SI8911362A - Process for lactonization of mevinic acids and analogs thereof - Google Patents
Process for lactonization of mevinic acids and analogs thereof Download PDFInfo
- Publication number
- SI8911362A SI8911362A SI8911362A SI8911362A SI8911362A SI 8911362 A SI8911362 A SI 8911362A SI 8911362 A SI8911362 A SI 8911362A SI 8911362 A SI8911362 A SI 8911362A SI 8911362 A SI8911362 A SI 8911362A
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- Slovenia
- Prior art keywords
- alkyl
- process according
- acid
- water
- compound
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 42
- 238000007273 lactonization reaction Methods 0.000 title claims abstract description 24
- 239000002253 acid Substances 0.000 title claims description 15
- 150000007513 acids Chemical class 0.000 title claims description 6
- 150000002596 lactones Chemical class 0.000 claims description 30
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 26
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 18
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical group OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 14
- 239000012535 impurity Substances 0.000 claims description 14
- 150000001875 compounds Chemical class 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- -1 2,2-dimethyl-butynyloxy Chemical group 0.000 claims description 11
- 239000003377 acid catalyst Substances 0.000 claims description 11
- 150000001768 cations Chemical class 0.000 claims description 10
- 239000000539 dimer Substances 0.000 claims description 10
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 10
- 239000003960 organic solvent Substances 0.000 claims description 9
- 238000002425 crystallisation Methods 0.000 claims description 8
- 230000008025 crystallization Effects 0.000 claims description 8
- 229910052751 metal Inorganic materials 0.000 claims description 8
- 239000002184 metal Substances 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 7
- 239000011541 reaction mixture Substances 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- OZJPLYNZGCXSJM-UHFFFAOYSA-N 5-valerolactone Chemical compound O=C1CCCCO1 OZJPLYNZGCXSJM-UHFFFAOYSA-N 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims description 4
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims description 4
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 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 claims description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical group COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Substances OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 2
- 239000011261 inert gas Substances 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 abstract description 3
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 abstract description 3
- BOZILQFLQYBIIY-INTXDZFKSA-N mevinic acid Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)CCC=C21 BOZILQFLQYBIIY-INTXDZFKSA-N 0.000 abstract description 2
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 abstract 1
- 239000000047 product Substances 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 5
- 150000001261 hydroxy acids Chemical class 0.000 description 5
- 239000012429 reaction media Substances 0.000 description 5
- 150000003839 salts Chemical group 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical class [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 4
