFFFAOYSA-N methyl 4-[[1-(4-chlorobenzoyl)piperidin-4-ylidene]methyl]-3-fluorobenzoate Chemical compound FC1=CC(C(=O)OC)=CC=C1C=C1CCN(C(=O)C=2C=CC(Cl)=CC=2)CC1 JYINJWRZBDFMGH-UHFFFAOYSA-N 0.000 description 2
- UMDMECGVNQUIDS-UHFFFAOYSA-N methyl 4-[[1-(4-chlorobenzoyl)piperidin-4-ylidene]methyl]-3-methoxybenzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1C=C1CCN(C(=O)C=2C=CC(Cl)=CC=2)CC1 UMDMECGVNQUIDS-UHFFFAOYSA-N 0.000 description 2
- 210000004400 mucous membrane Anatomy 0.000 description 2
- KFIGICHILYTCJF-UHFFFAOYSA-N n'-methylethane-1,2-diamine Chemical compound CNCCN KFIGICHILYTCJF-UHFFFAOYSA-N 0.000 description 2
- OZGNYLLQHRPOBR-DHZHZOJOSA-N naftifine Chemical compound C=1C=CC2=CC=CC=C2C=1CN(C)C\C=C\C1=CC=CC=C1 OZGNYLLQHRPOBR-DHZHZOJOSA-N 0.000 description 2
- 229960004313 naftifine Drugs 0.000 description 2
- NSNPSJGHTQIXDO-UHFFFAOYSA-N naphthalene-1-carbonyl chloride Chemical compound C1=CC=C2C(C(=O)Cl)=CC=CC2=C1 NSNPSJGHTQIXDO-UHFFFAOYSA-N 0.000 description 2
- XNLBCXGRQWUJLU-UHFFFAOYSA-N naphthalene-2-carbonyl chloride Chemical compound C1=CC=CC2=CC(C(=O)Cl)=CC=C21 XNLBCXGRQWUJLU-UHFFFAOYSA-N 0.000 description 2
- 230000035407 negative regulation of cell proliferation Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- ULSIYEODSMZIPX-UHFFFAOYSA-N phenylethanolamine Chemical compound NCC(O)C1=CC=CC=C1 ULSIYEODSMZIPX-UHFFFAOYSA-N 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 150000003053 piperidines Chemical class 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 230000008844 regulatory mechanism Effects 0.000 description 2
- 238000009097 single-agent therapy Methods 0.000 description 2
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 206010041823 squamous cell carcinoma Diseases 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- DOMXUEMWDBAQBQ-WEVVVXLNSA-N terbinafine Chemical compound C1=CC=C2C(CN(C\C=C\C#CC(C)(C)C)C)=CC=CC2=C1 DOMXUEMWDBAQBQ-WEVVVXLNSA-N 0.000 description 2
- 229960002722 terbinafine Drugs 0.000 description 2
- JJXKSFOFDFIQLM-UHFFFAOYSA-N tert-butyl 4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1=CC1=CC=C(C=2OCCN=2)C=C1 JJXKSFOFDFIQLM-UHFFFAOYSA-N 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- YSHOWEKUVWPFNR-UHFFFAOYSA-O triethyl(methoxycarbonylsulfamoyl)azanium Chemical compound CC[N+](CC)(CC)S(=O)(=O)NC(=O)OC YSHOWEKUVWPFNR-UHFFFAOYSA-O 0.000 description 2
- 230000001960 triggered effect Effects 0.000 description 2
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- RUDATBOHQWOJDD-UZVSRGJWSA-N ursodeoxycholic 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)CC1 RUDATBOHQWOJDD-UZVSRGJWSA-N 0.000 description 2
- 229960001661 ursodiol Drugs 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- KZJWDPNRJALLNS-VPUBHVLGSA-N (-)-beta-Sitosterol Natural products O[C@@H]1CC=2[C@@](C)([C@@H]3[C@H]([C@H]4[C@@](C)([C@H]([C@H](CC[C@@H](C(C)C)CC)C)CC4)CC3)CC=2)CC1 KZJWDPNRJALLNS-VPUBHVLGSA-N 0.000 description 1
- QYGAYYORBSAYHS-UHFFFAOYSA-N (2,5-difluorophenyl)-[4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]methanone Chemical compound FC1=CC=C(F)C(C(=O)N2CCC(CC2)=CC=2C=CC(=CC=2)C=2OCCN=2)=C1 QYGAYYORBSAYHS-UHFFFAOYSA-N 0.000 description 1
- ZECUIPMZTFIVOA-UHFFFAOYSA-N (2-chlorophenyl)-[4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methyl]piperidin-1-yl]methanone Chemical compound ClC1=CC=CC=C1C(=O)N1CCC(CC=2C=CC(=CC=2)C=2OCCN=2)CC1 ZECUIPMZTFIVOA-UHFFFAOYSA-N 0.000 description 1
- CSVWWLUMXNHWSU-UHFFFAOYSA-N (22E)-(24xi)-24-ethyl-5alpha-cholest-22-en-3beta-ol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)C=CC(CC)C(C)C)C1(C)CC2 CSVWWLUMXNHWSU-UHFFFAOYSA-N 0.000 description 1
- OILXMJHPFNGGTO-UHFFFAOYSA-N (22E)-(24xi)-24-methylcholesta-5,22-dien-3beta-ol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)C=CC(C)C(C)C)C1(C)CC2 OILXMJHPFNGGTO-UHFFFAOYSA-N 0.000 description 1
- RQOCXCFLRBRBCS-UHFFFAOYSA-N (22E)-cholesta-5,7,22-trien-3beta-ol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CCC(C)C)CCC33)C)C3=CC=C21 RQOCXCFLRBRBCS-UHFFFAOYSA-N 0.000 description 1
- STVVMTBJNDTZBF-SECBINFHSA-N (2r)-2-amino-3-phenylpropan-1-ol Chemical compound OC[C@H](N)CC1=CC=CC=C1 STVVMTBJNDTZBF-SECBINFHSA-N 0.000 description 1
- BKMMTJMQCTUHRP-GSVOUGTGSA-N (2r)-2-aminopropan-1-ol Chemical compound C[C@@H](N)CO BKMMTJMQCTUHRP-GSVOUGTGSA-N 0.000 description 1
- RPHQMRWKOPBZQY-VIFPVBQESA-N (2s)-2-amino-3-(4-chlorophenyl)propan-1-ol Chemical compound OC[C@@H](N)CC1=CC=C(Cl)C=C1 RPHQMRWKOPBZQY-VIFPVBQESA-N 0.000 description 1
- MIQJGZAEWQQAPN-YFKPBYRVSA-N (2s)-2-amino-4-methylsulfanylbutan-1-ol Chemical compound CSCC[C@H](N)CO MIQJGZAEWQQAPN-YFKPBYRVSA-N 0.000 description 1
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 1
- MFIHQEMSOWWULK-UHFFFAOYSA-N (3,4-dichlorophenyl)-[4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]methanone Chemical compound C1=C(Cl)C(Cl)=CC=C1C(=O)N(CC1)CCC1=CC1=CC=C(C=2OCCN=2)C=C1 MFIHQEMSOWWULK-UHFFFAOYSA-N 0.000 description 1
- OHZYOKBCFZAIAF-UHFFFAOYSA-N (3,4-difluorophenyl)-[4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]methanone Chemical compound C1=C(F)C(F)=CC=C1C(=O)N(CC1)CCC1=CC1=CC=C(C=2OCCN=2)C=C1 OHZYOKBCFZAIAF-UHFFFAOYSA-N 0.000 description 1
- KJOOPGBMLXPRPT-UHFFFAOYSA-N (3-chlorophenyl)-[4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methyl]piperidin-1-yl]methanone Chemical compound ClC1=CC=CC(C(=O)N2CCC(CC=3C=CC(=CC=3)C=3OCCN=3)CC2)=C1 KJOOPGBMLXPRPT-UHFFFAOYSA-N 0.000 description 1
- DKUJVSIXRNLXCN-UHFFFAOYSA-N (3-chlorophenyl)-[4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]methanone Chemical compound ClC1=CC=CC(C(=O)N2CCC(CC2)=CC=2C=CC(=CC=2)C=2OCCN=2)=C1 DKUJVSIXRNLXCN-UHFFFAOYSA-N 0.000 description 1
