CZ281493A3 - Hiv protease inhibitor, suitable for aids treatment, process of its preparation and pharmaceutical preparation in which it is comprised - Google Patents

Hiv protease inhibitor, suitable for aids treatment, process of its preparation and pharmaceutical preparation in which it is comprised Download PDF

Info

Publication number: CZ281493A3
Authority: CZ; Czechia
Prior art keywords: amino; butyl; hydroxy; aza; oxo
Prior art date: 1992-12-22

Application number

CZ932814A

Other languages

Czech (cs)

English (en)

Inventor

Louis Nickolaus Jungheim

Timothy Alan Shepherd

Original Assignee

Lilly Co Eli

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.)

1992-12-22

Filing date

1993-12-17

Publication date

1994-07-13

1993-10-12 Priority claimed from US08/134,329 external-priority patent/US5733906A/en

1993-12-17 Application filed by Lilly Co Eli filed Critical Lilly Co Eli

1994-07-13 Publication of CZ281493A3 publication Critical patent/CZ281493A3/cs

Links

238000000034 method Methods 0.000 title claims abstract description 47
239000004030 hiv protease inhibitor Substances 0.000 title claims abstract description 12
238000002360 preparation method Methods 0.000 title claims description 85
230000008569 process Effects 0.000 title claims description 8
229940122440 HIV protease inhibitor Drugs 0.000 title claims description 7
238000011282 treatment Methods 0.000 title description 10
239000000825 pharmaceutical preparation Substances 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 149
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 20
125000003275 alpha amino acid group Chemical group 0.000 claims abstract 2
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 339
-1 (N-Caryl) tetrazolyl Chemical group 0.000 claims description 278
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 155
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 69
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 66
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 63
125000004432 carbon atom Chemical group C* 0.000 claims description 39
150000003839 salts Chemical class 0.000 claims description 37
125000000217 alkyl group Chemical group 0.000 claims description 35
125000000623 heterocyclic group Chemical group 0.000 claims description 34
125000003118 aryl group Chemical group 0.000 claims description 18
239000004480 active ingredient Substances 0.000 claims description 15
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 14
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
239000001257 hydrogen Substances 0.000 claims description 11
229910052739 hydrogen Inorganic materials 0.000 claims description 11
125000003277 amino group Chemical group 0.000 claims description 10
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 9
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
229910052799 carbon Inorganic materials 0.000 claims description 7
230000002401 inhibitory effect Effects 0.000 claims description 7
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
229910052717 sulfur Inorganic materials 0.000 claims description 6
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
125000003710 aryl alkyl group Chemical group 0.000 claims description 5
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 4
125000004429 atom Chemical group 0.000 claims description 4
125000000753 cycloalkyl group Chemical group 0.000 claims description 4
125000004663 dialkyl amino group Chemical group 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 4
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 4
230000010076 replication Effects 0.000 claims description 4
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
125000003282 alkyl amino group Chemical group 0.000 claims description 3
239000003443 antiviral agent Substances 0.000 claims description 3
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 3
125000001624 naphthyl group Chemical group 0.000 claims description 3
239000000546 pharmaceutical excipient Substances 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 2
125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
125000004434 sulfur atom Chemical group 0.000 claims description 2
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101100248170 Mus musculus Rfc1 gene Proteins 0.000 claims 1
125000000592 heterocycloalkyl group Chemical group 0.000 claims 1
125000002768 hydroxyalkyl group Chemical group 0.000 claims 1
125000000446 sulfanediyl group Chemical group *S* 0.000 claims 1
208000030507 AIDS Diseases 0.000 abstract description 10
208000031886 HIV Infections Diseases 0.000 abstract description 5
208000037357 HIV infectious disease Diseases 0.000 abstract description 4
208000033519 human immunodeficiency virus infectious disease Diseases 0.000 abstract description 4
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 240
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 153
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239000000243 solution Substances 0.000 description 133
238000006243 chemical reaction Methods 0.000 description 119
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 78
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 53
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 52
239000011541 reaction mixture Substances 0.000 description 51
239000007787 solid Substances 0.000 description 48
239000002253 acid Substances 0.000 description 45
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230000002829 reductive effect Effects 0.000 description 44
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QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 33
239000000203 mixture Substances 0.000 description 32
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 31
239000002904 solvent Substances 0.000 description 27
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 26
239000000543 intermediate Substances 0.000 description 25
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 24
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 24
239000003480 eluent Substances 0.000 description 22
KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Substances [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 22
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 21
239000012043 crude product Substances 0.000 description 21
ZJSQZQMVXKZAGW-UHFFFAOYSA-N 2H-benzotriazol-4-ol hydrate Chemical compound O.OC1=CC=CC2=C1N=NN2 ZJSQZQMVXKZAGW-UHFFFAOYSA-N 0.000 description 19
125000006239 protecting group Chemical group 0.000 description 19
229910052938 sodium sulfate Inorganic materials 0.000 description 19
235000011152 sodium sulphate Nutrition 0.000 description 19
238000004809 thin layer chromatography Methods 0.000 description 19
238000004458 analytical method Methods 0.000 description 18
239000003153 chemical reaction reagent Substances 0.000 description 18
238000004587 chromatography analysis Methods 0.000 description 18
239000000872 buffer Substances 0.000 description 17
229910052757 nitrogen Inorganic materials 0.000 description 17
239000010410 layer Substances 0.000 description 16
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 16
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HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 14
229940086542 triethylamine Drugs 0.000 description 13
241000725303 Human immunodeficiency virus Species 0.000 description 12
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 12
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 12
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 12
239000012044 organic layer Substances 0.000 description 12
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 12
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239000000010 aprotic solvent Substances 0.000 description 11
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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 9
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 9
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239000000126 substance Substances 0.000 description 9
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 8
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241001646716 Escherichia coli K-12 Species 0.000 description 7
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PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical group O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 5
YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 5
108010010369 HIV Protease Proteins 0.000 description 5
102100034343 Integrase Human genes 0.000 description 5
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
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239000000706 filtrate Substances 0.000 description 5
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NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 5
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TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 4
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NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
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CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
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BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/58—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems with hetero atoms directly attached to the ring nitrogen atom
- C07D215/60—N-oxides
- 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
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
- C07D217/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- 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

