TW201006475A - HIV protease inhibitors - Google Patents

HIV protease inhibitors Download PDF

Info

Publication number: TW201006475A
Authority: TW; Taiwan
Prior art keywords: alkyl; amino; mmol; substituted; etoac
Prior art date: 2007-09-25

Application number

TW097146499A

Other languages

English (en)

Chinese (zh)

Inventor

Craig A Coburn

Joseph P Vacca

Hemaka A Rajapakse

Kristen L G Jones

Philippe Nantermet

James C Barrow

Keith P Moore

Cory Theberge

Abbas M Walji

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.)

2007-09-25

Filing date

2008-11-28

Publication date

2010-02-16

2008-11-28 Application filed by Merck & Co Inc filed Critical Merck & Co Inc

2010-02-16 Publication of TW201006475A publication Critical patent/TW201006475A/zh

Links

239000004030 hiv protease inhibitor Substances 0.000 title abstract description 8
150000001875 compounds Chemical class 0.000 claims abstract description 184
150000003839 salts Chemical class 0.000 claims abstract description 57
238000011282 treatment Methods 0.000 claims abstract description 27
208000015181 infectious disease Diseases 0.000 claims abstract description 16
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 15
125000000217 alkyl group Chemical group 0.000 claims description 227
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 161
-1 heteroaryl fluorene Chemical compound 0.000 claims description 134
UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims description 53
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 53
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 52
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 47
150000001412 amines Chemical class 0.000 claims description 43
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 43
239000002585 base Substances 0.000 claims description 38
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 claims description 36
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 33
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 30
125000001424 substituent group Chemical group 0.000 claims description 25
125000000753 cycloalkyl group Chemical group 0.000 claims description 24
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 24
229920006395 saturated elastomer Polymers 0.000 claims description 23
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 claims description 19
CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical group O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 19
125000003709 fluoroalkyl group Chemical group 0.000 claims description 17
125000001072 heteroaryl group Chemical group 0.000 claims description 16
125000005842 heteroatom Chemical group 0.000 claims description 16
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 15
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 14
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 14
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 13
229910052799 carbon Inorganic materials 0.000 claims description 13
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 13
238000002360 preparation method Methods 0.000 claims description 13
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 12
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 11
125000001188 haloalkyl group Chemical group 0.000 claims description 10
125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 10
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 10
239000003814 drug Substances 0.000 claims description 9
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 8
125000005843 halogen group Chemical group 0.000 claims description 8
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
125000003118 aryl group Chemical group 0.000 claims description 7
230000002401 inhibitory effect Effects 0.000 claims description 7
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 7
230000002265 prevention Effects 0.000 claims description 7
XXJGBENTLXFVFI-UHFFFAOYSA-N 1-amino-methylene Chemical compound N[CH2] XXJGBENTLXFVFI-UHFFFAOYSA-N 0.000 claims description 6
150000001335 aliphatic alkanes Chemical class 0.000 claims description 6
229910052794 bromium Inorganic materials 0.000 claims description 6
