OA10988A - Intermeditates for making hiv-protease inhibitors and methods of making hiv-protease inhibitors - Google Patents

Intermeditates for making hiv-protease inhibitors and methods of making hiv-protease inhibitors Download PDF

Info

Publication number: OA10988A
Authority: OA; OAPI
Prior art keywords: group; formula; compound; aryl; alkyl
Prior art date: 1996-09-05

Application number

OA9900049A

Other languages

English (en)

Inventor

Katheen R Whitten

Michael E Deason

Original Assignee

Agouron Pharma

Japan Tobacco 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.)

1996-09-05

Filing date

1999-03-03

Publication date

2001-11-01

1999-03-03 Application filed by Agouron Pharma, Japan Tobacco Inc filed Critical Agouron Pharma

2001-11-01 Publication of OA10988A publication Critical patent/OA10988A/en

Links

238000000034 method Methods 0.000 title claims description 69
239000004030 hiv protease inhibitor Substances 0.000 title abstract description 11
238000004519 manufacturing process Methods 0.000 claims abstract description 16
125000000217 alkyl group Chemical group 0.000 claims description 151
150000001875 compounds Chemical class 0.000 claims description 146
125000003118 aryl group Chemical group 0.000 claims description 141
125000001072 heteroaryl group Chemical group 0.000 claims description 80
125000000753 cycloalkyl group Chemical group 0.000 claims description 75
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 44
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical group CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 33
239000002904 solvent Substances 0.000 claims description 26
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 22
239000007787 solid Substances 0.000 claims description 21
125000003710 aryl alkyl group Chemical group 0.000 claims description 19
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 19
229910052760 oxygen Inorganic materials 0.000 claims description 19
239000001301 oxygen Substances 0.000 claims description 19
125000002577 pseudohalo group Chemical group 0.000 claims description 19
229910052736 halogen Inorganic materials 0.000 claims description 18
150000002367 halogens Chemical class 0.000 claims description 17
125000005842 heteroatom Chemical group 0.000 claims description 17
239000012296 anti-solvent Substances 0.000 claims description 13
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
125000006239 protecting group Chemical group 0.000 claims description 10
229960004132 diethyl ether Drugs 0.000 claims description 9
229940098779 methanesulfonic acid Drugs 0.000 claims description 8
239000003960 organic solvent Substances 0.000 claims description 8
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 6
238000001035 drying Methods 0.000 claims description 6
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
238000001914 filtration Methods 0.000 claims description 4
238000001694 spray drying Methods 0.000 claims description 3
239000007790 solid phase Substances 0.000 claims description 2
238000005406 washing Methods 0.000 claims description 2
239000007791 liquid phase Substances 0.000 claims 1
NQHXCOAXSHGTIA-SKXNDZRYSA-N nelfinavir mesylate Chemical compound CS(O)(=O)=O.CC1=C(O)C=CC=C1C(=O)N[C@H]([C@H](O)CN1[C@@H](C[C@@H]2CCCC[C@@H]2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 NQHXCOAXSHGTIA-SKXNDZRYSA-N 0.000 abstract description 11
229960005230 nelfinavir mesylate Drugs 0.000 abstract description 11
229940122440 HIV protease inhibitor Drugs 0.000 abstract description 2
-1 heteroaromatic ester Chemical class 0.000 description 79
239000000203 mixture Substances 0.000 description 57
239000002253 acid Substances 0.000 description 39
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 35
238000006243 chemical reaction Methods 0.000 description 35
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
239000002585 base Substances 0.000 description 29
239000012458 free base Substances 0.000 description 29
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 28
QAGYKUNXZHXKMR-UHFFFAOYSA-N CPD000469186 Natural products CC1=C(O)C=CC=C1C(=O)NC(C(O)CN1C(CC2CCCCC2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-UHFFFAOYSA-N 0.000 description 27
229960000884 nelfinavir Drugs 0.000 description 27
QAGYKUNXZHXKMR-HKWSIXNMSA-N nelfinavir Chemical compound CC1=C(O)C=CC=C1C(=O)N[C@H]([C@H](O)CN1[C@@H](C[C@@H]2CCCC[C@@H]2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-HKWSIXNMSA-N 0.000 description 27
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 18
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
150000002148 esters Chemical class 0.000 description 13
238000003756 stirring Methods 0.000 description 13
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 12
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
150000001412 amines Chemical class 0.000 description 12
239000000047 product Substances 0.000 description 12
239000002002 slurry Substances 0.000 description 12
235000011121 sodium hydroxide Nutrition 0.000 description 12
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
238000010992 reflux Methods 0.000 description 11
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 11
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
150000003839 salts Chemical class 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 9
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 9
125000003545 alkoxy group Chemical group 0.000 description 9
125000004432 carbon atom Chemical group C* 0.000 description 9
125000005843 halogen group Chemical group 0.000 description 9
125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
239000007921 spray Substances 0.000 description 9