- IYTKDFVHGXIKPT-UHFFFAOYSA-N (4-chlorophenyl)-[3-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methyl]piperidin-1-yl]methanone Chemical compound C1=CC(Cl)=CC=C1C(=O)N1CC(CC=2C=CC(=CC=2)C=2OCCN=2)CCC1 IYTKDFVHGXIKPT-UHFFFAOYSA-N 0.000 description 1
- ZAKWLCVMBNQLBM-UHFFFAOYSA-N (4-chlorophenyl)-[4-[[3-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]methanone Chemical compound C1=CC(Cl)=CC=C1C(=O)N(CC1)CCC1=CC1=CC=CC(C=2OCCN=2)=C1 ZAKWLCVMBNQLBM-UHFFFAOYSA-N 0.000 description 1
- XJAKFPRVKFQHKH-UHFFFAOYSA-N (4-chlorophenyl)-[4-[[4-(1-methyl-4,5-dihydroimidazol-2-yl)phenyl]methyl]piperidin-1-yl]methanone Chemical compound CN1CCN=C1C(C=C1)=CC=C1CC1CCN(C(=O)C=2C=CC(Cl)=CC=2)CC1 XJAKFPRVKFQHKH-UHFFFAOYSA-N 0.000 description 1
- VOLRAJLJVUHNBQ-UHFFFAOYSA-N (4-chlorophenyl)-[4-[[4-(4,4-dimethyl-5h-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]methanone Chemical compound CC1(C)COC(C=2C=CC(C=C3CCN(CC3)C(=O)C=3C=CC(Cl)=CC=3)=CC=2)=N1 VOLRAJLJVUHNBQ-UHFFFAOYSA-N 0.000 description 1
- DWSIFHMPCNSTNR-UHFFFAOYSA-N (4-chlorophenyl)-[4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]azepan-1-yl]methanone Chemical compound C1=CC(Cl)=CC=C1C(=O)N(CCC1)CCC1=CC1=CC=C(C=2OCCN=2)C=C1 DWSIFHMPCNSTNR-UHFFFAOYSA-N 0.000 description 1
- NFIJVSVPTQOVQJ-UHFFFAOYSA-N (4-chlorophenyl)-[4-[[4-(4,5-dihydro-1,3-thiazol-2-yl)phenyl]methylidene]piperidin-1-yl]methanone Chemical compound C1=CC(Cl)=CC=C1C(=O)N(CC1)CCC1=CC1=CC=C(C=2SCCN=2)C=C1 NFIJVSVPTQOVQJ-UHFFFAOYSA-N 0.000 description 1
- PBVSLSKYECYUAV-UHFFFAOYSA-N (4-chlorophenyl)-[4-[[4-(4,5-dihydro-1h-imidazol-2-yl)phenyl]methyl]piperidin-1-yl]methanone Chemical compound C1=CC(Cl)=CC=C1C(=O)N1CCC(CC=2C=CC(=CC=2)C=2NCCN=2)CC1 PBVSLSKYECYUAV-UHFFFAOYSA-N 0.000 description 1
- XFOCSOLDOUGPES-UHFFFAOYSA-N (4-chlorophenyl)-[4-[[4-(5,5-dimethyl-4h-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]methanone Chemical compound O1C(C)(C)CN=C1C(C=C1)=CC=C1C=C1CCN(C(=O)C=2C=CC(Cl)=CC=2)CC1 XFOCSOLDOUGPES-UHFFFAOYSA-N 0.000 description 1
- VVSBYEFOJCOZSY-UHFFFAOYSA-N (4-chlorophenyl)-[4-[[4-(oxazinan-2-yl)phenyl]methyl]piperidin-1-yl]methanone Chemical compound C1=CC(Cl)=CC=C1C(=O)N1CCC(CC=2C=CC(=CC=2)N2OCCCC2)CC1 VVSBYEFOJCOZSY-UHFFFAOYSA-N 0.000 description 1
- QMVAZSLFXUGWQR-SANMLTNESA-N (4-chlorophenyl)-[4-[[4-[(4r)-4-phenyl-4,5-dihydro-1,3-oxazol-2-yl]phenyl]methylidene]piperidin-1-yl]methanone Chemical compound C1=CC(Cl)=CC=C1C(=O)N(CC1)CCC1=CC1=CC=C(C=2OC[C@H](N=2)C=2C=CC=CC=2)C=C1 QMVAZSLFXUGWQR-SANMLTNESA-N 0.000 description 1
- IEJSZZDGLVWNCE-MRXNPFEDSA-N (4-chlorophenyl)-[4-[[4-[(5r)-5-methyl-4,5-dihydro-1,3-oxazol-2-yl]phenyl]methyl]piperidin-1-yl]methanone Chemical compound O1[C@H](C)CN=C1C(C=C1)=CC=C1CC1CCN(C(=O)C=2C=CC(Cl)=CC=2)CC1 IEJSZZDGLVWNCE-MRXNPFEDSA-N 0.000 description 1
- GRZUFZBZZLJFDX-MRXNPFEDSA-N (4-chlorophenyl)-[4-[[4-[(5r)-5-methyl-4,5-dihydro-1,3-oxazol-2-yl]phenyl]methylidene]piperidin-1-yl]methanone Chemical compound O1[C@H](C)CN=C1C(C=C1)=CC=C1C=C1CCN(C(=O)C=2C=CC(Cl)=CC=2)CC1 GRZUFZBZZLJFDX-MRXNPFEDSA-N 0.000 description 1
- NHYQZHCWVXPQQN-UHFFFAOYSA-N (4-chlorophenyl)-[4-[[4-[4-(2-methylsulfanylethyl)-4,5-dihydro-1,3-oxazol-2-yl]phenyl]methylidene]piperidin-1-yl]methanone Chemical compound CSCCC1COC(C=2C=CC(C=C3CCN(CC3)C(=O)C=3C=CC(Cl)=CC=3)=CC=2)=N1 NHYQZHCWVXPQQN-UHFFFAOYSA-N 0.000 description 1
- NOLBOXVHBSSDQL-UHFFFAOYSA-N (4-chlorophenyl)-[4-[[4-[4-[(4-chlorophenyl)methyl]-4,5-dihydro-1,3-oxazol-2-yl]phenyl]methylidene]piperidin-1-yl]methanone Chemical compound C1=CC(Cl)=CC=C1CC1N=C(C=2C=CC(C=C3CCN(CC3)C(=O)C=3C=CC(Cl)=CC=3)=CC=2)OC1 NOLBOXVHBSSDQL-UHFFFAOYSA-N 0.000 description 1
- LHXXHNXEIDHTJS-UHFFFAOYSA-N (4-tert-butylphenyl)-[4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methyl]piperidin-1-yl]methanone Chemical compound C1=CC(C(C)(C)C)=CC=C1C(=O)N1CCC(CC=2C=CC(=CC=2)C=2OCCN=2)CC1 LHXXHNXEIDHTJS-UHFFFAOYSA-N 0.000 description 1
- OBYAAZRQFIVRJS-GUUMBNHASA-N (4e,8e,12z,16z)-n,n,4,8,13,17,21-heptamethyldocosa-4,8,12,16,20-pentaen-1-amine Chemical compound CN(C)CCC\C(C)=C\CC\C(C)=C\CC\C=C(/C)CC\C=C(/C)CCC=C(C)C OBYAAZRQFIVRJS-GUUMBNHASA-N 0.000 description 1
- IJXJGQCXFSSHNL-QMMMGPOBSA-N (R)-(-)-2-Phenylglycinol Chemical compound OC[C@H](N)C1=CC=CC=C1 IJXJGQCXFSSHNL-QMMMGPOBSA-N 0.000 description 1
- PSCXFXNEYIHJST-QPJJXVBHSA-N (e)-4-phenylbut-3-enoic acid Chemical compound OC(=O)C\C=C\C1=CC=CC=C1 PSCXFXNEYIHJST-QPJJXVBHSA-N 0.000 description 1
- USVVENVKYJZFMW-ONEGZZNKSA-N (e)-carboxyiminocarbamic acid Chemical compound OC(=O)\N=N\C(O)=O USVVENVKYJZFMW-ONEGZZNKSA-N 0.000 description 1
- STVVMTBJNDTZBF-UHFFFAOYSA-N -2-Amino-3-phenyl-1-propanol Natural products OCC(N)CC1=CC=CC=C1 STVVMTBJNDTZBF-UHFFFAOYSA-N 0.000 description 1
- GBZFILBGEYHYAE-UHFFFAOYSA-N 1,2,3,4-tetrahydronaphthalene-2-carbonyl chloride Chemical compound C1=CC=C2CC(C(=O)Cl)CCC2=C1 GBZFILBGEYHYAE-UHFFFAOYSA-N 0.000 description 1
- ZSVVFDHOQJEHJQ-UHFFFAOYSA-N 1-(3-phenylpropanoyl)piperidin-4-one Chemical compound C1CC(=O)CCN1C(=O)CCC1=CC=CC=C1 ZSVVFDHOQJEHJQ-UHFFFAOYSA-N 0.000 description 1
- PCOGRVFBIDICIW-UHFFFAOYSA-N 1-(4-chlorophenyl)sulfonyl-4-[[4-(1-methyl-4,5-dihydroimidazol-2-yl)phenyl]methylidene]piperidine Chemical compound CN1CCN=C1C(C=C1)=CC=C1C=C1CCN(S(=O)(=O)C=2C=CC(Cl)=CC=2)CC1 PCOGRVFBIDICIW-UHFFFAOYSA-N 0.000 description 1
- RAKBJOQOOVBPHW-UHFFFAOYSA-N 1-(bromomethyl)-2-methoxy-4-methylbenzene Chemical compound COC1=CC(C)=CC=C1CBr RAKBJOQOOVBPHW-UHFFFAOYSA-N 0.000 description 1
- BSJADLYBLTWRDI-UHFFFAOYSA-N 1-[4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]-2-naphthalen-2-ylethanone Chemical compound C=1C=C2C=CC=CC2=CC=1CC(=O)N(CC1)CCC1=CC(C=C1)=CC=C1C1=NCCO1 BSJADLYBLTWRDI-UHFFFAOYSA-N 0.000 description 1