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Virology (AREA)
Pharmacology & Pharmacy (AREA)
General Health & Medical Sciences (AREA)
Oncology (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Public Health (AREA)
Communicable Diseases (AREA)
Animal Behavior & Ethology (AREA)
AIDS & HIV (AREA)
Tropical Medicine & Parasitology (AREA)
Molecular Biology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Medicines Containing Plant Substances (AREA)
Thiazole And Isothizaole Compounds (AREA)
Other In-Based Heterocyclic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Plural Heterocyclic Compounds (AREA)
Pyrrole Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

CZ932814A 1992-12-22 1993-12-17 Hiv protease inhibitor, suitable for aids treatment, process of its preparation and pharmaceutical preparation in which it is comprised CZ281493A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US99525692A	1992-12-22	1992-12-22
US08/134,329 US5733906A (en)	1993-10-12	1993-10-12	Inhibitors of HIV Protease useful for the treatment of Aids

Publications (1)

Publication Number	Publication Date
CZ281493A3 true CZ281493A3 (en)	1994-07-13

Family

ID=26832220

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CZ932814A CZ281493A3 (en)	1992-12-22	1993-12-17	Hiv protease inhibitor, suitable for aids treatment, process of its preparation and pharmaceutical preparation in which it is comprised

Country Status (21)