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 229910052782 aluminium Inorganic materials 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 238000010926 purge Methods 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 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 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 102000004316 Oxidoreductases Human genes 0.000 description 2
- 108090000854 Oxidoreductases Proteins 0.000 description 2
- PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 2
- 229940043253 butylated hydroxyanisole Drugs 0.000 description 2
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 229960004844 lovastatin Drugs 0.000 description 2
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 2
- 229940099246 mevacor Drugs 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000010956 selective crystallization Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- XKMRRTOUMJRJIA-UHFFFAOYSA-N ammonia nh3 Chemical compound N.N XKMRRTOUMJRJIA-UHFFFAOYSA-N 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- 229920000080 bile acid sequestrant Polymers 0.000 description 1
- 229940096699 bile acid sequestrants Drugs 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- 229940011051 isopropyl acetate Drugs 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/16—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D309/28—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with 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
- C07D309/30—Oxygen atoms, e.g. delta-lactones
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Steroid Compounds (AREA)
- Pyrane Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Saccharide Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/221,475 US4916239A (en) | 1988-07-19 | 1988-07-19 | Process for the lactonization of mevinic acids and analogs thereof |
| YU136289A YU47492B (sh) | 1988-07-19 | 1989-07-10 | Postupak za laktonizaciju mevinskih kiselina i analoga istih |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SI8911362A true SI8911362A (en) | 1997-02-28 |
Family
ID=22827965
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SI8911362A SI8911362A (en) | 1988-07-19 | 1989-07-10 | Process for lactonization of mevinic acids and analogs thereof |
Country Status (26)
| Country | Link |
|---|---|
| US (1) | US4916239A (Direct) |
| EP (1) | EP0351918B1 (Direct) |
| JP (3) | JPH0273078A (Direct) |
| KR (1) | KR970011286B1 (Direct) |
| CN (1) | CN1022831C (Direct) |
| AT (1) | ATE111459T1 (Direct) |
| AU (1) | AU609319B2 (Direct) |
| CA (1) | CA1287639C (Direct) |
| CS (1) | CS274640B2 (Direct) |
| CY (1) | CY1813A (Direct) |
| DE (1) | DE68918191C5 (Direct) |
| DK (1) | DK173115B1 (Direct) |
| ES (1) | ES2058475T3 (Direct) |
| FI (1) | FI92695C (Direct) |
| HK (1) | HK136894A (Direct) |
| HR (1) | HRP930685B2 (Direct) |
| HU (2) | HU202511B (Direct) |
| IE (1) | IE64304B1 (Direct) |
| IL (1) | IL90925A (Direct) |
| LV (1) | LV11033B (Direct) |
| NO (1) | NO172800C (Direct) |
| NZ (1) | NZ229879A (Direct) |
| PT (1) | PT91191B (Direct) |
| SI (1) | SI8911362A (Direct) |
| YU (1) | YU47492B (Direct) |
| ZA (1) | ZA895458B (Direct) |
Families Citing this family (96)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4916239A (en) * | 1988-07-19 | 1990-04-10 | Merck & Co., Inc. | Process for the lactonization of mevinic acids and analogs thereof |