229910052757 nitrogen Inorganic materials 0.000 description 8
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 7
229960000583 acetic acid Drugs 0.000 description 7
125000004453 alkoxycarbonyl group Chemical group 0.000 description 7
229940125898 compound 5 Drugs 0.000 description 7
239000012065 filter cake Substances 0.000 description 7
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
235000011054 acetic acid Nutrition 0.000 description 6
150000007513 acids Chemical class 0.000 description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 6
238000004128 high performance liquid chromatography Methods 0.000 description 6
239000000543 intermediate Substances 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
239000008213 purified water Substances 0.000 description 6
RIERSGULWXEJKL-UHFFFAOYSA-N 3-hydroxy-2-methylbenzoic acid Chemical compound CC1=C(O)C=CC=C1C(O)=O RIERSGULWXEJKL-UHFFFAOYSA-N 0.000 description 5
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 5
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 5
229910004373 HOAc Inorganic materials 0.000 description 5
125000005115 alkyl carbamoyl group Chemical group 0.000 description 5
229910052799 carbon Inorganic materials 0.000 description 5
239000000460 chlorine Substances 0.000 description 5
239000012973 diazabicyclooctane Substances 0.000 description 5
150000002170 ethers Chemical class 0.000 description 5
229940052303 ethers for general anesthesia Drugs 0.000 description 5
150000004820 halides Chemical class 0.000 description 5
150000007530 organic bases Chemical class 0.000 description 5
230000008569 process Effects 0.000 description 5
229920006395 saturated elastomer Polymers 0.000 description 5
125000000547 substituted alkyl group Chemical group 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 5
COLDUSGLGQXXEJ-UHFFFAOYSA-N (3-carbonochloridoyl-2-methylphenyl) acetate Chemical compound CC(=O)OC1=CC=CC(C(Cl)=O)=C1C COLDUSGLGQXXEJ-UHFFFAOYSA-N 0.000 description 4
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 4
LHVJUPHCLWIPLZ-UHFFFAOYSA-N 3-acetyloxy-2-methylbenzoic acid Chemical compound CC(=O)OC1=CC=CC(C(O)=O)=C1C LHVJUPHCLWIPLZ-UHFFFAOYSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 4
125000002252 acyl group Chemical group 0.000 description 4
150000001298 alcohols Chemical class 0.000 description 4
239000003513 alkali Substances 0.000 description 4
125000003282 alkyl amino group Chemical group 0.000 description 4
125000004429 atom Chemical group 0.000 description 4
125000002619 bicyclic group Chemical group 0.000 description 4
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 4
150000004649 carbonic acid derivatives Chemical class 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
230000008878 coupling Effects 0.000 description 4
238000010168 coupling process Methods 0.000 description 4
238000005859 coupling reaction Methods 0.000 description 4
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 4
150000004679 hydroxides Chemical class 0.000 description 4
150000007529 inorganic bases Chemical class 0.000 description 4
ULWOJODHECIZAU-UHFFFAOYSA-N n,n-diethylpropan-2-amine Chemical compound CCN(CC)C(C)C ULWOJODHECIZAU-UHFFFAOYSA-N 0.000 description 4
239000000137 peptide hydrolase inhibitor Substances 0.000 description 4
235000011118 potassium hydroxide Nutrition 0.000 description 4
150000003254 radicals Chemical class 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
229940083608 sodium hydroxide Drugs 0.000 description 4
125000001424 substituent group Chemical group 0.000 description 4
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical class CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 3
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical class OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 3
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
230000001476 alcoholic effect Effects 0.000 description 3
125000004414 alkyl thio group Chemical group 0.000 description 3
150000001409 amidines Chemical class 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
238000003556 assay Methods 0.000 description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 3
KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 3
125000000623 heterocyclic group Chemical group 0.000 description 3
JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 3
229940011051 isopropyl acetate Drugs 0.000 description 3
GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 3
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 3
150000007524 organic acids Chemical class 0.000 description 3
229940093932 potassium hydroxide Drugs 0.000 description 3
FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 3
239000000523 sample Substances 0.000 description 3
239000000126 substance Substances 0.000 description 3
229910052717 sulfur Inorganic materials 0.000 description 3
125000005270 trialkylamine group Chemical group 0.000 description 3
LNETULKMXZVUST-UHFFFAOYSA-M 1-naphthoate Chemical class C1=CC=C2C(C(=O)[O-])=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-M 0.000 description 2
SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 2
UOBYKYZJUGYBDK-UHFFFAOYSA-M 2-naphthoate Chemical class C1=CC=CC2=CC(C(=O)[O-])=CC=C21 UOBYKYZJUGYBDK-UHFFFAOYSA-M 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
238000010268 HPLC based assay Methods 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 2
150000001266 acyl halides Chemical class 0.000 description 2
150000001408 amides Chemical class 0.000 description 2
235000001014 amino acid Nutrition 0.000 description 2
150000001413 amino acids Chemical class 0.000 description 2