125000004122 cyclic group Chemical group 0.000 claims description 6
125000000623 heterocyclic group Chemical group 0.000 claims description 6
150000002923 oximes Chemical class 0.000 claims description 6
239000000126 substance Substances 0.000 claims description 6
229930194542 Keto Natural products 0.000 claims description 5
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
239000003937 drug carrier Substances 0.000 claims description 5
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 5
150000002367 halogens Chemical class 0.000 claims description 5
125000000468 ketone group Chemical group 0.000 claims description 5
125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 4
NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 claims description 4
229910052731 fluorine Inorganic materials 0.000 claims description 4
229910052736 halogen Inorganic materials 0.000 claims description 4
238000006467 substitution reaction Methods 0.000 claims description 4
238000002560 therapeutic procedure Methods 0.000 claims description 4
125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 3
125000004432 carbon atom Chemical group C* 0.000 claims description 3
229910052801 chlorine Inorganic materials 0.000 claims description 3
125000001624 naphthyl group Chemical group 0.000 claims description 3
239000012038 nucleophile Substances 0.000 claims description 3
229940126062 Compound A Drugs 0.000 claims description 2
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims description 2
KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical group [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 2
229910052783 alkali metal Inorganic materials 0.000 claims description 2
125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 2
125000002619 bicyclic group Chemical group 0.000 claims description 2
125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 claims description 2
VMWJCFLUSKZZDX-UHFFFAOYSA-N n,n-dimethylmethanamine Chemical compound [CH2]N(C)C VMWJCFLUSKZZDX-UHFFFAOYSA-N 0.000 claims description 2
229910052760 oxygen Inorganic materials 0.000 claims description 2
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 2
YBQZXXMEJHZYMB-UHFFFAOYSA-N 1,2-diphenylhydrazine Chemical compound C=1C=CC=CC=1NNC1=CC=CC=C1 YBQZXXMEJHZYMB-UHFFFAOYSA-N 0.000 claims 1
IJMARSXMLSCBJU-UHFFFAOYSA-N 1-phenyl-2-propylhydrazine Chemical compound CCCNNC1=CC=CC=C1 IJMARSXMLSCBJU-UHFFFAOYSA-N 0.000 claims 1
QGFYFOHMBDMGBZ-UHFFFAOYSA-N 5-[(7-chloroquinolin-4-yl)amino]-2-(diethylaminomethyl)phenol Chemical compound C1=C(O)C(CN(CC)CC)=CC=C1NC1=CC=NC2=CC(Cl)=CC=C12 QGFYFOHMBDMGBZ-UHFFFAOYSA-N 0.000 claims 1
241001122767 Theaceae Species 0.000 claims 1
150000001340 alkali metals Chemical class 0.000 claims 1
229910052784 alkaline earth metal Inorganic materials 0.000 claims 1
150000001342 alkaline earth metals Chemical class 0.000 claims 1
125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
125000005956 isoquinolyl group Chemical group 0.000 claims 1
125000005645 linoleyl group Chemical group 0.000 claims 1
229910052762 osmium Inorganic materials 0.000 claims 1
SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical group [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 claims 1
125000005493 quinolyl group Chemical group 0.000 claims 1
229910052707 ruthenium Inorganic materials 0.000 claims 1
208000030507 AIDS Diseases 0.000 abstract description 22
239000003443 antiviral agent Substances 0.000 abstract description 19
239000002955 immunomodulating agent Substances 0.000 abstract description 5
238000001727 in vivo Methods 0.000 abstract description 5
229940121354 immunomodulator Drugs 0.000 abstract description 4
239000004615 ingredient Substances 0.000 abstract description 4
229960005486 vaccine Drugs 0.000 abstract description 2
238000011321 prophylaxis Methods 0.000 abstract 2
239000003242 anti bacterial agent Substances 0.000 abstract 1
229940088710 antibiotic agent Drugs 0.000 abstract 1
229940042443 other antivirals in atc Drugs 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 327
235000019439 ethyl acetate Nutrition 0.000 description 158
239000000243 solution Substances 0.000 description 152
239000011541 reaction mixture Substances 0.000 description 144
OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 133
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 98
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 92
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 89
239000000203 mixture Substances 0.000 description 80
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 79
239000000047 product Substances 0.000 description 54
238000006243 chemical reaction Methods 0.000 description 50
238000000034 method Methods 0.000 description 50
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 47
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 44
206010012812 Diffuse cutaneous mastocytosis Diseases 0.000 description 36
238000003756 stirring Methods 0.000 description 35
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XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 31
239000012267 brine Substances 0.000 description 29
150000002148 esters Chemical class 0.000 description 29
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 29
241000725303 Human immunodeficiency virus Species 0.000 description 28
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
239000002253 acid Substances 0.000 description 26
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 24
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238000006722 reduction reaction Methods 0.000 description 22
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RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 20
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VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 18
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JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 15
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125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 13
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RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
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CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
108010010369 HIV Protease Proteins 0.000 description 12
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101150041968 CDC13 gene Proteins 0.000 description 11
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BGYPJLADNCZNGX-UHFFFAOYSA-N methoxycarbonylphosphonic acid Chemical compound COC(=O)P(O)(O)=O BGYPJLADNCZNGX-UHFFFAOYSA-N 0.000 description 1
JLBZBZHJMOVDLI-AWEZNQCLSA-N methyl (2s)-2-[bis[(2-methylpropan-2-yl)oxycarbonyl]amino]-6-nitrooct-5-enoate Chemical compound CCC([N+]([O-])=O)=CCC[C@@H](C(=O)OC)N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C JLBZBZHJMOVDLI-AWEZNQCLSA-N 0.000 description 1
MOVBJUGHBJJKOW-UHFFFAOYSA-N methyl 2-amino-5-methoxybenzoate Chemical compound COC(=O)C1=CC(OC)=CC=C1N MOVBJUGHBJJKOW-UHFFFAOYSA-N 0.000 description 1
HLAXXSHBUZMBGE-UHFFFAOYSA-N methyl 6-oxohex-4-enoate Chemical compound COC(=O)CCC=CC=O HLAXXSHBUZMBGE-UHFFFAOYSA-N 0.000 description 1
SOJSYOXMFGDLHY-UHFFFAOYSA-N methyl acetate;hydrochloride Chemical compound Cl.COC(C)=O SOJSYOXMFGDLHY-UHFFFAOYSA-N 0.000 description 1
JRYBSJGWHXACJU-JKYYMCRXSA-N methyl n-[(2s)-1-[[(1r,5s)-5-[(4-aminophenyl)sulfonyl-(3-methylbutyl)amino]-1-cyclopropyl-6-hydroxyhexyl]amino]-1-oxo-3,3-diphenylpropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C([C@H](NC(=O)OC)C(=O)N[C@H](CCC[C@@H](CO)N(CCC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)C1CC1)C1=CC=CC=C1 JRYBSJGWHXACJU-JKYYMCRXSA-N 0.000 description 1
QAHLFXYLXBBCPS-IZEXYCQBSA-N methyl n-[(2s)-1-[[(5s)-5-[(4-aminophenyl)sulfonyl-(2-methylpropyl)amino]-6-hydroxyhexyl]amino]-1-oxo-3,3-diphenylpropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C([C@H](NC(=O)OC)C(=O)NCCCC[C@@H](CO)N(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)C1=CC=CC=C1 QAHLFXYLXBBCPS-IZEXYCQBSA-N 0.000 description 1
230000000813 microbial effect Effects 0.000 description 1
229910052750 molybdenum Inorganic materials 0.000 description 1
239000011733 molybdenum Substances 0.000 description 1
125000002950 monocyclic group Chemical group 0.000 description 1
YWWNNLPSZSEZNZ-UHFFFAOYSA-N n,n-dimethyldecan-1-amine Chemical compound CCCCCCCCCCN(C)C YWWNNLPSZSEZNZ-UHFFFAOYSA-N 0.000 description 1