| GB9007738D0 (en) * | 1990-04-05 | 1990-06-06 | British Bio Technology | Compounds |
| US5223415A (en) * | 1990-10-15 | 1993-06-29 | Merck & Co., Inc. | Biosynthetic production of 7-[1',2',6',7',8',8a'(R)-hexahydro-2'(S),6'(R)-dimethyl-8'(S)-hydroxy-1'(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid (triol acid) |
| US5250435A (en) * | 1991-06-04 | 1993-10-05 | Merck & Co., Inc. | Mutant strains of Aspergillus terreus for producing 7-[1,2,6,7,8,8a(R)-hexa-hydro-2(S),6(R)-dimethyl-8(S)-hydroxy-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid (triol acid),I) |
| AU660132B2 (en) * | 1992-12-21 | 1995-06-08 | Bayer Aktiengesellschaft | Substituted 4-phenyl-pyridones and 4-phenyl-2-alkoxypyridine |
| DE69324504T2 (de) * | 1993-01-19 | 1999-08-26 | Warner-Lambert Co. | Stabilisierte, oral anzuwendende zusammensetzung enthaltend die verbindung ci-981 und verfahren |
| IN186880B (Direct) * | 1997-10-28 | 2001-12-01 | Ranbaxy Lab Ltd | |
| IN186879B (Direct) * | 1997-10-28 | 2001-12-01 | Ranbaxy Lab Ltd | |
| ZA9810764B (en) * | 1998-04-22 | 1999-08-13 | Ranbaxy Lab Ltd | An improved process of lactonization in the preparation of statins. |
| CA2240983A1 (en) | 1998-06-18 | 1999-12-18 | Yong Tao | Process to manufacture simvastatin and intermediates |
| CZ299522B6 (cs) * | 1998-12-10 | 2008-08-27 | Kaneka Corporation | Zpusob výroby diolu obsahujícího laktonovou skupinu |
| SK282679B6 (sk) * | 1999-04-16 | 2002-11-06 | Biotika, A. S. | Spôsob izolácie lovastatínu z vyfermentovanej pôdy |
| EP1110959A4 (en) * | 1999-06-29 | 2001-12-05 | Kaneka Corp | METHOD FOR SELECTIVE LACTONIZATION |
| AU8030900A (en) | 1999-10-27 | 2001-05-08 | Merck & Co., Inc. | Lactonization process |
| DE01913139T1 (de) | 2000-03-03 | 2005-03-31 | Plus Chemical S.A. | Ein verfahren zur reinigung von lovastatin und simvastatin mit verringertem gehalt an dimeren verunreinigungen |
| NL1017548C2 (nl) * | 2001-03-09 | 2002-09-10 | Synthon Bv | Een lactonisatie proces. |
| US6797831B2 (en) * | 2001-05-18 | 2004-09-28 | Aurobindo Pharma Limited | Process for lactonization to produce simvastatin |
| KR100407758B1 (ko) | 2001-08-27 | 2003-12-01 | 씨제이 주식회사 | 스타틴의 제조에 있어서 락톤화 방법 |
| KR100502834B1 (ko) * | 2002-03-25 | 2005-07-20 | 보령제약 주식회사 | 개선된 락톤화 반응에 의한 심바스타틴의 제조방법 및이의 정제방법 |
| CA2480325A1 (en) * | 2002-04-16 | 2003-10-30 | Merck & Co., Inc. | Solid forms of salts with tyrosine kinase activity |
| AR040588A1 (es) | 2002-07-26 | 2005-04-13 | Schering Corp | Formulacion farmaceutica que comprende un inhibidor de la absorcion del colesterol y un inhibidor de una hmg- co a reductasa |
| US20040132771A1 (en) * | 2002-12-20 | 2004-07-08 | Pfizer Inc | Compositions of choleseteryl ester transfer protein inhibitors and HMG-CoA reductase inhibitors |
| MXPA05005813A (es) | 2002-12-20 | 2005-12-12 | Pfizer Prod Inc | Formas de dosificacion que comprenden un inhibidor de la cetp y un inhibidor de la hmg-coa reductasa. |
| US6995277B2 (en) | 2003-02-11 | 2006-02-07 | Plus Chemicals, B.V. | Process for preparing simvastatin having controlled ranges of simvastatin dimer content |
| WO2005019161A1 (en) | 2003-08-21 | 2005-03-03 | Merck Frosst Canada Ltd. | Cathepsin cysteine protease inhibitors |
| BRPI0416639A (pt) | 2003-11-19 | 2007-01-16 | Metabasis Therapeutics Inc | tiromiméticos contendo fósforo |