Country	Link
US (1)	US5905077A (2)
EP (1)	EP0604185B1 (2)
JP (1)	JPH06271534A (2)
KR (1)	KR940014337A (2)
CN (1)	CN1044117C (2)
AT (1)	ATE178055T1 (2)
AU (1)	AU667146B2 (2)
BR (1)	BR9305162A (2)
CA (1)	CA2112042A1 (2)
CZ (1)	CZ281493A3 (2)
DE (1)	DE69324120T2 (2)
ES (1)	ES2132201T3 (2)
FI (1)	FI935778A7 (2)
HU (1)	HUT69693A (2)
IL (1)	IL108092A (2)
MX (1)	MX9308016A (2)
MY (1)	MY131388A (2)
NO (1)	NO934719L (2)
NZ (1)	NZ250491A (2)
PL (1)	PL301581A1 (2)
TW (1)	TW262468B (2)

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US6960576B2 (en) *	1999-09-13	2005-11-01	Bristol-Myers Squibb Pharma Company	Hydroxyalkanoylaminolactams and related structures as inhibitors of Aβ protein production
US6503902B2 (en)	1999-09-13	2003-01-07	Bristol-Myers Squibb Pharma Company	Hydroxyalkanoylaminolactams and related structures as inhibitors of a β protein production
WO2001027108A1 (en)	1999-10-08	2001-04-19	Bristol-Myers Squibb Pharma Company	AMINO LACTAM SULFONAMIDES AS INHIBITORS OF Aβ PROTEIN PRODUCTION
US6525044B2 (en)	2000-02-17	2003-02-25	Bristol-Myers Squibb Company	Succinoylamino carbocycles and heterocycles as inhibitors of a-β protein production
US6495540B2 (en)	2000-03-28	2002-12-17	Bristol - Myers Squibb Pharma Company	Lactams as inhibitors of A-β protein production
JP2004508289A (ja)	2000-04-03	2004-03-18	デュポン　ファーマシューティカルズ　カンパニー	Ａβタンパク質産生の阻害剤としての環状ラクタム
CN1436175A (zh)	2000-04-03	2003-08-13	布里斯托尔-迈尔斯斯奎布药品公司	作为Aβ－蛋白生产抑制剂的环状内酰胺
US20100009966A1 (en) *	2001-04-11	2010-01-14	Bristol-Myers Squibb Pharma Company	Substituted lactams as inhibitors of abeta protein production
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US6878363B2 (en) *	2000-05-17	2005-04-12	Bristol-Myers Squibb Pharma Company	Use of small molecule radioligands to discover inhibitors of amyloid-beta peptide production and for diagnostic imaging
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GB0028483D0 (en)	2000-11-22	2001-01-10	Hoffmann La Roche	Hydroxyethylamine HIV protease inhibitors
WO2002064553A1 (en) *	2001-02-14	2002-08-22	Kureha Chemical Industry Company, Limited	Process for preparation of halogenoalcohol derivatives
US20090062256A1 (en) *	2001-06-01	2009-03-05	Bristol-Myers Squibb Pharma Company	LACTAMS SUBSTITUTED BY CYCLIC SUCCINATES AS INHIBITORS OF Abeta PROTEIN PRODUCTION
GB0123467D0 (en)	2001-09-28	2001-11-21	Hoffmann La Roche	Carbocyclic HIV Protease inhibitors
KR101155335B1 (ko) *	2005-01-07	2012-06-11	엘지전자 주식회사	이동통신 단말기의 멀티미디어 메시지 동작방법
EP1910317B1 (en)	2005-07-20	2013-07-03	Eli Lilly And Company	1-amino linked compounds
CN101508664B (zh) *	2009-02-25	2012-08-22	江阴希迪医药科技有限公司	N-苄氧羰基-3-氨基-1-氯-4-苯硫基-2-丁醇合成方法
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1993
- 1993-12-15 MX MX9308016A patent/MX9308016A/es not_active IP Right Cessation
- 1993-12-17 CZ CZ932814A patent/CZ281493A3/cs unknown
- 1993-12-17 MY MYPI93002745A patent/MY131388A/en unknown
- 1993-12-17 NZ NZ250491A patent/NZ250491A/en unknown
- 1993-12-20 EP EP93310359A patent/EP0604185B1/en not_active Expired - Lifetime
- 1993-12-20 ES ES93310359T patent/ES2132201T3/es not_active Expired - Lifetime
- 1993-12-20 PL PL93301581A patent/PL301581A1/xx unknown
- 1993-12-20 AU AU52528/93A patent/AU667146B2/en not_active Ceased
- 1993-12-20 NO NO934719A patent/NO934719L/no unknown
- 1993-12-20 DE DE69324120T patent/DE69324120T2/de not_active Expired - Fee Related
- 1993-12-20 AT AT93310359T patent/ATE178055T1/de not_active IP Right Cessation
- 1993-12-20 HU HU9303679A patent/HUT69693A/hu unknown
- 1993-12-20 IL IL108092A patent/IL108092A/en active IP Right Grant
- 1993-12-21 JP JP5322750A patent/JPH06271534A/ja active Pending
- 1993-12-21 CA CA002112042A patent/CA2112042A1/en not_active Abandoned
- 1993-12-21 FI FI935778A patent/FI935778A7/fi not_active Application Discontinuation
- 1993-12-21 CN CN93112962A patent/CN1044117C/zh not_active Expired - Fee Related
- 1993-12-21 BR BR9305162A patent/BR9305162A/pt not_active Application Discontinuation
- 1993-12-22 KR KR1019930029121A patent/KR940014337A/ko not_active Abandoned
- 1993-12-22 TW TW082110893A patent/TW262468B/zh active
1997
- 1997-11-19 US US08/974,430 patent/US5905077A/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
IL108092A (en)	1998-06-15
AU5252893A (en)	1994-07-07
DE69324120T2 (de)	1999-11-25
US5905077A (en)	1999-05-18
CN1044117C (zh)	1999-07-14
AU667146B2 (en)	1996-03-07
DE69324120D1 (de)	1999-04-29
EP0604185A1 (en)	1994-06-29
PL301581A1 (en)	1994-06-27
ES2132201T3 (es)	1999-08-16
HUT69693A (en)	1995-09-28
KR940014337A (ko)	1994-07-18
TW262468B (2)	1995-11-11
MX9308016A (es)	1994-08-31
EP0604185B1 (en)	1999-03-24
CA2112042A1 (en)	1994-06-23
BR9305162A (pt)	1994-11-01
NO934719D0 (no)	1993-12-20
NZ250491A (en)	1995-08-28
MY131388A (en)	2007-08-30
FI935778A0 (fi)	1993-12-21
NO934719L (no)	1994-06-23
ATE178055T1 (de)	1999-04-15
CN1094399A (zh)	1994-11-02
IL108092A0 (en)	1994-04-12
JPH06271534A (ja)	1994-09-27
FI935778A7 (fi)	1994-06-23

