NO300632B1 - Amid-tetrazol ACAT-inhibitorer - Google Patents
Amid-tetrazol ACAT-inhibitorer Download PDFInfo
- Publication number
- NO300632B1 NO300632B1 NO940596A NO940596A NO300632B1 NO 300632 B1 NO300632 B1 NO 300632B1 NO 940596 A NO940596 A NO 940596A NO 940596 A NO940596 A NO 940596A NO 300632 B1 NO300632 B1 NO 300632B1
- Authority
- NO
- Norway
- Prior art keywords
- tetrazole
- carbon atoms
- phenyl
- dodecyl
- acetamide
- Prior art date
Links
- 239000003112 inhibitor Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 125
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 100
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 53
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 39
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 29
- 239000001257 hydrogen Substances 0.000 claims abstract description 29
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 16
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 14
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 7
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 6
- 125000001183 hydrocarbyl group Chemical group 0.000 claims abstract 7
- -1 hydroxy, phenyl Chemical group 0.000 claims description 76
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 28
- 239000000460 chlorine Substances 0.000 claims description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 14
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 13
- 229910052801 chlorine Inorganic materials 0.000 claims description 13
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 12
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 12
- 229910052794 bromium Inorganic materials 0.000 claims description 12
- SYBRGUHLESAOBM-UHFFFAOYSA-N 2-(2-dodecyltetrazol-5-yl)-2-phenyl-n-(2,4,6-trimethoxyphenyl)acetamide Chemical group CCCCCCCCCCCCN1N=NC(C(C(=O)NC=2C(=CC(OC)=CC=2OC)OC)C=2C=CC=CC=2)=N1 SYBRGUHLESAOBM-UHFFFAOYSA-N 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 150000001204 N-oxides Chemical class 0.000 claims description 10
- 125000000623 heterocyclic group Chemical group 0.000 claims description 10
- 229920006395 saturated elastomer Polymers 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 8
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 8
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 8
- 125000004414 alkyl thio group Chemical group 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 7
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 7
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 7
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- AQYSYJUIMQTRMV-UHFFFAOYSA-N hypofluorous acid Chemical compound FO AQYSYJUIMQTRMV-UHFFFAOYSA-N 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 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 5
- 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 5
- 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 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 125000002950 monocyclic group Chemical group 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 4
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 4
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 3
- 150000001721 carbon Chemical group 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 3
- GQPLMRYTRLFLPF-UHFFFAOYSA-N nitrous oxide Inorganic materials [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 claims description 3
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 3
- 125000004944 pyrazin-3-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- BXRGNWVAOFITIB-UHFFFAOYSA-N 1-(2-dodecyltetrazol-5-yl)-n-(2,4,6-trimethoxyphenyl)cyclopentane-1-carboxamide Chemical compound CCCCCCCCCCCCN1N=NC(C2(CCCC2)C(=O)NC=2C(=CC(OC)=CC=2OC)OC)=N1 BXRGNWVAOFITIB-UHFFFAOYSA-N 0.000 claims description 2
- 125000005808 2,4,6-trimethoxyphenyl group Chemical group [H][#6]-1=[#6](-[#8]C([H])([H])[H])-[#6](-*)=[#6](-[#8]C([H])([H])[H])-[#6]([H])=[#6]-1-[#8]C([H])([H])[H] 0.000 claims description 2
- XKWHBQPPZWJOQR-UHFFFAOYSA-N 3-(2-dodecyltetrazol-5-yl)-n-(2,4,6-trimethoxyphenyl)propanamide Chemical group CCCCCCCCCCCCN1N=NC(CCC(=O)NC=2C(=CC(OC)=CC=2OC)OC)=N1 XKWHBQPPZWJOQR-UHFFFAOYSA-N 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 2
- 125000001118 alkylidene group Chemical group 0.000 claims description 2
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000002619 bicyclic group Chemical group 0.000 claims description 2
- 125000005366 cycloalkylthio group Chemical group 0.000 claims description 2
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 2
- 125000005368 heteroarylthio group Chemical group 0.000 claims description 2
- NYHFLUOKPJTGGE-UHFFFAOYSA-N n-(2,4-difluorophenyl)-3-(2-dodecyltetrazol-5-yl)propanamide Chemical compound CCCCCCCCCCCCN1N=NC(CCC(=O)NC=2C(=CC(F)=CC=2)F)=N1 NYHFLUOKPJTGGE-UHFFFAOYSA-N 0.000 claims description 2
- AGUWSRGWPGKLPA-UHFFFAOYSA-N n-[2,6-di(propan-2-yl)phenyl]-2-(2-dodecyltetrazol-5-yl)acetamide Chemical group CCCCCCCCCCCCN1N=NC(CC(=O)NC=2C(=CC=CC=2C(C)C)C(C)C)=N1 AGUWSRGWPGKLPA-UHFFFAOYSA-N 0.000 claims description 2
- QQCBPDUYZUKFPM-UHFFFAOYSA-N n-[2,6-di(propan-2-yl)phenyl]-3-(2-dodecyltetrazol-5-yl)propanamide Chemical compound CCCCCCCCCCCCN1N=NC(CCC(=O)NC=2C(=CC=CC=2C(C)C)C(C)C)=N1 QQCBPDUYZUKFPM-UHFFFAOYSA-N 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 125000004660 phenylalkylthio group Chemical group 0.000 claims description 2
