TW470748B - Nucleotide analogs - Google Patents

Nucleotide analogs Download PDF

Info

Publication number: TW470748B
Authority: TW; Taiwan
Prior art keywords: twenty; compound; cns; ministry; pmpa
Prior art date: 1996-07-26

Application number

TW089123708A

Other languages

English (en)

Chinese (zh)

Inventor

Murty N Arimilli

Kenneth C Cundy

Joseph P Dougherty

Reza Oliyai

Choung Un Kim

Original Assignee

Gilead Sciences 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.)

1996-07-26

Filing date

1997-08-21

Publication date

2002-01-01

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=26696272&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=TW470748(B) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1997-08-21 Application filed by Gilead Sciences Inc filed Critical Gilead Sciences Inc

2002-01-01 Application granted granted Critical

2002-01-01 Publication of TW470748B publication Critical patent/TW470748B/zh

Links

125000003729 nucleotide group Chemical group 0.000 title description 7
150000001875 compounds Chemical class 0.000 claims abstract description 217
230000000840 anti-viral effect Effects 0.000 claims abstract description 17
230000002079 cooperative effect Effects 0.000 claims description 39
125000000217 alkyl group Chemical group 0.000 claims description 16
238000006467 substitution reaction Methods 0.000 claims description 2
-1 alkyenylaryl Chemical group 0.000 abstract description 91
125000003118 aryl group Chemical group 0.000 abstract description 19
238000002360 preparation method Methods 0.000 abstract description 15
239000000543 intermediate Substances 0.000 abstract description 14
150000002148 esters Chemical class 0.000 abstract description 12
125000000623 heterocyclic group Chemical group 0.000 abstract description 12
125000003342 alkenyl group Chemical group 0.000 abstract description 11
125000000304 alkynyl group Chemical group 0.000 abstract description 8
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract description 8
108091034117 Oligonucleotide Proteins 0.000 abstract description 6
125000002877 alkyl aryl group Chemical group 0.000 abstract description 6
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract description 6
229910052760 oxygen Inorganic materials 0.000 abstract description 6
239000001301 oxygen Substances 0.000 abstract description 6
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 abstract description 5
150000004649 carbonic acid derivatives Chemical class 0.000 abstract description 5
JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 abstract description 2
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125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 13
238000004128 high performance liquid chromatography Methods 0.000 description 13
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 13
210000002700 urine Anatomy 0.000 description 13
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238000003756 stirring Methods 0.000 description 12
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239000000651 prodrug Substances 0.000 description 11
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XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
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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 9
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230000002829 reductive effect Effects 0.000 description 7
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PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 description 1
ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
238000004445 quantitative analysis Methods 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
229960001860 salicylate Drugs 0.000 description 1
238000005185 salting out Methods 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
230000001568 sexual effect Effects 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
239000012064 sodium phosphate buffer Substances 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
235000010356 sorbitol Nutrition 0.000 description 1
238000009987 spinning Methods 0.000 description 1
239000007921 spray Substances 0.000 description 1
238000010186 staining Methods 0.000 description 1
239000012086 standard solution Substances 0.000 description 1
238000013517 stratification Methods 0.000 description 1
150000005846 sugar alcohols Polymers 0.000 description 1
150000003871 sulfonates Chemical class 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
238000007910 systemic administration Methods 0.000 description 1
239000003826 tablet Substances 0.000 description 1
HGHYERVLYRBRPJ-UHFFFAOYSA-N tert-butyl chloromethyl carbonate Chemical compound CC(C)(C)OC(=O)OCCl HGHYERVLYRBRPJ-UHFFFAOYSA-N 0.000 description 1
YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
229930192474 thiophene Chemical group 0.000 description 1
238000004448 titration Methods 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
229940100611 topical cream Drugs 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
229940100615 topical ointment Drugs 0.000 description 1
239000012049 topical pharmaceutical composition Substances 0.000 description 1
231100000440 toxicity profile Toxicity 0.000 description 1
125000004306 triazinyl group Chemical group 0.000 description 1
LGQXXHMEBUOXRP-UHFFFAOYSA-N tributyl borate Chemical compound CCCCOB(OCCCC)OCCCC LGQXXHMEBUOXRP-UHFFFAOYSA-N 0.000 description 1
GWBQKPSBYMTNOO-UHFFFAOYSA-N trilithium butan-1-olate Chemical compound [O-]CCCC.[O-]CCCC.[O-]CCCC.[Li+].[Li+].[Li+] GWBQKPSBYMTNOO-UHFFFAOYSA-N 0.000 description 1
PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 1
241000701161 unidentified adenovirus Species 0.000 description 1
241001529453 unidentified herpesvirus Species 0.000 description 1
238000001291 vacuum drying Methods 0.000 description 1
239000006216 vaginal suppository Substances 0.000 description 1
239000000052 vinegar Substances 0.000 description 1
235000021419 vinegar Nutrition 0.000 description 1
230000009385 viral infection Effects 0.000 description 1
230000003612 virological effect Effects 0.000 description 1
239000003039 volatile agent Substances 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000003021 water soluble solvent Substances 0.000 description 1
238000009736 wetting Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
- C07F9/65616—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings containing the ring system having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- 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
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
- C07F9/6509—Six-membered rings
- C07F9/6512—Six-membered rings having the nitrogen atoms in positions 1 and 3

