DK170779B1 - Substituerede guaninnucleosidderivater, immunreaktionsforstærkende præparater deraf, fremgangsmåde til forstærkning af en immunreaktion, anvendelse af derivaterne til fremstilling af et farmaceutisk præparat og fremgangsmåde til fremstilling af substituerede guaninnucleosidderivater - Google Patents

Substituerede guaninnucleosidderivater, immunreaktionsforstærkende præparater deraf, fremgangsmåde til forstærkning af en immunreaktion, anvendelse af derivaterne til fremstilling af et farmaceutisk præparat og fremgangsmåde til fremstilling af substituerede guaninnucleosidderivater Download PDF

Info

Publication number: DK170779B1
Authority: DK; Denmark
Prior art keywords: cells; guanosine; group; oxoguanosine; allyl
Prior art date: 1988-05-05

Application number

DK217189A

Other languages

Danish (da)

English (en)

Other versions

DK217189A (da

DK217189D0 (da

Inventor

Michael Goodman

William Weigle

Stanley Bell

Robert Chen

Roland K Robins

William J Hennen

Original Assignee

Scripps Clinic Res

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.)

1988-05-05

Filing date

1989-05-03

Publication date

1996-01-15

1989-05-03 Application filed by Scripps Clinic Res filed Critical Scripps Clinic Res

1989-05-03 Publication of DK217189D0 publication Critical patent/DK217189D0/da

1989-11-06 Publication of DK217189A publication Critical patent/DK217189A/da

1996-01-15 Application granted granted Critical

1996-01-15 Publication of DK170779B1 publication Critical patent/DK170779B1/da

Links

-1 guanine nucleoside derivatives Chemical class 0.000 title claims abstract description 65
238000000034 method Methods 0.000 title claims abstract description 59
230000028993 immune response Effects 0.000 title claims abstract description 25
230000002708 enhancing effect Effects 0.000 title claims abstract description 14
238000002360 preparation method Methods 0.000 title claims description 49
UYTPUPDQBNUYGX-UHFFFAOYSA-N Guanine Natural products O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 title claims description 35
230000008569 process Effects 0.000 title claims description 17
239000008194 pharmaceutical composition Substances 0.000 title claims description 4
239000000203 mixture Substances 0.000 claims abstract description 52
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract 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 abstract description 9
150000001875 compounds Chemical class 0.000 claims description 118
NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Natural products C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 claims description 98
210000003719 b-lymphocyte Anatomy 0.000 claims description 31
210000001744 T-lymphocyte Anatomy 0.000 claims description 29
229940029575 guanosine Drugs 0.000 claims description 29
MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 claims description 27
NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 claims description 27
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 22
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VDCRFBBZFHHYGT-IOSLPCCCSA-N 2-amino-9-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-enyl-3h-purine-6,8-dione Chemical compound O=C1N(CC=C)C=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O VDCRFBBZFHHYGT-IOSLPCCCSA-N 0.000 claims description 8
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55561—CpG containing adjuvants; Oligonucleotide containing adjuvants

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Immunology (AREA)
Veterinary Medicine (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
General Chemical & Material Sciences (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Public Health (AREA)
Epidemiology (AREA)
Microbiology (AREA)
Mycology (AREA)
Biochemistry (AREA)
Biotechnology (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Bioinformatics & Cheminformatics (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Saccharide Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

DK217189A 1988-05-05 1989-05-03 Substituerede guaninnucleosidderivater, immunreaktionsforstærkende præparater deraf, fremgangsmåde til forstærkning af en immunreaktion, anvendelse af derivaterne til fremstilling af et farmaceutisk præparat og fremgangsmåde til fremstilling af substituerede guaninnucleosidderivater DK170779B1 (da)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US07/190,697 US5011828A (en)	1985-11-15	1988-05-05	Immunostimulating guanine derivatives, compositions and methods
US19069788		1988-05-05

Publications (3)

Publication Number	Publication Date
DK217189D0 DK217189D0 (da)	1989-05-03
DK217189A DK217189A (da)	1989-11-06
DK170779B1 true DK170779B1 (da)	1996-01-15

Family

ID=22702393

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DK217189A DK170779B1 (da)	1988-05-05	1989-05-03	Substituerede guaninnucleosidderivater, immunreaktionsforstærkende præparater deraf, fremgangsmåde til forstærkning af en immunreaktion, anvendelse af derivaterne til fremstilling af et farmaceutisk præparat og fremgangsmåde til fremstilling af substituerede guaninnucleosidderivater