| EP1732912B1 (en) * | 2004-03-30 | 2008-11-12 | Lupin Ltd. | An improved method for manufacture of 4-hydroxy pyran-2-one derivatives |
| EP1786765B1 (en) * | 2004-09-08 | 2009-09-02 | Jubilant Organosys Limited | An improved process for lactonization in the preparation of statins |
| CA2581596A1 (en) * | 2004-09-29 | 2006-04-13 | Schering Corporation | Combinations of substituted azetidonones and cb1 antagonists |
| WO2006059346A2 (en) * | 2004-12-01 | 2006-06-08 | Morepen Laboratories Limited | An improved process for lactonization to produce highly pure statins |
| BRPI0518874A2 (pt) | 2004-12-09 | 2008-12-16 | Merck & Co Inc | composto, composiÇço farmacÊutica, e, usos de um composto, e de uma composiÇço |
| DK1855674T3 (da) | 2005-03-02 | 2014-10-20 | Merck Sharp & Dohme | Sammensætning til hæmning af cathepsin k |
| US8362075B2 (en) | 2005-05-17 | 2013-01-29 | Merck Sharp & Dohme Corp. | Cyclohexyl sulphones for treatment of cancer |
| EP1741427A1 (en) | 2005-07-06 | 2007-01-10 | KRKA, D.D., Novo Mesto | Pharmaceutical composition comprising simvastatin and ezetimibe |
| WO2007020079A2 (en) * | 2005-08-17 | 2007-02-22 | Synthon B.V. | Orally disintegratable simvastatin tablets |
| TW200804345A (en) * | 2005-08-30 | 2008-01-16 | Novartis Ag | Substituted benzimidazoles and methods of preparation |
| US20070117996A1 (en) * | 2005-11-21 | 2007-05-24 | Srinivasulu Gudipati | Process for preparing simvastatin |
| EP1965862A2 (en) * | 2005-12-21 | 2008-09-10 | Schering Corporation | Combination of an h3 antagonist/inverse agonist and an appetite suppressant |
| US20070161578A1 (en) * | 2005-12-21 | 2007-07-12 | Hwa Joyce J | Treatment of nonalcoholic fatty liver disease using cholesterol lowering agents and/or H3 receptor antagonist/inverse agonist |
| GB0603041D0 (en) | 2006-02-15 | 2006-03-29 | Angeletti P Ist Richerche Bio | Therapeutic compounds |
| TW200813039A (en) | 2006-04-19 | 2008-03-16 | Novartis Ag | 6-O-substituted benzoxazole and benzothiazole compounds and methods of inhibiting CSF-1R signaling |
| JP2010502702A (ja) * | 2006-09-05 | 2010-01-28 | シェーリング コーポレイション | 脂質管理およびアテローム性動脈硬化症および脂肪肝の治療治療において使用される医薬組成物 |
| JP5489333B2 (ja) | 2006-09-22 | 2014-05-14 | メルク・シャープ・アンド・ドーム・コーポレーション | 脂肪酸合成阻害剤を用いた治療の方法 |
| US20110218176A1 (en) | 2006-11-01 | 2011-09-08 | Barbara Brooke Jennings-Spring | Compounds, methods, and treatments for abnormal signaling pathways for prenatal and postnatal development |
| CA2674436C (en) | 2007-01-10 | 2012-07-17 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. | Amide substituted indazoles as poly(adp-ribose)polymerase (parp) inhibitors |
| AU2008221263B2 (en) | 2007-03-01 | 2012-02-23 | Novartis Ag | Pim kinase inhibitors and methods of their use |
| JP5378362B2 (ja) | 2007-05-21 | 2013-12-25 | ノバルティス アーゲー | Ｃｓｆ−１ｒ阻害剤、組成物および使用方法 |
| EP2170076B1 (en) | 2007-06-27 | 2016-05-18 | Merck Sharp & Dohme Corp. | 4-carboxybenzylamino derivatives as histone deacetylase inhibitors |
| US20090048335A1 (en) * | 2007-08-17 | 2009-02-19 | Venkata Naga Mandava | Process for preparing simvastatin |
| DK2222636T3 (da) | 2007-12-21 | 2013-06-03 | Ligand Pharm Inc | Selektive androgenreceptormodulatorer (SARMS) og anvendelser deraf |
| JP5492790B2 (ja) * | 2008-02-27 | 2014-05-14 | トーメン メディカル アーゲー | インプラント及びその製造方法 |