150000008064 anhydrides Chemical class 0.000 description 2
150000001540 azides Chemical class 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
150000001558 benzoic acid derivatives Chemical class 0.000 description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
150000001735 carboxylic acids Chemical class 0.000 description 2
125000004122 cyclic group Chemical group 0.000 description 2
JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 2
125000005670 ethenylalkyl group Chemical group 0.000 description 2
125000001033 ether group Chemical group 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
239000012467 final product Substances 0.000 description 2
235000019000 fluorine Nutrition 0.000 description 2
125000001153 fluoro group Chemical group F* 0.000 description 2
239000007789 gas Substances 0.000 description 2
229940093915 gynecological organic acid Drugs 0.000 description 2
MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical class CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 2
229910052739 hydrogen Inorganic materials 0.000 description 2
239000001257 hydrogen Substances 0.000 description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
238000007327 hydrogenolysis reaction Methods 0.000 description 2
239000012535 impurity Substances 0.000 description 2
239000012948 isocyanate Substances 0.000 description 2
150000002513 isocyanates Chemical class 0.000 description 2
125000001786 isothiazolyl group Chemical group 0.000 description 2
150000002540 isothiocyanates Chemical class 0.000 description 2
239000007788 liquid Substances 0.000 description 2
239000000463 material Substances 0.000 description 2
230000007246 mechanism Effects 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
125000001624 naphthyl group Chemical group 0.000 description 2
150000002825 nitriles Chemical class 0.000 description 2
125000004433 nitrogen atom Chemical group N* 0.000 description 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
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 2
239000003921 oil Substances 0.000 description 2
235000005985 organic acids Nutrition 0.000 description 2
239000002245 particle Substances 0.000 description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 2
239000003495 polar organic solvent Substances 0.000 description 2
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125000002098 pyridazinyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
229940107700 pyruvic acid Drugs 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
229910052701 rubidium Inorganic materials 0.000 description 1
YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical class OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 1
238000007127 saponification reaction Methods 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical class OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
229910052710 silicon Inorganic materials 0.000 description 1
239000010703 silicon Substances 0.000 description 1
229910001220 stainless steel Inorganic materials 0.000 description 1
239000010935 stainless steel Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000007858 starting material Substances 0.000 description 1
TYFQFVWCELRYAO-UHFFFAOYSA-N suberic acid Chemical class OC(=O)CCCCCCC(O)=O TYFQFVWCELRYAO-UHFFFAOYSA-N 0.000 description 1
125000003107 substituted aryl group Chemical group 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
150000003890 succinate salts Chemical class 0.000 description 1
239000001384 succinic acid Substances 0.000 description 1
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
235000011149 sulphuric acid Nutrition 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
150000003892 tartrate salts Chemical class 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
ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
150000003568 thioethers Chemical class 0.000 description 1
125000003396 thiol group Chemical class [H]S* 0.000 description 1
150000007944 thiolates Chemical class 0.000 description 1
230000007704 transition Effects 0.000 description 1
125000004306 triazinyl group Chemical group 0.000 description 1
150000008648 triflates Chemical class 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
230000003612 virological effect Effects 0.000 description 1
125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
GDJZZWYLFXAGFH-UHFFFAOYSA-M xylenesulfonate group Chemical group C1(C(C=CC=C1)C)(C)S(=O)(=O)[O-] GDJZZWYLFXAGFH-UHFFFAOYSA-M 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
- 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
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C65/21—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing ether groups, groups, groups, or groups
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/28—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group
- C07C67/287—Preparation of carboxylic acid esters by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group by introduction of halogen; by substitution of halogen atoms by other halogen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/02—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen
- C07C69/12—Acetic acid esters
- C07C69/14—Acetic acid esters of monohydroxylic compounds
- C07C69/145—Acetic acid esters of monohydroxylic compounds of unsaturated alcohols
- C07C69/157—Acetic acid esters of monohydroxylic compounds of unsaturated alcohols containing six-membered aromatic rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/62—Halogen-containing esters
- C07C69/63—Halogen-containing esters of saturated acids
- 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