Country Status (10)

Country	Link
US (1)	US5011828A (fr)
EP (1)	EP0341065B1 (fr)
JP (1)	JP2718542B2 (fr)
AT (1)	ATE109155T1 (fr)
AU (2)	AU620398B2 (fr)
CA (1)	CA1318666C (fr)
DE (1)	DE68917012T2 (fr)
DK (1)	DK170779B1 (fr)
IE (1)	IE63679B1 (fr)
PT (1)	PT90465B (fr)

Families Citing this family (81)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5093318A (en) *	1983-11-01	1992-03-03	Scripps Clinic And Research Foundation	Immunostimulating guanosine derivatives and their pharmaceutical compositions
US5229275A (en) *	1990-04-26	1993-07-20	Akzo N.V.	In-vitro method for producing antigen-specific human monoclonal antibodies
WO1994007904A1 (fr) *	1992-10-01	1994-04-14	Mcneilab, Inc.	Derives de guanosines a disubstitution en positions 7,8
US5392308A (en) *	1993-01-07	1995-02-21	Sdl, Inc.	Semiconductor laser with integral spatial mode filter
WO1995006716A1 (fr) *	1993-08-30	1995-03-09	Northwestern University	Cellules souches pluripotentes d'embryons de rats et leur procede d'obtention et d'utilisation
US5441942A (en) *	1994-05-27	1995-08-15	The Scripps Research Institute	2'3'-dideoxy-2',3'-didehydro-7,8-disubstituted guanosines and their immunostimulative effect
US5786359A (en) *	1994-05-27	1998-07-28	The Scripps Research Institute	N9 alkyl or aralkyl derivatives of 7, 8-disubstituted guanines
US5382580A (en) *	1994-05-27	1995-01-17	The Scripps Research Institute	N9 morpholino derivatives of 7,8-disubstituted guanines
EP1329220A1 (fr) *	1997-01-17	2003-07-23	ICN Pharmaceuticals, Inc.	Traitements liés à la cytokine destinés à des affections
AU743366B2 (en) *	1997-01-17	2002-01-24	Icn Pharmaceuticals, Inc.	Novel nucleosides
US20030100520A1 (en) *	1997-01-21	2003-05-29	Philip Needleman	Immunological process and constructs for increasing the hdl cholesterol concentration by dna vaccination
US7638496B2 (en)	2000-02-15	2009-12-29	Valeant Pharmaceuticals North America	Nucleoside analogs with carboxamidine modified monocyclic base
US20030138769A1 (en) *	2000-08-16	2003-07-24	Birkett Ashley J.	Immunogenic HBc chimer particles having enhanced stability
US20030175863A1 (en) *	2001-08-15	2003-09-18	Birkett Ashley J.	Influenza immunogen and vaccine
US7361352B2 (en) *	2001-08-15	2008-04-22	Acambis, Inc.	Influenza immunogen and vaccine
US20030185858A1 (en) *	2001-08-15	2003-10-02	Birkett Ashley J.	Immunogenic HBc chimer particles stabilized with an N-terminal cysteine
US7321033B2 (en) *	2001-11-27	2008-01-22	Anadys Pharmaceuticals, Inc.	3-B-D-ribofuranosylthiazolo [4,5-d] pyrimidine nucleosides and uses thereof
US7351413B2 (en) *	2002-02-21	2008-04-01	Lorantis, Limited	Stabilized HBc chimer particles as immunogens for chronic hepatitis
ATE465742T1 (de) *	2003-09-05	2010-05-15	Anadys Pharmaceuticals Inc	Tlr7-liganden zur behandlung von hepatitis c
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Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4643992A (en) *	1982-11-09	1987-02-17	Scripps Clinic And Research Foundation	Modulation of animal cellular responses with compositions containing 8-substituted guanine derivatives
US5093318A (en) *	1983-11-01	1992-03-03	Scripps Clinic And Research Foundation	Immunostimulating guanosine derivatives and their pharmaceutical compositions

