SK282021B6 - Spôsob výroby inhibítora hiv proteázy a medziprodukt na jeho výrobu - Google Patents

Spôsob výroby inhibítora hiv proteázy a medziprodukt na jeho výrobu Download PDF

Info

Publication number: SK282021B6
Authority: SK; Slovakia
Prior art keywords: mixture; formula; compound; solution; added
Prior art date: 1995-03-15

Application number

SK1225-97A

Other languages

English (en)

Slovak (sk)

Other versions

SK122597A3 (en

Inventor

David Askin

Kan K. Eng

Paul Reider

Ralph P. Volante

Original Assignee

Merck & Co., Inc.

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1995-03-15

Filing date

1996-03-11

Publication date

2001-10-08

1996-03-11 Application filed by Merck & Co., Inc. filed Critical Merck & Co., Inc.

1998-02-04 Publication of SK122597A3 publication Critical patent/SK122597A3/sk

2001-10-08 Publication of SK282021B6 publication Critical patent/SK282021B6/sk

Links

239000004030 hiv protease inhibitor Substances 0.000 title claims abstract description 9
229940122440 HIV protease inhibitor Drugs 0.000 title claims abstract description 7
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239000002904 solvent Substances 0.000 claims abstract description 23
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MQRJBSHKWOFOGF-UHFFFAOYSA-L disodium;carbonate;hydrate Chemical compound O.[Na+].[Na+].[O-]C([O-])=O MQRJBSHKWOFOGF-UHFFFAOYSA-L 0.000 description 2
239000012153 distilled water Substances 0.000 description 2
239000012458 free base Substances 0.000 description 2
FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 2
239000001257 hydrogen Substances 0.000 description 2
229910052739 hydrogen Inorganic materials 0.000 description 2
230000002458 infectious effect Effects 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
238000002156 mixing Methods 0.000 description 2
238000012986 modification Methods 0.000 description 2
230000004048 modification Effects 0.000 description 2
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
IPWFJLQDVFKJDU-UHFFFAOYSA-N pentanamide Chemical compound CCCCC(N)=O IPWFJLQDVFKJDU-UHFFFAOYSA-N 0.000 description 2
239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
239000008194 pharmaceutical composition Substances 0.000 description 2
IVXQBCUBSIPQGU-UHFFFAOYSA-N piperazine-1-carboxamide Chemical compound NC(=O)N1CCNCC1 IVXQBCUBSIPQGU-UHFFFAOYSA-N 0.000 description 2
150000004885 piperazines Chemical class 0.000 description 2
125000004193 piperazinyl group Chemical group 0.000 description 2
108700004029 pol Genes Proteins 0.000 description 2
101150088264 pol gene Proteins 0.000 description 2
235000015497 potassium bicarbonate Nutrition 0.000 description 2
229910000028 potassium bicarbonate Inorganic materials 0.000 description 2
239000011736 potassium bicarbonate Substances 0.000 description 2
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
230000002265 prevention Effects 0.000 description 2
238000012545 processing Methods 0.000 description 2
238000000926 separation method Methods 0.000 description 2
229940076133 sodium carbonate monohydrate Drugs 0.000 description 2
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
229910052938 sodium sulfate Inorganic materials 0.000 description 2
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
235000011152 sodium sulphate Nutrition 0.000 description 2
HIFJUMGIHIZEPX-UHFFFAOYSA-N sulfuric acid;sulfur trioxide Chemical compound O=S(=O)=O.OS(O)(=O)=O HIFJUMGIHIZEPX-UHFFFAOYSA-N 0.000 description 2
YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 2
241001430294 unidentified retrovirus Species 0.000 description 2
KMGCKSAIIHOKCX-UHFFFAOYSA-N 2,3-dihydro-1h-inden-2-ol Chemical compound C1=CC=C2CC(O)CC2=C1 KMGCKSAIIHOKCX-UHFFFAOYSA-N 0.000 description 1
YKXXBEOXRPZVCC-UHFFFAOYSA-N 2,3-dihydro-1h-indene-1,2-diol Chemical compound C1=CC=C2C(O)C(O)CC2=C1 YKXXBEOXRPZVCC-UHFFFAOYSA-N 0.000 description 1
NJWIMFZLESWFIM-UHFFFAOYSA-N 2-(chloromethyl)pyridine Chemical compound ClCC1=CC=CC=N1 NJWIMFZLESWFIM-UHFFFAOYSA-N 0.000 description 1
