WO2002062815A1 - Groupe protecteur hybride - Google Patents

Groupe protecteur hybride Download PDF

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Publication number
WO2002062815A1
WO2002062815A1 PCT/EP2002/001186 EP0201186W WO02062815A1 WO 2002062815 A1 WO2002062815 A1 WO 2002062815A1 EP 0201186 W EP0201186 W EP 0201186W WO 02062815 A1 WO02062815 A1 WO 02062815A1
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WO
WIPO (PCT)
Prior art keywords
group
synthon
compound according
compound
light
Prior art date
Application number
PCT/EP2002/001186
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German (de)
English (en)
Inventor
Markus Beier
Original Assignee
Febit Ag
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.)
Filing date
Publication date
Application filed by Febit Ag filed Critical Febit Ag
Priority to EP02722047A priority Critical patent/EP1358197A1/fr
Publication of WO2002062815A1 publication Critical patent/WO2002062815A1/fr

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C219/00—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C219/02—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C219/04—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C219/06—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having the hydroxy groups esterified by carboxylic acids having the esterifying carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms of an acyclic saturated carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids
    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/16—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids
    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/26—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring
    • 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
    • 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
    • C07H19/06—Pyrimidine radicals
    • 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
    • C07H19/06—Pyrimidine radicals
    • C07H19/10—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
    • 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
    • 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
    • C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/0059—Sequential processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00596—Solid-phase processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00709—Type of synthesis
    • B01J2219/00711—Light-directed synthesis
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/00722—Nucleotides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00—Systems containing at least three condensed rings
    • C07C2603/02—Ortho- or ortho- and peri-condensed systems
    • C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
    • C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
    • C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
    • C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
    • C07C2603/18—Fluorenes; Hydrogenated fluorenes
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B40/00—Libraries per se, e.g. arrays, mixtures
    • C40B40/04—Libraries containing only organic compounds
    • C40B40/06—Libraries containing nucleotides or polynucleotides, or derivatives thereof
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Definitions