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 229930195734 saturated hydrocarbon Natural products 0.000 claims description 2
- WMNOPPTUXPOBEN-UHFFFAOYSA-N 2-(1-dodecyltetrazol-5-yl)-n-(1,3,5-trimethylpyrazol-4-yl)acetamide Chemical compound CCCCCCCCCCCCN1N=NN=C1CC(=O)NC1=C(C)N(C)N=C1C WMNOPPTUXPOBEN-UHFFFAOYSA-N 0.000 claims 1
- SOJBZHFLSNYOKA-UHFFFAOYSA-N 2-(2-dodecyltetrazol-5-yl)-2-(4-fluorophenyl)-n-(2,4,6-trimethoxyphenyl)acetamide Chemical compound CCCCCCCCCCCCN1N=NC(C(C(=O)NC=2C(=CC(OC)=CC=2OC)OC)C=2C=CC(F)=CC=2)=N1 SOJBZHFLSNYOKA-UHFFFAOYSA-N 0.000 claims 1
- PLKISPZAORQQIW-UHFFFAOYSA-N 2-(2-dodecyltetrazol-5-yl)-2-(4-phenylphenyl)-n-(2,4,6-trimethoxyphenyl)acetamide Chemical compound CCCCCCCCCCCCN1N=NC(C(C(=O)NC=2C(=CC(OC)=CC=2OC)OC)C=2C=CC(=CC=2)C=2C=CC=CC=2)=N1 PLKISPZAORQQIW-UHFFFAOYSA-N 0.000 claims 1
- OASYSXJUCAQCJU-UHFFFAOYSA-N 2-(2-dodecyltetrazol-5-yl)-2-fluoro-2-phenyl-n-(2,4,6-trimethoxyphenyl)acetamide Chemical compound CCCCCCCCCCCCN1N=NC(C(F)(C(=O)NC=2C(=CC(OC)=CC=2OC)OC)C=2C=CC=CC=2)=N1 OASYSXJUCAQCJU-UHFFFAOYSA-N 0.000 claims 1
- GWQGDBQLQSFKGI-UHFFFAOYSA-N 2-(2-dodecyltetrazol-5-yl)-2-naphthalen-2-yl-n-(2,4,6-trimethoxyphenyl)acetamide Chemical compound CCCCCCCCCCCCN1N=NC(C(C(=O)NC=2C(=CC(OC)=CC=2OC)OC)C=2C=C3C=CC=CC3=CC=2)=N1 GWQGDBQLQSFKGI-UHFFFAOYSA-N 0.000 claims 1
- HKDWSIDOTZLSEN-UHFFFAOYSA-N 2-(2-dodecyltetrazol-5-yl)-2-phenyl-n-(1,3,5-trimethylpyrazol-4-yl)acetamide Chemical compound CCCCCCCCCCCCN1N=NC(C(C(=O)NC2=C(N(C)N=C2C)C)C=2C=CC=CC=2)=N1 HKDWSIDOTZLSEN-UHFFFAOYSA-N 0.000 claims 1
- MEMMTAWPJWXADR-UHFFFAOYSA-N 2-(2-dodecyltetrazol-5-yl)-2-phenyl-n-pyridin-2-ylacetamide Chemical compound CCCCCCCCCCCCN1N=NC(C(C(=O)NC=2N=CC=CC=2)C=2C=CC=CC=2)=N1 MEMMTAWPJWXADR-UHFFFAOYSA-N 0.000 claims 1
- JUERWJJIWDLXSH-UHFFFAOYSA-N 2-(2-dodecyltetrazol-5-yl)-2-pyridin-2-yl-n-(2,4,6-trimethoxyphenyl)acetamide Chemical group CCCCCCCCCCCCN1N=NC(C(C(=O)NC=2C(=CC(OC)=CC=2OC)OC)C=2N=CC=CC=2)=N1 JUERWJJIWDLXSH-UHFFFAOYSA-N 0.000 claims 1
- DRXAKLMWOXJAQV-UHFFFAOYSA-N 2-(2-dodecyltetrazol-5-yl)-3-phenyl-n-(2,4,6-trimethoxyphenyl)propanamide Chemical compound CCCCCCCCCCCCN1N=NC(C(CC=2C=CC=CC=2)C(=O)NC=2C(=CC(OC)=CC=2OC)OC)=N1 DRXAKLMWOXJAQV-UHFFFAOYSA-N 0.000 claims 1
- VXZYGNLMYHYANI-UHFFFAOYSA-N 2-(2-dodecyltetrazol-5-yl)-n-(1,3,5-trimethylpyrazol-4-yl)acetamide Chemical group CCCCCCCCCCCCN1N=NC(CC(=O)NC2=C(N(C)N=C2C)C)=N1 VXZYGNLMYHYANI-UHFFFAOYSA-N 0.000 claims 1
- WWPYXOIAKWVXQD-UHFFFAOYSA-N 2-(2-dodecyltetrazol-5-yl)-n-(2,4,6-trimethoxyphenyl)acetamide Chemical compound CCCCCCCCCCCCN1N=NC(CC(=O)NC=2C(=CC(OC)=CC=2OC)OC)=N1 WWPYXOIAKWVXQD-UHFFFAOYSA-N 0.000 claims 1
- OTXIVEYOPBSPJI-UHFFFAOYSA-N 2-(2-dodecyltetrazol-5-yl)-n-(2,4,6-trimethoxyphenyl)propanamide Chemical compound CCCCCCCCCCCCN1N=NC(C(C)C(=O)NC=2C(=CC(OC)=CC=2OC)OC)=N1 OTXIVEYOPBSPJI-UHFFFAOYSA-N 0.000 claims 1
- PZUKTMTYJWVKNR-UHFFFAOYSA-N 2-(2-dodecyltetrazol-5-yl)-n-(3-methylpyridin-2-yl)-2-phenylacetamide Chemical compound CCCCCCCCCCCCN1N=NC(C(C(=O)NC=2C(=CC=CN=2)C)C=2C=CC=CC=2)=N1 PZUKTMTYJWVKNR-UHFFFAOYSA-N 0.000 claims 1
- DMPDYTLZZYMXPQ-UHFFFAOYSA-N 2-(2-dodecyltetrazol-5-yl)-n-(3-methylpyridin-2-yl)acetamide Chemical group CCCCCCCCCCCCN1N=NC(CC(=O)NC=2C(=CC=CN=2)C)=N1 DMPDYTLZZYMXPQ-UHFFFAOYSA-N 0.000 claims 1
- MXOAEMDJHMGOOE-UHFFFAOYSA-N 2-(2-hexadecyltetrazol-5-yl)-2-phenyl-n-(2,4,6-trimethoxyphenyl)acetamide Chemical compound CCCCCCCCCCCCCCCCN1N=NC(C(C(=O)NC=2C(=CC(OC)=CC=2OC)OC)C=2C=CC=CC=2)=N1 MXOAEMDJHMGOOE-UHFFFAOYSA-N 0.000 claims 1
- FATLYHZGGUIAQA-UHFFFAOYSA-N 2-(2-octyltetrazol-5-yl)-2-phenyl-n-(2,4,6-trimethoxyphenyl)acetamide Chemical compound CCCCCCCCN1N=NC(C(C(=O)NC=2C(=CC(OC)=CC=2OC)OC)C=2C=CC=CC=2)=N1 FATLYHZGGUIAQA-UHFFFAOYSA-N 0.000 claims 1
- YASBPDLXOYLLPJ-UHFFFAOYSA-N 2-(2-tetradecyltetrazol-5-yl)-n-(2,4,6-trimethoxyphenyl)acetamide Chemical compound CCCCCCCCCCCCCCN1N=NC(CC(=O)NC=2C(=CC(OC)=CC=2OC)OC)=N1 YASBPDLXOYLLPJ-UHFFFAOYSA-N 0.000 claims 1
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- SHWVSJMDDYMIGI-UHFFFAOYSA-N n-(2,4-difluorophenyl)-2-(2-dodecyltetrazol-5-yl)-2-phenylacetamide Chemical compound CCCCCCCCCCCCN1N=NC(C(C(=O)NC=2C(=CC(F)=CC=2)F)C=2C=CC=CC=2)=N1 SHWVSJMDDYMIGI-UHFFFAOYSA-N 0.000 claims 1
- SBNXVSBZXUDEQZ-UHFFFAOYSA-N n-(2,4-difluorophenyl)-2-(2-dodecyltetrazol-5-yl)acetamide Chemical compound CCCCCCCCCCCCN1N=NC(CC(=O)NC=2C(=CC(F)=CC=2)F)=N1 SBNXVSBZXUDEQZ-UHFFFAOYSA-N 0.000 claims 1
- ZBDLMHBYLNCFPZ-UHFFFAOYSA-N n-(4,6-dimethoxypyrimidin-5-yl)-2-(2-dodecyl-1,3-dihydrotetrazol-5-yl)acetamide Chemical compound N1N(CCCCCCCCCCCC)NN=C1CC(=O)NC1=C(OC)N=CN=C1OC ZBDLMHBYLNCFPZ-UHFFFAOYSA-N 0.000 claims 1
- AFIHTRJHIVOCLA-UHFFFAOYSA-N n-(4,6-dimethoxypyrimidin-5-yl)-2-(2-dodecyltetrazol-5-yl)-2-phenylacetamide Chemical compound CCCCCCCCCCCCN1N=NC(C(C(=O)NC=2C(=NC=NC=2OC)OC)C=2C=CC=CC=2)=N1 AFIHTRJHIVOCLA-UHFFFAOYSA-N 0.000 claims 1
- WNKKVWFVDLCCEN-UHFFFAOYSA-N n-(4,6-dimethoxypyrimidin-5-yl)-2-(2-dodecyltetrazol-5-yl)acetamide Chemical group CCCCCCCCCCCCN1N=NC(CC(=O)NC=2C(=NC=NC=2OC)OC)=N1 WNKKVWFVDLCCEN-UHFFFAOYSA-N 0.000 claims 1
- MJIYUFBEGZDHKC-UHFFFAOYSA-N n-(5,7-dimethyl-1,8-naphthyridin-2-yl)-2-(2-dodecyltetrazol-5-yl)-2-phenylacetamide Chemical compound CCCCCCCCCCCCN1N=NC(C(C(=O)NC=2N=C3N=C(C)C=C(C)C3=CC=2)C=2C=CC=CC=2)=N1 MJIYUFBEGZDHKC-UHFFFAOYSA-N 0.000 claims 1