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Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Virology (AREA)
Pharmacology & Pharmacy (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Molecular Biology (AREA)
Tropical Medicine & Parasitology (AREA)
AIDS & HIV (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Peptides Or Proteins (AREA)
Other In-Based Heterocyclic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)

OA9900049A 1996-09-05 1999-03-03 Intermeditates for making hiv-protease inhibitors and methods of making hiv-protease inhibitors OA10988A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US70841196A	1996-09-05	1996-09-05

Publications (1)

Publication Number	Publication Date
OA10988A true OA10988A (en)	2001-11-01

Family

ID=24845703

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA9900049A OA10988A (en)	1996-09-05	1999-03-03	Intermeditates for making hiv-protease inhibitors and methods of making hiv-protease inhibitors

Country Status (32)

Country	Link
EP (2)	EP0927165B1 (cs)
JP (3)	JP4149000B2 (cs)
KR (1)	KR100563289B1 (cs)
CN (2)	CN1305854C (cs)
AP (2)	AP1322A (cs)
AT (2)	ATE309990T1 (cs)
AU (2)	AU740369B2 (cs)
BG (2)	BG64793B1 (cs)
BR (1)	BR9713192A (cs)
CA (1)	CA2264756A1 (cs)
CZ (2)	CZ298175B6 (cs)
DE (2)	DE69726298T2 (cs)
DK (2)	DK0927165T3 (cs)
EA (1)	EA002051B1 (cs)
EE (1)	EE04465B1 (cs)
ES (2)	ES2252586T3 (cs)
GE (1)	GEP20022799B (cs)
HU (1)	HUP0000028A3 (cs)
IL (1)	IL128567A (cs)
IS (1)	IS2030B (cs)
NO (1)	NO313287B1 (cs)
NZ (1)	NZ334909A (cs)
OA (1)	OA10988A (cs)
PL (2)	PL201758B1 (cs)
PT (1)	PT927165E (cs)
SG (1)	SG94780A1 (cs)
SI (2)	SI1361216T1 (cs)
SK (2)	SK284899B6 (cs)
TR (1)	TR199900473T2 (cs)
UA (1)	UA67727C2 (cs)
WO (1)	WO1998009951A2 (cs)
YU (1)	YU11599A (cs)

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPH0641038A (ja) *	1992-07-17	1994-02-15	Mitsubishi Kasei Corp	カルボン酸誘導体
US5484926A (en) *	1993-10-07	1996-01-16	Agouron Pharmaceuticals, Inc.	HIV protease inhibitors
JPH07248183A (ja) *	1994-03-11	1995-09-26	Osaka Gas Co Ltd	浴室兼用衣類乾燥室
JP3298293B2 (ja) *	1994-03-14	2002-07-02	松下電器産業株式会社	厨芥処理機
AU4953796A (en) *	1995-03-15	1996-10-02	Sanyko Company, Limited	Dipeptide compounds having ahpba structure
WO1997011937A1 (en) *	1995-09-26	1997-04-03	Japan Tobacco Inc.	Process for producing amide derivatives and intermediates
US5962704A (en) *	1995-09-26	1999-10-05	Japan Tobacco Inc.	Production of amide derivatives and intermediate compounds therefor
US6121468A (en) *	1995-09-26	2000-09-19	Japan Tobacco Inc.	Process for producing amide derivatives and intermediate compounds
CZ230398A3 (cs) *	1996-02-24	1999-01-13	Basf Aktiengesellschaft	Derivát pyrazol-4-ylhetaroylu, způsob jeho přípravy a herbicidní prostředek, který ho obsahuje

