LV12460B - Finasterīda iegūšanas paņēmiens - Google Patents
Finasterīda iegūšanas paņēmiens Download PDFInfo
- Publication number
- LV12460B LV12460B LVP-00-26A LV000026A LV12460B LV 12460 B LV12460 B LV 12460B LV 000026 A LV000026 A LV 000026A LV 12460 B LV12460 B LV 12460B
- Authority
- LV
- Latvia
- Prior art keywords
- ester
- magnesium halide
- halide
- butylamino
- finasteride
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 35
- DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 title claims abstract description 26
- 229960004039 finasteride Drugs 0.000 title claims abstract description 25
- -1 t-butylamino magnesium halide Chemical class 0.000 claims abstract description 49
- 150000002148 esters Chemical class 0.000 claims abstract description 46
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 15
- 239000003960 organic solvent Substances 0.000 claims abstract description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 9
- 239000011541 reaction mixture Substances 0.000 claims abstract description 8
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 claims description 20
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 19
- 125000001931 aliphatic group Chemical group 0.000 claims description 18
- 239000011777 magnesium Substances 0.000 claims description 18
- 229910052749 magnesium Inorganic materials 0.000 claims description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 150000004820 halides Chemical class 0.000 claims description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 150000001649 bromium compounds Chemical group 0.000 claims description 3
- 239000012442 inert solvent Substances 0.000 claims description 3
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 3
- 229920002554 vinyl polymer Polymers 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 2
- 125000004122 cyclic group Chemical group 0.000 claims 2
- 241000251468 Actinopterygii Species 0.000 claims 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 1
- 229910052794 bromium Inorganic materials 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 239000000460 chlorine Substances 0.000 claims 1
- 125000006165 cyclic alkyl group Chemical group 0.000 claims 1
- 230000037213 diet Effects 0.000 claims 1
- 235000005911 diet Nutrition 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract description 8
- 238000003786 synthesis reaction Methods 0.000 abstract description 7
- 238000006243 chemical reaction Methods 0.000 description 19
- 235000001055 magnesium Nutrition 0.000 description 14
- 229940091250 magnesium supplement Drugs 0.000 description 14
- 150000004792 aryl magnesium halides Chemical class 0.000 description 13
- 125000000217 alkyl group Chemical group 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 230000005595 deprotonation Effects 0.000 description 2
- 238000010537 deprotonation reaction Methods 0.000 description 2
- 229960004132 diethyl ether Drugs 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 229910001623 magnesium bromide Inorganic materials 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 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 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
- 150000000520 4-azasteroids Chemical class 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
- 238000010639 Bodroux reaction Methods 0.000 description 1
- OLIBVNMJDNNSKI-UHFFFAOYSA-N CC(C)(C)[Mg] Chemical compound CC(C)(C)[Mg] OLIBVNMJDNNSKI-UHFFFAOYSA-N 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- 206010020112 Hirsutism Diseases 0.000 description 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
- 229940123934 Reductase inhibitor Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 238000011938 amidation process Methods 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 150000005840 aryl radicals Chemical class 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical group 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 150000004292 cyclic ethers Chemical class 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- XEHVFKKSDRMODV-UHFFFAOYSA-N ethynyl Chemical group C#[C] XEHVFKKSDRMODV-UHFFFAOYSA-N 0.000 description 1