  • the present invention relates to photolabile hybrid protective groups and their use for the production of protected synthons for the light-controlled synthesis of biopolymers, in particular nucleic acids.
  • Biopolymer arrays are very important in research and diagnostics because they allow fast and highly parallel processing of complex biological questions.
  • Photolabile nucleoside derivatives are used in the light-controlled synthesis of nucleic acid chips.
  • the chain structure of the nucleic acid fragments usually takes place by means of phosphoramidite synthons.
  • the modules each have a temporary photo protection group that can be removed by exposure to light.
  • the synthesis principle provides for a cyclical sequence of condensation and deprotection steps (by light).
  • the efficiency with which such a light-controlled synthesis can take place is essentially determined by the photolabile protective groups used, in particular by the efficiency with which these can be removed in the irradiation step.
  • the photo-protecting groups hitherto used for light-controlled synthesis are the NVOC (SPA Fodor et al., Science 251 (1 991), 767 ff.), MeNPOC (AC Pease et al., Proc. Natl. Acad. Sci. 91 (1 994), 5022 ff.), DMBOC (MC Pirrung, J. Org. Chem. 60 (1 995), 1 1 1 6 ff.) And the NPPOC protecting groups (A. Hassan et al., Tetrahedron 53 ( 1 997), 4247 ff.).
  • NVOC SPA Fodor et al., Science 251 (1 991), 767 ff.
  • MeNPOC AC Pease et al., Proc. Natl. Acad. Sci. 91 (1 994), 5022 ff.
  • DMBOC MC Pirrung, J. Org. Chem. 60 (1 995), 1 1 1 6 ff.
  • NPPOC protecting groups
  • photolabile protective groups in nucleoside or nucleotide chemistry are the o-nitrobenzyl group and its derivatives (see, for example, Pillai, Org. Photochem. 9 (1 987), 225; Walker et al., J. Am. Chem Soc. 1 1 0 (1 988), 71 70).
  • the 2- (o-nitrophenyl) ethyl group is also known as a photolabile protective group for nucleosides (cf.
  • the photolabile protective groups currently used for the light-controlled synthesis of nucleic acids are generally characterized by the fact that they are abstracted in a single step.
  • the protective groups used to date are all colorless or non-fluorescent molecules. This has among other things in addition to only a very low absorption of the incident light, the result is that the abstraction process of these protective groups cannot be tracked / detected.
  • the object of the invention was therefore to provide photo protection groups which enable a two-stage abstraction process. Furthermore, the provision of novel photolabile nucleoside derivatives for the light-controlled synthesis of nucleic acid arrays was an object of the invention.
  • the two-stage cleavage process is used to introduce an additional quasi-pause function, ie it can be decided when and where a photolabile protective group is generated from a previously non-photoactive protective group by a chemical transformation.
  • the invention thus relates to a compound of the general formula (I)
  • RH or an organic residue e.g. B. C -, - C 10 alkyl radical, an optionally substituted aryl radical or a cleavable group,
  • R 'each independently halogen, CN, OCH 3 , OC 2 H 5 , NO 2 , -N NR "or an optionally substituted C T -C ⁇ alkyl, alkenyl, alkynyl or
  • R is an optionally substituted aryl radical
  • m is an integer from 0 to 4
  • n is an integer from 0 to 4, preferably from 0 to 2
  • p is 0 or 1
  • X is a group selected from
  • Y is a leaving group
  • Substituents of alkyl, alkenyl, alkynyl or aryl groups are preferably selected from halogen, e.g. B. F, Cl, Br or J, OH, SH, -O-,
  • Aryl groups can also include ring systems with heteroatoms such as O, N or / and S.
  • R can be hydrogen or an organic radical, preferably a removable group, e.g. a protective group and / or an optically detectable group, e.g. a dye or fluorescent group, in which case R is preferably a photostable group, i.e. a group that is not affected by radiation but in other ways, e.g. by treatment with base or acid, by reduction or oxidation, or by enzymatic cleavage.
  • a removable group e.g. a protective group and / or an optically detectable group, e.g. a dye or fluorescent group
  • R is preferably a photostable group, i.e. a group that is not affected by radiation but in other ways, e.g. by treatment with base or acid, by reduction or oxidation, or by enzymatic cleavage.
  • the symbol m is preferably an integer from 0 to 2, particularly preferably 0 or 1.
  • the symbol n is preferably an integer from 0 to 2 and particularly preferably 0 or 1.
  • the leaving group Y is a group which can be split off when the compound (I) reacts with another compound.
  • Y is preferably a leaving group which can be split off by reaction with a nucleophile, if appropriate in the presence of an auxiliary base such as pyridine.
  • Preferred examples of Y are: Cl, Br, J, aryl, e.g. B. phenyl, tosylate, mesylate, trifluorosulfonate,
  • the abstraction of the photo protection group is partially or completely achieved is blocked.
  • the usually one-step abstraction process can be expanded to a two-step process.
  • the photo protection group is then abstracted by exposure to light.
  • a coloring function e.g. UV or fluorescent dye
  • UV or fluorescent dye e.g. UV or fluorescent dye
  • a protective group known to the person skilled in the art is used.
  • this photo-protective group can only be split off by light entry if a base-unstable deprotection step is carried out.
  • Another object of the invention is the use of a compound (I) for the production of protected synthons for the light-controlled synthesis of biopolymers, such as nucleic acids, for example DNA or RNA.
  • the compounds are also suitable for the synthesis of other biopolymers, such as peptides, peptide nucleic acids (PNA) or saccharides.
  • the synthon can be a monomeric building block, for example a nucleoside derivative, but also an oligomeric building block, for example a dimer or trimer, ie for example a di- or trinucleoside derivative.
  • the synthon is particularly preferably a phosphoramidite building block.
  • other nucleotide synthesis building blocks for example phosphate or phosphonate building blocks, can also be used.
  • linkers or spacer units for. B. be used as phosphoramidites.
  • Yet another object of the invention is a protected synthon for the light-controlled synthesis of biopolymers, which carries at least one photolabile or (if R is different from H) by activation (abstraction of R) photolabilizable protective group Z, which by reaction (of the synthon) with Compound (!) Was created by substitution of Y.
  • synthons for the construction of nucleic acid polymers are compounds of the general formulas (Ila), (Mb), ⁇ l Je) or (lld):
  • B is hydrogen or an organic radical, e.g. B. an optionally substituted C, -C 10 alkyl radical such as CH 3 , and preferably a heterocyclic base, in particular a nucleobase, for example a pyrimidine base, selected from natural pyrimidine bases such as cytosine, thymine or uracil, and non-natural pyrimidine bases, such as 5-methylcytosine, or a purine base selected from natural purine bases, such as adenine or guanine, or non-natural purine bases, such as 2,6-diaminopurine, hypoxanthine or xanthine, and wherein the nucleobase can optionally carry one or more protective groups, Z from compound (I) is formed by substitution of Y,
  • R 1 is H, OH, R 4 or OR 4 , where R 4 is each independently halogen, CN or an optionally substituted C r C 4 alkyl, alkenyl or alkoxy radical which, if necessary, can also carry a protective group, one of R 2 and R 3 is an optionally protected phosphate, phosphonate or phosphoramidite group and the other is H or a protective group, wherein protective groups which are customary in the field of solid-phase nucleic acid synthesis can be used as protective groups, provided they are not associated with the protective group Z or interfere with other protecting groups present in the connection.
  • the protected synthons according to the invention can be used for the light-controlled synthesis of biopolymers, in particular nucleic acids.
  • a two-stage elimination of the protective group Z or an optical monitoring of the activation (photoiabilization) and / or the elimination of the protective group Z can take place.
  • the compound (I) is coupled to the 5'-OH group of a nucleoside in the presence of base and then reacted with phosphine to form a protected phosphoramidite derivative.
  • a corresponding reaction can also be carried out with a masked compound (!) With R ⁇ H, e.g. B. Fmoc or dye.
  • FIG. 3 Two embodiments of the carrier-supported oligonucleotide synthesis using the protected synthons according to the invention are shown in FIG. 3.
  • the hydrogen on the aniline group is blocked by Fmoc, so that no chain growth takes place in the light without prior activation. Only after the Fmoc group has been split off by base is there activation to the photolabile protective group, which can be split off by subsequent irradiation.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • General Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • Nanotechnology (AREA)
  • Physics & Mathematics (AREA)
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  • Condensed Matter Physics & Semiconductors (AREA)
  • General Physics & Mathematics (AREA)
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  • Crystallography & Structural Chemistry (AREA)
  • Saccharide Compounds (AREA)