RIVIDPPYRINTTH-UHFFFAOYSA-N n-ethylpropan-2-amine Chemical compound CCNC(C)C RIVIDPPYRINTTH-UHFFFAOYSA-N 0.000 description 1
CRSOQBOWXPBRES-UHFFFAOYSA-N neopentane Chemical group CC(C)(C)C CRSOQBOWXPBRES-UHFFFAOYSA-N 0.000 description 1
125000004971 nitroalkyl group Chemical group 0.000 description 1
CJSZWOGCKKDSJG-UHFFFAOYSA-N nitrocyclopentane Chemical compound [O-][N+](=O)C1CCCC1 CJSZWOGCKKDSJG-UHFFFAOYSA-N 0.000 description 1
MCSAJNNLRCFZED-UHFFFAOYSA-N nitroethane Chemical compound CC[N+]([O-])=O MCSAJNNLRCFZED-UHFFFAOYSA-N 0.000 description 1
WJUVYTUYXVCIBP-UHFFFAOYSA-N nitrosulfanylbenzene Chemical compound [O-][N+](=O)SC1=CC=CC=C1 WJUVYTUYXVCIBP-UHFFFAOYSA-N 0.000 description 1
229940042402 non-nucleoside reverse transcriptase inhibitor Drugs 0.000 description 1
239000002726 nonnucleoside reverse transcriptase inhibitor Substances 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
235000012149 noodles Nutrition 0.000 description 1
229940072250 norvir Drugs 0.000 description 1
239000002777 nucleoside Substances 0.000 description 1
125000003835 nucleoside group Chemical group 0.000 description 1
238000011017 operating method Methods 0.000 description 1
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244000052769 pathogen Species 0.000 description 1
230000001717 pathogenic effect Effects 0.000 description 1
230000001575 pathological effect Effects 0.000 description 1
HVAMZGADVCBITI-UHFFFAOYSA-N pent-4-enoic acid Chemical compound OC(=O)CCC=C HVAMZGADVCBITI-UHFFFAOYSA-N 0.000 description 1
WQEPLUUGTLDZJY-UHFFFAOYSA-N pentadecanoic acid Chemical compound CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
IGEIPFLJVCPEKU-UHFFFAOYSA-N pentan-2-amine Chemical compound CCCC(C)N IGEIPFLJVCPEKU-UHFFFAOYSA-N 0.000 description 1
239000000816 peptidomimetic Substances 0.000 description 1
230000010412 perfusion Effects 0.000 description 1
230000002085 persistent effect Effects 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
229960000964 phenelzine Drugs 0.000 description 1
ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
ZAEQTGTVGUJEFV-UHFFFAOYSA-N phenylmethanesulfonate;pyridin-1-ium Chemical compound C1=CC=[NH+]C=C1.[O-]S(=O)(=O)CC1=CC=CC=C1 ZAEQTGTVGUJEFV-UHFFFAOYSA-N 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
MVXXTYYBNQKGKT-UHFFFAOYSA-N phenylsulfanium;chloride Chemical compound [Cl-].[SH2+]C1=CC=CC=C1 MVXXTYYBNQKGKT-UHFFFAOYSA-N 0.000 description 1
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
239000006187 pill Substances 0.000 description 1
230000001323 posttranslational effect Effects 0.000 description 1
WVULZDFWPQCPPJ-UHFFFAOYSA-N potassium;hydrochloride Chemical compound Cl.[K] WVULZDFWPQCPPJ-UHFFFAOYSA-N 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
238000002203 pretreatment Methods 0.000 description 1
229940068586 prezista Drugs 0.000 description 1
150000003138 primary alcohols Chemical class 0.000 description 1
SJMCLWCCNYAWRQ-UHFFFAOYSA-N propane-2-sulfonamide Chemical compound CC(C)S(N)(=O)=O SJMCLWCCNYAWRQ-UHFFFAOYSA-N 0.000 description 1
125000006308 propyl amino group Chemical group 0.000 description 1
125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
235000018102 proteins Nutrition 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
150000003242 quaternary ammonium salts Chemical class 0.000 description 1
229940063627 rescriptor Drugs 0.000 description 1
229940064914 retrovir Drugs 0.000 description 1
230000001177 retroviral effect Effects 0.000 description 1
229940107904 reyataz Drugs 0.000 description 1
238000007142 ring opening reaction Methods 0.000 description 1
102220254284 rs755928199 Human genes 0.000 description 1
YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 0.000 description 1
238000012216 screening Methods 0.000 description 1
238000007423 screening assay Methods 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
239000011986 second-generation catalyst Substances 0.000 description 1
150000003334 secondary amides Chemical class 0.000 description 1
229940031307 selzentry Drugs 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 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
WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