- 238000001879 gelation Methods 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000001421 myristyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 125000001400 nonyl 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])C([H])([H])[H] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- FHPZOWOEILXXBD-UHFFFAOYSA-N phenylseleninyl benzeneseleninate Chemical compound C=1C=CC=CC=1[Se](=O)O[Se](=O)C1=CC=CC=C1 FHPZOWOEILXXBD-UHFFFAOYSA-N 0.000 description 1
- 229940072254 proscar Drugs 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000004079 stearyl 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])C([H])([H])C([H])([H])C([H])([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
- 150000003431 steroids Chemical class 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F3/00—Compounds containing elements of Groups 2 or 12 of the Periodic Table
- C07F3/003—Compounds containing elements of Groups 2 or 12 of the Periodic Table without C-Metal linkages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J73/00—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms
- C07J73/001—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms by one hetero atom
- C07J73/005—Steroids in which the cyclopenta[a]hydrophenanthrene skeleton has been modified by substitution of one or two carbon atoms by hetero atoms by one hetero atom by nitrogen as hetero atom
-
- H—ELECTRICITY
- H04—ELECTRIC COMMUNICATION TECHNIQUE
- H04N—PICTORIAL COMMUNICATION, e.g. TELEVISION
- H04N5/00—Details of television systems
- H04N5/74—Projection arrangements for image reproduction, e.g. using eidophor
- H04N5/7416—Projection arrangements for image reproduction, e.g. using eidophor involving the use of a spatial light modulator, e.g. a light valve, controlled by a video signal
- H04N5/7458—Projection arrangements for image reproduction, e.g. using eidophor involving the use of a spatial light modulator, e.g. a light valve, controlled by a video signal the modulator being an array of deformable mirrors, e.g. digital micromirror device [DMD]
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Multimedia (AREA)
- Signal Processing (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Urology & Nephrology (AREA)
- Dermatology (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Confectionery (AREA)
- Dental Preparations (AREA)
- Seasonings (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Claims (14)
- LV 12460 Izgudrojuma formula 1. Paņēmiens finasterīda ar formulu (2)kurā R ir lineārā, sazarota vai cikliska Ci.10alkilgrupa, neobligāti aizvietota ar vienu vai vairākām fenilgrupām, iegūšanai, kas ietver šādus posmus: (a) estera ar formulu (1) apstrādi ar t-butilaminomagnija halogenīdu, pie kam t-butilaminomagnija halogenīda molārā attiecība pret esteri ir vismaz 2:1, inertā organiskā šķīdinātājā un inertā atmosfērā; (b) reakcijas maisījuma izturēšanu vismaz 10 °C temperatūrā; (c) iegūtā produkta - fiansterīda (2) izdalīšanu.
- 2. Paņēmiens pēc 1. punkta, kas papildus ietver posmu, kurā pirms t-butilaminomagnija halogenīda iedarbības uz esteri (1), to pagatavo t-butilamīnu apstrādājot ar alifātisku vai aromātisku magnija halogenīdu inertā šķīdinātājā.
- 3. Paņēmiens pēc 2. punkta, kas papildus ietver posmu, kur pirms estera (1) apstrādes ar t-butilaminomagnija halogenīdu, to vispirms apstrādā inertā organiskā šķīdinātājā -20 līdz 30 °C temperatūrā ar alifātisku vai aromātisku magnija halogenīdu, iegūstot estera (1) magnijhalogenīda sāli.
- 4. Paņēmiens pēc 1. punkta, kur halogenīds ir bromīds vai hlorīds.
- 5. Paņēmiens pēc 2. punkta, kur alifātiskais vai aromātiskais magnija halogenīds satur lineāru, sazarotu vai ciklisku alkilgrupu, benzilgrupu, allilgrupu, vinilgrupu vai etinilgrupu, bet arilgrupa ir fenilgrupa vai fenilgrupa, kas aizvietota ar 1-3 aizvietotājiem no rindas: C^alkilgrupa, C^alkoksigrupa un fluora atoms.
- 6. Paņēmiens pēc 5. punkta, kur aiifātiskais vai aromātiskais aikiihalogenīds ir ņemts no rindas: alkilmagnija bromīds un cikloalkiimagnija bromīds.
- 7. Paņēmiens pēc 1. punkta, kur inertais šķīdinātājs ir lineārs vai ciklisks C^sēteris.
- 8. Paņēmiens pēc 7. punkta, kur inertais organiskais šķīdinātājs ir ņemts no rindas: dietilēteris, di-n-butilēsteris, dimetoksietāns, terahidrofurāns un dioksāns.