- CPDNBAYHTTWJRJ-UHFFFAOYSA-N 1-[4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]-3-phenylpropan-1-one Chemical compound C1CC(=CC=2C=CC(=CC=2)C=2OCCN=2)CCN1C(=O)CCC1=CC=CC=C1 CPDNBAYHTTWJRJ-UHFFFAOYSA-N 0.000 description 1
- IJKUPSCCJUTDHK-UHFFFAOYSA-N 1-[4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]-4-phenylbut-3-en-1-one Chemical compound C1CC(=CC=2C=CC(=CC=2)C=2OCCN=2)CCN1C(=O)CC=CC1=CC=CC=C1 IJKUPSCCJUTDHK-UHFFFAOYSA-N 0.000 description 1
- VUOAYKDIYGZVNX-UHFFFAOYSA-N 1-[4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]hexan-1-one Chemical compound C1CN(C(=O)CCCCC)CCC1=CC1=CC=C(C=2OCCN=2)C=C1 VUOAYKDIYGZVNX-UHFFFAOYSA-N 0.000 description 1
- OWNJHFWEWYTDEI-UHFFFAOYSA-N 1-[4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]octadecan-1-one Chemical compound C1CN(C(=O)CCCCCCCCCCCCCCCCC)CCC1=CC1=CC=C(C=2OCCN=2)C=C1 OWNJHFWEWYTDEI-UHFFFAOYSA-N 0.000 description 1
- PEWZYEDZYIBXPY-UHFFFAOYSA-N 1-[4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]pent-4-yn-1-one Chemical compound C1CN(C(CCC#C)=O)CCC1=CC1=CC=C(C=2OCCN=2)C=C1 PEWZYEDZYIBXPY-UHFFFAOYSA-N 0.000 description 1
- YLHUPYSUKYAIBW-UHFFFAOYSA-N 1-acetylpyrrolidin-2-one Chemical compound CC(=O)N1CCCC1=O YLHUPYSUKYAIBW-UHFFFAOYSA-N 0.000 description 1
- LXQMHOKEXZETKB-UHFFFAOYSA-N 1-amino-2-methylpropan-2-ol Chemical compound CC(C)(O)CN LXQMHOKEXZETKB-UHFFFAOYSA-N 0.000 description 1
- LEJMOTVCCRDZNE-UHFFFAOYSA-N 1-amino-3-(diethylamino)propan-2-ol Chemical compound CCN(CC)CC(O)CN LEJMOTVCCRDZNE-UHFFFAOYSA-N 0.000 description 1
- BBQQULRBTOMLTC-UHFFFAOYSA-N 1-benzylpiperidin-3-one Chemical compound C1C(=O)CCCN1CC1=CC=CC=C1 BBQQULRBTOMLTC-UHFFFAOYSA-N 0.000 description 1
- ARUHDSZAWXAVAY-UHFFFAOYSA-N 1-tritylazepan-4-one Chemical compound C1CC(=O)CCCN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 ARUHDSZAWXAVAY-UHFFFAOYSA-N 0.000 description 1
- TTWLMWSWSQUXDB-UHFFFAOYSA-N 1-tritylpiperidin-4-one Chemical compound C1CC(=O)CCN1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 TTWLMWSWSQUXDB-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- DOTTUEYUTNVWMJ-KSTFQPQISA-N 2,2-dimethyl-3-[(3e,7e,11e,15e,19z)-3,7,12-trimethyl-16-prop-2-enylhenicosa-3,7,11,15,19-pentaenyl]oxirane Chemical compound C\C=C/CC\C(CC=C)=C/CC\C(C)=C\CC\C=C(/C)CC\C=C(/C)CCC1OC1(C)C DOTTUEYUTNVWMJ-KSTFQPQISA-N 0.000 description 1
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
- RLRUKKDFNWXXRT-UHFFFAOYSA-N 2,5-difluorobenzoyl chloride Chemical compound FC1=CC=C(F)C(C(Cl)=O)=C1 RLRUKKDFNWXXRT-UHFFFAOYSA-N 0.000 description 1
- ABIFHXWQHMSZHV-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-1-[4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]ethanone Chemical compound C1=C(Cl)C(Cl)=CC=C1CC(=O)N(CC1)CCC1=CC1=CC=C(C=2OCCN=2)C=C1 ABIFHXWQHMSZHV-UHFFFAOYSA-N 0.000 description 1
- CJJURHKDGQSBLE-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)acetyl chloride Chemical compound ClC(=O)CC1=CC=C(Cl)C(Cl)=C1 CJJURHKDGQSBLE-UHFFFAOYSA-N 0.000 description 1
- UMQUIRYNOVNYPA-UHFFFAOYSA-N 2-(4-chlorophenyl)acetyl chloride Chemical compound ClC(=O)CC1=CC=C(Cl)C=C1 UMQUIRYNOVNYPA-UHFFFAOYSA-N 0.000 description 1
- MXIUWSYTQJLIKE-UHFFFAOYSA-N 2-(trifluoromethyl)benzoyl chloride Chemical compound FC(F)(F)C1=CC=CC=C1C(Cl)=O MXIUWSYTQJLIKE-UHFFFAOYSA-N 0.000 description 1
- HAZGPPFPMLSDFM-UHFFFAOYSA-N 2-[4-(pyrrolidin-3-ylidenemethyl)phenyl]-4,5-dihydro-1,3-oxazole Chemical compound C1NCCC1=CC1=CC=C(C=2OCCN=2)C=C1 HAZGPPFPMLSDFM-UHFFFAOYSA-N 0.000 description 1
- IWSZXYRQTKCIHA-UHFFFAOYSA-N 2-[4-[[1-(4-chlorophenyl)sulfonylpiperidin-4-yl]methyl]phenyl]-4,5-dihydro-1,3-oxazole Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1CCC(CC=2C=CC(=CC=2)C=2OCCN=2)CC1 IWSZXYRQTKCIHA-UHFFFAOYSA-N 0.000 description 1
- KJJPLEZQSCZCKE-UHFFFAOYSA-N 2-aminopropane-1,3-diol Chemical compound OCC(N)CO KJJPLEZQSCZCKE-UHFFFAOYSA-N 0.000 description 1
- ONIKNECPXCLUHT-UHFFFAOYSA-N 2-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1Cl ONIKNECPXCLUHT-UHFFFAOYSA-N 0.000 description 1
- QEJGMKHQXSZCOS-UHFFFAOYSA-N 2-naphthalen-2-ylacetyl chloride Chemical compound C1=CC=CC2=CC(CC(=O)Cl)=CC=C21 QEJGMKHQXSZCOS-UHFFFAOYSA-N 0.000 description 1
- KLEXDBGYSOIREE-UHFFFAOYSA-N 24xi-n-propylcholesterol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CCC)C(C)C)C1(C)CC2 KLEXDBGYSOIREE-UHFFFAOYSA-N 0.000 description 1
- VTXNOVCTHUBABW-UHFFFAOYSA-N 3,4-dichlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)C(Cl)=C1 VTXNOVCTHUBABW-UHFFFAOYSA-N 0.000 description 1
- RPQWXGVZELKOEU-UHFFFAOYSA-N 3,4-difluorobenzoyl chloride Chemical compound FC1=CC=C(C(Cl)=O)C=C1F RPQWXGVZELKOEU-UHFFFAOYSA-N 0.000 description 1
- WAKMMQSMEDJRRI-UHFFFAOYSA-N 3,5-bis(trifluoromethyl)benzoyl chloride Chemical compound FC(F)(F)C1=CC(C(Cl)=O)=CC(C(F)(F)F)=C1 WAKMMQSMEDJRRI-UHFFFAOYSA-N 0.000 description 1
- QEAKAWUPYLOWOZ-UHFFFAOYSA-N 3-(4-chlorophenyl)-1-[4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]prop-2-en-1-one Chemical compound C1=CC(Cl)=CC=C1C=CC(=O)N(CC1)CCC1=CC1=CC=C(C=2OCCN=2)C=C1 QEAKAWUPYLOWOZ-UHFFFAOYSA-N 0.000 description 1
- ZFOVCSTVYYYRSU-UHFFFAOYSA-N 3-(4-chlorophenyl)prop-2-enoyl chloride Chemical compound ClC(=O)C=CC1=CC=C(Cl)C=C1 ZFOVCSTVYYYRSU-UHFFFAOYSA-N 0.000 description 1
- CVKOOKPNCVYHNY-UHFFFAOYSA-N 3-(bromomethyl)benzonitrile Chemical compound BrCC1=CC=CC(C#N)=C1 CVKOOKPNCVYHNY-UHFFFAOYSA-N 0.000 description 1
- RUJYJCANMOTJMO-UHFFFAOYSA-N 3-(trifluoromethyl)benzoyl chloride Chemical compound FC(F)(F)C1=CC=CC(C(Cl)=O)=C1 RUJYJCANMOTJMO-UHFFFAOYSA-N 0.000 description 1
