ZA200510277B - Substituted pyrrole derivatives and their use as HMB-Co inhibitors - Google Patents
Substituted pyrrole derivatives and their use as HMB-Co inhibitors Download PDFInfo
- Publication number
- ZA200510277B ZA200510277B ZA200510277A ZA200510277A ZA200510277B ZA 200510277 B ZA200510277 B ZA 200510277B ZA 200510277 A ZA200510277 A ZA 200510277A ZA 200510277 A ZA200510277 A ZA 200510277A ZA 200510277 B ZA200510277 B ZA 200510277B
- Authority
- ZA
- South Africa
- Prior art keywords
- formula
- compound
- alkyl
- optionally substituted
- phenyl
- Prior art date
Links
- 239000003112 inhibitor Substances 0.000 title description 5
- 150000003233 pyrroles Chemical class 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims description 386
- 125000000217 alkyl group Chemical group 0.000 claims description 191
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 171
- 125000001424 substituent group Chemical group 0.000 claims description 146
- 229910052736 halogen Inorganic materials 0.000 claims description 119
- 150000002367 halogens Chemical class 0.000 claims description 119
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 100
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 92
- -1 cyano, acetyl Chemical group 0.000 claims description 66
- 125000003545 alkoxy group Chemical group 0.000 claims description 64
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 57
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 53
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 51
- 229910052799 carbon Inorganic materials 0.000 claims description 48
- 150000003839 salts Chemical class 0.000 claims description 48
- 238000000034 method Methods 0.000 claims description 47
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 46
- 125000005842 heteroatom Chemical group 0.000 claims description 45
- 125000003118 aryl group Chemical group 0.000 claims description 38
- 229910052739 hydrogen Inorganic materials 0.000 claims description 38
- 239000001257 hydrogen Substances 0.000 claims description 37
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 36
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 33
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 31
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 30
- 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 description 28
- 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 26
- 239000012453 solvate Substances 0.000 claims description 26
- 229910052757 nitrogen Inorganic materials 0.000 claims description 24
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 23
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 23
- 229910052760 oxygen Inorganic materials 0.000 claims description 23
- 239000001301 oxygen Substances 0.000 claims description 23
- 239000002253 acid Substances 0.000 claims description 21
- 201000010099 disease Diseases 0.000 claims description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
- 230000008569 process Effects 0.000 claims description 19
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 18
- 239000002207 metabolite Substances 0.000 claims description 18
- 239000000651 prodrug Substances 0.000 claims description 18
- 229940002612 prodrug Drugs 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 17
- 150000001204 N-oxides Chemical class 0.000 claims description 16
- 235000012000 cholesterol Nutrition 0.000 claims description 14
- 150000002596 lactones Chemical group 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 14
- 239000011593 sulfur Substances 0.000 claims description 14
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 14
- 230000007062 hydrolysis Effects 0.000 claims description 13
- 238000006460 hydrolysis reaction Methods 0.000 claims description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 11
- 125000003107 substituted aryl group Chemical group 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- 229940124530 sulfonamide Drugs 0.000 claims description 10
- 150000003456 sulfonamides Chemical class 0.000 claims description 10
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 9
- 239000005864 Sulphur Substances 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 241000124008 Mammalia Species 0.000 claims description 8
- 150000001412 amines Chemical class 0.000 claims description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 7
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 7
- 201000001320 Atherosclerosis Diseases 0.000 claims description 6
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 6
- 125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 6
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- ABYZSYDGJGVCHS-ZETCQYMHSA-N (2s)-2-acetamido-n-(4-nitrophenyl)propanamide Chemical group CC(=O)N[C@@H](C)C(=O)NC1=CC=C([N+]([O-])=O)C=C1 ABYZSYDGJGVCHS-ZETCQYMHSA-N 0.000 claims description 5
- 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 claims description 5
- 206010020772 Hypertension Diseases 0.000 claims description 5
- 208000006011 Stroke Diseases 0.000 claims description 5
- 239000007822 coupling agent Substances 0.000 claims description 5
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 4
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 4
- 206010012601 diabetes mellitus Diseases 0.000 claims description 4
- 208000020346 hyperlipoproteinemia Diseases 0.000 claims description 4
- 208000006575 hypertriglyceridemia Diseases 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000000169 tricyclic heterocycle group Chemical group 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 3
- 206010002383 Angina Pectoris Diseases 0.000 claims description 3
- 206010012289 Dementia Diseases 0.000 claims description 3
- 208000029725 Metabolic bone disease Diseases 0.000 claims description 3
- 206010049088 Osteopenia Diseases 0.000 claims description 3
- 208000001132 Osteoporosis Diseases 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 208000028867 ischemia Diseases 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 49
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 21
- 150000002431 hydrogen Chemical class 0.000 claims 10
- 230000003301 hydrolyzing effect Effects 0.000 claims 8
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 claims 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 5