XUXNAKZDHHEHPC-UHFFFAOYSA-M sodium bromate Chemical compound [Na+].[O-]Br(=O)=O XUXNAKZDHHEHPC-UHFFFAOYSA-M 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
SRRKNRDXURUMPP-UHFFFAOYSA-N sodium disulfide Chemical compound [Na+].[Na+].[S-][S-] SRRKNRDXURUMPP-UHFFFAOYSA-N 0.000 description 1
239000012439 solid excipient Substances 0.000 description 1
238000003797 solvolysis reaction Methods 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
239000007921 spray Substances 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
238000003860 storage Methods 0.000 description 1
238000012437 strong cation exchange chromatography Methods 0.000 description 1
239000012607 strong cation exchange resin Substances 0.000 description 1
238000002305 strong-anion-exchange chromatography Methods 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
239000001384 succinic acid Substances 0.000 description 1
RINCXYDBBGOEEQ-UHFFFAOYSA-N succinic anhydride Chemical compound O=C1CCC(=O)O1 RINCXYDBBGOEEQ-UHFFFAOYSA-N 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical compound [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
229940054565 sustiva Drugs 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
210000004233 talus Anatomy 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
210000002435 tendon Anatomy 0.000 description 1
SGOIRFVFHAKUTI-ZCFIWIBFSA-N tenofovir (anhydrous) Chemical compound N1=CN=C2N(C[C@@H](C)OCP(O)(O)=O)C=NC2=C1N SGOIRFVFHAKUTI-ZCFIWIBFSA-N 0.000 description 1
229960001355 tenofovir disoproxil Drugs 0.000 description 1
125000001443 terpenyl group Chemical group 0.000 description 1
UORHQLNXWYFBIL-UHFFFAOYSA-N tert-butyl carbamate hydrochloride Chemical compound Cl.CC(C)(C)OC(N)=O UORHQLNXWYFBIL-UHFFFAOYSA-N 0.000 description 1
RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical group CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 description 1
KYDJQJAIHCVQPO-UHFFFAOYSA-N tert-butyl n-tert-butylcarbamate Chemical compound CC(C)(C)NC(=O)OC(C)(C)C KYDJQJAIHCVQPO-UHFFFAOYSA-N 0.000 description 1
125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
150000003535 tetraterpenes Chemical class 0.000 description 1
235000009657 tetraterpenes Nutrition 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
235000019157 thiamine Nutrition 0.000 description 1
239000011721 thiamine Substances 0.000 description 1
125000003396 thiol group Chemical group [H]S* 0.000 description 1
150000003573 thiols Chemical group 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
229940098465 tincture Drugs 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
238000012546 transfer Methods 0.000 description 1
230000007704 transition Effects 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
229940111527 trizivir Drugs 0.000 description 1
229940005605 valeric acid Drugs 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229940023080 viracept Drugs 0.000 description 1
229940098802 viramune Drugs 0.000 description 1
239000003643 water by type Substances 0.000 description 1
230000004580 weight loss Effects 0.000 description 1
208000016261 weight loss Diseases 0.000 description 1
229940087450 zerit Drugs 0.000 description 1
229940052255 ziagen Drugs 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/30—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/37—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
- C07C311/38—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton
- C07C311/39—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
- C07C311/41—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by nitrogen atoms, not being part of nitro or nitroso groups
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
- C07C311/18—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by nitrogen atoms, not being part of nitro or nitroso groups
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
- C07C311/29—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Virology (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Oncology (AREA)
Molecular Biology (AREA)
Chemical Kinetics & Catalysis (AREA)
Tropical Medicine & Parasitology (AREA)
Medicinal Chemistry (AREA)
Communicable Diseases (AREA)
AIDS & HIV (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