- GYVLGBIWWVCRCW-UHFFFAOYSA-N n-[2,6-di(propan-2-yl)phenyl]-2-(2-dodecyltetrazol-5-yl)-2-fluoro-2-phenylacetamide Chemical compound CCCCCCCCCCCCN1N=NC(C(F)(C(=O)NC=2C(=CC=CC=2C(C)C)C(C)C)C=2C=CC=CC=2)=N1 GYVLGBIWWVCRCW-UHFFFAOYSA-N 0.000 claims 1
- NPQWVLZCVMVSEX-UHFFFAOYSA-N n-[2,6-di(propan-2-yl)phenyl]-2-(2-dodecyltetrazol-5-yl)-2-phenylacetamide Chemical compound CCCCCCCCCCCCN1N=NC(C(C(=O)NC=2C(=CC=CC=2C(C)C)C(C)C)C=2C=CC=CC=2)=N1 NPQWVLZCVMVSEX-UHFFFAOYSA-N 0.000 claims 1
- JMOQIAAFYBJRDC-UHFFFAOYSA-N n-[2,6-di(propan-2-yl)phenyl]-2-(2-dodecyltetrazol-5-yl)-2-pyridin-2-ylacetamide Chemical compound CCCCCCCCCCCCN1N=NC(C(C(=O)NC=2C(=CC=CC=2C(C)C)C(C)C)C=2N=CC=CC=2)=N1 JMOQIAAFYBJRDC-UHFFFAOYSA-N 0.000 claims 1
- URSMRQBFOIJSLC-UHFFFAOYSA-N n-cyclopropyl-2-(2-dodecyltetrazol-5-yl)-2-phenylacetamide Chemical compound CCCCCCCCCCCCN1N=NC(C(C(=O)NC2CC2)C=2C=CC=CC=2)=N1 URSMRQBFOIJSLC-UHFFFAOYSA-N 0.000 claims 1
- BKRNSKVEUPYRRO-UHFFFAOYSA-N n-tert-butyl-2-(2-dodecyltetrazol-5-yl)-2-phenylacetamide Chemical compound CCCCCCCCCCCCN1N=NC(C(C(=O)NC(C)(C)C)C=2C=CC=CC=2)=N1 BKRNSKVEUPYRRO-UHFFFAOYSA-N 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 abstract description 2
- 125000001475 halogen functional group Chemical group 0.000 abstract 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 103
- 239000000243 solution Substances 0.000 description 102
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 68
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 59
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 56
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 50
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 48
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 48
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
- 239000000203 mixture Substances 0.000 description 38
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 34
- 235000019439 ethyl acetate Nutrition 0.000 description 34
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 32
- 230000015572 biosynthetic process Effects 0.000 description 31
- 238000003786 synthesis reaction Methods 0.000 description 31
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 30
- 238000000034 method Methods 0.000 description 30
- 239000007787 solid Substances 0.000 description 28
- 238000010992 reflux Methods 0.000 description 26
- 239000007788 liquid Substances 0.000 description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- FNSAKXLEFPFZOM-UHFFFAOYSA-N 2,4,6-trimethoxyaniline Chemical compound COC1=CC(OC)=C(N)C(OC)=C1 FNSAKXLEFPFZOM-UHFFFAOYSA-N 0.000 description 20
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
- 239000002253 acid Substances 0.000 description 20
- 239000012267 brine Substances 0.000 description 20
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
- 238000007429 general method Methods 0.000 description 19
- 239000000047 product Substances 0.000 description 19
- 150000007513 acids Chemical class 0.000 description 18
- 150000003536 tetrazoles Chemical class 0.000 description 18
- 239000000706 filtrate Substances 0.000 description 17
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 16
- 150000001412 amines Chemical class 0.000 description 16
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 13
- 150000001408 amides Chemical class 0.000 description 13
- ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 12
- 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 description 12
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 238000004587 chromatography analysis Methods 0.000 description 11
- 239000003480 eluent Substances 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- PBLNBZIONSLZBU-UHFFFAOYSA-N 1-bromododecane Chemical compound CCCCCCCCCCCCBr PBLNBZIONSLZBU-UHFFFAOYSA-N 0.000 description 10
- 239000002585 base Substances 0.000 description 10
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 10
- 235000019341 magnesium sulphate Nutrition 0.000 description 10
- WKBALTUBRZPIPZ-UHFFFAOYSA-N 2,6-di(propan-2-yl)aniline Chemical compound CC(C)C1=CC=CC(C(C)C)=C1N WKBALTUBRZPIPZ-UHFFFAOYSA-N 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- 239000002775 capsule Substances 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- VOXNMOCHRNJMIS-UHFFFAOYSA-N 5-decyl-2h-tetrazole Chemical compound CCCCCCCCCCC1=NN=NN1 VOXNMOCHRNJMIS-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 8
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 8
- 150000002431 hydrogen Chemical class 0.000 description 8
- 150000002825 nitriles Chemical class 0.000 description 8
- 239000010410 layer Substances 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- 238000010898 silica gel chromatography Methods 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- WXYLAISVMKNNHE-UHFFFAOYSA-N 2-(5-decyltetrazol-2-yl)acetic acid Chemical compound CCCCCCCCCCC=1N=NN(CC(O)=O)N=1 WXYLAISVMKNNHE-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 235000012000 cholesterol Nutrition 0.000 description 6
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- BZPBWSWQQGPODG-UHFFFAOYSA-N 5-dodecyl-2h-tetrazole Chemical compound CCCCCCCCCCCCC1=NN=NN1 BZPBWSWQQGPODG-UHFFFAOYSA-N 0.000 description 5