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 3
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 claims 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims 2
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 claims 2
- 239000001639 calcium acetate Substances 0.000 claims 2
- 229960005147 calcium acetate Drugs 0.000 claims 2
- 235000011092 calcium acetate Nutrition 0.000 claims 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 2
- 239000003814 drug Substances 0.000 claims 2
- PMFRPLBQEYHUMG-VSGBNLITSA-N (3r,5r)-7-[2-(4-fluorophenyl)-4-[[4-(hydroxymethyl)phenyl]carbamoyl]-3-phenyl-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=C(CO)C=C1 PMFRPLBQEYHUMG-VSGBNLITSA-N 0.000 claims 1
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 1
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims 1
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims 1
- 125000001318 4-trifluoromethylbenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])*)C(F)(F)F 0.000 claims 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 1
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims 1
- 102100040996 Cochlin Human genes 0.000 claims 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
- 101100295741 Gallus gallus COR4 gene Proteins 0.000 claims 1
- 101100134922 Gallus gallus COR5 gene Proteins 0.000 claims 1
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 claims 1
- 101000748988 Homo sapiens Cochlin Proteins 0.000 claims 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims 1
- 241000288147 Meleagris gallopavo Species 0.000 claims 1
- 101150089916 Miox gene Proteins 0.000 claims 1
- 101100238304 Mus musculus Morc1 gene Proteins 0.000 claims 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims 1
- 239000004411 aluminium Substances 0.000 claims 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims 1
- 229910052782 aluminium Inorganic materials 0.000 claims 1
- 150000001413 amino acids Chemical class 0.000 claims 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 1
- 239000011575 calcium Substances 0.000 claims 1
- 229910052791 calcium Inorganic materials 0.000 claims 1
- OYPRJOBELJOOCE-LZFNBGRKSA-N calcium-46 Chemical compound [46Ca] OYPRJOBELJOOCE-LZFNBGRKSA-N 0.000 claims 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- 125000005131 dialkylammonium group Chemical group 0.000 claims 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims 1
- 229910052731 fluorine Inorganic materials 0.000 claims 1
- 239000011737 fluorine Substances 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 229910052744 lithium Inorganic materials 0.000 claims 1
- 239000011777 magnesium Substances 0.000 claims 1
- 229910052749 magnesium Inorganic materials 0.000 claims 1
- 125000002757 morpholinyl group Chemical group 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000003386 piperidinyl group Chemical group 0.000 claims 1
- 239000011591 potassium Substances 0.000 claims 1
- 229910052700 potassium Inorganic materials 0.000 claims 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical group [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims 1
- 208000037803 restenosis Diseases 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 159000000000 sodium salts Chemical group 0.000 claims 1
- 239000011701 zinc Substances 0.000 claims 1
- 229910052725 zinc Inorganic materials 0.000 claims 1
- OIWCYIUQAVBPGV-DAQGAKHBSA-N {1-O-hexadecanoyl-2-O-[(Z)-octadec-9-enoyl]-sn-glycero-3-phospho}serine Chemical group CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCC\C=C/CCCCCCCC OIWCYIUQAVBPGV-DAQGAKHBSA-N 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 38
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 21
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 21
- 159000000007 calcium salts Chemical class 0.000 description 18
- 238000003776 cleavage reaction Methods 0.000 description 18
- 230000007017 scission Effects 0.000 description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 150000007530 organic bases Chemical class 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 239000012454 non-polar solvent Substances 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 6
- 229910052500 inorganic mineral Inorganic materials 0.000 description 6
- 239000011707 mineral Substances 0.000 description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- 239000008096 xylene Substances 0.000 description 6
- CABVTRNMFUVUDM-VRHQGPGLSA-N (3S)-3-hydroxy-3-methylglutaryl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C[C@@](O)(CC(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 CABVTRNMFUVUDM-VRHQGPGLSA-N 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 150000007529 inorganic bases Chemical class 0.000 description 5
- 150000007524 organic acids Chemical class 0.000 description 5
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 239000002798 polar solvent Substances 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- IWSVLBKHBJGMAA-UHFFFAOYSA-M 2-(3-benzyl-4-methyl-1,3-thiazol-3-ium-5-yl)ethanol;chloride Chemical compound [Cl-].CC1=C(CCO)SC=[N+]1CC1=CC=CC=C1 IWSVLBKHBJGMAA-UHFFFAOYSA-M 0.000 description 3
- BDQRQMLWZJQQKS-UHFFFAOYSA-M 2-(3-ethyl-4-methyl-1,3-thiazol-3-ium-5-yl)ethanol;bromide Chemical compound [Br-].CC[N+]1=CSC(CCO)=C1C BDQRQMLWZJQQKS-UHFFFAOYSA-M 0.000 description 3
- 239000005711 Benzoic acid Substances 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 108090000854 Oxidoreductases Proteins 0.000 description 3
- 102000004316 Oxidoreductases Human genes 0.000 description 3
- 208000018262 Peripheral vascular disease Diseases 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 230000001476 alcoholic effect Effects 0.000 description 3
- 235000010233 benzoic acid Nutrition 0.000 description 3
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 3
- 208000029078 coronary artery disease Diseases 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000012362 glacial acetic acid Substances 0.000 description 3
- 208000010125 myocardial infarction Diseases 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- KJTLQQUUPVSXIM-ZCFIWIBFSA-N (R)-mevalonic acid Chemical compound OCC[C@](O)(C)CC(O)=O KJTLQQUUPVSXIM-ZCFIWIBFSA-N 0.000 description 2