GUXJXWKCUUWCLX-UHFFFAOYSA-N 2-methyl-2-oxazoline Chemical compound CC1=NCCO1 GUXJXWKCUUWCLX-UHFFFAOYSA-N 0.000 description 1
BUBVLQDEIIUIQG-UHFFFAOYSA-N 3,4,5-tris(phenylmethoxy)-6-(phenylmethoxymethyl)oxan-2-one Chemical compound C=1C=CC=CC=1COC1C(OCC=2C=CC=CC=2)C(OCC=2C=CC=CC=2)C(=O)OC1COCC1=CC=CC=C1 BUBVLQDEIIUIQG-UHFFFAOYSA-N 0.000 description 1
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
CCJGDJMDVAGOJM-VTLYIQCISA-N Br[C@H]1[C@@H](C2=CC=CC=C2C1)O.C1(CCC2=CC=CC=C12)O Chemical compound Br[C@H]1[C@@H](C2=CC=CC=C2C1)O.C1(CCC2=CC=CC=C12)O CCJGDJMDVAGOJM-VTLYIQCISA-N 0.000 description 1
XRPHFZRZETURBH-UHFFFAOYSA-N C(C)(C)(C)N.C(C(=O)Cl)(=O)Cl Chemical compound C(C)(C)(C)N.C(C(=O)Cl)(=O)Cl XRPHFZRZETURBH-UHFFFAOYSA-N 0.000 description 1
UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
108091026890 Coding region Proteins 0.000 description 1
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
108010042407 Endonucleases Proteins 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
229940126544 HIV-1 protease inhibitor Drugs 0.000 description 1
VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 1
108700026244 Open Reading Frames Proteins 0.000 description 1
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
102000035195 Peptidases Human genes 0.000 description 1
108010076039 Polyproteins Proteins 0.000 description 1
229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
108090000783 Renin Proteins 0.000 description 1
102100028255 Renin Human genes 0.000 description 1
229910004298 SiO 2 Inorganic materials 0.000 description 1
239000004809 Teflon Substances 0.000 description 1
229920006362 Teflon® Polymers 0.000 description 1
WUSFIHFUGBEBHO-UHFFFAOYSA-N [CH2-]C(=O)CO Chemical compound [CH2-]C(=O)CO WUSFIHFUGBEBHO-UHFFFAOYSA-N 0.000 description 1
PHZYZQWQIQMLBY-UHFFFAOYSA-N acetonitrile;propan-1-ol Chemical compound CC#N.CCCO PHZYZQWQIQMLBY-UHFFFAOYSA-N 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
230000001476 alcoholic effect Effects 0.000 description 1
150000001299 aldehydes Chemical class 0.000 description 1
125000003275 alpha amino acid group Chemical group 0.000 description 1
QQQCWVDPMPFUGF-ZDUSSCGKSA-N alpinetin Chemical compound C1([C@H]2OC=3C=C(O)C=C(C=3C(=O)C2)OC)=CC=CC=C1 QQQCWVDPMPFUGF-ZDUSSCGKSA-N 0.000 description 1
230000009435 amidation Effects 0.000 description 1
238000007112 amidation reaction Methods 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
238000013459 approach Methods 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
238000010533 azeotropic distillation Methods 0.000 description 1
239000002585 base Substances 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
239000012455 biphasic mixture Substances 0.000 description 1
210000001124 body fluid Anatomy 0.000 description 1
239000010839 body fluid Substances 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
229910002091 carbon monoxide Inorganic materials 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
150000003857 carboxamides Chemical class 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
238000004296 chiral HPLC Methods 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
238000000576 coating method Methods 0.000 description 1
230000006957 competitive inhibition Effects 0.000 description 1
229940125904 compound 1 Drugs 0.000 description 1
229940126214 compound 3 Drugs 0.000 description 1
238000001816 cooling Methods 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
239000013058 crude material Substances 0.000 description 1
239000012043 crude product Substances 0.000 description 1
239000013078 crystal Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
239000008367 deionised water Substances 0.000 description 1
229910021641 deionized water Inorganic materials 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
238000011161 development Methods 0.000 description 1
238000007865 diluting Methods 0.000 description 1
229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
229910000397 disodium phosphate Inorganic materials 0.000 description 1