- 150000001299 aldehydes Chemical class 0.000 description 5
- 239000012298 atmosphere Substances 0.000 description 5
- 150000001735 carboxylic acids Chemical class 0.000 description 5
- MZQXAVZPEZUJIJ-UHFFFAOYSA-N ethyl 2-(2-bromophenyl)acetate Chemical compound CCOC(=O)CC1=CC=CC=C1Br MZQXAVZPEZUJIJ-UHFFFAOYSA-N 0.000 description 5
- YDGRMYQCQCJTKT-UHFFFAOYSA-N ethyl 2-(5-decyltetrazol-2-yl)-2-phenylacetate Chemical compound N1=C(CCCCCCCCCC)N=NN1C(C(=O)OCC)C1=CC=CC=C1 YDGRMYQCQCJTKT-UHFFFAOYSA-N 0.000 description 5
- 150000002430 hydrocarbons Chemical group 0.000 description 5
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 150000001350 alkyl halides Chemical class 0.000 description 4
- 239000002168 alkylating agent Substances 0.000 description 4
- 229940100198 alkylating agent Drugs 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 239000002274 desiccant Substances 0.000 description 4
- 235000005911 diet Nutrition 0.000 description 4
- 230000037213 diet Effects 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000006188 syrup Substances 0.000 description 4
- 235000020357 syrup Nutrition 0.000 description 4
- JKVRTUCVPZTEQZ-UHFFFAOYSA-N tributyltin azide Chemical compound CCCC[Sn](CCCC)(CCCC)N=[N+]=[N-] JKVRTUCVPZTEQZ-UHFFFAOYSA-N 0.000 description 4
- 238000010626 work up procedure Methods 0.000 description 4
- NEBPTMCRLHKPOB-UHFFFAOYSA-N 2,2-diphenylacetonitrile Chemical compound C=1C=CC=CC=1C(C#N)C1=CC=CC=C1 NEBPTMCRLHKPOB-UHFFFAOYSA-N 0.000 description 3
- CEPCPXLLFXPZGW-UHFFFAOYSA-N 2,4-difluoroaniline Chemical compound NC1=CC=C(F)C=C1F CEPCPXLLFXPZGW-UHFFFAOYSA-N 0.000 description 3
- MIFHJAMYBYAUMY-UHFFFAOYSA-N 2-(5-benzhydryltetrazol-2-yl)-2-phenylacetic acid Chemical compound N1=NC(C(C=2C=CC=CC=2)C=2C=CC=CC=2)=NN1C(C(=O)O)C1=CC=CC=C1 MIFHJAMYBYAUMY-UHFFFAOYSA-N 0.000 description 3
- JDEFPFLTCXIVDH-UHFFFAOYSA-N 2-cyanopropanoic acid Chemical class N#CC(C)C(O)=O JDEFPFLTCXIVDH-UHFFFAOYSA-N 0.000 description 3
- ZWGGBMXSZGMEBP-UHFFFAOYSA-N 3-(2-dodecyltetrazol-5-yl)propanoic acid Chemical compound CCCCCCCCCCCCN1N=NC(CCC(O)=O)=N1 ZWGGBMXSZGMEBP-UHFFFAOYSA-N 0.000 description 3
- IJIBRSFAXRFPPN-UHFFFAOYSA-N 5-bromo-2-methoxybenzaldehyde Chemical compound COC1=CC=C(Br)C=C1C=O IJIBRSFAXRFPPN-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 208000035150 Hypercholesterolemia Diseases 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 229910004298 SiO 2 Inorganic materials 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 238000005903 acid hydrolysis reaction Methods 0.000 description 3
- 230000001476 alcoholic effect Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000007822 coupling agent Substances 0.000 description 3
- XMIAHVJXWQQMCI-UHFFFAOYSA-N ethyl 2-(2-dodecyltetrazol-5-yl)acetate Chemical compound CCCCCCCCCCCCN1N=NC(CC(=O)OCC)=N1 XMIAHVJXWQQMCI-UHFFFAOYSA-N 0.000 description 3
- KZAJBFIAOCMJCJ-UHFFFAOYSA-N ethyl 2-(5-decyltetrazol-2-yl)acetate Chemical compound CCCCCCCCCCC=1N=NN(CC(=O)OCC)N=1 KZAJBFIAOCMJCJ-UHFFFAOYSA-N 0.000 description 3
- FYGRPGOHQCPZCV-UHFFFAOYSA-N ethyl 2-cyano-2-methylpropanoate Chemical compound CCOC(=O)C(C)(C)C#N FYGRPGOHQCPZCV-UHFFFAOYSA-N 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 239000012948 isocyanate Substances 0.000 description 3
- 150000002513 isocyanates Chemical class 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
- ULTHEAFYOOPTTB-UHFFFAOYSA-N 1,4-dibromobutane Chemical group BrCCCCBr ULTHEAFYOOPTTB-UHFFFAOYSA-N 0.000 description 2
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 2
- IVHYLHNNVVULOC-UHFFFAOYSA-N 2-(2-dodecyltetrazol-5-yl)-2-fluoro-2-phenylacetic acid Chemical compound CCCCCCCCCCCCN1N=NC(C(F)(C(O)=O)C=2C=CC=CC=2)=N1 IVHYLHNNVVULOC-UHFFFAOYSA-N 0.000 description 2
- XXSUYIPTSOFKRD-UHFFFAOYSA-N 2-(2-dodecyltetrazol-5-yl)acetic acid Chemical compound CCCCCCCCCCCCN1N=NC(CC(O)=O)=N1 XXSUYIPTSOFKRD-UHFFFAOYSA-N 0.000 description 2
- BOVLQFSBLDKFAK-UHFFFAOYSA-N 2-(5-decyltetrazol-1-yl)acetic acid Chemical compound CCCCCCCCCCC1=NN=NN1CC(O)=O BOVLQFSBLDKFAK-UHFFFAOYSA-N 0.000 description 2
- OXWCVRPDHIEALA-UHFFFAOYSA-N 2-(5-dodecyltetrazol-2-yl)acetic acid Chemical compound CCCCCCCCCCCCC=1N=NN(CC(O)=O)N=1 OXWCVRPDHIEALA-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 2
- LULAYUGMBFYYEX-UHFFFAOYSA-N 3-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 2
- FTLSAYRDWMBGCQ-UHFFFAOYSA-N 5-benzhydryl-2h-tetrazole Chemical compound C1=CC=CC=C1C(C=1C=CC=CC=1)C1=NN=NN1 FTLSAYRDWMBGCQ-UHFFFAOYSA-N 0.000 description 2
- VJTVVUHZHHKMLG-UHFFFAOYSA-N 5-dodecylsulfanyl-2h-tetrazole Chemical compound CCCCCCCCCCCCSC1=NN=NN1 VJTVVUHZHHKMLG-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- OJRUSAPKCPIVBY-KQYNXXCUSA-N C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)I)N Chemical compound C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)I)N OJRUSAPKCPIVBY-KQYNXXCUSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
- 239000005642 Oleic acid Substances 0.000 description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 102000001494 Sterol O-Acyltransferase Human genes 0.000 description 2
- 108010054082 Sterol O-acyltransferase Proteins 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229940125758 compound 15 Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 2