- SEOZPKYDFRZJMV-UHFFFAOYSA-N 3-[(2-oxo-1,3-oxazolidin-3-yl)phosphanyl]-1,3-oxazolidin-2-one Chemical compound O=C1OCCN1PN1C(=O)OCC1 SEOZPKYDFRZJMV-UHFFFAOYSA-N 0.000 description 2
- 208000037260 Atherosclerotic Plaque Diseases 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
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 2
- 108010028554 LDL Cholesterol Proteins 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- 208000005764 Peripheral Arterial Disease Diseases 0.000 description 2
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical class C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 2
- 239000003849 aromatic solvent Substances 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- 238000010945 base-catalyzed hydrolysis reactiony Methods 0.000 description 2
- 206010008118 cerebral infarction Diseases 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 238000006264 debenzylation reaction Methods 0.000 description 2
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 230000008694 endothelial dysfunction Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 2
- 230000002107 myocardial effect Effects 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 2
- 230000007505 plaque formation Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 206010008132 Cerebral thrombosis Diseases 0.000 description 1
- 101100295738 Gallus gallus COR3 gene Proteins 0.000 description 1
- 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 1
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 206010022657 Intestinal infarction Diseases 0.000 description 1
- 201000001429 Intracranial Thrombosis Diseases 0.000 description 1
- 238000008214 LDL Cholesterol Methods 0.000 description 1
- 102000007330 LDL Lipoproteins Human genes 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 239000012317 TBTU Substances 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 239000003529 anticholesteremic agent Substances 0.000 description 1
- 229940127226 anticholesterol agent Drugs 0.000 description 1
- 210000002565 arteriole Anatomy 0.000 description 1
- 229960005370 atorvastatin Drugs 0.000 description 1
- FQCKMBLVYCEXJB-MNSAWQCASA-L atorvastatin calcium Chemical compound [Ca+2].C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1.C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 FQCKMBLVYCEXJB-MNSAWQCASA-L 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 description 1
- 230000006696 biosynthetic metabolic pathway Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000012320 chlorinating reagent Substances 0.000 description 1
- 239000005515 coenzyme Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000000 cycloalkoxy group Chemical group 0.000 description 1
- 230000005786 degenerative changes Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 229960004132 diethyl ether Drugs 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 229940052303 ethers for general anesthesia Drugs 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- RBBOWEDMXHTEPA-UHFFFAOYSA-N hexane;toluene Chemical compound CCCCCC.CC1=CC=CC=C1 RBBOWEDMXHTEPA-UHFFFAOYSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 150000001261 hydroxy acids Chemical class 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229940002661 lipitor Drugs 0.000 description 1
- 230000006984 memory degeneration Effects 0.000 description 1
- 208000023060 memory loss Diseases 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003431 oxalo group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000004001 thioalkyl group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/67—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of saturated acids
- C07C69/716—Esters of keto-carboxylic acids or aldehydo-carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/738—Esters of keto-carboxylic acids or aldehydo-carboxylic acids
-
- 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
- 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
- C07D403/04—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 directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero 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
- C07D413/02—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
- C07D413/04—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 directly linked by a ring-member-to-ring-member bond
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US44941803A | 2003-05-30 | 2003-05-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200510277B true ZA200510277B (en) | 2006-09-27 |
Family
ID=33489407
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200510277A ZA200510277B (en) | 2003-05-30 | 2005-12-19 | Substituted pyrrole derivatives and their use as HMB-Co inhibitors |
Country Status (29)
| Country | Link |
|---|---|
| US (3) | US7923467B2 (pt) |
| EP (2) | EP2319843B1 (pt) |
| JP (2) | JP4901474B2 (pt) |
| KR (2) | KR20110117731A (pt) |
| CN (2) | CN1812983A (pt) |
| AP (2) | AP2501A (pt) |
| AR (1) | AR044470A1 (pt) |
| AU (1) | AU2004242777B2 (pt) |
| BR (1) | BRPI0410840A (pt) |
| CA (2) | CA2753318A1 (pt) |
| CO (1) | CO5720994A2 (pt) |
| CR (1) | CR8111A (pt) |
| EA (1) | EA009646B1 (pt) |
| EC (1) | ECSP056193A (pt) |
| GE (1) | GEP20084406B (pt) |
| IL (1) | IL172257A0 (pt) |
| IS (1) | IS8195A (pt) |
| MA (1) | MA27844A1 (pt) |
| MX (1) | MXPA05012900A (pt) |
| MY (1) | MY148499A (pt) |
| NO (1) | NO20056218L (pt) |
| NZ (2) | NZ543741A (pt) |
| OA (1) | OA13174A (pt) |
| RS (1) | RS20050890A (pt) |
| SG (1) | SG141430A1 (pt) |
| TN (1) | TNSN05306A1 (pt) |
| UA (1) | UA82698C2 (pt) |
| WO (1) | WO2004106299A2 (pt) |
| ZA (1) | ZA200510277B (pt) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| UA82698C2 (uk) | 2003-05-30 | 2008-05-12 | Ранбакси Лабораториз Лимитед | Заміщені похідні піролу та їх використання в якості інгібіторів hmg-co |
| US20090209612A1 (en) * | 2004-05-31 | 2009-08-20 | Sattigeri Jitendra A | Process for the preparation of atorvastatin |
| EP1671947A1 (en) | 2004-12-20 | 2006-06-21 | Ratiopharm GmbH | Process for preparing pyrrole derivatives and intermediates |
| EP1705175A1 (en) * | 2005-03-24 | 2006-09-27 | ratiopharm GmbH | Process for preparing C5 products and their use for Atorvastatin synthesis |
