ZA200110177B - Inhibitors of aspartyl protease. - Google Patents

Inhibitors of aspartyl protease. Download PDF

Info

Publication number: ZA200110177B
Authority: ZA; South Africa
Prior art keywords: alkyl; optionally substituted; membered saturated; aryl; unsaturated
Prior art date: 1999-06-11

Application number

ZA200110177A

Other languages

English (en)

Inventor

Michael Robin Hale

Roger Tung

Stephen Price

Robin David Wilkes

Wayne Carl Schairer

Ashley Nicholas Jarvis

Andrew Spaltenstein

Eric Steven Furfine

Vicente Samano

Istvan Kaldor

John Franklin Miller

Michael Stephen Brieger

Original Assignee

Vertex Pharma

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.)

1999-06-11

Filing date

2001-12-11

Publication date

2003-01-13

2001-12-11 Application filed by Vertex Pharma filed Critical Vertex Pharma

2003-01-13 Publication of ZA200110177B publication Critical patent/ZA200110177B/en

Links

239000003112 inhibitor Substances 0.000 title claims description 24
108010017640 Aspartic Acid Proteases Proteins 0.000 title claims description 13
102000004580 Aspartic Acid Proteases Human genes 0.000 title claims description 13
125000000217 alkyl group Chemical group 0.000 claims description 130
229920006395 saturated elastomer Polymers 0.000 claims description 108
229910052757 nitrogen Inorganic materials 0.000 claims description 84
125000000623 heterocyclic group Chemical group 0.000 claims description 68
229910052717 sulfur Inorganic materials 0.000 claims description 66
150000001875 compounds Chemical class 0.000 claims description 65
125000003342 alkenyl group Chemical group 0.000 claims description 51
125000005842 heteroatom Chemical group 0.000 claims description 49
-1 methylenedioxy Chemical group 0.000 claims description 42
125000003118 aryl group Chemical group 0.000 claims description 40
229910052760 oxygen Inorganic materials 0.000 claims description 38
229910052799 carbon Inorganic materials 0.000 claims description 37
239000000203 mixture Substances 0.000 claims description 31
229910020008 S(O) Inorganic materials 0.000 claims description 29
125000001424 substituent group Chemical group 0.000 claims description 29
125000000753 cycloalkyl group Chemical group 0.000 claims description 28
125000005843 halogen group Chemical group 0.000 claims description 25
125000004432 carbon atom Chemical group C* 0.000 claims description 24
229910052739 hydrogen Inorganic materials 0.000 claims description 24
125000000304 alkynyl group Chemical group 0.000 claims description 23
125000000392 cycloalkenyl group Chemical group 0.000 claims description 23
125000003545 alkoxy group Chemical group 0.000 claims description 16
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 15
239000003795 chemical substances by application Substances 0.000 claims description 11
125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 11
239000003696 aspartic proteinase inhibitor Substances 0.000 claims description 10
239000001257 hydrogen Substances 0.000 claims description 10
208000030507 AIDS Diseases 0.000 claims description 9
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
125000000896 monocarboxylic acid group Chemical group 0.000 claims description 7
229960001830 amprenavir Drugs 0.000 claims description 6
YMARZQAQMVYCKC-OEMFJLHTSA-N amprenavir Chemical compound C([C@@H]([C@H](O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1COCC1)C1=CC=CC=C1 YMARZQAQMVYCKC-OEMFJLHTSA-N 0.000 claims description 6
125000004122 cyclic group Chemical group 0.000 claims description 6
238000004519 manufacturing process Methods 0.000 claims description 6
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
150000003254 radicals Chemical class 0.000 claims description 6