TW097146499A 2007-09-25 2008-11-28 HIV protease inhibitors TW201006475A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US99520207P	2007-09-25	2007-09-25
US18872008P	2008-08-12	2008-08-12

Publications (1)

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TW201006475A true TW201006475A (en)	2010-02-16

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Application Number	Title	Priority Date	Filing Date
TW097146499A TW201006475A (en)	2007-09-25	2008-11-28	HIV protease inhibitors

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TW (1)	TW201006475A (fr)
WO (1)	WO2009042094A2 (fr)

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EP2632895B1 (fr) *	2010-10-28	2018-10-03	Merck Canada Inc.	Inhibiteurs de la protéase du vih
EP2632908B1 (fr)	2010-10-29	2016-05-25	Merck Canada Inc.	Sulfonamides en tant qu'inhibiteurs de la protéase du vih
WO2013059928A1 (fr)	2011-10-26	2013-05-02	Merck Canada Inc.	Inhibiteurs de la protéase du vih
JP2015527403A (ja)	2012-09-11	2015-09-17	メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋＳｈａｒｐ＆ＤｏｈｍｅＣｏｒｐ．	Ｈｉｖプロテアーゼ阻害剤
WO2015013835A1 (fr)	2013-07-31	2015-02-05	Merck Sharp & Dohme Corp.	Dérivés de pipérazine utilisés en tant qu'inhibiteurs de la protéase du vih
WO2015095276A1 (fr)	2013-12-19	2015-06-25	Merck Sharp & Dohme Corp.	Inhibiteurs de la protéase du vih
EP3083609B1 (fr)	2013-12-19	2018-08-15	Merck Sharp & Dohme Corp.	Inhibiteurs de la protéase du vih
US10138255B2 (en)	2014-03-10	2018-11-27	Merck Sharp & Dohme Corp.	Piperazine derivatives as HIV protease inhibitors

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WO2008077070A2 (fr) *	2006-12-18	2008-06-26	University Of Massachusetts	Structures cristallines d'inhibiteurs de la protéase du vih-1 reliées à la protéase du vih-1

2008
- 2008-09-22 WO PCT/US2008/010972 patent/WO2009042094A2/fr not_active Ceased
- 2008-11-28 TW TW097146499A patent/TW201006475A/zh unknown

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WO2009042094A2 (fr)	2009-04-02
WO2009042094A3 (fr)	2009-07-30

Publication	Publication Date	Title
TW201006475A (en)	2010-02-16	HIV protease inhibitors
JP5250732B2 (ja)	2013-07-31	Ｈｉｖアスパルチルプロテアーゼ阻害剤としての芳香族誘導体
US9079834B2 (en)	2015-07-14	HIV protease inhibitors
US20100093811A1 (en)	2010-04-15	Hiv protease inhibitors
CN105001165B (zh)	2020-06-23	取代的二氨基嘧啶其组合物，和用其治疗的方法
EP2632908B1 (fr)	2016-05-25	Sulfonamides en tant qu'inhibiteurs de la protéase du vih
AU2010254415B2 (en)	2013-07-04	HIV protease inhibitors
ES2294103T3 (es)	2008-04-01	Inhibidores de vih proteasa con base en derivados de aminoacidos.
EP3083609B1 (fr)	2018-08-15	Inhibiteurs de la protéase du vih
CN112105601A (zh)	2020-12-18	作为细胞死亡抑制剂用于治疗例如卒中的3-(苄基氨基)-4-(环己基氨基)-n-(2-哌嗪-1-基)乙基)苯磺酰胺衍生物和相关的ferrostatin-1类似物
WO2011080562A1 (fr)	2011-07-07	Nouveau aza-peptides contenant du cyclobutyl 2,2-disubstitué et/ou des dérivés alcoxy benzyle substitués comme agents antiviraux
CA2374362C (fr)	2008-01-22	Derives d'uree employes comme inhibiteurs de l'aspartyl protease du vih
US20190337902A1 (en)	2019-11-07	Heterocyclic compounds as hiv protease inhibitors
EP3558285A1 (fr)	2019-10-30	Composés hétérocycliques utiles en tant qu'inhibiteurs de la protéase du vih
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