- CVIULFUJKSHISG-UHFFFAOYSA-N ethyl 2-(1-dodecyltetrazol-5-yl)acetate Chemical compound CCCCCCCCCCCCN1N=NN=C1CC(=O)OCC CVIULFUJKSHISG-UHFFFAOYSA-N 0.000 description 2
- HUASALLWADSENT-UHFFFAOYSA-N ethyl 2-(5-decyltetrazol-1-yl)acetate Chemical compound CCCCCCCCCCC1=NN=NN1CC(=O)OCC HUASALLWADSENT-UHFFFAOYSA-N 0.000 description 2
- UEHIOFRWEBNIKF-UHFFFAOYSA-N ethyl 2-(5-dodecyltetrazol-2-yl)acetate Chemical compound CCCCCCCCCCCCC=1N=NN(CC(=O)OCC)N=1 UEHIOFRWEBNIKF-UHFFFAOYSA-N 0.000 description 2
- 239000002024 ethyl acetate extract Substances 0.000 description 2
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 2
- QKLCQKPAECHXCQ-UHFFFAOYSA-N ethyl phenylglyoxylate Chemical compound CCOC(=O)C(=O)C1=CC=CC=C1 QKLCQKPAECHXCQ-UHFFFAOYSA-N 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- KJDJPXUIZYHXEZ-UHFFFAOYSA-N hydrogen sulfate;methylaminoazanium Chemical compound CN[NH3+].OS([O-])(=O)=O KJDJPXUIZYHXEZ-UHFFFAOYSA-N 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 150000005375 primary alkyl halides Chemical class 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical class CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- OYOKNASZLZRFFM-UHFFFAOYSA-N 1,1-dioxo-n-prop-2-enylthiolan-3-amine Chemical compound C=CCNC1CCS(=O)(=O)C1 OYOKNASZLZRFFM-UHFFFAOYSA-N 0.000 description 1
- YSZYFGMARJFMJK-UHFFFAOYSA-N 1,3,5-trimethyl-4-nitropyrazole Chemical compound CC1=NN(C)C(C)=C1[N+]([O-])=O YSZYFGMARJFMJK-UHFFFAOYSA-N 0.000 description 1
- SSDGMKHZMNTWLS-UHFFFAOYSA-N 1,3,5-trimethylpyrazol-4-amine Chemical compound CC1=NN(C)C(C)=C1N SSDGMKHZMNTWLS-UHFFFAOYSA-N 0.000 description 1
- HNOQAFMOBRWDKQ-UHFFFAOYSA-N 1,3,5-trimethylpyrazole Chemical compound CC=1C=C(C)N(C)N=1 HNOQAFMOBRWDKQ-UHFFFAOYSA-N 0.000 description 1
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 1
- MYMSJFSOOQERIO-UHFFFAOYSA-N 1-bromodecane Chemical compound CCCCCCCCCCBr MYMSJFSOOQERIO-UHFFFAOYSA-N 0.000 description 1
- VMKOFRJSULQZRM-UHFFFAOYSA-N 1-bromooctane Chemical compound CCCCCCCCBr VMKOFRJSULQZRM-UHFFFAOYSA-N 0.000 description 1
- CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 1
- BFDNZQUBFCYTIC-UHFFFAOYSA-N 1-bromotridecane Chemical compound CCCCCCCCCCCCCBr BFDNZQUBFCYTIC-UHFFFAOYSA-N 0.000 description 1
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 1
- GRHAUEFIQOUKAY-UHFFFAOYSA-N 2,4,6-trimethoxyaniline;hydrochloride Chemical compound Cl.COC1=CC(OC)=C(N)C(OC)=C1 GRHAUEFIQOUKAY-UHFFFAOYSA-N 0.000 description 1
- WPPSRUDTCBIYRB-UHFFFAOYSA-N 2-(2-dodecyltetrazol-5-yl)-2-phenylacetic acid Chemical compound CCCCCCCCCCCCN1N=NC(C(C(O)=O)C=2C=CC=CC=2)=N1 WPPSRUDTCBIYRB-UHFFFAOYSA-N 0.000 description 1
- PSZCIBHPIUUYJR-UHFFFAOYSA-N 2-(2-dodecyltetrazol-5-yl)cyclopentane-1-carbonitrile Chemical compound CCCCCCCCCCCCN1N=NC(C2C(CCC2)C#N)=N1 PSZCIBHPIUUYJR-UHFFFAOYSA-N 0.000 description 1
- ZDTJZRPVNVIAIV-UHFFFAOYSA-N 2-(2h-tetrazol-5-yl)acetamide Chemical compound NC(=O)CC1=NN=NN1 ZDTJZRPVNVIAIV-UHFFFAOYSA-N 0.000 description 1
- JUNAPQMUUHSYOV-UHFFFAOYSA-N 2-(2h-tetrazol-5-yl)acetic acid Chemical compound OC(=O)CC=1N=NNN=1 JUNAPQMUUHSYOV-UHFFFAOYSA-N 0.000 description 1
- LPSFGGNCSYDAOK-UHFFFAOYSA-N 2-(2h-tetrazol-5-yl)cyclopentane-1-carbonitrile Chemical compound N#CC1CCCC1C1=NN=NN1 LPSFGGNCSYDAOK-UHFFFAOYSA-N 0.000 description 1
- RSFVRXVCIYJIFX-UHFFFAOYSA-N 2-(2h-tetrazol-5-ylmethyl)pyridine Chemical compound C=1C=CC=NC=1CC1=NN=NN1 RSFVRXVCIYJIFX-UHFFFAOYSA-N 0.000 description 1
- PMRVEKNTRCTXAG-UHFFFAOYSA-N 2-(5-dodecyltetrazol-2-yl)heptanoic acid Chemical compound CCCCCCCCCCCCC=1N=NN(C(CCCCC)C(O)=O)N=1 PMRVEKNTRCTXAG-UHFFFAOYSA-N 0.000 description 1
- XJFDPWKIACURRQ-UHFFFAOYSA-N 2-[(3-dodecyl-2h-tetrazol-1-yl)methyl]pyridine Chemical compound C1=NN(CCCCCCCCCCCC)NN1CC1=CC=CC=N1 XJFDPWKIACURRQ-UHFFFAOYSA-N 0.000 description 1
- APLNAFMUEHKRLM-UHFFFAOYSA-N 2-[5-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]-1-(3,4,6,7-tetrahydroimidazo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NN=C(O1)CC(=O)N1CC2=C(CC1)N=CN2 APLNAFMUEHKRLM-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- MLIREBYILWEBDM-UHFFFAOYSA-M 2-cyanoacetate Chemical compound [O-]C(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-M 0.000 description 1
- DEBLFDKWNOXBDF-UHFFFAOYSA-N 2-cyclohexyl-2-(2-dodecyltetrazol-5-yl)-n-(2,4,6-trimethoxyphenyl)acetamide Chemical compound CCCCCCCCCCCCN1N=NC(C(C2CCCCC2)C(=O)NC=2C(=CC(OC)=CC=2OC)OC)=N1 DEBLFDKWNOXBDF-UHFFFAOYSA-N 0.000 description 1
- UUNYMVCYBTWXJT-UHFFFAOYSA-N 2-dodecyltetrazole Chemical compound CCCCCCCCCCCCN1N=CN=N1 UUNYMVCYBTWXJT-UHFFFAOYSA-N 0.000 description 1
- WOZKEJOOLKSDTE-UHFFFAOYSA-N 2-dodecyltetrazole-5-carboxylic acid Chemical compound CCCCCCCCCCCCN1N=NC(C(O)=O)=N1 WOZKEJOOLKSDTE-UHFFFAOYSA-N 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- JXPDNDHCMMOJPC-UHFFFAOYSA-N 2-hydroxybutanedinitrile Chemical compound N#CC(O)CC#N JXPDNDHCMMOJPC-UHFFFAOYSA-N 0.000 description 1
- AGLWLXYDTLVWKM-UHFFFAOYSA-N 2-isocyanato-1,3,5-trimethoxybenzene Chemical compound COC1=CC(OC)=C(N=C=O)C(OC)=C1 AGLWLXYDTLVWKM-UHFFFAOYSA-N 0.000 description 1
- FEUFNKALUGDEMQ-UHFFFAOYSA-N 2-isocyanato-1,3-di(propan-2-yl)benzene Chemical compound CC(C)C1=CC=CC(C(C)C)=C1N=C=O FEUFNKALUGDEMQ-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- UKVQBONVSSLJBB-UHFFFAOYSA-N 2-pyridin-2-ylacetonitrile Chemical compound N#CCC1=CC=CC=N1 UKVQBONVSSLJBB-UHFFFAOYSA-N 0.000 description 1