235000019800 disodium phosphate Nutrition 0.000 description 1
238000009826 distribution Methods 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
239000003480 eluent Substances 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
150000003948 formamides Chemical class 0.000 description 1
BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
229940084388 gammar Drugs 0.000 description 1
230000002068 genetic effect Effects 0.000 description 1
239000012456 homogeneous solution Substances 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
210000000987 immune system Anatomy 0.000 description 1
230000002779 inactivation Effects 0.000 description 1
YIAPLDFPUUJILH-UHFFFAOYSA-N indan-1-ol Chemical compound C1=CC=C2C(O)CCC2=C1 YIAPLDFPUUJILH-UHFFFAOYSA-N 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
230000010354 integration Effects 0.000 description 1
238000010829 isocratic elution Methods 0.000 description 1
125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
ZRPMCQJKUJELGP-UHFFFAOYSA-N n,n'-ditert-butyloxamide Chemical compound CC(C)(C)NC(=O)C(=O)NC(C)(C)C ZRPMCQJKUJELGP-UHFFFAOYSA-N 0.000 description 1
FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
239000002773 nucleotide Substances 0.000 description 1
125000003729 nucleotide group Chemical group 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
239000002245 particle Substances 0.000 description 1
230000001575 pathological effect Effects 0.000 description 1
210000001428 peripheral nervous system Anatomy 0.000 description 1
238000005191 phase separation Methods 0.000 description 1
230000001323 posttranslational effect Effects 0.000 description 1
239000001120 potassium sulphate Substances 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
239000002243 precursor Substances 0.000 description 1
230000002028 premature Effects 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
ZOFWDSYSIJNFMU-UHFFFAOYSA-N pyrazine-2-carbonyl chloride;hydrochloride Chemical compound Cl.ClC(=O)C1=CN=CC=N1 ZOFWDSYSIJNFMU-UHFFFAOYSA-N 0.000 description 1
QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 1
238000004445 quantitative analysis Methods 0.000 description 1
230000010076 replication Effects 0.000 description 1
238000012216 screening Methods 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
HELHAJAZNSDZJO-OLXYHTOASA-L sodium L-tartrate Chemical compound [Na+].[Na+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O HELHAJAZNSDZJO-OLXYHTOASA-L 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
235000009518 sodium iodide Nutrition 0.000 description 1
239000004296 sodium metabisulphite Substances 0.000 description 1
235000010262 sodium metabisulphite Nutrition 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
239000001433 sodium tartrate Substances 0.000 description 1
229960002167 sodium tartrate Drugs 0.000 description 1
235000011004 sodium tartrates Nutrition 0.000 description 1
CLJTZNIHUYFUMR-UHFFFAOYSA-M sodium;hydrogen carbonate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].OC([O-])=O.OC(=O)CC(O)(C(O)=O)CC(O)=O CLJTZNIHUYFUMR-UHFFFAOYSA-M 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000000758 substrate Substances 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical compound [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000012360 testing method Methods 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
239000010936 titanium Substances 0.000 description 1
238000004448 titration Methods 0.000 description 1
238000002054 transplantation Methods 0.000 description 1
230000009385 viral infection Effects 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Virology (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Oncology (AREA)
Molecular Biology (AREA)
Chemical Kinetics & Catalysis (AREA)
Tropical Medicine & Parasitology (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
AIDS & HIV (AREA)
Communicable Diseases (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Pyridine Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Hydrogenated Pyridines (AREA)