239000003443 antiviral agent Substances 0.000 claims description 5
229910052791 calcium Inorganic materials 0.000 claims description 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
GOWMBYUZXIZENX-CAUSLRQDSA-N 1-[(2r,3s,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-(hexadecylamino)pyrimidin-2-one Chemical compound O=C1N=C(NCCCCCCCCCCCCCCCC)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 GOWMBYUZXIZENX-CAUSLRQDSA-N 0.000 claims description 4
BXZVVICBKDXVGW-NKWVEPMBSA-N Didanosine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 BXZVVICBKDXVGW-NKWVEPMBSA-N 0.000 claims description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
239000002955 immunomodulating agent Substances 0.000 claims description 4
229940121354 immunomodulator Drugs 0.000 claims description 4
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
229910052744 lithium Inorganic materials 0.000 claims description 4
229910052749 magnesium Inorganic materials 0.000 claims description 4
229910052700 potassium Inorganic materials 0.000 claims description 4
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
150000003839 salts Chemical class 0.000 claims description 4
229910052708 sodium Inorganic materials 0.000 claims description 4
ATHGHQPFGPMSJY-UHFFFAOYSA-N spermidine Chemical compound NCCCCNCCCN ATHGHQPFGPMSJY-UHFFFAOYSA-N 0.000 claims description 4
HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 claims description 4
206010001513 AIDS related complex Diseases 0.000 claims description 3
125000003302 alkenyloxy group Chemical group 0.000 claims description 3
125000005133 alkynyloxy group Chemical group 0.000 claims description 3
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 3
229910052788 barium Inorganic materials 0.000 claims description 3
125000002837 carbocyclic group Chemical group 0.000 claims description 3
238000006073 displacement reaction Methods 0.000 claims description 3
125000005647 linker group Chemical group 0.000 claims description 3
125000001624 naphthyl group Chemical group 0.000 claims description 3
229910052698 phosphorus Inorganic materials 0.000 claims description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
125000004076 pyridyl group Chemical group 0.000 claims description 3
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 2
239000004472 Lysine Substances 0.000 claims description 2
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 2
241000700605 Viruses Species 0.000 claims description 2
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JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims description 2
150000002500 ions Chemical class 0.000 claims description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
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239000002777 nucleoside Substances 0.000 claims 16
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ZJAOAACCNHFJAH-UHFFFAOYSA-N phosphonoformic acid Chemical compound OC(=O)P(O)(O)=O ZJAOAACCNHFJAH-UHFFFAOYSA-N 0.000 claims 10
102000014150 Interferons Human genes 0.000 claims 9
108010050904 Interferons Proteins 0.000 claims 9
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 9
239000003814 drug Substances 0.000 claims 7
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PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 claims 6
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XWNMORIHKRROGW-UHFFFAOYSA-N Ro 5-3335 Chemical compound C12=CC(Cl)=CC=C2NC(=O)CN=C1C1=CC=CN1 XWNMORIHKRROGW-UHFFFAOYSA-N 0.000 claims 6
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XPOQHMRABVBWPR-ZDUSSCGKSA-N efavirenz Chemical compound C([C@]1(C2=CC(Cl)=CC=C2NC(=O)O1)C(F)(F)F)#CC1CC1 XPOQHMRABVBWPR-ZDUSSCGKSA-N 0.000 claims 6