| EP2204170A1 (en) | 2008-12-01 | 2010-07-07 | LEK Pharmaceuticals D.D. | Pharmaceutical composition comprising ezetimibe and simvastatin |
| EP2216016A1 (en) | 2009-02-06 | 2010-08-11 | LEK Pharmaceuticals d.d. | Process for the preparation of a pharmaceutical composition comprising ezetimibe |
| US20120046364A1 (en) | 2009-02-10 | 2012-02-23 | Metabasis Therapeutics, Inc. | Novel Sulfonic Acid-Containing Thyromimetics, and Methods for Their Use |
| US8691825B2 (en) | 2009-04-01 | 2014-04-08 | Merck Sharp & Dohme Corp. | Inhibitors of AKT activity |
| US8859776B2 (en) | 2009-10-14 | 2014-10-14 | Merck Sharp & Dohme Corp. | Substituted piperidines that increase p53 activity and the uses thereof |
| CN104098537A (zh) * | 2009-11-20 | 2014-10-15 | 北大医药股份有限公司 | 制备他汀类化合物的内酯化方法 |
| CN101704808A (zh) | 2009-11-20 | 2010-05-12 | 西南合成制药股份有限公司 | 制备他汀类化合物的内酯化方法 |
| EP2368543A1 (en) | 2010-03-25 | 2011-09-28 | KRKA, tovarna zdravil, d.d., Novo mesto | Method of preparing a granulated pharmaceutical composition comprising simvastatin and/or ezetimibe |
| WO2011163330A1 (en) | 2010-06-24 | 2011-12-29 | Merck Sharp & Dohme Corp. | Novel heterocyclic compounds as erk inhibitors |
| CA2805265A1 (en) | 2010-08-02 | 2012-02-09 | Merck Sharp & Dohme Corp. | Rna interference mediated inhibition of catenin (cadherin-associated protein), beta 1 (ctnnb1) gene expression using short interfering nucleic acid (sina) |
| HRP20191232T1 (hr) | 2010-08-17 | 2019-11-01 | Sirna Therapeutics Inc | Inhibicija, posredovana rna interferencijom, ekspresije gena virusa hepatitisa b (hbv) korištenjem kratkih interferirajućih nukleinskih kiselina (sina) |
| EP2608669B1 (en) | 2010-08-23 | 2016-06-22 | Merck Sharp & Dohme Corp. | NOVEL PYRAZOLO[1,5-a]PYRIMIDINE DERIVATIVES AS mTOR INHIBITORS |
| US8946216B2 (en) | 2010-09-01 | 2015-02-03 | Merck Sharp & Dohme Corp. | Indazole derivatives useful as ERK inhibitors |
| US9242981B2 (en) | 2010-09-16 | 2016-01-26 | Merck Sharp & Dohme Corp. | Fused pyrazole derivatives as novel ERK inhibitors |
| CA139852S (en) | 2010-10-15 | 2011-11-23 | Reno de Medici SpA | Christmas tree |
| DK2632472T3 (en) | 2010-10-29 | 2018-03-19 | Sirna Therapeutics Inc | RNA INTERFERENCE-MEDIATED INHIBITION OF GENE EXPRESSION USING SHORT INTERFERRING NUCLEIC ACIDS (SINA) |
| EP2654748B1 (en) | 2010-12-21 | 2016-07-27 | Merck Sharp & Dohme Corp. | Indazole derivatives useful as erk inhibitors |
| US8791162B2 (en) | 2011-02-14 | 2014-07-29 | Merck Sharp & Dohme Corp. | Cathepsin cysteine protease inhibitors |
| AU2012245455A1 (en) | 2011-04-21 | 2013-10-31 | Merck Sharp & Dohme Corp. | Insulin-Like Growth Factor-1 Receptor inhibitors |
| WO2013031729A1 (ja) | 2011-08-26 | 2013-03-07 | 国立大学法人大阪大学 | 糖尿病性心血管合併症の予防・治療剤 |
| EP2770987B1 (en) | 2011-10-27 | 2018-04-04 | Merck Sharp & Dohme Corp. | Novel compounds that are erk inhibitors |
| EP2597092A1 (en) | 2011-11-24 | 2013-05-29 | Sterling Biotech Limited | A process for purification of lovastatin |
| EP2844261B1 (en) | 2012-05-02 | 2018-10-17 | Sirna Therapeutics, Inc. | SHORT INTERFERING NUCLEIC ACID (siNA) COMPOSITIONS |
| JP6280554B2 (ja) | 2012-09-28 | 2018-02-14 | メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． | Ｅｒｋ阻害剤である新規化合物 |
| AU2013352568B2 (en) | 2012-11-28 | 2019-09-19 | Merck Sharp & Dohme Llc | Compositions and methods for treating cancer |
| KR102196882B1 (ko) | 2012-12-20 | 2020-12-30 | 머크 샤프 앤드 돔 코포레이션 | Hdm2 억제제로서의 치환된 이미다조피리딘 |