- YFBBGBTUXAEVKO-UHFFFAOYSA-N 3-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]pyrrolidin-2-one Chemical compound O=C1NCCC1=CC1=CC=C(C=2OCCN=2)C=C1 YFBBGBTUXAEVKO-UHFFFAOYSA-N 0.000 description 1
- MCSXGCZMEPXKIW-UHFFFAOYSA-N 3-hydroxy-4-[(4-methyl-2-nitrophenyl)diazenyl]-N-(3-nitrophenyl)naphthalene-2-carboxamide Chemical compound Cc1ccc(N=Nc2c(O)c(cc3ccccc23)C(=O)Nc2cccc(c2)[N+]([O-])=O)c(c1)[N+]([O-])=O MCSXGCZMEPXKIW-UHFFFAOYSA-N 0.000 description 1
- UMLFTCYAQPPZER-UHFFFAOYSA-N 4-(bromomethyl)benzonitrile Chemical compound BrCC1=CC=C(C#N)C=C1 UMLFTCYAQPPZER-UHFFFAOYSA-N 0.000 description 1
- XYSHFGZNSFLXIM-UHFFFAOYSA-N 4-(piperidin-3-ylidenemethyl)benzonitrile;hydrochloride Chemical compound Cl.C1=CC(C#N)=CC=C1C=C1CNCCC1 XYSHFGZNSFLXIM-UHFFFAOYSA-N 0.000 description 1
- OXZYBOLWRXENKT-UHFFFAOYSA-N 4-(trifluoromethyl)benzoyl chloride Chemical compound FC(F)(F)C1=CC=C(C(Cl)=O)C=C1 OXZYBOLWRXENKT-UHFFFAOYSA-N 0.000 description 1
- FKWHSEVXBBEGHY-UHFFFAOYSA-N 4-[(2-oxopyrrolidin-3-ylidene)methyl]benzonitrile Chemical compound O=C1NCCC1=CC1=CC=C(C#N)C=C1 FKWHSEVXBBEGHY-UHFFFAOYSA-N 0.000 description 1
- SYYBOGCJLLPBKD-UHFFFAOYSA-N 4-[4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methyl]piperidine-1-carbonyl]benzonitrile Chemical compound C(#N)C1=CC=C(C(=O)N2CCC(CC2)CC2=CC=C(C=C2)C=2OCCN=2)C=C1 SYYBOGCJLLPBKD-UHFFFAOYSA-N 0.000 description 1
- FUEOIPLPACLDON-UHFFFAOYSA-N 4-[[1-(4-chlorobenzoyl)piperidin-4-ylidene]methyl]-3-fluorobenzoic acid Chemical compound FC1=CC(C(=O)O)=CC=C1C=C1CCN(C(=O)C=2C=CC(Cl)=CC=2)CC1 FUEOIPLPACLDON-UHFFFAOYSA-N 0.000 description 1
- CMVYOZWCMWODBP-UHFFFAOYSA-N 4-[[1-(4-chlorophenyl)sulfonylpiperidin-4-ylidene]methyl]benzonitrile Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N(CC1)CCC1=CC1=CC=C(C#N)C=C1 CMVYOZWCMWODBP-UHFFFAOYSA-N 0.000 description 1
- DENKGPBHLYFNGK-UHFFFAOYSA-N 4-bromobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Br)C=C1 DENKGPBHLYFNGK-UHFFFAOYSA-N 0.000 description 1
- NECBSSKNQDXVKN-UHFFFAOYSA-N 4-chloro-3-methylbenzoyl chloride Chemical compound CC1=CC(C(Cl)=O)=CC=C1Cl NECBSSKNQDXVKN-UHFFFAOYSA-N 0.000 description 1
- ZLYBFBAHAQEEQQ-UHFFFAOYSA-N 4-chlorobenzenesulfonyl chloride Chemical compound ClC1=CC=C(S(Cl)(=O)=O)C=C1 ZLYBFBAHAQEEQQ-UHFFFAOYSA-N 0.000 description 1
- WZWIQYMTQZCSKI-UHFFFAOYSA-N 4-cyanobenzaldehyde Chemical compound O=CC1=CC=C(C#N)C=C1 WZWIQYMTQZCSKI-UHFFFAOYSA-N 0.000 description 1
- CQLBEAMZOMLJJY-UHFFFAOYSA-N 4-fluoronaphthalene-1-carbonyl chloride Chemical compound C1=CC=C2C(F)=CC=C(C(Cl)=O)C2=C1 CQLBEAMZOMLJJY-UHFFFAOYSA-N 0.000 description 1
- IPEIDGXNXFPGBG-UHFFFAOYSA-N 4-methylsulfonylbenzoyl chloride Chemical compound CS(=O)(=O)C1=CC=C(C(Cl)=O)C=C1 IPEIDGXNXFPGBG-UHFFFAOYSA-N 0.000 description 1
- SKDHHIUENRGTHK-UHFFFAOYSA-N 4-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=C(C(Cl)=O)C=C1 SKDHHIUENRGTHK-UHFFFAOYSA-N 0.000 description 1
- JPVUWCPKMYXOKW-UHFFFAOYSA-N 4-phenylbenzoyl chloride Chemical compound C1=CC(C(=O)Cl)=CC=C1C1=CC=CC=C1 JPVUWCPKMYXOKW-UHFFFAOYSA-N 0.000 description 1
- BMPDCQVRKDNUAP-UHFFFAOYSA-N 5-chlorothiophene-2-carbonyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)S1 BMPDCQVRKDNUAP-UHFFFAOYSA-N 0.000 description 1
- OQMZNAMGEHIHNN-UHFFFAOYSA-N 7-Dehydrostigmasterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CC(CC)C(C)C)CCC33)C)C3=CC=C21 OQMZNAMGEHIHNN-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- DJQOOSBJCLSSEY-UHFFFAOYSA-N Acipimox Chemical compound CC1=CN=C(C(O)=O)C=[N+]1[O-] DJQOOSBJCLSSEY-UHFFFAOYSA-N 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 241000228245 Aspergillus niger Species 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- 229920001268 Cholestyramine Polymers 0.000 description 1
- LPZCCMIISIBREI-MTFRKTCUSA-N Citrostadienol Natural products CC=C(CC[C@@H](C)[C@H]1CC[C@H]2C3=CC[C@H]4[C@H](C)[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C)C(C)C LPZCCMIISIBREI-MTFRKTCUSA-N 0.000 description 1
- OXVGKRNCNGPOKY-UHFFFAOYSA-N Cl.C(C)OP(OCC)(=O)CC1=CC=CC=C1 Chemical compound Cl.C(C)OP(OCC)(=O)CC1=CC=CC=C1 OXVGKRNCNGPOKY-UHFFFAOYSA-N 0.000 description 1
- 241001207508 Cladosporium sp. Species 0.000 description 1
- ACTIUHUUMQJHFO-UHFFFAOYSA-N Coenzym Q10 Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UHFFFAOYSA-N 0.000 description 1
- 229920002911 Colestipol Polymers 0.000 description 1
- ARVGMISWLZPBCH-UHFFFAOYSA-N Dehydro-beta-sitosterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)CCC(CC)C(C)C)CCC33)C)C3=CC=C21 ARVGMISWLZPBCH-UHFFFAOYSA-N 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- BDCFUHIWJODVNG-UHFFFAOYSA-N Desmosterol Natural products C1C=C2CC(O)C=CC2(C)C2C1C1CCC(C(C)CCC(CC)C(C)C)C1(C)CC2 BDCFUHIWJODVNG-UHFFFAOYSA-N 0.000 description 1
- 206010014476 Elevated cholesterol Diseases 0.000 description 1
- 241001125671 Eretmochelys imbricata Species 0.000 description 1
- DNVPQKQSNYMLRS-NXVQYWJNSA-N Ergosterol Natural products CC(C)[C@@H](C)C=C[C@H](C)[C@H]1CC[C@H]2C3=CC=C4C[C@@H](O)CC[C@]4(C)[C@@H]3CC[C@]12C DNVPQKQSNYMLRS-NXVQYWJNSA-N 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 108010022535 Farnesyl-Diphosphate Farnesyltransferase Proteins 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 description 1
- 241000250507 Gigaspora candida Species 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 101000839025 Homo sapiens Hydroxymethylglutaryl-CoA synthase, cytoplasmic Proteins 0.000 description 1
- 108010000775 Hydroxymethylglutaryl-CoA synthase Proteins 0.000 description 1
- 102100028888 Hydroxymethylglutaryl-CoA synthase, cytoplasmic Human genes 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 241000699673 Mesocricetus auratus Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- 125000003047 N-acetyl group Chemical group 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 241000228168 Penicillium sp. Species 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 229940123934 Reductase inhibitor Drugs 0.000 description 1