Abstract

Groupes protecteurs hybrides instables à la lumière et leur utilisation pour la production de synthons protégés destinés à la synthèse commandée par la lumière de biopolymères, en particulier d'acides nucléiques.
PCT/EP2002/001186 2001-02-05 2002-02-05 Groupe protecteur hybride WO2002062815A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP02722047A EP1358197A1 (fr) 2001-02-05 2002-02-05 Groupe protecteur hybride

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10105077A DE10105077A1 (de) 2001-02-05 2001-02-05 Hybrid-Schutzgruppe
DE10105077.1 2001-02-05

Publications (1)

Publication Number Publication Date
WO2002062815A1 true WO2002062815A1 (fr) 2002-08-15

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DE (1) DE10105077A1 (fr)
WO (1) WO2002062815A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004058392A2 (fr) * 2002-12-23 2004-07-15 Febit Ag Groupes protecteurs photoactivables a base de o-nitrophenylethyle a sensibilisation intramoleculaire a l'etat triplet
EP1466663A1 (fr) * 2003-03-19 2004-10-13 F. Hoffmann-La Roche Ag Procédé de controle qualité lors de la synthèse de matrices d'acides nucléiques

Citations (6)

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Publication number Priority date Publication date Assignee Title
US3991071A (en) * 1973-06-21 1976-11-09 The Boots Company Limited Fungicidal compositions containing substituted imidazoles
EP0555537A2 (fr) * 1991-12-04 1993-08-18 Banyu Pharmaceutical Co., Ltd. Antagonistes d'endothéline
WO1996018634A2 (fr) * 1994-12-16 1996-06-20 Wolfgang Pfleiderer Derives de nucleosides comportant des groupes protecteurs photolabiles
WO1996022966A1 (fr) * 1995-01-23 1996-08-01 Biogen, Inc. Inhibiteurs de l'adherence cellulaire
WO1997044345A1 (fr) * 1996-05-20 1997-11-27 Wolfgang Pfleiderer Derives de nucleosides a groupes protecteurs photolabiles
WO1999000357A1 (fr) * 1997-06-27 1999-01-07 Vertex Pharmaceuticals Incorporated INHIBITEURS DE p38