1997
- 1997-04-09 UA UA99041906A patent/UA67727C2/uk unknown
- 1997-09-04 GE GEAP19974736A patent/GEP20022799B/en unknown
- 1997-09-04 HU HU0000028A patent/HUP0000028A3/hu unknown
- 1997-09-04 AP APAP/P/1999/001497A patent/AP1322A/en active
- 1997-09-04 EP EP97941402A patent/EP0927165B1/en not_active Expired - Lifetime
- 1997-09-04 SI SI9730719T patent/SI1361216T1/sl unknown
- 1997-09-04 SK SK282-99A patent/SK284899B6/sk not_active IP Right Cessation
- 1997-09-04 AT AT03013275T patent/ATE309990T1/de not_active IP Right Cessation
- 1997-09-04 PL PL381445A patent/PL201758B1/pl not_active IP Right Cessation
- 1997-09-04 PT PT97941402T patent/PT927165E/pt unknown
- 1997-09-04 DE DE69726298T patent/DE69726298T2/de not_active Expired - Fee Related
- 1997-09-04 SI SI9730605T patent/SI0927165T1/xx unknown
- 1997-09-04 CN CNB2004100073691A patent/CN1305854C/zh not_active Expired - Fee Related
- 1997-09-04 DK DK97941402T patent/DK0927165T3/da active
- 1997-09-04 CZ CZ20070084A patent/CZ298175B6/cs not_active IP Right Cessation
- 1997-09-04 DE DE69734689T patent/DE69734689T2/de not_active Expired - Fee Related
- 1997-09-04 BR BR9713192-0A patent/BR9713192A/pt not_active Application Discontinuation
- 1997-09-04 AU AU43317/97A patent/AU740369B2/en not_active Ceased
- 1997-09-04 IL IL12856797A patent/IL128567A/en not_active IP Right Cessation
- 1997-09-04 ES ES03013275T patent/ES2252586T3/es not_active Expired - Lifetime
- 1997-09-04 AT AT97941402T patent/ATE254603T1/de not_active IP Right Cessation
- 1997-09-04 SK SK90-2005A patent/SK285278B6/sk not_active IP Right Cessation
- 1997-09-04 SG SG200101308A patent/SG94780A1/en unknown
- 1997-09-04 YU YU11599A patent/YU11599A/sh unknown
- 1997-09-04 NZ NZ334909A patent/NZ334909A/en unknown
- 1997-09-04 CZ CZ0071699A patent/CZ298174B6/cs not_active IP Right Cessation
- 1997-09-04 CN CNB971984484A patent/CN1183117C/zh not_active Expired - Fee Related
- 1997-09-04 EP EP03013275A patent/EP1361216B1/en not_active Expired - Lifetime
- 1997-09-04 CA CA002264756A patent/CA2264756A1/en not_active Abandoned
- 1997-09-04 ES ES97941402T patent/ES2210573T3/es not_active Expired - Lifetime
- 1997-09-04 AP APAP/P/2003/002938A patent/AP2003002938A0/en unknown
- 1997-09-04 JP JP51283198A patent/JP4149000B2/ja not_active Expired - Fee Related
- 1997-09-04 EE EEP199900109A patent/EE04465B1/xx not_active IP Right Cessation
- 1997-09-04 WO PCT/US1997/015468 patent/WO1998009951A2/en not_active Ceased
- 1997-09-04 TR TR1999/00473T patent/TR199900473T2/xx unknown
- 1997-09-04 DK DK03013275T patent/DK1361216T3/da active
- 1997-09-04 KR KR1019997001902A patent/KR100563289B1/ko not_active Expired - Fee Related
- 1997-09-04 EA EA199900257A patent/EA002051B1/ru not_active IP Right Cessation
- 1997-09-04 PL PL331801A patent/PL198408B1/pl not_active IP Right Cessation
1999
- 1999-02-19 IS IS4982A patent/IS2030B/is unknown
- 1999-03-03 OA OA9900049A patent/OA10988A/en unknown
- 1999-03-04 NO NO19991072A patent/NO313287B1/no not_active IP Right Cessation
- 1999-04-02 BG BG103305A patent/BG64793B1/bg unknown
2002
- 2002-01-31 AU AU14736/02A patent/AU766155B2/en not_active Ceased
2006
- 2006-01-18 BG BG109411A patent/BG65237B1/bg unknown
2007
- 2007-10-29 JP JP2007280975A patent/JP2008088178A/ja active Pending
- 2007-10-29 JP JP2007280974A patent/JP2008056693A/ja not_active Withdrawn