- 206010040914 Skin reaction Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 235000019764 Soybean Meal Nutrition 0.000 description 1
- 241001045770 Trichophyton mentagrophytes Species 0.000 description 1
- QYKIQEUNHZKYBP-UHFFFAOYSA-N Vinyl ether Chemical compound C=COC=C QYKIQEUNHZKYBP-UHFFFAOYSA-N 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- CQFUJYRZIACHNS-UHFFFAOYSA-N [3,5-bis(trifluoromethyl)phenyl]-[4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]methanone Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C(=O)N2CCC(CC2)=CC=2C=CC(=CC=2)C=2OCCN=2)=C1 CQFUJYRZIACHNS-UHFFFAOYSA-N 0.000 description 1
- NXKRPBASXOOEDP-UHFFFAOYSA-N [4-[[2-bromo-4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]-(4-chlorophenyl)methanone Chemical compound C1=CC(Cl)=CC=C1C(=O)N(CC1)CCC1=CC1=CC=C(C=2OCCN=2)C=C1Br NXKRPBASXOOEDP-UHFFFAOYSA-N 0.000 description 1
- KPGLZPVYEBXPGC-UHFFFAOYSA-N [4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methyl]piperidin-1-yl]-(4-methylphenyl)methanone Chemical compound C1=CC(C)=CC=C1C(=O)N1CCC(CC=2C=CC(=CC=2)C=2OCCN=2)CC1 KPGLZPVYEBXPGC-UHFFFAOYSA-N 0.000 description 1
- JRSLFDCOWGXVCC-UHFFFAOYSA-N [4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methyl]piperidin-1-yl]-(4-phenylphenyl)methanone Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1C(=O)N(CC1)CCC1CC(C=C1)=CC=C1C1=NCCO1 JRSLFDCOWGXVCC-UHFFFAOYSA-N 0.000 description 1
- OWHFSMAEVRLJQZ-UHFFFAOYSA-N [4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methyl]piperidin-1-yl]-naphthalen-1-ylmethanone Chemical compound C=1C=CC2=CC=CC=C2C=1C(=O)N(CC1)CCC1CC(C=C1)=CC=C1C1=NCCO1 OWHFSMAEVRLJQZ-UHFFFAOYSA-N 0.000 description 1
- KNTCWBHQXNCCOO-UHFFFAOYSA-N [4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methyl]piperidin-1-yl]-naphthalen-2-ylmethanone Chemical compound C=1C=C2C=CC=CC2=CC=1C(=O)N(CC1)CCC1CC(C=C1)=CC=C1C1=NCCO1 KNTCWBHQXNCCOO-UHFFFAOYSA-N 0.000 description 1
- ZPYIGRQPZFYYPT-UHFFFAOYSA-N [4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methyl]piperidin-1-yl]-phenylmethanone Chemical compound C=1C=CC=CC=1C(=O)N(CC1)CCC1CC(C=C1)=CC=C1C1=NCCO1 ZPYIGRQPZFYYPT-UHFFFAOYSA-N 0.000 description 1
- LHDMHTFSHBEGSZ-UHFFFAOYSA-N [4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methyl]piperidin-1-yl]-pyridin-4-ylmethanone Chemical compound C=1C=NC=CC=1C(=O)N(CC1)CCC1CC(C=C1)=CC=C1C1=NCCO1 LHDMHTFSHBEGSZ-UHFFFAOYSA-N 0.000 description 1
- PEVOXMAYCOSPBW-UHFFFAOYSA-N [4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]-(1,2,3,4-tetrahydronaphthalen-2-yl)methanone Chemical compound C1CC2=CC=CC=C2CC1C(=O)N(CC1)CCC1=CC(C=C1)=CC=C1C1=NCCO1 PEVOXMAYCOSPBW-UHFFFAOYSA-N 0.000 description 1
- ZMTRVSSWNKUESL-UHFFFAOYSA-N [4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]-(4-fluoronaphthalen-1-yl)methanone Chemical compound C12=CC=CC=C2C(F)=CC=C1C(=O)N(CC1)CCC1=CC(C=C1)=CC=C1C1=NCCO1 ZMTRVSSWNKUESL-UHFFFAOYSA-N 0.000 description 1
- LAPWBHKXJALOOA-UHFFFAOYSA-N [4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]-(4-methylphenyl)methanone Chemical compound C1=CC(C)=CC=C1C(=O)N(CC1)CCC1=CC1=CC=C(C=2OCCN=2)C=C1 LAPWBHKXJALOOA-UHFFFAOYSA-N 0.000 description 1
- SCHVDNCUQCJZIO-UHFFFAOYSA-N [4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]-(4-methylsulfonylphenyl)methanone Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C(=O)N(CC1)CCC1=CC1=CC=C(C=2OCCN=2)C=C1 SCHVDNCUQCJZIO-UHFFFAOYSA-N 0.000 description 1
- ACSLQLLUYLBGGK-UHFFFAOYSA-N [4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]-[2-(trifluoromethyl)phenyl]methanone Chemical compound FC(F)(F)C1=CC=CC=C1C(=O)N(CC1)CCC1=CC1=CC=C(C=2OCCN=2)C=C1 ACSLQLLUYLBGGK-UHFFFAOYSA-N 0.000 description 1
- JWCHPIWKRPJAJE-UHFFFAOYSA-N [4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]-[3-(trifluoromethyl)phenyl]methanone Chemical compound FC(F)(F)C1=CC=CC(C(=O)N2CCC(CC2)=CC=2C=CC(=CC=2)C=2OCCN=2)=C1 JWCHPIWKRPJAJE-UHFFFAOYSA-N 0.000 description 1
- UXSWKSZXYYGMBX-UHFFFAOYSA-N [4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]-naphthalen-2-ylmethanone Chemical compound C=1C=C2C=CC=CC2=CC=1C(=O)N(CC1)CCC1=CC(C=C1)=CC=C1C1=NCCO1 UXSWKSZXYYGMBX-UHFFFAOYSA-N 0.000 description 1
- FLMCIOCLAVAMOL-HHHXNRCGSA-N [4-[[4-[(4r)-4-benzyl-4,5-dihydro-1,3-oxazol-2-yl]phenyl]methylidene]piperidin-1-yl]-(4-chlorophenyl)methanone Chemical compound C1=CC(Cl)=CC=C1C(=O)N(CC1)CCC1=CC1=CC=C(C=2OC[C@@H](CC=3C=CC=CC=3)N=2)C=C1 FLMCIOCLAVAMOL-HHHXNRCGSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229960003526 acipimox Drugs 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 231100000360 alopecia Toxicity 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- CBTVGIZVANVGBH-UHFFFAOYSA-N aminomethyl propanol Chemical compound CC(C)(N)CO CBTVGIZVANVGBH-UHFFFAOYSA-N 0.000 description 1
- MXMOTZIXVICDSD-UHFFFAOYSA-N anisoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C=C1 MXMOTZIXVICDSD-UHFFFAOYSA-N 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000001857 anti-mycotic effect Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 239000003524 antilipemic agent Substances 0.000 description 1
- GMHPWGYTSXHHPI-UHFFFAOYSA-N azepan-4-one Chemical compound O=C1CCCNCC1 GMHPWGYTSXHHPI-UHFFFAOYSA-N 0.000 description 1
- 210000000270 basal cell Anatomy 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- MJVXAPPOFPTTCA-UHFFFAOYSA-N beta-Sistosterol Natural products CCC(CCC(C)C1CCC2C3CC=C4C(C)C(O)CCC4(C)C3CCC12C)C(C)C MJVXAPPOFPTTCA-UHFFFAOYSA-N 0.000 description 1