| US8026377B2 (en) | 2005-11-08 | 2011-09-27 | Ranbaxy Laboratories, Limited | Process for (3R, 5R)-7-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-[(4-hydroxy methyl phenyl amino) carbonyl]-pyrrol-1-yl]-3,5-dihydroxy-heptanoic acid hemi calcium salt |
| WO2008020314A2 (en) * | 2006-03-14 | 2008-02-21 | Ranbaxy Laboratories Limited | Statin stabilizing dosage formulations |
| CL2007002044A1 (es) * | 2006-07-14 | 2008-06-13 | Ranbaxy Lab Ltd | Polimorfo cristalino de la sal hemicalcica del acido (3r,5r)-7-[2-(4-fluorofenil)-5-isopropil-3-fenil-4-[(4-hidroximetilfenilamino)carbonil]-pirrol-1-il]-3,5-dihidroxiheptanoico; composicion farmaceutica; y uso para el tratamiento de la diabetes, enf |
| US8624063B2 (en) | 2009-06-30 | 2014-01-07 | Wisconsin Alumni Research Foundation | Non-lactone carbocyclic and heterocyclic antagonists and agonists of bacterial quorum sensing |
| WO2011153247A1 (en) * | 2010-06-01 | 2011-12-08 | Furiex Pharmaceuticals, Inc. | Combination therapies |
| KR102013157B1 (ko) * | 2015-03-31 | 2019-08-23 | 대원제약주식회사 | 결정형 및 이의 제조방법 |
| US10526278B2 (en) | 2017-10-19 | 2020-01-07 | Wisconsin Alumni Research Foundation | Inhibitors of quorum sensing receptor LasR |
| KR102218320B1 (ko) * | 2019-07-12 | 2021-02-23 | 대원제약주식회사 | (3r,5r)-7-(2-(4-플루오로페닐)-5-이소프로필-3-페닐-4-((4-히드록시메틸페닐아미노)카보닐)-피롤-1-일)-3,5-디히드록시 헵탄산 헤미칼슘염의 제조방법, 및 이에 사용되는 중간체의 제조방법 |
Family Cites Families (186)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2990173A (en) * | 1957-12-23 | 1961-06-27 | Melville Wilbur | Registration control methods and devices |
| FR148F (pt) | 1962-01-24 | |||
| US3262977A (en) * | 1962-03-10 | 1966-07-26 | Chinoin Gyogyszer Es Vegyeszet | N-aralkyl-1, 1-diphenyl-propylamine derivatives |
| US3238215A (en) | 1963-10-17 | 1966-03-01 | Sterling Drug Inc | 1-[(3-, 2-, and 1-indolyl)-lower-alkyl-, lower-alkenyl-, and lower-alkynyl]piperidines |
| US3483221A (en) | 1964-09-10 | 1969-12-09 | Ciba Geigy Corp | 1 - (isopropylamino)-2-hydroxy-3-(alkenyloxyphenoxy) - propanes and the salts thereof |
| US3471515A (en) | 1965-02-01 | 1969-10-07 | Sandoz Ag | (2-hydroxy-3-substituted aminopropoxy)indoles |
| US3454635A (en) * | 1965-07-27 | 1969-07-08 | Hoechst Ag | Benzenesulfonyl-ureas and process for their manufacture |
| GB1200886A (en) * | 1966-09-23 | 1970-08-05 | Allen & Hanburys Ltd | Phenylaminoethanol derivatives |
| US3937838A (en) * | 1966-10-19 | 1976-02-10 | Aktiebolaget Draco | Orally active bronchospasmolytic compounds and their preparation |
| US3868460A (en) * | 1967-02-06 | 1975-02-25 | Boehringer Sohn Ingelheim | Therapeutic compositions and method |
| US3562257A (en) * | 1967-10-28 | 1971-02-09 | Tanabe Seiyaku Co | Benzothiazepine derivatives |
| US3857952A (en) | 1967-12-22 | 1974-12-31 | May & Baker Ltd | Certain benzene derivatives useful in treating cardiac disorders |
| US3674836A (en) * | 1968-05-21 | 1972-07-04 | Parke Davis & Co | 2,2-dimethyl-{11 -aryloxy-alkanoic acids and salts and esters thereof |
| US4058552A (en) | 1969-01-31 | 1977-11-15 | Orchimed Sa | Esters of p-carbonylphenoxy-isobutyric acids |
| US3934032A (en) * | 1969-02-21 | 1976-01-20 | Imperial Chemical Industries Limited | Alkanolamine derivatives for treating hypertension |
| US3716583A (en) * | 1969-04-16 | 1973-02-13 | Sumitomo Chemical Co | Phenoxy carboxylic acid derivative |
| US3655663A (en) * | 1969-04-21 | 1972-04-11 | Burton K Wasson | 4-(3-secondary amino-2-hydroxy-proxy) 1 2 5-thiadiazoles |
| US3663570A (en) * | 1969-04-28 | 1972-05-16 | Sankyo Co | Coumarin derivatives |
| US3576883A (en) * | 1969-06-30 | 1971-04-27 | Consolidation Coal Co | Alkylidenedithiobisphenols |
| US4012444A (en) * | 1969-07-08 | 1977-03-15 | Allen & Hanburys Limited | 5-[1-Hydroxy-2-(1-methyl-3-phenylpropyl)aminoethyl] salicylamide and physiologically acceptable acid addition salts thereof |
| AT296986B (de) * | 1969-08-13 | 1972-03-10 | Merz & Co | Verfahren zur Herstellung von neuen α-Halogenphenoxy-isobutyroyl-β-nicotinoyl-glykolen |
| BE755071A (fr) * | 1969-09-17 | 1971-02-22 | Warner Lambert Pharmaceutical | Procede de resolution de la dl-5-/3-(terbutylamino)-2- hydroxy-propoxy/-3,4-dihydro-1(2h) naphtalenone |
| US3663706A (en) * | 1969-09-29 | 1972-05-16 | Pfizer | Use of 2,4-diaminoquinazolines as hypotensive agents |
| SE354851B (pt) | 1970-02-18 | 1973-03-26 | Haessle Ab | |
| US3879554A (en) * | 1970-03-20 | 1975-04-22 | Farmaceutici Italia | Use of 1,6-dimethyl-8-{62 -(5-bromonicotinoyloxymethyl)-10 {60 -methoxyergoline in treating cerebral and peripheral metabolic vascular disorders |
| US4032648A (en) * | 1970-04-06 | 1977-06-28 | Science Union Et Cie | Method and compositions containing thiochroman compounds for treating cardiac rhythm disorders |
| US3669968A (en) * | 1970-05-21 | 1972-06-13 | Pfizer | Trialkoxy quinazolines |
| US3932645A (en) * | 1971-04-10 | 1976-01-13 | Farbenfabriken Bayer Ag | Pharmaceutical compositions containing unsymmetrical esters of 1,4-dihydropyridine 3,5-dicarboxylic acid |
| US4056626A (en) | 1971-05-13 | 1977-11-01 | Kakenyaku Kako Co., Ltd. | Pharmaceutical composition containing benzofuran derivative |
| DE2230383C3 (de) | 1971-10-01 | 1981-12-03 | Boehringer Mannheim Gmbh, 6800 Mannheim | Phenoxyalkylcarbonsäurederivate und Verfahren zur Herstellung derselben |
| DE2815926A1 (de) * | 1978-04-13 | 1979-10-18 | Boehringer Mannheim Gmbh | Neue carbazolyl-(4)-oxy-propanolamin-derivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| US3773939A (en) | 1971-11-24 | 1973-11-20 | Janssen Pharmaceutica Nv | N-arallyl-n'-aralkyl piperazine pharmaceutical compositions |
| US3982021A (en) | 1971-12-01 | 1976-09-21 | E. R. Squibb & Sons, Inc. | Compositions for the treatment of coronary diseases containing tetrahydronaphthyloxy-aminopropanols |
| BE790165A (fr) | 1971-12-14 | 1973-02-15 | Parke Davis & Co | Nouveaux aminoalcanols et procede pour les preparer |
| US3994974A (en) | 1972-02-05 | 1976-11-30 | Yamanouchi Pharmaceutical Co., Ltd. | α-Aminomethylbenzyl alcohol derivatives |
| BE795735A (fr) * | 1972-03-06 | 1973-06-18 | Cerm Cent Europ Rech Mauvernay | Nouvelles ethylenediamines substituees a activite cardiovasculaire |
| JPS5229318B2 (pt) | 1972-03-30 | 1977-08-01 | ||
| US3910924A (en) | 1972-04-13 | 1975-10-07 | Otsuka Pharma Co Ltd | 3,4-Dihydrocarbostyril derivatives and a process for preparing the same |