Also Published As

Publication number	Publication date
DE69726298D1 (de)	2003-12-24
NO991072D0 (no)	1999-03-04
DE69734689T2 (de)	2006-06-08
BG64793B1 (bg)	2006-04-28
JP4149000B2 (ja)	2008-09-10
CN1537846A (zh)	2004-10-20
AU766155B2 (en)	2003-10-09
BG103305A (en)	2000-01-31
PT927165E (pt)	2004-04-30
SK28299A3 (en)	1999-11-08
NO313287B1 (no)	2002-09-09
YU11599A (sh)	2000-03-21
DK1361216T3 (da)	2006-01-23
CA2264756A1 (en)	1998-03-12
CZ298175B6 (cs)	2007-07-11
EP0927165B1 (en)	2003-11-19
PL331801A1 (en)	1999-08-02
EA199900257A1 (ru)	1999-08-26
KR100563289B1 (ko)	2006-03-22
EE04465B1 (et)	2005-04-15
JP2008088178A (ja)	2008-04-17
DE69734689D1 (de)	2005-12-22
DE69726298T2 (de)	2004-05-27
ES2252586T3 (es)	2006-05-16
WO1998009951A2 (en)	1998-03-12
DK0927165T3 (da)	2004-03-15
AU4331797A (en)	1998-03-26
IL128567A (en)	2004-03-28
EA002051B1 (ru)	2001-12-24
KR20010029489A (ko)	2001-04-06
IS2030B (is)	2005-08-15
PL198408B1 (pl)	2008-06-30
EP1361216B1 (en)	2005-11-16
NZ334909A (en)	2000-06-23
HUP0000028A3 (en)	2003-05-28
AU1473602A (en)	2002-03-14
SI1361216T1 (sl)	2006-02-28
AP9901497A0 (en)	1999-06-30
HK1062171A1 (en)	2004-10-21
ATE254603T1 (de)	2003-12-15
TR199900473T2 (xx)	1999-06-21
HUP0000028A2 (hu)	2000-05-28
WO1998009951A3 (en)	1998-07-09
CN1305854C (zh)	2007-03-21
EP1361216A1 (en)	2003-11-12
ES2210573T3 (es)	2004-07-01
JP2008056693A (ja)	2008-03-13
ATE309990T1 (de)	2005-12-15
SK285278B6 (sk)	2006-10-05
CN1232455A (zh)	1999-10-20
EE9900109A (et)	1999-12-15
JP2001500495A (ja)	2001-01-16
SK284899B6 (sk)	2006-02-02
AP2003002938A0 (en)	2003-12-31
SG94780A1 (en)	2003-03-18
BG65237B1 (bg)	2007-09-28
GEP20022799B (en)	2002-09-25
AP1322A (en)	2004-11-04
PL201758B1 (pl)	2009-05-29
SI0927165T1 (en)	2004-04-30
CN1183117C (zh)	2005-01-05
NO991072L (no)	1999-03-04
AU740369B2 (en)	2001-11-01
IL128567A0 (en)	2000-01-31
CZ298174B6 (cs)	2007-07-11
CZ71699A3 (cs)	1999-06-16
EP0927165A2 (en)	1999-07-07
UA67727C2 (uk)	2004-07-15
BR9713192A (pt)	1999-12-21
IS4982A (is)	1999-02-19

Publication	Publication Date	Title
US6605721B2 (en)	2003-08-12	Intermediates for making HIV-protease inhibitors and methods for making HIV-protease inhibitors
US5705647A (en)	1998-01-06	Intermediates for making HIV-protease inhibitors
US5925759A (en)	1999-07-20	Methods of making HIV-protease inhibitors and intermediates for making HIV-protease inhibitors
AP1322A (en)	2004-11-04	Intermediates for making HIV- protease inhibitors and methods of making HIV protease inhibitors.
JP2527319B2 (ja)	1996-08-21	７―ブロモ―β―カルボリン誘導体の製造方法
MXPA99002152A (en)	2000-11-01	Intermediates for making hiv-protease inhibitors and methods of making hiv-protease inhibitors
US6084107A (en)	2000-07-04	Intermediates for making HIV-protease inhibitors
JPS6259707B2 (cs)	1987-12-12
JPH0559904B2 (cs)	1993-09-01