- LGJMUZUPVCAVPU-UHFFFAOYSA-N beta-Sitostanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CC)C(C)C)C1(C)CC2 LGJMUZUPVCAVPU-UHFFFAOYSA-N 0.000 description 1
- NJKOMDUNNDKEAI-UHFFFAOYSA-N beta-sitosterol Natural products CCC(CCC(C)C1CCC2(C)C3CC=C4CC(O)CCC4C3CCC12C)C(C)C NJKOMDUNNDKEAI-UHFFFAOYSA-N 0.000 description 1
- 229960000516 bezafibrate Drugs 0.000 description 1
- IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 description 1
- 229920000080 bile acid sequestrant Polymers 0.000 description 1
- 230000008687 biosynthesis inhibition Effects 0.000 description 1
- 125000006267 biphenyl group Chemical group 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- 229940095731 candida albicans Drugs 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 210000003850 cellular structure Anatomy 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- JESCPVSKEGXYSC-UHFFFAOYSA-N chlorobenzene;sulfurochloridic acid Chemical compound OS(Cl)(=O)=O.ClC1=CC=CC=C1 JESCPVSKEGXYSC-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 208000024980 claudication Diseases 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229960001214 clofibrate Drugs 0.000 description 1
- KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 description 1
- 235000017471 coenzyme Q10 Nutrition 0.000 description 1
- GMRWGQCZJGVHKL-UHFFFAOYSA-N colestipol Chemical compound ClCC1CO1.NCCNCCNCCNCCN GMRWGQCZJGVHKL-UHFFFAOYSA-N 0.000 description 1
- 229960002604 colestipol Drugs 0.000 description 1
- 230000001332 colony forming effect Effects 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 238000007887 coronary angioplasty Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- RVOJTCZRIKWHDX-UHFFFAOYSA-N cyclohexanecarbonyl chloride Chemical compound ClC(=O)C1CCCCC1 RVOJTCZRIKWHDX-UHFFFAOYSA-N 0.000 description 1
- ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 1
- HCBDPGVEZOZDJN-UHFFFAOYSA-N cyclopropyl-[4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methylidene]piperidin-1-yl]methanone Chemical compound C1CC(=CC=2C=CC(=CC=2)C=2OCCN=2)CCN1C(=O)C1CC1 HCBDPGVEZOZDJN-UHFFFAOYSA-N 0.000 description 1
- 125000004855 decalinyl group Chemical group C1(CCCC2CCCCC12)* 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- AVSXSVCZWQODGV-DPAQBDIFSA-N desmosterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@@H](CCC=C(C)C)C)[C@@]1(C)CC2 AVSXSVCZWQODGV-DPAQBDIFSA-N 0.000 description 1
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 210000001339 epidermal cell Anatomy 0.000 description 1
- 210000005175 epidermal keratinocyte Anatomy 0.000 description 1
- DNVPQKQSNYMLRS-SOWFXMKYSA-N ergosterol Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H](CC[C@]3([C@H]([C@H](C)/C=C/[C@@H](C)C(C)C)CC[C@H]33)C)C3=CC=C21 DNVPQKQSNYMLRS-SOWFXMKYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 244000053095 fungal pathogen Species 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 229960003627 gemfibrozil Drugs 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 210000000224 granular leucocyte Anatomy 0.000 description 1
- 230000009548 growth disturbance Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- YWGHUJQYGPDNKT-UHFFFAOYSA-N hexanoyl chloride Chemical compound CCCCCC(Cl)=O YWGHUJQYGPDNKT-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 230000001329 hyperkeratotic effect Effects 0.000 description 1
- 208000020346 hyperlipoproteinemia Diseases 0.000 description 1
- 208000006575 hypertriglyceridemia Diseases 0.000 description 1
- 206010021198 ichthyosis Diseases 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical class C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 208000021156 intermittent vascular claudication Diseases 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- CFJQBNFFHMBNKQ-UHFFFAOYSA-N methyl 3-bromo-4-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=C(CBr)C(Br)=C1 CFJQBNFFHMBNKQ-UHFFFAOYSA-N 0.000 description 1
- MASRAGFWFYHMFI-UHFFFAOYSA-N methyl 3-bromo-4-methylbenzoate Chemical compound COC(=O)C1=CC=C(C)C(Br)=C1 MASRAGFWFYHMFI-UHFFFAOYSA-N 0.000 description 1
- RAFFOVQBMRBRCS-UHFFFAOYSA-N methyl 3-fluoro-4-methylbenzoate Chemical compound COC(=O)C1=CC=C(C)C(F)=C1 RAFFOVQBMRBRCS-UHFFFAOYSA-N 0.000 description 1
- LLEXCSBUSVRBCA-UHFFFAOYSA-N methyl 3-methoxy-4-methylbenzoate Chemical compound COC(=O)C1=CC=C(C)C(OC)=C1 LLEXCSBUSVRBCA-UHFFFAOYSA-N 0.000 description 1
- MABHQNNTZZMWCU-UHFFFAOYSA-N methyl 4-(bromomethyl)-2-methylbenzoate Chemical compound COC(=O)C1=CC=C(CBr)C=C1C MABHQNNTZZMWCU-UHFFFAOYSA-N 0.000 description 1
- OJBQAHZJVDWSFD-UHFFFAOYSA-N methyl 4-(bromomethyl)-3-fluorobenzoate Chemical compound COC(=O)C1=CC=C(CBr)C(F)=C1 OJBQAHZJVDWSFD-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- WTBAHSZERDXKKZ-UHFFFAOYSA-N octadecanoyl chloride Chemical compound CCCCCCCCCCCCCCCCCC(Cl)=O WTBAHSZERDXKKZ-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000002918 oxazolines Chemical class 0.000 description 1
- 150000002924 oxiranes Chemical class 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- MLBYLEUJXUBIJJ-UHFFFAOYSA-N pent-4-ynoic acid Chemical compound OC(=O)CCC#C MLBYLEUJXUBIJJ-UHFFFAOYSA-N 0.000 description 1
- MYHOHFDYWMPGJY-UHFFFAOYSA-N pentafluorobenzoyl chloride Chemical compound FC1=C(F)C(F)=C(C(Cl)=O)C(F)=C1F MYHOHFDYWMPGJY-UHFFFAOYSA-N 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- AQSJGOWTSHOLKH-UHFFFAOYSA-N phosphite(3-) Chemical class [O-]P([O-])[O-] AQSJGOWTSHOLKH-UHFFFAOYSA-N 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- FYPMFJGVHOHGLL-UHFFFAOYSA-N probucol Chemical compound C=1C(C(C)(C)C)=C(O)C(C(C)(C)C)=CC=1SC(C)(C)SC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 FYPMFJGVHOHGLL-UHFFFAOYSA-N 0.000 description 1