1988
- 1988-05-05 US US07/190,697 patent/US5011828A/en not_active Expired - Lifetime
1989
- 1989-05-03 DK DK217189A patent/DK170779B1/da not_active IP Right Cessation
- 1989-05-03 AU AU33998/89A patent/AU620398B2/en not_active Ceased
- 1989-05-04 EP EP89304510A patent/EP0341065B1/fr not_active Expired - Lifetime
- 1989-05-04 CA CA000598700A patent/CA1318666C/fr not_active Expired - Fee Related
- 1989-05-04 DE DE68917012T patent/DE68917012T2/de not_active Expired - Fee Related
- 1989-05-04 IE IE146289A patent/IE63679B1/en not_active IP Right Cessation
- 1989-05-04 PT PT90465A patent/PT90465B/pt not_active IP Right Cessation
- 1989-05-04 AT AT89304510T patent/ATE109155T1/de not_active IP Right Cessation
- 1989-05-06 JP JP1113991A patent/JP2718542B2/ja not_active Expired - Fee Related
1991
- 1991-11-29 AU AU88345/91A patent/AU634679B2/en not_active Ceased

Also Published As

Publication number	Publication date
EP0341065A2 (fr)	1989-11-08
DK217189A (da)	1989-11-06
DK217189D0 (da)	1989-05-03
IE63679B1 (en)	1995-05-31
PT90465B (pt)	1994-11-30
EP0341065B1 (fr)	1994-07-27
ATE109155T1 (de)	1994-08-15
DE68917012T2 (de)	1995-03-16
EP0341065A3 (en)	1990-06-13
AU620398B2 (en)	1992-02-20
AU634679B2 (en)	1993-02-25
US5011828A (en)	1991-04-30
CA1318666C (fr)	1993-06-01
AU3399889A (en)	1989-11-09
DE68917012D1 (de)	1994-09-01
JPH0285293A (ja)	1990-03-26
AU8834591A (en)	1992-02-13
PT90465A (pt)	1989-11-30
JP2718542B2 (ja)	1998-02-25
IE891462L (en)	1989-11-05

Legal Events

Date	Code	Title	Description
2009-01-12	PBP	Patent lapsed	Country of ref document: DK

Publication	Publication Date	Title
DK170780B1 (da)	1996-01-15	Substituerede guaninnucleosidderivater, immunreaktionsforstærkende præparater deraf, og fremgangsmåde til at forøge en immunreaktion
US5011828A (en)	1991-04-30	Immunostimulating guanine derivatives, compositions and methods
US4643992A (en)	1987-02-17	Modulation of animal cellular responses with compositions containing 8-substituted guanine derivatives
US5166141A (en)	1992-11-24	Immunostimulating 7-deaza-7-oxa- and 7-deaza-7-oxo-analogs of 8-substituted-guanine-9-(1'-beta-D-aldoglycosidyl) derivatives and methods of treating test animals
PL167682B1 (pl)	1995-10-31	(1H) -plrymidyn-2-onu PL PL PL PL PL PL PL PL PL PL PL
JP2012516287A (ja)	2012-07-19	ヌクレオシド類似体
CS276965B6 (en)	1992-11-18	Novel lipophilic muramyl peptides and process for preparing thereof
HU199155B (en)	1990-01-29	Process for producing adenosine-5'-carboxamide derivatives and pharmaceutical compositions comprising same
IL99466A (en)	1996-07-23	Carbocyclic adenosine analogs and immunosuppressant pharmaceutical compositions containing them
AU2003271478B2 (en)	2010-03-04	Substituted gamma-phenyl-delta-lactams and uses related thereto
US5786359A (en)	1998-07-28	N9 alkyl or aralkyl derivatives of 7, 8-disubstituted guanines
US5136030A (en)	1992-08-04	Immunostimulating guanine derivatives, compositions and methods
WO1989008115A1 (fr)	1989-09-08	NOUVEAUX DERIVES DE LA DEOXY-2'-URIDINE SUBSTITUEE EN POSITION 5, 3' ou 5' PAR DES GROUPEMENTS alpha-AMINO ACYLES, PROCEDE POUR LEUR OBTENTION ET MEDICAMENTS LES CONTENANT
WO1994007904A1 (fr)	1994-04-14	Derives de guanosines a disubstitution en positions 7,8
US5382580A (en)	1995-01-17	N9 morpholino derivatives of 7,8-disubstituted guanines
US5441942A (en)	1995-08-15	2'3'-dideoxy-2',3'-didehydro-7,8-disubstituted guanosines and their immunostimulative effect
JP4354016B2 (ja)	2009-10-28	新規プリン誘導体およびこれを含む医薬組成物
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EP0456514A1 (fr)	1991-11-13	2-Fluoronéplanocine et sa préparation