230000029142 excretion Effects 0.000 claims 6
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NQDJXKOVJZTUJA-UHFFFAOYSA-N nevirapine Chemical compound C12=NC=CC=C2C(=O)NC=2C(C)=CC=NC=2N1C1CC1 NQDJXKOVJZTUJA-UHFFFAOYSA-N 0.000 claims 6
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XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims 6
WTEBTXWQAAHZCX-XLNBVVSQSA-N 5-[(e)-2-bromoethenyl]-1-[(2r,4r)-2-(hydroxymethyl)-1,3-oxathiolan-4-yl]pyrimidine-2,4-dione Chemical compound S1[C@H](CO)OC[C@@H]1N1C(=O)NC(=O)C(\C=C\Br)=C1 WTEBTXWQAAHZCX-XLNBVVSQSA-N 0.000 claims 5
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SYZIUAAQNFJPJY-UHFFFAOYSA-N 1,4-dihydro-3,1-benzoxazin-2-one Chemical class C1=CC=C2COC(=O)NC2=C1 SYZIUAAQNFJPJY-UHFFFAOYSA-N 0.000 claims 4
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229940104302 cytosine Drugs 0.000 claims 4
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BMLMGCPTLHPWPY-REOHCLBHSA-N (4R)-2-oxo-4-thiazolidinecarboxylic acid Chemical compound OC(=O)[C@@H]1CSC(=O)N1 BMLMGCPTLHPWPY-REOHCLBHSA-N 0.000 claims 3
RBEXWVGCIBHYAD-HTQZYQBOSA-N 1-[(2r,5r)-4-hydroxy-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1C=C(O)[C@@H](CO)O1 RBEXWVGCIBHYAD-HTQZYQBOSA-N 0.000 claims 3
ASOMNDIOOKDVDC-UHFFFAOYSA-N 1h-indol-2-yl-[4-[3-(propan-2-ylamino)pyridin-2-yl]piperazin-1-yl]methanone Chemical compound CC(C)NC1=CC=CN=C1N1CCN(C(=O)C=2NC3=CC=CC=C3C=2)CC1 ASOMNDIOOKDVDC-UHFFFAOYSA-N 0.000 claims 3
AJKVQEKCUACUMD-UHFFFAOYSA-N 2-Acetylpyridine Chemical compound CC(=O)C1=CC=CC=N1 AJKVQEKCUACUMD-UHFFFAOYSA-N 0.000 claims 3
BCSLVBZWCFTDPK-UDJQAZALSA-N 2-amino-9-[(2r,3r,4s)-3,4-bis(hydroxymethyl)oxetan-2-yl]-3h-purin-6-one Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](CO)[C@H]1CO BCSLVBZWCFTDPK-UDJQAZALSA-N 0.000 claims 3
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102000007644 Colony-Stimulating Factors Human genes 0.000 claims 3
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102000000588 Interleukin-2 Human genes 0.000 claims 3
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JNTOCHDNEULJHD-UHFFFAOYSA-N Penciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(CCC(CO)CO)C=N2 JNTOCHDNEULJHD-UHFFFAOYSA-N 0.000 claims 3
BYPFEZZEUUWMEJ-UHFFFAOYSA-N Pentoxifylline Chemical compound O=C1N(CCCCC(=O)C)C(=O)N(C)C2=C1N(C)C=N2 BYPFEZZEUUWMEJ-UHFFFAOYSA-N 0.000 claims 3
IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims 3
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102000007501 Thymosin Human genes 0.000 claims 3
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229940047120 colony stimulating factors Drugs 0.000 claims 3
IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical group C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 claims 3
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IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 claims 3
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CBVCZFGXHXORBI-PXQQMZJSSA-N indinavir Chemical compound C([C@H](N(CC1)C[C@@H](O)C[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H]2C3=CC=CC=C3C[C@H]2O)C(=O)NC(C)(C)C)N1CC1=CC=CN=C1 CBVCZFGXHXORBI-PXQQMZJSSA-N 0.000 claims 3
229940047124 interferons Drugs 0.000 claims 3
KELNNWMENBUHNS-NSHDSACASA-N isopropyl (2s)-2-ethyl-7-fluoro-3-oxo-3,4-dihydroquinoxaline-1(2h)-carboxylate Chemical compound FC1=CC=C2NC(=O)[C@H](CC)N(C(=O)OC(C)C)C2=C1 KELNNWMENBUHNS-NSHDSACASA-N 0.000 claims 3
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CJPLEFFCVDQQFZ-UHFFFAOYSA-N loviride Chemical compound CC(=O)C1=CC=C(C)C=C1NC(C(N)=O)C1=C(Cl)C=CC=C1Cl CJPLEFFCVDQQFZ-UHFFFAOYSA-N 0.000 claims 3
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Classifications