| GB1435139A (en) * | 1972-08-17 | 1976-05-12 | Sumitomo Chemical Co | Thiazole derivatives |
| GB1422263A (en) | 1973-01-30 | 1976-01-21 | Ferrosan As | 4-phenyl-piperidine compounds |
| DE2308826C3 (de) | 1973-02-22 | 1980-03-27 | Ludwig Merckle Kg Chem. Pharm. Fabrik, 7902 Blaubeuren | Phenoxyalkancarbonsäureester von Oxyalkyltheophyllinen, Verfahren zu ihrer Herstellung und Arzneimittel |
| DE2322232A1 (de) * | 1973-05-03 | 1974-11-14 | Thomae Gmbh Dr K | Neue acylaminosaeureamide |
| US4011258A (en) * | 1973-06-21 | 1977-03-08 | Aktiebolaget Draco | Orally active bronchospasmolytic compounds |
| US4062950A (en) | 1973-09-22 | 1977-12-13 | Bayer Aktiengesellschaft | Amino sugar derivatives |
| AT334385B (de) * | 1973-12-20 | 1976-01-10 | Chemie Linz Ag | Verfahren zur herstellung von neuen phenoxypropylaminderivaten und deren salzen |
| US4314081A (en) * | 1974-01-10 | 1982-02-02 | Eli Lilly And Company | Arloxyphenylpropylamines |
| NL175059C (nl) | 1974-02-23 | Boehringer Mannheim Gmbh | Bereiding van bloeddrukverlagende stoffen en van preparaten die ze bevatten. | |
| GB1501632A (en) * | 1974-06-28 | 1978-02-22 | Cm Ind | Aromatic ketones having cardiovascular activity |
| US4051143A (en) | 1974-09-05 | 1977-09-27 | Merz & Co. | Process for the production of α-[2-(p-chlorophenoxy)-isobutyryl]-β-nicotinoyl glycol ester |
| US4129565A (en) | 1975-07-11 | 1978-12-12 | Nisshin Flour Milling Co., Ltd. | Isocarbostyril derivatives |
| DE2635209C2 (de) * | 1975-08-15 | 1983-01-27 | Sandoz-Patent-GmbH, 7850 Lörrach | 4-(2-Benzoyloxy-3-tert.butylamino-propoxy)-2-methylindol, dessen (S)-Enantiomeres, deren Säureadditionssalze, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Heilmittel |
| GB1555654A (en) * | 1977-06-25 | 1979-11-14 | Exxon Research Engineering Co | Agricultural burner apparatus |
| US4105776A (en) | 1976-06-21 | 1978-08-08 | E. R. Squibb & Sons, Inc. | Proline derivatives and related compounds |
| US4154839A (en) * | 1975-11-05 | 1979-05-15 | Bayer Aktiengesellschaft | 2,6-Dimethyl-3-carboxymethoxy-4-(2-nitrophenyl)-5-carbisobutoxy-1,4-dihydropyridine |
| FR2330383A1 (fr) * | 1975-11-06 | 1977-06-03 | Synthelabo | Nouveaux ethers de phenols substitues, leurs sels, leur preparation et les medicaments qui les renferment |
| HU172137B (hu) * | 1976-03-02 | 1978-06-28 | Gyogyszerkutato Intezet | Sposob poluchenija zamehhjonnykh proizvodnykh fenoksi-propanolamina |
| DE2645710C2 (de) * | 1976-10-09 | 1985-06-27 | Merck Patent Gmbh, 6100 Darmstadt | Phenoxy-amino-propanole, Verfahren zu ihrer Herstellung und pharmazeutische Zubereitung |
| US4466972A (en) | 1977-06-20 | 1984-08-21 | Sandoz Ltd. | Benzoxadiazoles and benzothiadiazoles, their preparation and pharmaceutical compositions containing them |
| NO154918C (no) * | 1977-08-27 | 1987-01-14 | Bayer Ag | Analogifremgangsmaate til fremstilling av terapeutisk aktive derivater av 3,4,5-trihydroksypiperidin. |
| CA1147342A (en) | 1977-10-12 | 1983-05-31 | Kazuo Imai | Process of producing novel phenylethanolamine derivatives |
| US4188390A (en) * | 1977-11-05 | 1980-02-12 | Pfizer Inc. | Antihypertensive 4-amino-2-[4-(1,4-benzodioxan-2-carbonyl) piperazin-1-yl or homopiperazin-1-yl]quinazolines |
| IT1094076B (it) * | 1978-04-18 | 1985-07-26 | Acraf | Cicloalchiltriazoli |
| SE429652B (sv) * | 1978-06-30 | 1983-09-19 | Haessle Ab | 2.6-dimetyl-4-(2.3-diklorfenyl)-1.4-dihydropyridin-3.5-dikarboxylsyra-3-metylester-5-etylester |
| JPS559058A (en) * | 1978-07-06 | 1980-01-22 | Dainippon Pharmaceut Co Ltd | 1-(3-mercapto-2-methylpropanoyl)prolyl amino acid derivative |
| JPS5522636A (en) * | 1978-08-04 | 1980-02-18 | Takeda Chem Ind Ltd | Thiazoliding derivative |
| IL58849A (en) | 1978-12-11 | 1983-03-31 | Merck & Co Inc | Carboxyalkyl dipeptides and derivatives thereof,their preparation and pharmaceutical compositions containing them |
| US4508729A (en) * | 1979-12-07 | 1985-04-02 | Adir | Substituted iminodiacids, their preparation and pharmaceutical compositions containing them |
| JPS56110665A (en) * | 1980-02-08 | 1981-09-01 | Yamanouchi Pharmaceut Co Ltd | Sulfamoyl-substituted phenetylamine derivative and its preparation |
| US4344949A (en) | 1980-10-03 | 1982-08-17 | Warner-Lambert Company | Substituted acyl derivatives of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids |
| US4470972A (en) | 1981-04-28 | 1984-09-11 | Schering Corporation | 7-Carboxyalkylaminoacyl-1,4-dithia-7-azaspiro[4.4]-nonane-8-carboxylic acids |
| ZA817261B (en) * | 1980-10-23 | 1982-09-29 | Schering Corp | Carboxyalkyl dipeptides,processes for their production and pharmaceutical compositions containing them |
| AU543804B2 (en) * | 1980-10-31 | 1985-05-02 | Takeda Chemical Industries Ltd. | Amides having bicyclic substituents on nitrogen |
| US4337201A (en) * | 1980-12-04 | 1982-06-29 | E. R. Squibb & Sons, Inc. | Phosphinylalkanoyl substituted prolines |
| DE3166093D1 (en) | 1981-01-05 | 1984-10-18 | Takeda Chemical Industries Ltd | N-substituted pseudo-aminosugars, their production and use |
| US4425355A (en) * | 1981-02-17 | 1984-01-10 | Warner-Lambert Company | Substituted acyl derivatives of chair form of octahydro-1H-indole-2-carboxylic acids |
| ZA821577B (en) * | 1981-04-06 | 1983-03-30 | Boots Co Plc | Therapeutic agents |
| JPS57171968A (en) * | 1981-04-17 | 1982-10-22 | Kyowa Hakko Kogyo Co Ltd | 1,4-dihydropyridine derivative |
| US4410520A (en) | 1981-11-09 | 1983-10-18 | Ciba-Geigy Corporation | 3-Amino-[1]-benzazepin-2-one-1-alkanoic acids |
| DK161312C (da) * | 1982-03-11 | 1991-12-09 | Pfizer | Analogifremgangsmaade til fremstilling af 2-aminoalkoxymethyl-4-phenyl-6-methyl-1,4-dihydropyridin-3,5-dicarboxylsyreestere eller syreadditionssalte deraf samt phthalimidoderivater til anvendelse som udgangsmateriale ved fremgangsmaaden |
| CA1247547A (en) * | 1983-06-22 | 1988-12-28 | Paul Hadvary | Leucine derivatives |
| GB8403866D0 (en) | 1984-02-14 | 1984-03-21 | Recordati Chem Pharm | Diphenylalkylaminoalkyl esters |
| JPS60222472A (ja) * | 1984-03-30 | 1985-11-07 | Kanebo Ltd | 新規なピペラジン誘導体および該化合物を有効成分とする医薬組成物 |
| US4699905A (en) | 1984-04-10 | 1987-10-13 | Sankyo Company, Limited | Perhydrothiazepine derivatives, their preparation and their therapeutic use |