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- VCNSPZYMJXPVDA-UHFFFAOYSA-N 3,5-dimethyl-1-pyridin-2-ylpyrazol-4-amine Chemical compound CC1=C(N)C(C)=NN1C1=CC=CC=N1 VCNSPZYMJXPVDA-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- GMPNSKPTQXVWAF-UHFFFAOYSA-N 3-cyano-3-phenylpropanoic acid Chemical compound OC(=O)CC(C#N)C1=CC=CC=C1 GMPNSKPTQXVWAF-UHFFFAOYSA-N 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 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
- VYIBCOSBNVFEIW-UHFFFAOYSA-N 3-phenylpropanamide Chemical compound NC(=O)CCC1=CC=CC=C1 VYIBCOSBNVFEIW-UHFFFAOYSA-N 0.000 description 1
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical compound [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
- VLVQOBVFQIECDG-UHFFFAOYSA-N 5-benzhydryl-2-dodecyltetrazole Chemical compound CCCCCCCCCCCCN1N=NC(C(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 VLVQOBVFQIECDG-UHFFFAOYSA-N 0.000 description 1
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 101100219382 Caenorhabditis elegans cah-2 gene Proteins 0.000 description 1
- 101100181929 Caenorhabditis elegans lin-3 gene Proteins 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 239000004380 Cholic acid Substances 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 244000178870 Lavandula angustifolia Species 0.000 description 1
- 235000010663 Lavandula angustifolia Nutrition 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 238000006845 Michael addition reaction Methods 0.000 description 1
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- RJECHNNFRHZQKU-UHFFFAOYSA-N Oelsaeurecholesterylester Natural products C12CCC3(C)C(C(C)CCCC(C)C)CCC3C2CC=C2C1(C)CCC(OC(=O)CCCCCCCC=CCCCCCCCC)C2 RJECHNNFRHZQKU-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- FHKPLLOSJHHKNU-INIZCTEOSA-N [(3S)-3-[8-(1-ethyl-5-methylpyrazol-4-yl)-9-methylpurin-6-yl]oxypyrrolidin-1-yl]-(oxan-4-yl)methanone Chemical compound C(C)N1N=CC(=C1C)C=1N(C2=NC=NC(=C2N=1)O[C@@H]1CN(CC1)C(=O)C1CCOCC1)C FHKPLLOSJHHKNU-INIZCTEOSA-N 0.000 description 1
- WLLIXJBWWFGEHT-UHFFFAOYSA-N [tert-butyl(dimethyl)silyl] trifluoromethanesulfonate Chemical compound CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F WLLIXJBWWFGEHT-UHFFFAOYSA-N 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001347 alkyl bromides Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
- UAZDIGCOBKKMPU-UHFFFAOYSA-O azanium;azide Chemical compound [NH4+].[N-]=[N+]=[N-] UAZDIGCOBKKMPU-UHFFFAOYSA-O 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- RRKTZKIUPZVBMF-IBTVXLQLSA-N brucine Chemical compound O([C@@H]1[C@H]([C@H]2C3)[C@@H]4N(C(C1)=O)C=1C=C(C(=CC=11)OC)OC)CC=C2CN2[C@@H]3[C@]41CC2 RRKTZKIUPZVBMF-IBTVXLQLSA-N 0.000 description 1
- RRKTZKIUPZVBMF-UHFFFAOYSA-N brucine Natural products C1=2C=C(OC)C(OC)=CC=2N(C(C2)=O)C3C(C4C5)C2OCC=C4CN2C5C31CC2 RRKTZKIUPZVBMF-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- RJECHNNFRHZQKU-RMUVNZEASA-N cholesteryl oleate Chemical compound C([C@@H]12)C[C@]3(C)[C@@H]([C@H](C)CCCC(C)C)CC[C@H]3[C@@H]1CC=C1[C@]2(C)CC[C@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)C1 RJECHNNFRHZQKU-RMUVNZEASA-N 0.000 description 1
- 235000019416 cholic acid Nutrition 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 229960002471 cholic acid Drugs 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000006352 cycloaddition reaction Methods 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 125000004982 dihaloalkyl group Chemical group 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 229960002179 ephedrine Drugs 0.000 description 1
- UYMKPFRHYYNDTL-UHFFFAOYSA-N ethenamine Chemical class NC=C UYMKPFRHYYNDTL-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- HWJHWSBFPPPIPD-UHFFFAOYSA-N ethoxyethane;propan-2-one Chemical compound CC(C)=O.CCOCC HWJHWSBFPPPIPD-UHFFFAOYSA-N 0.000 description 1
- LGQSNBWWSNTNJY-UHFFFAOYSA-N ethyl 2-(2-dodecyltetrazol-5-yl)-2-fluoro-2-phenylacetate Chemical compound CCCCCCCCCCCCN1N=NC(C(F)(C(=O)OCC)C=2C=CC=CC=2)=N1 LGQSNBWWSNTNJY-UHFFFAOYSA-N 0.000 description 1
- NPNSJKLOEOHOJC-UHFFFAOYSA-N ethyl 2-(2-dodecyltetrazol-5-yl)-2-hydroxy-2-phenylacetate Chemical compound CCCCCCCCCCCCN1N=NC(C(O)(C(=O)OCC)C=2C=CC=CC=2)=N1 NPNSJKLOEOHOJC-UHFFFAOYSA-N 0.000 description 1
- NAOHMNNTUFFTBF-UHFFFAOYSA-N ethyl 2-(2h-tetrazol-5-yl)acetate Chemical compound CCOC(=O)CC=1N=NNN=1 NAOHMNNTUFFTBF-UHFFFAOYSA-N 0.000 description 1
- UXSVBCHLRCDPHT-UHFFFAOYSA-N ethyl 2-(4-decyl-5h-tetrazol-1-yl)acetate Chemical compound CCCCCCCCCCN1CN(CC(=O)OCC)N=N1 UXSVBCHLRCDPHT-UHFFFAOYSA-N 0.000 description 1
- AHVROBBOYIAGRD-UHFFFAOYSA-N ethyl 2-(5-benzhydryltetrazol-2-yl)-2-phenylacetate Chemical compound N1=NC(C(C=2C=CC=CC=2)C=2C=CC=CC=2)=NN1C(C(=O)OCC)C1=CC=CC=C1 AHVROBBOYIAGRD-UHFFFAOYSA-N 0.000 description 1
- JMOCHQFOEGMQRN-UHFFFAOYSA-N ethyl 2-(5-dodecyltetrazol-2-yl)-2-phenylacetate Chemical compound N1=C(CCCCCCCCCCCC)N=NN1C(C(=O)OCC)C1=CC=CC=C1 JMOCHQFOEGMQRN-UHFFFAOYSA-N 0.000 description 1
- IOLQWGVDEFWYNP-UHFFFAOYSA-N ethyl 2-bromo-2-methylpropanoate Chemical compound CCOC(=O)C(C)(C)Br IOLQWGVDEFWYNP-UHFFFAOYSA-N 0.000 description 1
- GNCLPIAYAPQPOU-UHFFFAOYSA-N ethyl 2-bromoheptanoate Chemical compound CCCCCC(Br)C(=O)OCC GNCLPIAYAPQPOU-UHFFFAOYSA-N 0.000 description 1
- DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229960002598 fumaric acid Drugs 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 229950006191 gluconic acid Drugs 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229960000443 hydrochloric acid Drugs 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 150000002440 hydroxy compounds Chemical class 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229960000448 lactic acid Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000001102 lavandula vera Substances 0.000 description 1
- 235000018219 lavender Nutrition 0.000 description 1
- GUWHRJQTTVADPB-UHFFFAOYSA-N lithium azide Chemical compound [Li+].[N-]=[N+]=[N-] GUWHRJQTTVADPB-UHFFFAOYSA-N 0.000 description 1
- 210000001853 liver microsome Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- BFDDHZDAVFUWCA-UHFFFAOYSA-L magnesium;carboxylato carbonate Chemical compound [Mg+2].[O-]C(=O)OC([O-])=O BFDDHZDAVFUWCA-UHFFFAOYSA-L 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229940098895 maleic acid Drugs 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229940099690 malic acid Drugs 0.000 description 1
- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical compound N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- KVMHSSWXEKETSL-UHFFFAOYSA-N methyl 3-(1-dodecyltetrazol-5-yl)propanoate Chemical compound CCCCCCCCCCCCN1N=NN=C1CCC(=O)OC KVMHSSWXEKETSL-UHFFFAOYSA-N 0.000 description 1
- CXWUSLAGKKARPZ-UHFFFAOYSA-N methyl 3-(2-dodecyltetrazol-5-yl)propanoate Chemical compound CCCCCCCCCCCCN1N=NC(CCC(=O)OC)=N1 CXWUSLAGKKARPZ-UHFFFAOYSA-N 0.000 description 1
- BPSKURPOKFSLHJ-UHFFFAOYSA-N methyl 3-cyanopropanoate Chemical compound COC(=O)CCC#N BPSKURPOKFSLHJ-UHFFFAOYSA-N 0.000 description 1
- 210000001589 microsome Anatomy 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- KFIGICHILYTCJF-UHFFFAOYSA-N n'-methylethane-1,2-diamine Chemical compound CNCCN KFIGICHILYTCJF-UHFFFAOYSA-N 0.000 description 1
- LEZIAJGFEVLNPA-UHFFFAOYSA-N n-(2,4-difluorophenyl)-2-(5-dodecyltetrazol-2-yl)acetamide Chemical compound N1=C(CCCCCCCCCCCC)N=NN1CC(=O)NC1=CC=C(F)C=C1F LEZIAJGFEVLNPA-UHFFFAOYSA-N 0.000 description 1
- RLKHFSNWQCZBDC-UHFFFAOYSA-N n-(benzenesulfonyl)-n-fluorobenzenesulfonamide Chemical compound C=1C=CC=CC=1S(=O)(=O)N(F)S(=O)(=O)C1=CC=CC=C1 RLKHFSNWQCZBDC-UHFFFAOYSA-N 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- NWELCUKYUCBVKK-UHFFFAOYSA-N pyridin-2-ylhydrazine Chemical compound NNC1=CC=CC=N1 NWELCUKYUCBVKK-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000012798 spherical particle Substances 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 239000007885 tablet disintegrant Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- IIHPVYJPDKJYOU-UHFFFAOYSA-N triphenylcarbethoxymethylenephosphorane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OCC)C1=CC=CC=C1 IIHPVYJPDKJYOU-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000011345 viscous material Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- 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
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- 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
- C07D403/12—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 chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyridine Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US74856891A | 1991-08-22 | 1991-08-22 | |
| US91364392A | 1992-07-20 | 1992-07-20 | |
| PCT/US1992/006388 WO1993004052A1 (en) | 1991-08-22 | 1992-08-03 | Amide tetrazole acat inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO940596D0 NO940596D0 (no) | 1994-02-21 |
| NO940596L NO940596L (no) | 1994-02-22 |
| NO300632B1 true NO300632B1 (no) | 1997-06-30 |
Family
ID=27114964
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO940596A NO300632B1 (no) | 1991-08-22 | 1994-02-21 | Amid-tetrazol ACAT-inhibitorer |
Country Status (20)
| Country | Link |
|---|---|
| EP (1) | EP0600950B1 (el) |
| JP (1) | JP3113678B2 (el) |
| KR (1) | KR100221764B1 (el) |
| AT (1) | ATE144501T1 (el) |
| AU (1) | AU657790B2 (el) |
| CA (1) | CA2114017C (el) |
| CZ (1) | CZ281314B6 (el) |
| DE (1) | DE69214827T2 (el) |
| DK (1) | DK0600950T3 (el) |
| ES (1) | ES2093270T3 (el) |
| FI (1) | FI112221B (el) |
| GR (1) | GR3021942T3 (el) |
| HK (1) | HK1005187A1 (el) |
| HU (1) | HU221190B1 (el) |
| MX (1) | MX9204877A (el) |
| NO (1) | NO300632B1 (el) |
| NZ (1) | NZ244029A (el) |
| PT (1) | PT100804B (el) |
| RU (1) | RU2117664C1 (el) |
| WO (1) | WO1993004052A1 (el) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5366987A (en) * | 1991-08-22 | 1994-11-22 | Warner-Lambert Company | Isoxazolyl-substituted alkyl amide ACAT inhibitors |
| US5239082A (en) * | 1992-08-03 | 1993-08-24 | Warner-Lambert Company | Sulfonamide tetrazole ACAT inhibitors |
| US5461049A (en) * | 1994-05-27 | 1995-10-24 | Warner-Lambert Company | Amide tetrazole ACAT inhibitors |
| ATE386716T1 (de) | 2000-12-26 | 2008-03-15 | Pola Pharma Inc | Biphenylderivate |
| US7365199B2 (en) * | 2001-04-20 | 2008-04-29 | Fujifilm Corporation | Dye-forming coupler, silver halide photographic light-sensitive material, and azomethine dye compound |