- 229960003912 probucol Drugs 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000001185 psoriatic effect Effects 0.000 description 1
- RVQZKNOMKUSGCI-UHFFFAOYSA-N pyridine-4-carbonyl chloride Chemical compound ClC(=O)C1=CC=NC=C1 RVQZKNOMKUSGCI-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- NPCOQXAVBJJZBQ-UHFFFAOYSA-N reduced coenzyme Q9 Natural products COC1=C(O)C(C)=C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)C(O)=C1OC NPCOQXAVBJJZBQ-UHFFFAOYSA-N 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 238000006884 silylation reaction Methods 0.000 description 1
- KZJWDPNRJALLNS-VJSFXXLFSA-N sitosterol 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)CC[C@@H](CC)C(C)C)[C@@]1(C)CC2 KZJWDPNRJALLNS-VJSFXXLFSA-N 0.000 description 1
- 229950005143 sitosterol Drugs 0.000 description 1
- 235000015500 sitosterol Nutrition 0.000 description 1
- NLQLSVXGSXCXFE-UHFFFAOYSA-N sitosterol Natural products CC=C(/CCC(C)C1CC2C3=CCC4C(C)C(O)CCC4(C)C3CCC2(C)C1)C(C)C NLQLSVXGSXCXFE-UHFFFAOYSA-N 0.000 description 1
- 210000004927 skin cell Anatomy 0.000 description 1
- 231100000430 skin reaction Toxicity 0.000 description 1
- 230000035483 skin reaction Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 239000004455 soybean meal Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000004059 squalene synthase inhibitor Substances 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
- HPNGBFRWLFYGTL-UHFFFAOYSA-N tert-butyl 4-[[4-(4,5-dihydro-1,3-oxazol-2-yl)phenyl]methyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CC1=CC=C(C=2OCCN=2)C=C1 HPNGBFRWLFYGTL-UHFFFAOYSA-N 0.000 description 1
- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- PSCXFXNEYIHJST-UHFFFAOYSA-N trans-styrilacetic acid Natural products OC(=O)CC=CC1=CC=CC=C1 PSCXFXNEYIHJST-UHFFFAOYSA-N 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 239000005051 trimethylchlorosilane Substances 0.000 description 1
- SYHDSBBKRLVLFF-UHFFFAOYSA-N triparanol Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(O)(C=1C=CC(C)=CC=1)CC1=CC=C(Cl)C=C1 SYHDSBBKRLVLFF-UHFFFAOYSA-N 0.000 description 1
- 229950005498 triparanol Drugs 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 229940035936 ubiquinone Drugs 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- DFKDOZMCHOGOBR-NCSQYGPNSA-N zaragozic acid A Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CC[C@]12[C@H](O)[C@H]([C@](O2)(C(O)=O)[C@@](O)([C@H](O1)C(O)=O)C(O)=O)OC(=O)/C=C/[C@@H](C)C[C@@H](C)CC)C1=CC=CC=C1 DFKDOZMCHOGOBR-NCSQYGPNSA-N 0.000 description 1
- DFKDOZMCHOGOBR-UHFFFAOYSA-N zaragozic acid A Natural products O1C(C(O)(C(O2)C(O)=O)C(O)=O)(C(O)=O)C(OC(=O)C=CC(C)CC(C)CC)C(O)C21CCC(=C)C(OC(C)=O)C(C)CC1=CC=CC=C1 DFKDOZMCHOGOBR-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
- C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Diabetes (AREA)
- Communicable Diseases (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Catalysts (AREA)
- Ink Jet (AREA)
- Developing Agents For Electrophotography (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE4235590A DE4235590A1 (de) | 1992-10-22 | 1992-10-22 | Aryliden-l-azacycloalkane, deren Salze, diese Verbindungen enthaltende Arzneimittel und deren Verwendung sowie Verfahren zu ihrer Herstellung |
DE4303840A DE4303840A1 (de) | 1992-10-22 | 1993-02-10 | Aryliden-1-azacycloalkane und Arylalkyl-1-azacycloalkane, deren Salze, diese Verbindungen enthaltende Arzneimittel und deren Verwendung sowie Verfahren zu ihrer Herstellung |
Publications (3)
Publication Number | Publication Date |
---|---|
NO933790D0 NO933790D0 (no) | 1993-10-21 |
NO933790L NO933790L (no) | 1994-04-25 |
NO300843B1 true NO300843B1 (no) | 1997-08-04 |
Family
ID=25919689
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO933790A NO300843B1 (no) | 1992-10-22 | 1993-10-21 | Aryliden-l-azacykloalkaner og arylalkyl-l-azacykloalkaner, salter av disse, og legemidler som inneholder disse forbindelser |
Country Status (21)
Country | Link |
---|---|
EP (1) | EP0596326B1 (sk) |
JP (1) | JP3396517B2 (sk) |
KR (1) | KR100306520B1 (sk) |
CN (1) | CN1040873C (sk) |
AT (1) | ATE126797T1 (sk) |
AU (1) | AU665648B2 (sk) |
CA (1) | CA2108817C (sk) |
CZ (1) | CZ286025B6 (sk) |
DE (2) | DE4303840A1 (sk) |
DK (1) | DK0596326T3 (sk) |
ES (1) | ES2078787T3 (sk) |
FI (1) | FI934665A (sk) |
GR (1) | GR3017692T3 (sk) |
HK (1) | HK1000285A1 (sk) |
HU (1) | HU221630B1 (sk) |
IL (1) | IL107342A (sk) |
NO (1) | NO300843B1 (sk) |
NZ (1) | NZ250018A (sk) |
PL (1) | PL173775B1 (sk) |
RU (1) | RU2126400C1 (sk) |
SK (1) | SK281222B6 (sk) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4234295A1 (de) * | 1992-10-12 | 1994-04-14 | Thomae Gmbh Dr K | Carbonsäurederivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
IL110943A (en) * | 1994-09-13 | 1997-02-18 | Univ Ramot | Compositions comprising an inhibitor of cholesterol synthesis for the treatment of skin disorders |
DE19754795A1 (de) * | 1997-12-10 | 1999-06-17 | Boehringer Ingelheim Pharma | Neue Urethane, ihre Thio- und Dithioanaloga, deren Salze, diese Verbindungen enthaltende Arzneimittel und deren Verwendung sowie Verfahren zu ihrer Herstellung |
US6228868B1 (en) | 1998-07-27 | 2001-05-08 | Abbott Laboratories | Oxazoline antiproliferative agents |
WO2000006556A1 (en) * | 1998-07-27 | 2000-02-10 | Abbott Laboratories | Substituted oxazolines as antiproliferative agents |
US7667053B2 (en) | 2002-04-12 | 2010-02-23 | Merck & Co., Inc. | Bicyclic amides |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4863932A (en) * | 1988-03-11 | 1989-09-05 | Somatogenetics International, Inc. | Squalene oxide cyclase inhibitors and therapeutic use thereof |