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DE19915867A1 (de) * 1999-04-08 2000-10-19 Deutsches Krebsforsch Nucleosid-Derivate mit photolabilen Schutzgruppen

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Publication number Priority date Publication date Assignee Title
US3991071A (en) * 1973-06-21 1976-11-09 The Boots Company Limited Fungicidal compositions containing substituted imidazoles
EP0555537A2 (fr) * 1991-12-04 1993-08-18 Banyu Pharmaceutical Co., Ltd. Antagonistes d'endothéline
WO1996018634A2 (fr) * 1994-12-16 1996-06-20 Wolfgang Pfleiderer Derives de nucleosides comportant des groupes protecteurs photolabiles
WO1996022966A1 (fr) * 1995-01-23 1996-08-01 Biogen, Inc. Inhibiteurs de l'adherence cellulaire
WO1997044345A1 (fr) * 1996-05-20 1997-11-27 Wolfgang Pfleiderer Derives de nucleosides a groupes protecteurs photolabiles
WO1999000357A1 (fr) * 1997-06-27 1999-01-07 Vertex Pharmaceuticals Incorporated INHIBITEURS DE p38

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CAI S X ET AL: "STRUCTURE-ACTIVITY RELATIONSHIPS OF ALKYL- AND ALKOXY-SUBSTITUTED 1,4-DIHYDROQUINOXALINE-2,3-DIONES: POTENT AND SYSTEMICALLY ACTIVE ANTAGONISTS FOR THE GLYCINE SITE OF THE NMDA RECEPTOR", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY. WASHINGTON, US, vol. 40, no. 5, 1997, pages 730 - 738, XP000652328, ISSN: 0022-2623 *
HELFERT, H. ET AL.: "NEW METHOD FOR THE PREPARATION OF 1,3-DIAZETIDINEDIONES", ANGEW. CHEM. INTERN. EDIT., vol. 9, 1970, pages 372 - 373, XP008003978 *
SCHAEFER, G. ET AL.: "ENERGY TRANSFER INHIBITION IN PHOTOPHOSPHORYLATION AND OXIDATIVE PHOSPHORYLATION BY 3'-ESTERS OF ADP", COLLOQ. GES. BIOL.CHEM., vol. 29, 1978, pages 220 - 227, XP008003926 *
SUN Q ET AL: "STRUCTURE ACTIVITY OF TOPOISOMERASE I POISONS RELATED TO HOECHST 33342", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, OXFORD, GB, vol. 4, no. 24, 1994, pages 2871 - 2876, XP002066290, ISSN: 0960-894X *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004058392A2 (fr) * 2002-12-23 2004-07-15 Febit Ag Groupes protecteurs photoactivables a base de o-nitrophenylethyle a sensibilisation intramoleculaire a l'etat triplet
WO2004058391A2 (fr) * 2002-12-23 2004-07-15 Febit Biotech Gmbh Groupes protecteurs photoactivables subissant un traitement en deux etapes, destines a la synthese de biopolymeres
WO2004058392A3 (fr) * 2002-12-23 2004-08-26 Febit Ag Groupes protecteurs photoactivables a base de o-nitrophenylethyle a sensibilisation intramoleculaire a l'etat triplet
WO2004058391A3 (fr) * 2002-12-23 2004-08-26 Febit Ag Groupes protecteurs photoactivables subissant un traitement en deux etapes, destines a la synthese de biopolymeres
US7737089B2 (en) 2002-12-23 2010-06-15 Febit Holding Gmbh Photoactivatable two-stage protective groups for the synthesis of biopolymers
EP1466663A1 (fr) * 2003-03-19 2004-10-13 F. Hoffmann-La Roche Ag Procédé de controle qualité lors de la synthèse de matrices d'acides nucléiques

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Publication number Publication date
EP1358197A1 (fr) 2003-11-05
DE10105077A1 (de) 2002-08-08

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