Landscapes

Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Virology (AREA)
General Chemical & Material Sciences (AREA)
Molecular Biology (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Communicable Diseases (AREA)
Oncology (AREA)
Biochemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
AIDS & HIV (AREA)
Tropical Medicine & Parasitology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

TW089123708A 1996-07-26 1997-08-21 Nucleotide analogs TW470748B (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US2270896P	1996-07-26	1996-07-26
US68683896A	1996-07-26	1996-07-26

Publications (1)

Publication Number	Publication Date
TW470748B true TW470748B (en)	2002-01-01

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ID=26696272

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Application Number	Title	Priority Date	Filing Date
TW089123708A TW470748B (en)	1996-07-26	1997-08-21	Nucleotide analogs
TW086110757A TW444020B (en)	1996-07-26	1997-08-21	Nucleotide analogs

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
TW086110757A TW444020B (en)	1996-07-26	1997-08-21	Nucleotide analogs

Country Status (4)

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JP (6)	JP4033494B2 (2)
CA (1)	CA2261619C (2)
TW (2)	TW470748B (2)
WO (1)	WO1998004569A1 (2)

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ME03423B (me)	2004-07-27	2020-01-20	Gilead Sciences Inc	Fosfonatni analozi jedinjenja hiv inhibitora
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1997
- 1997-07-25 CA CA002261619A patent/CA2261619C/en not_active Expired - Lifetime
- 1997-07-25 WO PCT/US1997/013244 patent/WO1998004569A1/en not_active Ceased
- 1997-07-25 JP JP50831898A patent/JP4033494B2/ja not_active Expired - Lifetime
- 1997-08-21 TW TW089123708A patent/TW470748B/zh not_active IP Right Cessation
- 1997-08-21 TW TW086110757A patent/TW444020B/zh not_active IP Right Cessation
2007
- 2007-07-09 JP JP2007180398A patent/JP2007297406A/ja not_active Withdrawn
2010
- 2010-10-15 JP JP2010233086A patent/JP2011016847A/ja not_active Withdrawn
2014
- 2014-04-15 JP JP2014083387A patent/JP2014159450A/ja not_active Withdrawn
2015
- 2015-04-28 JP JP2015091141A patent/JP2015164934A/ja not_active Withdrawn
2016
- 2016-10-31 JP JP2016212748A patent/JP2017031212A/ja not_active Withdrawn

Also Published As

Publication number	Publication date
JP2011016847A (ja)	2011-01-27
WO1998004569A1 (en)	1998-02-05
JP2015164934A (ja)	2015-09-17
CA2261619C (en)	2006-05-23
JP2000515866A (ja)	2000-11-28
JP2007297406A (ja)	2007-11-15
JP2017031212A (ja)	2017-02-09
JP2014159450A (ja)	2014-09-04
CA2261619A1 (en)	1998-02-05
TW444020B (en)	2001-07-01
JP4033494B2 (ja)	2008-01-16

Legal Events

Date	Code	Title	Description
2002-05-02	GD4A	Issue of patent certificate for granted invention patent
2017-10-01	MK4A	Expiration of patent term of an invention patent

Publication	Publication Date	Title
TW470748B (en)	2002-01-01	Nucleotide analogs
USRE38333E1 (en)	2003-11-25	Antiviral phosphonomethoxy nucleotide analogs having increased oral bioavailability
ES2350197T3 (es)	2011-01-20	Nuevos derivados de fosfonato nucleósido acíclicos, sales de los mismos y procedimiento para su preparación.
EP0915894B1 (en)	2003-05-14	Nucleotide analogs
CN100383148C (zh)	2008-04-23	含核苷酸类似物的复合物或盐及其合成方法
JP2019069984A (ja)	2019-05-09	非環式ヌクレオシドホスホン酸ジエステル
JPH07500317A (ja)	1995-01-12	１，３−オキサチオランヌクレオシド類似体
KR20020093824A (ko)	2002-12-16	포스포네이트 뉴클레오티드 화합물
AU2015317972A1 (en)	2017-03-23	Nucleotide analogs
NZ238774A (en)	1993-08-26	9-purinyl phosphonic acid derivatives and their use as pharmaceutical agents
KR19990022752A (ko)	1999-03-25	포스포네이트 뉴클레오티드 유도체
EP0173624A2 (en)	1986-03-05	4-(guanin-9-yl) butanals and antiviral compositions containing them
JP3172801B2 (ja)	2001-06-04	抗ウィルス剤としてのキラル２−（ホスホノメトキシ）プロピルグアニン
JP3580377B2 (ja)	2004-10-20	ホスホナートヌクレオチドエステル誘導体
JPH04316590A (ja)	1992-11-06	複素環化合物
EP3145939A1 (en)	2017-03-29	Phosphonate nucleosides useful in the treatment of viral diseases
CN102781462A (zh)	2012-11-14	新的核苷膦酸酯及类似物
HK1020964B (en)	2004-01-16	Nucleotide analogs
Jeffery	1998	Acyclic nucleoside phosphonates: design and synthesis of novel antiviral agents
JPWO2001064693A1 (ja)	2003-07-02	ホスホナートヌクレオチド化合物
HK1025334A (en)	2000-11-10	Nucleotide analogs