CA2025490C (en) * | 1989-09-22 | 2003-09-16 | James R. Mccarthy | Novel substituted alkyl piperidines and their use as inhibitors of cholesterol synthesis |
CA2047375C (en) * | 1990-07-25 | 2003-04-15 | Charlotte L. Barney | Piperidyl ethers and thioethers as inhibitors of cholesterol biosynthesis |
US5084461A (en) * | 1991-03-27 | 1992-01-28 | Merrell Dow Pharmaceuticals Inc. | Azadecalin amides and thioamides as inhibitors of cholesterol biosynthesis |
-
1993
- 1993-02-10 DE DE4303840A patent/DE4303840A1/de not_active Ceased
- 1993-10-05 SK SK1073-93A patent/SK281222B6/sk unknown
- 1993-10-20 ES ES93116959T patent/ES2078787T3/es not_active Expired - Lifetime
- 1993-10-20 DE DE59300507T patent/DE59300507D1/de not_active Expired - Lifetime
- 1993-10-20 DK DK93116959.3T patent/DK0596326T3/da active
- 1993-10-20 AT AT93116959T patent/ATE126797T1/de active
- 1993-10-20 CA CA002108817A patent/CA2108817C/en not_active Expired - Fee Related
- 1993-10-20 EP EP93116959A patent/EP0596326B1/de not_active Expired - Lifetime
- 1993-10-21 NZ NZ250018A patent/NZ250018A/en unknown
- 1993-10-21 KR KR1019930021923A patent/KR100306520B1/ko not_active IP Right Cessation
- 1993-10-21 AU AU49135/93A patent/AU665648B2/en not_active Ceased
- 1993-10-21 NO NO933790A patent/NO300843B1/no not_active IP Right Cessation
- 1993-10-21 HU HU9302986A patent/HU221630B1/hu not_active IP Right Cessation
- 1993-10-21 IL IL107342A patent/IL107342A/xx not_active IP Right Cessation
- 1993-10-21 RU RU93048154/04A patent/RU2126400C1/ru not_active IP Right Cessation
- 1993-10-21 JP JP26321493A patent/JP3396517B2/ja not_active Expired - Fee Related
- 1993-10-22 CN CN93119156A patent/CN1040873C/zh not_active Expired - Fee Related
- 1993-10-22 FI FI934665A patent/FI934665A/fi unknown
- 1993-10-22 PL PL93300834A patent/PL173775B1/pl unknown
- 1993-10-22 CZ CZ932236A patent/CZ286025B6/cs not_active IP Right Cessation
-
1995
- 1995-10-11 GR GR950402801T patent/GR3017692T3/el unknown
-
1997
- 1997-09-26 HK HK97101852A patent/HK1000285A1/xx not_active IP Right Cessation
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
DE602004006431T2 (de) | Derivate von n-äheteroaryl(piperidin-2-yl)methylübenzamid, verfahren zu deren herstellung und deren anwendung in therapeutika | |
AU617139B2 (en) | New phenylethanolamines | |
EP1690858B1 (en) | Monohydrochloride salt of 1-[3-[3-(4-chlorophenyl)propoxy]propyl]-piperidine | |
CN103068800B (zh) | 作为趋化因子受体活性调节剂的哌啶基化合物 | |
CN100516040C (zh) | 具有2,6-二取代苯乙烯基的含氮杂环衍生物 | |
US4935419A (en) | Novel 1-piperazinecarboxamide derivatives | |
NO300843B1 (no) | Aryliden-l-azacykloalkaner og arylalkyl-l-azacykloalkaner, salter av disse, og legemidler som inneholder disse forbindelser | |
US5466687A (en) | Arylidene-1-azacycloalkanes and arylalkyl-1-azacyclo-alkanes, their salts, medicaments containing these compounds and their use, and processes for their preparation | |
US5726205A (en) | O-acyl-4-phenyl-cyclohexanols, their salts, medicaments containing such compounds and their use, as well as a method of preparing them | |
EP1060162B1 (de) | Von azacycloalkanen abgeleitete urethane, ihre thio- und dithioanaloga, deren herstellung und deren verwendung als 2,3-epoxisqualen-lanosterol-cyclase inhibitoren | |
JP4001317B2 (ja) | 新規ウレタン、それらのチオ類似体及びジチオ類似体、これらの塩、これらの化合物を含む医薬組成物並びにそれらの使用及びそれらの調製方法 | |
DE4407138A1 (de) | Aryliden-1-azacycloalkane und Arylalkyl-1-azacycloalkane, deren Salze, diese Verbindungen enthaltende Arzneimittel und deren Verwendung sowie Verfahren zu ihrer Herstellung | |
DE4407139A1 (de) | Aryl-1-azacycloalkane und deren Salze, diese Verbindungen enthaltende Arzneimittel und deren Verwendung sowie Verfahren zu ihrer Herstellung | |
DE4235590A1 (de) | Aryliden-l-azacycloalkane, deren Salze, diese Verbindungen enthaltende Arzneimittel und deren Verwendung sowie Verfahren zu ihrer Herstellung | |
DE4438083A1 (de) | Basisch substituierte Acylpyrrolidine und Acylpiperidine, deren Salze, diese Verbindungen enthaltende Arzneimittel und deren Verwendung sowie Verfahren zu ihrer Herstellung | |
DE4412691A1 (de) | Heteroaryliden-1-azacycloalkane und Heteroarylalkyl-1-azacycloalkane, deren Salze, diese Verbindungen enthaltende Arzneimittel und deren Verwendung sowie Verfahren zu ihrer Herstellung | |
DE4407135A1 (de) | Arylcycloalkylamine, deren Salze, diese Verbindungen enthaltende Arzneimittel und deren Verwendung sowie Verfahren zu ihrer Herstellung | |
DE19806713A1 (de) | Neue Urethane, ihre Thio- und Dithioanaloga, deren Salze, diese Verbindungen enthaltende Arzneimittel und deren Verwendung sowie Verfahren zu ihrer Herstellung | |
CZ20002149A3 (cs) | Od azacykloalkanů odvozené urethany a jejich thio- a dithioanaloga | |
NZ227196A (en) | Phenylethanolamine derivatives and their pharmaceutical and veterinary compositions | |
DE19806714A1 (de) | Neue Thio- und Dithiocarbonate, deren Salze, diese Verbindungen enthaltende Arzneimittel und deren Verwendung sowie Verfahren zu ihrer Herstellung | |
CA2188784A1 (en) | O-acyl-4-phenyl-cycloalkanols, their salts, medicaments containing such compounds, and their use, as well as a method of preparing them | |
DE19806717A1 (de) | Neue Urethane, ihre Thio- und Dithioanaloga, deren Salze, diese Verbindungen enthaltende Arzneimittel und deren Verwendung sowie Verfahren zu ihrer Herstellung | |
WO1996031483A1 (en) | Novel heterocyclic compounds | |
DE19806715A1 (de) | Neue Urethane, ihre Thio- und Dithioanaloga, deren Salze, diese Verbindungen enthaltende Arzneimittel und deren Verwendung sowie Verfahren zu ihrer Herstellung |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MM1K | Lapsed by not paying the annual fees |