| US4672068A (en) * | 1984-05-04 | 1987-06-09 | Fujirebio Kabushiki Kaisha | Antihypertensive 1,4-dihydropyridines having a conjugated ester |
| GB8418424D0 (en) * | 1984-07-19 | 1984-08-22 | Scras | Inhibition of platelets aggregation |
| NZ212895A (en) * | 1984-08-22 | 1988-07-28 | Glaxo Spa | 1,4-dihydropyridine derivatives and pharmaceutical compositions |
| AR240698A1 (es) | 1985-01-19 | 1990-09-28 | Takeda Chemical Industries Ltd | Procedimiento para preparar compuestos de 5-(4-(2-(5-etil-2-piridil)-etoxi)benzil)-2,4-tiazolidindiona y sus sales |
| DE3502392A1 (de) | 1985-01-25 | 1986-07-31 | Boehringer Ingelheim KG, 6507 Ingelheim | Neue thieno-triazolo-1,4-diazepino-2- carbonsaeureamide, verfahren zu ihrer herstellung und pharmazeutische zusammensetzungen |
| GB8608335D0 (en) | 1986-04-04 | 1986-05-08 | Pfizer Ltd | Pharmaceutically acceptable salts |
| US4681893A (en) | 1986-05-30 | 1987-07-21 | Warner-Lambert Company | Trans-6-[2-(3- or 4-carboxamido-substituted pyrrol-1-yl)alkyl]-4-hydroxypyran-2-one inhibitors of cholesterol synthesis |
| US5138069A (en) * | 1986-07-11 | 1992-08-11 | E. I. Du Pont De Nemours And Company | Angiotensin II receptor blocking imidazoles |
| US4873259A (en) | 1987-06-10 | 1989-10-10 | Abbott Laboratories | Indole, benzofuran, benzothiophene containing lipoxygenase inhibiting compounds |
| JP2625190B2 (ja) * | 1987-03-27 | 1997-07-02 | ビイク グルデン ロンベルク ヒエーミツシエ フアブリーク ゲゼルシヤフト ミツト ベシユレンクテル ハフツング | １，４―ジヒドロピリジン―エナンチオマーおよびその製法 |
| EP0842925A1 (en) * | 1987-09-04 | 1998-05-20 | Beecham Group Plc | Substituted thiazolidinedione derivatives |
| US5114976A (en) * | 1989-01-06 | 1992-05-19 | Norden Michael J | Method for treating certain psychiatric disorders and certain psychiatric symptoms |
| GB8907256D0 (en) * | 1989-03-31 | 1989-05-17 | Rech Et D Applic Scient Scras | New derivatives of hetrazepine as anti-asthmatic anti-allergic and gastro-intestinal protectors |
| GB8911030D0 (en) | 1989-05-13 | 1989-06-28 | Scras | Hetrazepine derivatives |
| US5185351A (en) * | 1989-06-14 | 1993-02-09 | Smithkline Beecham Corporation | Imidazolyl-alkenoic acids useful as angiotensin II receptor antagonists |
| FI94339C (fi) | 1989-07-21 | 1995-08-25 | Warner Lambert Co | Menetelmä farmaseuttisesti käyttökelpoisen /R-(R*,R*)/-2-(4-fluorifenyyli)- , -dihydroksi-5-(1-metyylietyyli)-3-fenyyli-4-/(fenyyliamino)karbonyyli/-1H-pyrroli-1-heptaanihapon ja sen farmaseuttisesti hyväksyttävien suolojen valmistamiseksi |
| NZ234883A (en) | 1989-08-22 | 1995-01-27 | Merck Frosst Canada Inc | Quinolin-2-ylmethoxy indole derivatives, preparation and pharmaceutical compositions thereof |
| DE122007000050I1 (de) * | 1990-02-19 | 2007-11-08 | Novartis Ag | Acylverbindungen |
| US5270317A (en) | 1990-03-20 | 1993-12-14 | Elf Sanofi | N-substituted heterocyclic derivatives, their preparation and the pharmaceutical compositions in which they are present |
| ZA914764B (en) * | 1990-06-22 | 1992-03-25 | Schering Corp | Bis-benzo or benzopyrido cyclohepta piperidene,piperidylidene and piperazine compounds,compositions and methods of use |
| US5274094A (en) | 1990-08-15 | 1993-12-28 | British Bio-Technology Limited | Production of heterobicyclic containing benzene sulfonamides |
| US5994510A (en) | 1990-12-21 | 1999-11-30 | Celltech Therapeutics Limited | Recombinant antibodies specific for TNFα |
| US5155120A (en) | 1991-01-14 | 1992-10-13 | Pfizer Inc | Method for treating congestive heart failure |
| US5254541A (en) | 1991-11-15 | 1993-10-19 | Merck Frosst Canada, Inc. | (Quinolin-2-ylmethoxy)indole/cyclodextrin complex |
| EP0542355A1 (en) | 1991-11-15 | 1993-05-19 | Merck Frosst Canada Inc. | Amorphous (Quinolin-2-ylmethoxy)indoles as leukotriene antagonists |
| HU9203780D0 (en) | 1991-12-12 | 1993-03-29 | Sandoz Ag | Stabilized pharmaceutical products of hmg-coa reductase inhibitor and method for producing them |
| EP0633776B1 (en) | 1992-04-02 | 2001-05-09 | Smithkline Beecham Corporation | Compounds useful for treating allergic and inflammatory diseases |
| FR2692575B1 (fr) * | 1992-06-23 | 1995-06-30 | Sanofi Elf | Nouveaux derives du pyrazole, procede pour leur preparation et compositions pharmaceutiques les contenant. |
| GB9215665D0 (en) | 1992-07-23 | 1992-09-09 | British Bio Technology | Compounds |
| US5344914A (en) | 1992-10-05 | 1994-09-06 | The Center For Innovative Technology* | Commercially valuable polymeric ketones and method of preparing same |
| US5349056A (en) | 1992-10-09 | 1994-09-20 | Regeneron Pharmaceuticals | Modified ciliary neurotrophic factors |
| EP0606646B1 (en) | 1992-12-28 | 1997-09-24 | Asahi Medical Co., Ltd. | Filtermaterial, apparatus and method for removing leukocytes |
| US5362647A (en) * | 1993-02-12 | 1994-11-08 | Allergan, Inc. | Compositions and methods for destroying hydrogen peroxide |
| US5491172A (en) * | 1993-05-14 | 1996-02-13 | Warner-Lambert Company | N-acyl sulfamic acid esters (or thioesters), N-acyl sulfonamides, and N-sulfonyl carbamic acid esters (or thioesters) as hypercholesterolemic agents |
| US5424286A (en) * | 1993-05-24 | 1995-06-13 | Eng; John | Exendin-3 and exendin-4 polypeptides, and pharmaceutical compositions comprising same |
| US5474995A (en) | 1993-06-24 | 1995-12-12 | Merck Frosst Canada, Inc. | Phenyl heterocycles as cox-2 inhibitors |
| ES2176252T3 (es) * | 1993-07-02 | 2002-12-01 | Altana Pharma Ag | Benzamidas sustituidas con fluoro-alcoxi y su utilizacion como agentes inhibidores de fosfodiesterasas de nucleotidos ciclicos. |
| JP3286745B2 (ja) * | 1993-09-10 | 2002-05-27 | 日清食品株式会社 | シクロヘキサンジウレア誘導体及びその製法 |
| US5631365A (en) * | 1993-09-21 | 1997-05-20 | Schering Corporation | Hydroxy-substituted azetidinone compounds useful as hypocholesterolemic agents |
| US5466823A (en) | 1993-11-30 | 1995-11-14 | G.D. Searle & Co. | Substituted pyrazolyl benzenesulfonamides |
| KR0136986B1 (ko) * | 1993-12-31 | 1998-04-25 | 김준웅 | 신규 징코라이드 유도체와 이의 제조방법 |
| US5385929A (en) * | 1994-05-04 | 1995-01-31 | Warner-Lambert Company | [(Hydroxyphenylamino) carbonyl] pyrroles |
| TW474813B (en) | 1994-06-10 | 2002-02-01 | Geltex Pharma Inc | Alkylated composition for removing bile salts from a patient |
| US5510332A (en) * | 1994-07-07 | 1996-04-23 | Texas Biotechnology Corporation | Process to inhibit binding of the integrin α4 62 1 to VCAM-1 or fibronectin and linear peptides therefor |