- 9. Paņēmiens pēc 1. punkta, kur R ir ņemts no rindas: metilgrupa, etilgrupa, propilgrupa un butilgrupa.
- 10. Paņēmiens pēc 9. punkta, kur R ir metilgrupa.
- 11. Paņēmiens pēc 1. punkta, kur t-butilaminomagnija halogenīda molārā attiecība pret esteri (1) ir robežās no apmēram 3,5:1 līdz 5,5:1.
- 12. Paņēmiens pēc 11. punkta, kur t-butilaminomagnija halogenīda molārā attiecība pret esteri (1) ir robežās no apmēram 4:1 līdz 5:1.
- 13. Savienojums ar formulukurā R ir lineāra, sazarota vartaktiska Ci-ioalkffgrupa, neobligāti aifWtetota ar vienu vai vairākām fenilgrupām.
- 14. Savienojums pēc 13. punkta, kur hal ir broma vai hlora atoms.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US97853592A | 1992-11-19 | 1992-11-19 | |
| US08/010,734 US5468860A (en) | 1992-11-19 | 1993-01-29 | New finasteride processes |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| LV12460A LV12460A (lv) | 2000-04-20 |
| LV12460B true LV12460B (lv) | 2000-09-20 |
Family
ID=26681536
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| LVP-98-236A LV12212B (lv) | 1992-11-19 | 1998-10-26 | Finasterīda iegūšanas paņēmiens |
| LVP-00-26A LV12460B (lv) | 1992-11-19 | 2000-02-23 | Finasterīda iegūšanas paņēmiens |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| LVP-98-236A LV12212B (lv) | 1992-11-19 | 1998-10-26 | Finasterīda iegūšanas paņēmiens |
Country Status (32)
| Country | Link |
|---|---|
| US (3) | US5468860A (lv) |
| EP (3) | EP0655458B1 (lv) |
| JP (2) | JPH07110875B2 (lv) |
| CN (1) | CN1058018C (lv) |
| AT (2) | ATE177112T1 (lv) |
| AU (1) | AU658774B2 (lv) |
| BG (2) | BG62362B1 (lv) |
| CA (1) | CA2103107C (lv) |
| CY (1) | CY2135B1 (lv) |
| CZ (3) | CZ301160B6 (lv) |
| DE (4) | DE69323754T2 (lv) |
| DK (2) | DK0599376T4 (lv) |
| DZ (1) | DZ1733A1 (lv) |
| ES (2) | ES2072848T3 (lv) |
| FI (4) | FI107450B (lv) |
| GR (4) | GR940300045T1 (lv) |
| HR (2) | HRP931410B1 (lv) |
| HU (2) | HU216195B (lv) |
| IL (1) | IL107574A (lv) |
| IS (2) | IS1692B (lv) |
| LV (2) | LV12212B (lv) |
| MX (1) | MX9307222A (lv) |
| MY (2) | MY110410A (lv) |
| NO (3) | NO305912B1 (lv) |
| PH (1) | PH31120A (lv) |
| RO (2) | RO115164B1 (lv) |
| RU (1) | RU2120445C1 (lv) |
| SI (1) | SI9300603B (lv) |
| SK (2) | SK286488B6 (lv) |
| TW (1) | TW257766B (lv) |
| UA (1) | UA41341C2 (lv) |
| WO (1) | WO1994011387A2 (lv) |
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| US5468860A (en) * | 1992-11-19 | 1995-11-21 | Merck & Co., Inc. | New finasteride processes |
| TW408127B (en) * | 1993-09-17 | 2000-10-11 | Glaxo Inc | Androstenones |
| IT1270660B (it) * | 1994-10-13 | 1997-05-07 | Poli Ind Chimica Spa | Procedimento microbiologico per la preparazione di 3-oxo-4-azasteroidi-17beta-carbossi sostituiti e uso dei prodotti come inibitori dell'enzima 5alfa-riduttasi |
| US5670643A (en) * | 1995-03-16 | 1997-09-23 | Glaxo Wellcome Inc. | Method for preparing finasteride |