SK1225-97A 1995-03-15 1996-03-11 Spôsob výroby inhibítora hiv proteázy a medziprodukt na jeho výrobu SK282021B6 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US08/404,798 US5618937A (en)	1995-03-15	1995-03-15	Process to make HIV protease inhibitor from (2S)-4-picolyl-2-piperazine-t-butylcarboxamide
PCT/US1996/002556 WO1996028439A1 (en)	1995-03-15	1996-03-11	PROCESS TO MAKE HIV PROTEASE INHIBITOR FROM 2(S)-4-PICOLYL-2-PIPERAZINE-t-BUTYLCARBOXAMIDE

Publications (2)

Publication Number	Publication Date
SK122597A3 SK122597A3 (en)	1998-02-04
SK282021B6 true SK282021B6 (sk)	2001-10-08

Family

ID=23601087

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1225-97A SK282021B6 (sk)	1995-03-15	1996-03-11	Spôsob výroby inhibítora hiv proteázy a medziprodukt na jeho výrobu

Country Status (16)

Country	Link
US (1)	US5618937A (cs)
EP (1)	EP0815101B1 (cs)
CN (1)	CN1100054C (cs)
AR (1)	AR002712A1 (cs)
AT (1)	ATE181916T1 (cs)
AU (1)	AU5173896A (cs)
BR (1)	BR9607376A (cs)
CZ (1)	CZ292549B6 (cs)
DE (1)	DE69603163D1 (cs)
EA (1)	EA000178B1 (cs)
HR (1)	HRP960114B1 (cs)
SK (1)	SK282021B6 (cs)
TW (1)	TW332205B (cs)
UA (1)	UA49826C2 (cs)
WO (1)	WO1996028439A1 (cs)
YU (1)	YU15496A (cs)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5700364A (en) *	1995-10-30	1997-12-23	Merck & Co., Inc.	Electrochemical oxidation
NL1006305C2 (nl) *	1997-06-13	1998-12-15	Dsm Nv	Werkwijze voor de bereiding van (1S,2R)-1-amino-2-indanol-(R,R)-tartraat methanol solvaat.
US7199240B2 (en) *	2002-12-11	2007-04-03	Merck & Co., Inc.	Reductive alkylation of saturated cyclic amines
US10620330B2 (en)	2013-03-19	2020-04-14	Westerngeco L.L.C.	Estimating translational data
CN110835405B (zh) *	2019-11-28	2020-09-15	安阳师范学院	用于肿瘤检测的高分子生物传感器及制备方法及应用

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5169952A (en) *	1991-07-02	1992-12-08	Merck & Co., Inc.	Stereoselective production of hydroxyamide compounds from chiral α-amino epoxides
US5413999A (en) *	1991-11-08	1995-05-09	Merck & Co., Inc.	HIV protease inhibitors useful for the treatment of AIDS
DK0541168T3 (da) *	1991-11-08	1998-05-11	Merck & Co Inc	HIV-proteaseinhibitorer, som er egnede til behandling af AIDS
MX9308016A (es) *	1992-12-22	1994-08-31	Lilly Co Eli	Compuestos inhibidores de la proteasa del virus de la inmunodeficiencia humana, procedimiento para su preparacion y formulacion farmaceutica que los contiene.
US5463067A (en) *	1993-07-16	1995-10-31	Merck & Co., Inc.	Process for making HIV protease inhibitors
TW472047B (en) *	1994-02-04	2002-01-11	Merck & Co Inc	Process for making HIV protease inhibitors
US5449830A (en) *	1994-03-11	1995-09-12	Marck & Co., Inc.	Regiospecific processes to make CIS-1-Amino-2-Alkanol from Diol or Halohydrin
US5420353A (en) *	1994-03-11	1995-05-30	Merck & Co., Inc.	Regiospecific process to make cis-1-amino-2-alkanol from epoxide