| US6642268B2 (en) | 1994-09-13 | 2003-11-04 | G.D. Searle & Co. | Combination therapy employing ileal bile acid transport inhibiting benzothipines and HMG Co-A reductase inhibitors |
| US6268392B1 (en) * | 1994-09-13 | 2001-07-31 | G. D. Searle & Co. | Combination therapy employing ileal bile acid transport inhibiting benzothiepines and HMG Co-A reductase inhibitors |
| DE4439947A1 (de) | 1994-11-09 | 1996-05-15 | Boehringer Mannheim Gmbh | 2,2-Dichloralkancarbonsäuren, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel |
| US5633272A (en) * | 1995-02-13 | 1997-05-27 | Talley; John J. | Substituted isoxazoles for the treatment of inflammation |
| RU2158607C2 (ru) | 1995-07-03 | 2000-11-10 | Санкио Компани Лимитед | Лечение артериосклероза и ксантомы |
| FR2741619B1 (fr) | 1995-11-28 | 1998-02-13 | Pf Medicament | Nouveaux derives de 2,3,5-trimethyl-4-hydroxy-anilides, leur preparation et leur application en therapeutique |
| US5753653A (en) * | 1995-12-08 | 1998-05-19 | Agouron Pharmaceuticals, Inc. | Metalloproteinase inhibitors, pharmaceutical compositions containing them and their pharmaceutical uses |
| CA2249009C (en) | 1996-04-12 | 2003-09-16 | G.D. Searle & Co. | Substituted benzenesulfonamide derivatives as prodrugs of cox-2 inhibitors |
| DE19627431A1 (de) | 1996-07-08 | 1998-01-15 | Bayer Ag | Heterocyclisch kondensierte Pyridine |
| HRP970330B1 (en) | 1996-07-08 | 2004-06-30 | Bayer Ag | Cycloalkano pyridines |
| DE19647380A1 (de) | 1996-11-15 | 1998-05-20 | Hoechst Ag | 5-Ring-Heterocyclen als Inhibitoren der Leukozytenadhäsion und VLA-4-Antagonisten |
| JP2894445B2 (ja) * | 1997-02-12 | 1999-05-24 | 日本たばこ産業株式会社 | Ｃｅｔｐ活性阻害剤として有効な化合物 |
| US5910319A (en) | 1997-05-29 | 1999-06-08 | Eli Lilly And Company | Fluoxetine enteric pellets and methods for their preparation and use |
| DE19741235A1 (de) | 1997-09-18 | 1999-03-25 | Hoechst Marion Roussel De Gmbh | Neue Imidazolidinderivate, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate |
| DE19741873A1 (de) | 1997-09-23 | 1999-03-25 | Hoechst Marion Roussel De Gmbh | Neue 5-Ring-Heterocyclen, ihre Herstellung, ihre Verwendung und sie enthaltende pharmazeutische Präparate |
| DE19751251A1 (de) | 1997-11-19 | 1999-05-20 | Hoechst Marion Roussel De Gmbh | Substituierte Imidazolidinderivate, ihre Herstellung, ihre Verwendung und sie enthaltende pharmezeutische Präparate |
| US20040029962A1 (en) * | 1997-12-12 | 2004-02-12 | Chih-Ming Chen | HMG-COA reductase inhibitor extended release formulation |
| WO1999041237A1 (en) | 1998-02-13 | 1999-08-19 | G.D. Searle & Co. | Substituted pyridines useful for inhibiting cholesteryl ester transfer protein activity |
| GT199900147A (es) | 1998-09-17 | 1999-09-06 | 1, 2, 3, 4- tetrahidroquinolinas 2-sustituidas 4-amino sustituidas. | |
| US6147090A (en) * | 1998-09-17 | 2000-11-14 | Pfizer Inc. | 4-carboxyamino-2-methyl-1,2,3,4,-tetrahydroquinolines |
| US6197786B1 (en) * | 1998-09-17 | 2001-03-06 | Pfizer Inc | 4-Carboxyamino-2-substituted-1,2,3,4-tetrahydroquinolines |
| US6329344B1 (en) | 1998-10-22 | 2001-12-11 | Ranbaxy Laboratories Limited | Derivatives of monosaccharides as cell adhesion inhibitors |
| DE19858789A1 (de) * | 1998-12-18 | 2000-06-21 | Bayer Ag | Kombination von Cerivastatin und Fibraten |
| IN190975B (pt) | 1999-01-15 | 2003-09-06 | Ranbaxy Lab Ltd | |
| US6015557A (en) * | 1999-02-24 | 2000-01-18 | Tobinick; Edward L. | Tumor necrosis factor antagonists for the treatment of neurological disorders |
| US6569461B1 (en) * | 1999-03-08 | 2003-05-27 | Merck & Co., Inc. | Dihydroxy open-acid and salts of HMG-CoA reductase inhibitors |
| CN1191273C (zh) | 1999-05-17 | 2005-03-02 | 康久化学公司 | 长效促胰岛肽 |
| ATE320800T1 (de) * | 1999-08-21 | 2006-04-15 | Altana Pharma Ag | Synergistische kombination von roflumilast und salmeterol |
| US20010018446A1 (en) | 1999-09-23 | 2001-08-30 | G.D. Searle & Co. | Substituted N-Aliphatic-N-Aromatictertiary-Heteroalkylamines useful for inhibiting cholesteryl ester transfer protein activity |
| US6683113B2 (en) | 1999-09-23 | 2004-01-27 | Pharmacia Corporation | (R)-chiral halogenated substituted N,N-Bis-benzyl aminioalcohol compounds useful for inhibiting cholesteryl ester transfer protein activity |
| EE05351B1 (et) | 1999-12-10 | 2010-10-15 | Pfizer Products Inc. | Prrolo[2,3-d]primidiinhendid |
| US20020052312A1 (en) * | 2000-05-30 | 2002-05-02 | Reiss Theodore F. | Combination therapy of chronic obstructive pulmonary disease using muscarinic receptor antagonists |
| US20020028826A1 (en) | 2000-06-15 | 2002-03-07 | Robl Jeffrey A. | HMG-CoA reductase inhibitors and method |
| HUP0303083A3 (en) * | 2000-08-15 | 2005-05-30 | Pfizer Prod Inc | Pharmaceutical compositions containing therapeutic combination of a cetp inhibitor and atorvastatin and their use |
| IL156055A0 (en) * | 2000-11-30 | 2003-12-23 | Teva Pharma | Novel crystal forms of atorvastatin hemi calcium and processes for their preparation as well as novel processes for preparing other forms |
| US20040097555A1 (en) * | 2000-12-26 | 2004-05-20 | Shinegori Ohkawa | Concomitant drugs |
| PL202778B1 (pl) * | 2001-02-22 | 2009-07-31 | Skyepharma Canada Inc | Postać dawkowana kombinacji statyny i fenofibratu, sposób jej wytwarzania i zastosowanie |
| WO2003013608A1 (en) * | 2001-08-07 | 2003-02-20 | Galephar M/F | ORAL PHARMACEUTICAL COMPOSITION CONTAINING A COMBINAITION OF PPARα AND A HMG-COA REDUCTASE INHIBITOR |
| US7361772B2 (en) * | 2001-08-16 | 2008-04-22 | Biocon Limited | Process for the production of atorvastatin calcium |
| EP1291017A3 (en) * | 2001-09-10 | 2003-07-02 | Warner-Lambert Company | Use of statins to inhibit formation of osteoclasts |
| US20030153617A1 (en) | 2001-12-18 | 2003-08-14 | Dalen Frans Van | Simvastatin dosage forms |
| TW200810743A (en) | 2002-03-22 | 2008-03-01 | Novartis Ag | Combination of organic compounds |
| MY131170A (en) | 2002-03-28 | 2007-07-31 | Nissan Chemical Ind Ltd | Therapeutic agent for glomerular disease |
| US20040053842A1 (en) * | 2002-07-02 | 2004-03-18 | Pfizer Inc. | Methods of treatment with CETP inhibitors and antihypertensive agents |
| PL375415A1 (en) | 2002-08-06 | 2005-11-28 | Warner-Lambert Company Llc | Process for preparing 5-(4-fluorophenyl)-1-[2-((2r,4r)-4-hydroxy -6-oxo-tetrahydro-pyran-2-yl)ethyl]-2-isopropyl-4-phenyl-1h-pyrrole-3-carboxylic acid phenylamide |