| US7320967B2 (en) * | 2002-04-23 | 2008-01-22 | L'oreal | Cosmetic composition, method of cosmetic treatment and preparation of a composition for promoting the growth and/or preventing or delaying the loss of hair |
| FR2845991B1 (fr) * | 2002-10-16 | 2005-02-04 | Pf Medicament | Derives d'alpha-phenyl acetanilides et leur application en therapeutique humaine |
| GB0316546D0 (en) | 2003-07-15 | 2003-08-20 | Novartis Ag | Process for the manufacture of organic compounds |
| UA85706C2 (en) | 2004-05-06 | 2009-02-25 | Уорнер-Ламберт Компани Ллси | 4-phenylaminoquinazolin-6-yl amides |
| BRPI0924997B1 (pt) * | 2009-06-22 | 2024-01-16 | Sk Biopharmaceuticals Co., Ltd | Método para preparar um composto de éster do ácido 1-aril-2- tetrazoil etil carbâmico |
| CN102153591B (zh) * | 2011-01-17 | 2013-11-06 | 天津师范大学 | 2-(1h-四唑-5-甲基)吡啶和5-硝基间苯二甲酸混合配体锰(ii)配合物及制备方法与应用 |
| WO2020113094A1 (en) | 2018-11-30 | 2020-06-04 | Nuvation Bio Inc. | Pyrrole and pyrazole compounds and methods of use thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5536447A (en) * | 1978-09-07 | 1980-03-14 | Otsuka Pharmaceut Co Ltd | Butyramide derivative |
| US5073565A (en) * | 1990-04-27 | 1991-12-17 | Warner-Lambert Company | Tetrazole ureas and thioureas and their use as acat inhibitors |
-
1992
- 1992-08-03 WO PCT/US1992/006388 patent/WO1993004052A1/en active IP Right Grant
- 1992-08-03 CA CA002114017A patent/CA2114017C/en not_active Expired - Fee Related
- 1992-08-03 JP JP05504315A patent/JP3113678B2/ja not_active Expired - Fee Related
- 1992-08-03 ES ES92917230T patent/ES2093270T3/es not_active Expired - Lifetime
- 1992-08-03 HU HU9400491A patent/HU221190B1/hu not_active IP Right Cessation
- 1992-08-03 AT AT92917230T patent/ATE144501T1/de not_active IP Right Cessation
- 1992-08-03 CZ CZ94361A patent/CZ281314B6/cs not_active IP Right Cessation
- 1992-08-03 AU AU24147/92A patent/AU657790B2/en not_active Ceased
- 1992-08-03 KR KR1019940700515A patent/KR100221764B1/ko not_active IP Right Cessation
- 1992-08-03 DE DE69214827T patent/DE69214827T2/de not_active Expired - Fee Related
- 1992-08-03 EP EP92917230A patent/EP0600950B1/en not_active Expired - Lifetime
- 1992-08-03 DK DK92917230.2T patent/DK0600950T3/da active
- 1992-08-03 RU RU94016198A patent/RU2117664C1/ru not_active IP Right Cessation
- 1992-08-20 NZ NZ244029A patent/NZ244029A/en not_active IP Right Cessation
- 1992-08-21 MX MX9204877A patent/MX9204877A/es not_active IP Right Cessation
- 1992-08-21 PT PT100804A patent/PT100804B/pt not_active IP Right Cessation
-
1994
- 1994-02-16 FI FI940731A patent/FI112221B/fi not_active IP Right Cessation
- 1994-02-21 NO NO940596A patent/NO300632B1/no unknown
-
1996
- 1996-12-06 GR GR960403360T patent/GR3021942T3/el unknown
-
1998
- 1998-05-15 HK HK98104234A patent/HK1005187A1/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| FI112221B (fi) | 2003-11-14 |
| NZ244029A (en) | 1995-09-26 |
| NO940596L (no) | 1994-02-22 |
| GR3021942T3 (en) | 1997-03-31 |
| HU221190B1 (en) | 2002-08-28 |
| KR100221764B1 (ko) | 1999-09-15 |
| CZ281314B6 (cs) | 1996-08-14 |
| MX9204877A (es) | 1993-04-01 |
| HK1005187A1 (en) | 1998-12-24 |
| PT100804A (pt) | 1993-09-30 |
| ATE144501T1 (de) | 1996-11-15 |
| FI940731A0 (fi) | 1994-02-16 |
| EP0600950B1 (en) | 1996-10-23 |
| HU9400491D0 (en) | 1994-05-30 |
| WO1993004052A1 (en) | 1993-03-04 |
| CA2114017C (en) | 2004-09-21 |
| NO940596D0 (no) | 1994-02-21 |
| AU2414792A (en) | 1993-03-16 |
| HUT70754A (en) | 1995-10-30 |
| DE69214827T2 (de) | 1997-03-06 |
| FI940731A (fi) | 1994-04-15 |
| CA2114017A1 (en) | 1993-03-04 |
| DE69214827D1 (de) | 1996-11-28 |
| DK0600950T3 (da) | 1997-04-21 |
| ES2093270T3 (es) | 1996-12-16 |
| CZ36194A3 (en) | 1994-07-13 |
| PT100804B (pt) | 1999-07-30 |
| JP3113678B2 (ja) | 2000-12-04 |
| AU657790B2 (en) | 1995-03-23 |
| EP0600950A1 (en) | 1994-06-15 |
| JPH06510040A (ja) | 1994-11-10 |
| RU2117664C1 (ru) | 1998-08-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2155104C (en) | Heterocyclic-substituted alkyl amide acat inhibitors | |
| US8598355B2 (en) | Amide compound | |
| KR101638671B1 (ko) | 글루카곤 수용체 조절자 | |
| KR101302796B1 (ko) | 시클로헥실 아미드 유도체 및 ｃｒｆ－１ 수용체 길항제로서의 그의 용도 | |
| US11999699B2 (en) | Substituted pyrazole amides | |
| EA037257B1 (ru) | Новые агонисты рецептора апелина и способы применения | |
| AU2006232660A1 (en) | 1H-Pyrazole 4-Carboxylamides, their preparation and their use as 11Beta-hydroxysteroid dehydrogenase | |
| NO300632B1 (no) | Amid-tetrazol ACAT-inhibitorer | |
| JPH05186431A (ja) | Ｎ−置換ヘテロ環誘導体、製法および医薬組成物 | |
| JP4069074B2 (ja) | Ｎ−ビフェニルメチルアミノシクロアルカンカルボキサミド誘導体 | |
| US20220089573A1 (en) | Substituted pyrrolidine amides iii | |
| US20090286990A1 (en) | Process for preparing irbesartan | |
| WO1997001551A1 (en) | Pyrazole compounds and pharmaceutical compositions | |
| US20080167371A1 (en) | Diaryl, Dipyridinyl and Aryl-Pyridinyl Derivatives and Uses Thereof | |
| JP5666468B2 (ja) | システインプロテアーゼ阻害剤 | |
| JP5306189B2 (ja) | アリールおよびヘテロアリール−エチル−アシルグアニジン誘導体、これらの調製、および治療におけるこれらの適用 | |
| JP2007501790A (ja) | スルホニル置換ｎ−（ビアリールメチル）アミノシクロプロパンカルボキサミド | |
| AU2017371443B2 (en) | A substituted benzimidazole derivative as a modulator of TNF activity | |
| AU2011328521A1 (en) | Substituted bicyclic carboxamide and urea derivatives as vanilloid receptor ligands | |
| AU2003218068B2 (en) | Substituted amides | |
| NZ623627B2 (en) | Protein kinase inhibitors |