| US5585383A (en) * | 1995-05-03 | 1996-12-17 | Merck & Co., Inc. | Process for crystallizing a 4-azasteroid 5alpha-reductase inhibitor |
| JPH11512434A (ja) * | 1995-09-15 | 1999-10-26 | メルク エンド カンパニー インコーポレーテッド | アンドロゲン過剰状態治療用の４−アザステロイド |
| GB2338234B (en) * | 1998-06-10 | 2000-05-03 | Torcan Chemical Ltd | Preparation of finasteride |
| ES2153789B1 (es) * | 1999-07-05 | 2001-10-16 | Raga Consultores S L | Procedimiento para la obtencion de 178-(n-terc-butlcarbamoil)-3-ona-4-aza-esteroides |
| EP1228084A1 (en) * | 1999-11-01 | 2002-08-07 | TORCAN CHEMICAL Ltd | Production of polymorphic forms i and ii of finasteride by complexation with group i or ii metal salts |
| EP1790653A3 (en) * | 2000-09-07 | 2010-06-02 | Dr. Reddy's Laboratories Ltd. | Novel polymorphic form of 17-beta-(n-ter.butyl carbamoyl)-4-aza-5-alpha-androst-1-en-3-one and a process for preparing it |
| KR20030029947A (ko) * | 2000-09-07 | 2003-04-16 | 닥터 레디스 레보러터리즈 리미티드 | 17-β-(엔-티-부틸카르바모일)-4-아자-5-α-안드로스트-1-엔-3-온의 신규의다형태 및 그 제조방법 |
| PL361014A1 (en) * | 2000-09-07 | 2004-09-20 | Dr.Reddy's Laboratories Ltd. | Novel polymorphic form of 17-beta-(n-ter.butyl carbamoyl)-4-aza-5-alpha-androst-1-en-3-one and a process for preparing it |
| KR100415858B1 (ko) * | 2001-09-22 | 2004-01-24 | 한미약품 주식회사 | 17베타-(엔-3차-부틸카바모일)-3-온 스테로이드 화합물의제조방법 |
| CN100428897C (zh) * | 2002-08-16 | 2008-10-29 | 浙江寿峰堂生物工程有限公司 | 抗疲劳改善亚健康的保健食品及其制备方法 |
| ES2206065B1 (es) * | 2002-10-31 | 2005-08-16 | Ragactives, S.L. | Procedimiento para la obtencion de la forma polimorfica i de finasterida. |
| AU2003217439A1 (en) * | 2003-03-19 | 2004-10-11 | Hetero Drugs Limited | Novel crystalline forms of finasteride |
| US7550593B2 (en) * | 2003-07-03 | 2009-06-23 | Cipla Limited | Process for the preparation of finasteride Form I |
| US20050136015A1 (en) * | 2003-12-17 | 2005-06-23 | McKie Derrick B. | Topical use of halosalicylic acid derivatives |
| US20070167477A1 (en) * | 2006-01-13 | 2007-07-19 | Mandava Venkata Naga Brahmeswa | Processes to prepare finasteride polymorphs |
| US7531658B2 (en) * | 2006-01-20 | 2009-05-12 | Apotex Pharmachem Inc. | Process for the preparation of 17-N-substituted-carbamoyl-4-aza-androst-1-en-3-ones |
| US7897800B2 (en) | 2006-02-03 | 2011-03-01 | Jr Chem, Llc | Chemical compositions and methods of making them |
| US7687650B2 (en) | 2006-02-03 | 2010-03-30 | Jr Chem, Llc | Chemical compositions and methods of making them |
| KR101324578B1 (ko) | 2006-02-03 | 2013-11-01 | 제이알 켐, 엘엘씨 | 구리 및 아연 조성물을 사용하는 노화 방지 치료법 |
| US7867522B2 (en) | 2006-09-28 | 2011-01-11 | Jr Chem, Llc | Method of wound/burn healing using copper-zinc compositions |
| US20090076058A1 (en) * | 2007-09-17 | 2009-03-19 | Protia, Llc | Deuterium-enriched finasteride |
| US8273791B2 (en) | 2008-01-04 | 2012-09-25 | Jr Chem, Llc | Compositions, kits and regimens for the treatment of skin, especially décolletage |