| US20050187204A1 (en) | 2002-08-08 | 2005-08-25 | Sankyo Company, Limited | Medicinal composition for lowering blood lipid level |
| WO2004028456A2 (en) | 2002-09-26 | 2004-04-08 | Myriad Genetics, Inc | Method and composition for treating neurodegenerative disorders |
| US20040102511A1 (en) * | 2002-11-21 | 2004-05-27 | Jitendra Sattigeri | Substituted pyrrole derivatives |
| US20040132771A1 (en) | 2002-12-20 | 2004-07-08 | Pfizer Inc | Compositions of choleseteryl ester transfer protein inhibitors and HMG-CoA reductase inhibitors |
| DE10301371A1 (de) | 2003-01-16 | 2004-08-05 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Pharmazeutische Kombination zur Prophylaxe oder Therapie von kardiovaskulären, kardiopulmonalen, pulmonalen oder renalen Krankheiten |
| UA82698C2 (uk) * | 2003-05-30 | 2008-05-12 | Ранбакси Лабораториз Лимитед | Заміщені похідні піролу та їх використання в якості інгібіторів hmg-co |
| SE527189C2 (sv) * | 2003-06-19 | 2006-01-17 | Microdrug Ag | Inhalatoranordning samt kombinerade doser för formaterol och ett antikolinergiskt medel |
| US6884226B2 (en) * | 2003-07-02 | 2005-04-26 | Fred Pereira | Crib patting device |
| US7250444B2 (en) | 2003-08-11 | 2007-07-31 | Pfizer Inc. | Pyrrole-based HMG-CoA reductase inhibitors |
| EP1510208A1 (en) | 2003-08-22 | 2005-03-02 | Fournier Laboratories Ireland Limited | Pharmaceutical composition comprising a combination of metformin and statin |
| WO2005051931A2 (en) | 2003-11-26 | 2005-06-09 | Ranbaxy Laboratories Limited | Phosphodiesterase inhibitors |
| US8026377B2 (en) | 2005-11-08 | 2011-09-27 | Ranbaxy Laboratories, Limited | Process for (3R, 5R)-7-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-[(4-hydroxy methyl phenyl amino) carbonyl]-pyrrol-1-yl]-3,5-dihydroxy-heptanoic acid hemi calcium salt |
| WO2008020314A2 (en) | 2006-03-14 | 2008-02-21 | Ranbaxy Laboratories Limited | Statin stabilizing dosage formulations |
| CL2007002044A1 (es) * | 2006-07-14 | 2008-06-13 | Ranbaxy Lab Ltd | Polimorfo cristalino de la sal hemicalcica del acido (3r,5r)-7-[2-(4-fluorofenil)-5-isopropil-3-fenil-4-[(4-hidroximetilfenilamino)carbonil]-pirrol-1-il]-3,5-dihidroxiheptanoico; composicion farmaceutica; y uso para el tratamiento de la diabetes, enf |
-
2004
- 2004-05-28 UA UAA200512851A patent/UA82698C2/uk unknown
- 2004-05-28 BR BRPI0410840-0A patent/BRPI0410840A/pt not_active IP Right Cessation
- 2004-05-28 US US10/558,859 patent/US7923467B2/en not_active Expired - Fee Related
- 2004-05-28 EA EA200501881A patent/EA009646B1/ru not_active IP Right Cessation
- 2004-05-28 CA CA2753318A patent/CA2753318A1/en not_active Abandoned
- 2004-05-28 NZ NZ543741A patent/NZ543741A/en not_active IP Right Cessation
- 2004-05-28 WO PCT/IB2004/001761 patent/WO2004106299A2/en active Application Filing
- 2004-05-28 EP EP10179877A patent/EP2319843B1/en not_active Not-in-force
- 2004-05-28 MX MXPA05012900A patent/MXPA05012900A/es active IP Right Grant
- 2004-05-28 NZ NZ577031A patent/NZ577031A/en not_active IP Right Cessation
- 2004-05-28 OA OA1200500340A patent/OA13174A/en unknown
- 2004-05-28 RS YUP-2005/0890A patent/RS20050890A/sr unknown
- 2004-05-28 SG SG200800558-9A patent/SG141430A1/en unknown
- 2004-05-28 EP EP04735296A patent/EP1658283A2/en not_active Withdrawn
- 2004-05-28 CN CNA2004800180992A patent/CN1812983A/zh active Pending
- 2004-05-28 AP AP2009004783A patent/AP2501A/xx active
- 2004-05-28 JP JP2006530701A patent/JP4901474B2/ja not_active Expired - Fee Related
- 2004-05-28 AU AU2004242777A patent/AU2004242777B2/en not_active Ceased
- 2004-05-28 AP AP2005003459A patent/AP1963A/xx active
- 2004-05-28 GE GEAP20049124A patent/GEP20084406B/en unknown
- 2004-05-28 KR KR1020117023497A patent/KR20110117731A/ko not_active Application Discontinuation
- 2004-05-28 CA CA002526730A patent/CA2526730A1/en not_active Abandoned
- 2004-05-28 CN CN2010102819298A patent/CN101967117A/zh active Pending
- 2004-05-28 KR KR1020057022879A patent/KR20060021870A/ko not_active Application Discontinuation
- 2004-05-31 AR ARP040101872A patent/AR044470A1/es not_active Application Discontinuation
- 2004-05-31 MY MYPI20042094A patent/MY148499A/en unknown
-
2005
- 2005-11-29 MA MA28627A patent/MA27844A1/fr unknown
- 2005-11-29 CO CO05121080A patent/CO5720994A2/es not_active Application Discontinuation
- 2005-11-29 IL IL172257A patent/IL172257A0/en unknown
- 2005-11-29 TN TNP2005000306A patent/TNSN05306A1/en unknown
- 2005-11-30 CR CR8111A patent/CR8111A/es unknown
- 2005-11-30 EC EC2005006193A patent/ECSP056193A/es unknown
- 2005-12-19 ZA ZA200510277A patent/ZA200510277B/en unknown
- 2005-12-22 IS IS8195A patent/IS8195A/is unknown
- 2005-12-28 NO NO20056218A patent/NO20056218L/no unknown
-
2011
- 2011-04-11 US US13/084,374 patent/US20110190296A1/en not_active Abandoned
- 2011-04-11 US US13/084,390 patent/US20110190369A1/en not_active Abandoned
- 2011-06-15 JP JP2011133014A patent/JP2011236218A/ja not_active Withdrawn
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ZA200510277B (en) | Substituted pyrrole derivatives and their use as HMB-Co inhibitors | |
| KR101329113B1 (ko) | (3ｒ,5ｒ)-7-〔2-(4-플루오로페닐)-5-이소프로필-3-페닐-4-〔(4-히드록시 메틸 페닐 아미노)카르보닐〕-피롤-1-일〕-3,5-디히드록시 헵탄산 헤미 칼슘염의 제조 방법 | |
| SK7212003A3 (en) | Hydrolysis of [R(R*,R*)]-2-(4-fluorophenyl)-beta,delta-dihydroxy- 5-(1-methylethyl)-3-fenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1- heptanoic acid esters with calcium hydroxide | |
| US20090209612A1 (en) | Process for the preparation of atorvastatin | |
| CA2582778A1 (fr) | Derives de pyridine, leur preparation, leur application en therapeutique | |
| JP2007500203A5 (pt) | ||
| US8497370B2 (en) | Processes for preparing amine salts of sildenafil-analogues and use thereof | |
| US7915302B2 (en) | Crystal forms of pyrrolylheptanoic acid derivatives | |
| US20070149605A1 (en) | Substituted pyrrole derivatives as hmg-coa reductase inhibitors | |
| AU2011211338A1 (en) | Substituted pyrrole derivatives and their use as HMG-CO inhibitors | |
| KR101249868B1 (ko) | 아토르바스타틴의 제조를 위한 키랄 중간체의 제조방법 | |
| KR20080076124A (ko) | 아토르바스타틴의 제조방법 | |
| CA2019464A1 (en) | Bis (benzylpyrrolidine) derivatives as dopamine agonists |