1995
- 1995-03-15 US US08/404,798 patent/US5618937A/en not_active Expired - Fee Related
1996
- 1996-03-05 AR ARP960101629A patent/AR002712A1/es unknown
- 1996-03-06 TW TW085102721A patent/TW332205B/zh active
- 1996-03-11 AT AT96908523T patent/ATE181916T1/de not_active IP Right Cessation
- 1996-03-11 WO PCT/US1996/002556 patent/WO1996028439A1/en not_active Ceased
- 1996-03-11 EA EA199700235A patent/EA000178B1/ru not_active IP Right Cessation
- 1996-03-11 BR BR9607376A patent/BR9607376A/pt not_active Application Discontinuation
- 1996-03-11 HR HR08/404,798A patent/HRP960114B1/xx not_active IP Right Cessation
- 1996-03-11 SK SK1225-97A patent/SK282021B6/sk unknown
- 1996-03-11 DE DE69603163T patent/DE69603163D1/de not_active Expired - Lifetime
- 1996-03-11 CZ CZ19972860A patent/CZ292549B6/cs not_active IP Right Cessation
- 1996-03-11 AU AU51738/96A patent/AU5173896A/en not_active Abandoned
- 1996-03-11 CN CN96193730A patent/CN1100054C/zh not_active Expired - Fee Related
- 1996-03-11 EP EP96908523A patent/EP0815101B1/en not_active Expired - Lifetime
- 1996-03-15 YU YU15496A patent/YU15496A/sh unknown
- 1996-11-03 UA UA97105014A patent/UA49826C2/uk unknown

Also Published As

Publication number	Publication date
CN1183779A (zh)	1998-06-03
EA000178B1 (ru)	1998-12-24
HRP960114B1 (en)	2000-02-29
SK122597A3 (en)	1998-02-04
EP0815101B1 (en)	1999-07-07
TW332205B (en)	1998-05-21
YU15496A (sh)	1999-03-04
HRP960114A2 (en)	1997-10-31
CZ286097A3 (cs)	1998-02-18
AU5173896A (en)	1996-10-02
EP0815101A1 (en)	1998-01-07
UA49826C2 (uk)	2002-10-15
DE69603163D1 (de)	1999-08-12
AR002712A1 (es)	1998-04-29
WO1996028439A1 (en)	1996-09-19
US5618937A (en)	1997-04-08
BR9607376A (pt)	1997-12-30
ATE181916T1 (de)	1999-07-15
EA199700235A1 (ru)	1998-04-30
CZ292549B6 (cs)	2003-10-15
CN1100054C (zh)	2003-01-29

Publication	Publication Date	Title
AU691941B2 (en)	1998-05-28	New HIV protease inhibitors
HK1006060B (en)	1999-02-05	Hiv protease inhibitors useful for the treatment of aids
DE69523038T2 (de)	2002-06-06	Verfahren zur herstellung von hiv proteasinhibitoren
AU676079B2 (en)	1997-02-27	Process for making HIV protease inhibitors
SK115096A3 (en)	1997-06-04	Regiospecific process to make cis-1-amino-2-alkanols
US5612484A (en)	1997-03-18	Process for making HIV protease inhibitors
SK122597A3 (en)	1998-02-04	Process to make hiv protease inhibitor
US5489710A (en)	1996-02-06	Regiospecific processes to make cis-1-amino-2-alkanol from diol
EP0528661A2 (en)	1993-02-24	HIV protease inhibitors with N-terminal polyether substituents
US5723615A (en)	1998-03-03	Process for preparing 4-tert-butyloxycarbonyl-(S)-piperazine-2-tert-butylcarboxamide
US5508404A (en)	1996-04-16	Reductive amination process
US6156895A (en)	2000-12-05	Process for preparing 4-tert-butyloxycarbonyl-(S)-piperazine-2-tert-butylcarboxamide
GB2302690A (en)	1997-01-29	Process for preparing chiral 1,4-diacyl-(S)-piperazine-2-carboxamides using a diene/chiral bisphosphine/rhodium or iridium hydrogenation catalyst
GB2333775A (en)	1999-08-04	Process for preparing 4-alkylcarbonyl-(s)-piperazine-2-alkylcarboxamide