| ATE551604T1 (de) * | 2008-05-05 | 2012-04-15 | Abbott Gmbh & Co Kg | Verfahren zur beurteilung der löslichkeit eines kristallinen stoffes in einem polymer |
| CA2750636C (en) | 2009-01-23 | 2017-07-25 | Jr Chem, Llc | Rosacea treatments and kits for performing them |
| US8952057B2 (en) | 2011-01-11 | 2015-02-10 | Jr Chem, Llc | Compositions for anorectal use and methods for treating anorectal disorders |
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| NZ211145A (en) * | 1984-02-27 | 1988-10-28 | Merck & Co Inc | 4-aza-5-alpha-androst-1-en-3-ones and pharmaceutical compositions |
| US4760071A (en) * | 1984-02-27 | 1988-07-26 | Merck & Co., Inc. | 17β-N-monosubstituted carbamoyl-4-aza-5α-androst-1-en-3-ones which are active as testosterone 5α-reductase inhibitors |
| EP0285383B1 (en) * | 1987-04-03 | 1994-03-16 | Merck & Co. Inc. | Treatment of prostatic carcinoma with 17beta-n-monosubstituted-carbamoyl-4-aza-5alpha-androst-1-en-3-ones |
| NZ225100A (en) | 1987-06-29 | 1991-09-25 | Merck & Co Inc | Reaction of steroids (including 4-azasteroids) with a silylating agent in the presence of a quinone to introduce a delta' double bond and silylated intermediates |
| US5084574A (en) * | 1988-04-18 | 1992-01-28 | Merck & Co., Inc. | Dehydrogenation process |
| US5237061A (en) * | 1988-10-31 | 1993-08-17 | Merck & Co., Inc. | Methods of synthesizing benign prostatic hypertropic agents and their intermediates |
| US5021575A (en) * | 1989-11-13 | 1991-06-04 | Merck & Co., Inc. | Method for introducing a 1,2 double bond into azasteroids |
| ES2078447T3 (es) * | 1990-06-15 | 1995-12-16 | Merck & Co Inc | Un procedimiento de cristalizacion para mejorar la estructura y el tamaño de los cristales. |
| EP0462662A3 (en) * | 1990-06-20 | 1992-08-19 | Merck & Co. Inc. | 17beta-n-monosubstituted adamantyl/norbornanyl carbamoyl-4-aza-5alpha-androst-1-en-3-ones and androstan-3-ones |
| US5120847A (en) † | 1990-08-27 | 1992-06-09 | Merck & Co., Inc. | Process for iodinating or brominating the α-methylenic carbon of a secondary amide |
| US5091534A (en) | 1990-08-27 | 1992-02-25 | Merck & Co., Inc. | Trialkylsilyl trifluoromethanesulfonate mediated α-methylenic carbon functionalization of 4-AZA-5α-androstan-3-one steroids |
| CA2050824A1 (en) * | 1990-09-24 | 1992-03-25 | John M. Williams | Process for making 3-oxo-4-aza-androst-1-ene 17-.beta.-ketones |
| US5061801A (en) * | 1990-09-24 | 1991-10-29 | Merck & Co., Inc. | Intermediate for making 3-oxo-4-aza-androst-1-ene 17β-ketones |
| US5468860A (en) * | 1992-11-19 | 1995-11-21 | Merck & Co., Inc. | New finasteride processes |
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1993
- 1993-01-29 US US08/010,734 patent/US5468860A/en not_active Expired - Fee Related
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1994
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