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- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
- 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
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- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
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- A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
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- 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
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- 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
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- 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
- 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
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- 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
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- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-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

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ZA200110177A 1999-06-11 2001-12-11 Inhibitors of aspartyl protease. ZA200110177B (en)

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Application Number	Priority Date	Filing Date	Title
US13907099P	1999-06-11	1999-06-11
US19021100P	2000-03-17	2000-03-17

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ZA200110177B true ZA200110177B (en)	2003-01-13

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ZA200110177A ZA200110177B (en)	1999-06-11	2001-12-11	Inhibitors of aspartyl protease.

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EP (2)	EP1194404B1 (pl)
JP (2)	JP4503896B2 (pl)
KR (1)	KR100762188B1 (pl)
CN (2)	CN101245058A (pl)
AR (1)	AR031520A1 (pl)
AT (2)	ATE534622T1 (pl)
AU (1)	AU779994B2 (pl)
BR (1)	BR0011745A (pl)
CA (1)	CA2380858C (pl)
CO (1)	CO5160337A1 (pl)
CY (1)	CY1112632T1 (pl)
CZ (1)	CZ303052B6 (pl)
DE (1)	DE60027722T2 (pl)
DK (2)	DK1194404T3 (pl)
ES (2)	ES2375823T3 (pl)
HK (1)	HK1046899B (pl)
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IL (3)	IL146918A0 (pl)
MX (1)	MXPA01012808A (pl)
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PT (2)	PT1194404E (pl)
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TN (1)	TNSN00129A1 (pl)
TR (3)	TR200200407T2 (pl)
TW (3)	TWI318116B (pl)
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2000
- 2000-06-07 AR ARP000102852A patent/AR031520A1/es active IP Right Grant
- 2000-06-08 KR KR1020017016293A patent/KR100762188B1/ko not_active Expired - Fee Related
- 2000-06-08 ES ES06009072T patent/ES2375823T3/es not_active Expired - Lifetime
- 2000-06-08 PL PL352830A patent/PL210227B1/pl not_active IP Right Cessation
- 2000-06-08 NZ NZ516003A patent/NZ516003A/xx not_active IP Right Cessation
- 2000-06-08 AU AU56006/00A patent/AU779994B2/en not_active Ceased
- 2000-06-08 TW TW096138754A patent/TWI318116B/zh not_active IP Right Cessation
- 2000-06-08 EP EP00941279A patent/EP1194404B1/en not_active Expired - Lifetime
- 2000-06-08 DK DK00941279T patent/DK1194404T3/da active
- 2000-06-08 PT PT00941279T patent/PT1194404E/pt unknown
- 2000-06-08 TW TW093114799A patent/TWI299000B/zh not_active IP Right Cessation
- 2000-06-08 PE PE2000000573A patent/PE20010230A1/es not_active Application Discontinuation
- 2000-06-08 BR BR0011745-5A patent/BR0011745A/pt not_active Application Discontinuation
- 2000-06-08 HU HU0300385A patent/HUP0300385A3/hu unknown
- 2000-06-08 AT AT06009072T patent/ATE534622T1/de active
- 2000-06-08 TR TR2002/00407T patent/TR200200407T2/xx unknown
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- 2000-06-08 JP JP2001503821A patent/JP4503896B2/ja not_active Expired - Fee Related
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- 2000-06-08 ES ES00941279T patent/ES2263478T3/es not_active Expired - Lifetime
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2001
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- 2001-12-11 ZA ZA200110177A patent/ZA200110177B/en unknown
2008
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2009
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Also Published As