Publication	Publication Date	Title
CZ281493A3 (en)	1994-07-13	Hiv protease inhibitor, suitable for aids treatment, process of its preparation and pharmaceutical preparation in which it is comprised
FI114794B (fi)	2004-12-31	HIV-proteaasin estäjät
US5502061A (en)	1996-03-26	Peptidyl substituted benzamides and naphthamies
AU700417B2 (en)	1999-01-07	Protease inhibitors
EP0604183B1 (en)	1997-03-05	Inhibitors of HIV protease useful for the treatment of aids
CZ281393A3 (en)	1994-07-13	Hiv protease inhibitor, suitable for aids treatment, process of its preparation and pharmaceutical preparation in which it is comprised
EP0604184B1 (en)	1997-07-09	Inhibitors of HIV protease useful for the treatment of aids
US5578608A (en)	1996-11-26	Symmetrical diaryl and diheteroanyl cis epoxy alkanes antiviral compounds
US5733906A (en)	1998-03-31	Inhibitors of HIV Protease useful for the treatment of Aids
JPH09509657A (ja)	1997-09-30	中間体および製造のための方法
JPH06234716A (ja)	1994-08-23	Ａｉｄｓの処置に有用なｈｉｖ−プロテアーゼ阻害剤
US5475136A (en)	1995-12-12	Inhibitors of HIV protease useful for the treatment of AIDS
BG63540B1 (bg)	2002-04-30	Инхибитори на нiv-протеазата