| US9540377B2 (en) | 2013-01-30 | 2017-01-10 | Merck Sharp & Dohme Corp. | 2,6,7,8 substituted purines as HDM2 inhibitors |
| US20160194368A1 (en) | 2013-09-03 | 2016-07-07 | Moderna Therapeutics, Inc. | Circular polynucleotides |
| WO2015051479A1 (en) | 2013-10-08 | 2015-04-16 | Merck Sharp & Dohme Corp. | Cathepsin cysteine protease inhibitors |
| AU2014332250B2 (en) | 2013-10-08 | 2018-07-19 | Merck Sharp & Dohme Corp. | Cathepsin cysteine protease inhibitors |
| WO2015108988A2 (en) | 2014-01-17 | 2015-07-23 | Ligand Pharmaceuticals, Inc. | Methods and compositions for modulating hormone levels |
| WO2015120580A1 (en) | 2014-02-11 | 2015-08-20 | Merck Sharp & Dohme Corp. | Cathepsin cysteine protease inhibitors |
| JO3589B1 (ar) | 2014-08-06 | 2020-07-05 | Novartis Ag | مثبطات كيناز البروتين c وطرق استخداماتها |
| US10975084B2 (en) | 2016-10-12 | 2021-04-13 | Merck Sharp & Dohme Corp. | KDM5 inhibitors |
| WO2019094312A1 (en) | 2017-11-08 | 2019-05-16 | Merck Sharp & Dohme Corp. | Prmt5 inhibitors |
| WO2019094311A1 (en) | 2017-11-08 | 2019-05-16 | Merck Sharp & Dohme Corp. | Prmt5 inhibitors |
| EP3833667B1 (en) | 2018-08-07 | 2024-03-13 | Merck Sharp & Dohme LLC | Prmt5 inhibitors |
| CN112805006B (zh) | 2018-08-07 | 2024-09-24 | 默沙东有限责任公司 | Prmt5抑制剂 |
| EP3833668B1 (en) | 2018-08-07 | 2025-03-19 | Merck Sharp & Dohme LLC | Prmt5 inhibitors |
| CN114096522A (zh) | 2019-04-19 | 2022-02-25 | 利亘制药公司 | 化合物的晶型和制备化合物的晶型的方法 |
| US12441730B2 (en) | 2019-12-17 | 2025-10-14 | Merck Sharp & Dohme Llc | PRMT5 inhibitors |
| WO2021126731A1 (en) | 2019-12-17 | 2021-06-24 | Merck Sharp & Dohme Corp. | Prmt5 inhibitors |
| US20230108114A1 (en) | 2019-12-17 | 2023-04-06 | Merck Sharp & Dohme Llc | Prmt5 inhibitors |
| KR20250152667A (ko) | 2023-03-02 | 2025-10-23 | 카르치문 바이오테크 게엠베하 | 암 및/또는 급성 염증성 질환을 진단하는 수단 및 방법 |
| WO2025147589A1 (en) | 2024-01-05 | 2025-07-10 | Osanni Bio, Inc. | Implants, compositions, and methods for treating retinal diseases and disorders |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA81703B (en) * | 1980-02-04 | 1982-09-29 | Merck & Co Inc | New antihypercholesterolemic compounds,intermediates and processes |
| JPS5948418A (ja) * | 1982-09-10 | 1984-03-19 | Sankyo Co Ltd | 高血清過酸化脂質血症治療剤 |
| US4582915A (en) * | 1983-10-11 | 1986-04-15 | Merck & Co., Inc. | Process for C-methylation of 2-methylbutyrates |
| US4611068A (en) * | 1984-11-19 | 1986-09-09 | Merck Frosst Canada, Inc. | Process for the preparation of HMG-CoA reductase inhibitors and intermediate compounds employed therein |
| US4611067A (en) * | 1985-01-31 | 1986-09-09 | Merck & Co., Inc. | Process for the preparation of HMG-CoA reductase inhibitors and intermediate compounds employed therein |
| US4772626A (en) * | 1986-01-31 | 1988-09-20 | Merck & Co., Inc. | Antihypercholesterolemic compounds |
| PT85109A (en) * | 1986-06-23 | 1987-07-01 | Merck & Co Inc | Process for the preparation of hydroxy-tetrahydropyranone derivatives or corresponding ring opened dihydroxy acids which are hmg-coa reductase inhibitors |
| US4857546A (en) * | 1988-01-07 | 1989-08-15 | Merck & Co., Inc. | Novel HMG-CoA reductase inhibitors |
| US4916239A (en) * | 1988-07-19 | 1990-04-10 | Merck & Co., Inc. | Process for the lactonization of mevinic acids and analogs thereof |
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