Publication number	Publication date
TWI318116B (en)	2009-12-11
DE60027722T2 (de)	2007-04-26
KR20020033642A (ko)	2002-05-07
NZ516003A (en)	2004-02-27
HUP0300385A2 (hu)	2003-07-28
KR100762188B1 (ko)	2007-10-04
DK1194404T3 (da)	2006-09-04
TNSN00129A1 (fr)	2005-11-10
NO20016034D0 (no)	2001-12-10
TW200804252A (en)	2008-01-16
CZ303052B6 (cs)	2012-03-14
IL146918A (en)	2010-06-16
WO2000076961A1 (en)	2000-12-21
HUP0300385A3 (en)	2007-05-29
AR031520A1 (es)	2003-09-24
CZ20014431A3 (cs)	2002-06-12
CN1361765A (zh)	2002-07-31
ATE325091T1 (de)	2006-06-15
BR0011745A (pt)	2002-03-19
TW200425891A (en)	2004-12-01
MY137777A (en)	2009-03-31
PT1686113E (pt)	2012-02-20
EP1194404B1 (en)	2006-05-03
ES2263478T3 (es)	2006-12-16
EP1686113B1 (en)	2011-11-23
CO5160337A1 (es)	2002-05-30
DE60027722D1 (en)	2006-06-08
NO323951B1 (no)	2007-07-23
ATE534622T1 (de)	2011-12-15
SI1194404T1 (sl)	2006-10-31
AU5600600A (en)	2001-01-02
IL146918A0 (en)	2002-08-14
EP1686113A1 (en)	2006-08-02
DK1686113T3 (da)	2012-02-20
JP2009046493A (ja)	2009-03-05
IL202633A0 (en)	2010-06-30
MXPA01012808A (es)	2002-07-22
IL202633A (en)	2013-02-28
NO20016034L (no)	2002-01-18
CY1112632T1 (el)	2016-02-10
PT1194404E (pt)	2006-08-31
AU779994B2 (en)	2005-02-24
PL352830A1 (pl)	2003-09-08
HK1046899B (en)	2007-03-02
EP1194404A1 (en)	2002-04-10
TW593248B (en)	2004-06-21
HK1046899A1 (en)	2003-01-30
TR200603871T2 (tr)	2007-01-22
CA2380858C (en)	2011-12-06
TR200202528T2 (tr)	2003-02-21
TR200200407T2 (tr)	2002-08-21
CN101245058A (zh)	2008-08-20
CA2380858A1 (en)	2000-12-21
JP4503896B2 (ja)	2010-07-14
TWI299000B (en)	2008-07-21
PE20010230A1 (es)	2001-03-15
JP2003502309A (ja)	2003-01-21
ES2375823T3 (es)	2012-03-06
PL210227B1 (pl)	2011-12-30
CN100516034C (zh)	2009-07-22

Publication	Publication Date	Title
ZA200110177B (en)	2003-01-13	Inhibitors of aspartyl protease.
US7115590B1 (en)	2006-10-03	Phosphoramidate, and mono-, di-, and tri-phosphate esters of (1R, cis)-4-(6-amino-9H-purin-9-yl)-2-cyclopentene-1-methanol as antiviral agents
JPS63290895A (ja)	1988-11-28	抗ウイルスヌクレオシド
US5672625A (en)	1997-09-30	Sulfonic stilbene derivatives in the treatment of viral diseases
EP0631783A1 (en)	1995-01-04	Antiviral combinations of 2',3'-di-deoxyribonucleosides with 6-benzyl-1-ethoxymethyl-5-substituted uracil derivatives
ES2254156T3 (es)	2006-06-16	Inhibidores de aspartil-proteasa.
GB2544439B (en)	2019-11-13	Antiviral composition
WO1991001137A1 (en)	1991-02-07	Antiviral composition
US5616566A (en)	1997-04-01	Method of inhibiting HIV replication with 2',3'-dideoxyadenosine
EP1804816B1 (en)	2011-12-21	Combination therapy comprising cloretazine(tm)
EP1235833A1 (en)	2002-09-04	Analogs of (1s, cis)-4-(2-amino-9h-purin-9-yl)-2-cyclopentene-1-methanol as antiviral
HK1093057A (en)	2007-02-23	Inhibitors of aspartyl protease
MXPA01008129A (es)	2002-06-05	Esteres de fosforamidato, y mono-, di-, y tri-fosfato de (1r, cis)-4-(6-amino-9h-purin-9-il)-2- ciclopenteno-1-metanol como agentes antivirales.
MXPA00006316A (es)	2001-07-03	Profarmacos de inhibidores de aspartil proteasa
ZA200305423B (en)	2005-05-09	DAPD combination therapy with IMDPH inhibitors such as ribavirin or mycophenolic acid.