Temple University

Hoechst Aktiengesellschaft

Nigu Chemie Gmbh

4 Aza Bioscience Nv

The United States of America, As Represented by the Secretary, Department of Health and Human Services

The United States of America As Represented by the Secretary of

The United States of America As Represented by the Department of Health

K.u. Leuven Research & Development

Vasopharm Biotech Gmbh

Sanrx Pharmaceuticals, Inc.

Vasopharm Buitech Gmbh

Wolfgang Pfleiderer

Robert J Suhadolnik

Mark Jozef Albert Waer

Piet André Maurits Maria Herdewijn

Harald Schmidt

Mary E Hawkins

Frank Balis

Frank Bergmann

Michael D Davis

Ralf Schnell

Stephan Matysiak

Markus Ott

Rainer Henning

Steven Cesar Alfons De Jonghe

Lothar Fröhlich

Sigrid B&uuml;hler

Sigrid Buehler

Phillip Moheno

Arnaud Didier Marie Marchand

Sigrid Buhler

Piet André´ M M Herdewijn

Markus Beier

Peter Kotsonis

Shahriyar Taghavi-Moghadam

Sigrid Bühler

Heiner Giegrich

The present invention discloses novel and improved nucleosidic and nucleotidic compounds that are useful in the light-directed synthesis of oligonucleotides, as well as, methods and reagents for their preparation. These compounds are characterized by novel photolabile protective groups that are attached to either the 5'- or the 3&#x2032;-hydroxyl group of a nucleoside moiety. The photolabile protective group is comprised of a 2-(2-nitrophenyl)-ethyoxycarbonyl skeleton with at least one substituent on the aromatic ring that is either an aryl, an aroyl, a heteroaryl or an alkoxycarbonyl group. The present invention includes the use of the aforementioned compounds in light-directed oligonucleotide synthesis, the respective assembly of nucleic acid microarrays and their application.

Photolabile protective groups for improved processes to prepare oligonucleotide arrays

Provided herein is dipterinyl calcium pentahydrate (DCP) and therapeutic methods based thereon. Also provided herein is the compound dipterinyl calcium pentahydrate (DCP) or an analog or polymorph thereof.

Dipterinyl calcium pentahydrate (DCP) and therapeutic methods based thereon

This invention relates to a group of trisubstituted and tetrasubstituted pteridine derivatives, their pharmaceutically acceptable salts, N-oxides, solvates, dihydro- and tetrahydro-derivatives and enantiomers, possessing unexpectedly desirable pharmaceutical properties, in particular which are highly active immunosuppressive agents, and as such are useful in the treatment in transplant rejection and/or in the treatment of certain inflammatory diseases. These compounds are also useful in preventing or treating cardiovascular disorders, allergic conditions, disorders of the central nervous system and cell proliferative disorders.

Immunosuppressive effects of pteridine derivatives

This invention relates to a group of trisubstituted and tetrasubstituted pteridine derivatives, having the formula: wherein X represents an oxygen atom or a group with the formula NZ and wherein: RCalkyl or arylalkyl; Z is a group independently defined as Ror the group NZ together with Ris an optionally substituted heterocyclic group containing at least one nitrogen atom; Ris amino or acylamino; Ris an atom or a group selected from the group consisting of hydrogen; Calkyl; and Calkoxy; and Ris an atom or a group selected from the group consisting of aryl optionally substituted with one or more substituents selected from the group consisting of halogen, Calkyl, and Calkoxy, their pharmaceutically acceptable salts, and enantiomers, possessing unexpectedly desirable pharmaceutical properties, in particular which are highly active immunosuppressive agents, and being useful in the treatment in transplant rejection, certain inflammatory diseases, cardiovascular disorders, allergic conditions, disorders of the central nervous system and cell proliferative disorders.

The invention relates to a novel use of 8-substituted xanthine derivatives for the manufacture of a medicament for the treatment of auto-immuno disorders.

Immunosuppressive effects of 8-substituted xanthine derivatives

Novel poly-substituted pteridinediones (lumazines), and mono- or polysubstituted 2-thiolumazines, 4-thiolumazines or 2,4-dithiolumazines, having disclosed substituents in positions 1, 3, 6 and 7 of the pteridine ring, and pharmaceutically acceptable salts thereof, being represented by the general formula (I).are useful as biologically active ingredients in preparing pharmaceutical compositions especially for the treatment or prevention of a CNS disorder, a cell proliferative disorder, a viral infection, an immune or auto-immune disorder or a transplant rejection. Combinations of the pteridine derivatives of the invention with an immunosuppressant or immunomodulator drug, an antineoplastic drug or an antiviral agent, providing potential synergistic effects, are also disclosed.

The present invention relates to the use of pteridine derivatives of the formula Iin which X is O or NH and R, for example, is hydrogen, phenyl or the radical R&#x2014;CH&#x2014; and R, for example, is hydrogen, (C-C)-alkylmercapto, the radical &#x2014;NRRor the radical &#x2014;OR, and in which R, R, R, R, R, R, R, Rand Rhave the meanings given in claimwhich are nitric oxide synthase inhibitors, for the treatment of diseases which are caused by an increased nitric oxide level.

Use of tetrahydropteridine derivatives as no synthase inhibitors

Compounds of formula (I), where preferably: A=a bridge of partial formula (II) or (III), Rand R=independently (substituted) alkyl, aryl or aralkyl, or together form a heterocycle, R=H, &#x2014;CO-Alkyl, or &#x2014;CO-Aryl, R=Aryl, &#x2014;CO&#x2014;O-Aryl or &#x2014;CO-Aryl and R=H, are potent inhibitors of NO-synthase and are suitable as pharmaceutical agents of prophylaxis and treatment of disease states associates with a disturbed NO metabolism.

N-substituted 4-aminopteridines, synthesis and use thereof as pharmaceutical agent

Nucleoside derivatives with photolabile protective groups

The invention provides pteridine nucleotides of formula (I) which are highly fluorescent and which can be used in the chemical synthesis of fluorescent oligonucleotide. The invention further provides for fluorescent oligonucleotide comprising one or more pteridine nucleotides. In addition the invention provides for pteridine nucleotide triphosphates which may be used as the constituent monomers in DNA amplification procedures. The pteridine nucleotides are more stable and possess higher quantum yields than structurally similar pteridine nucleotides.

Pteridine nucleotide analogs

Antiviral compounds and the water-soluble salts thereof have formula (I), wherein n is from 1 to 8; R is selected from the group consisting of (a), wherein m is zero, 1, 2 or 3; and (b), wherein q is from 1 to 20; R is independently selected from the group consisting of oxygen and sulfur; R is independently selected from the group consisting of hydrogen and hydroxyl; and R is selected from the group consisting of hydrogen, hydroxyl and (b); R is selected from the group consisting of hydroxyl and (b); R is selected from the group consisting of (c), (d) et (e), wherein x is from 1 to 20; provided that one of R , R and R is (b) wherein R is defined as above; or water soluble salt thereof.

Aminoaklanoyl-linked conjugates of 2&prime;,5&prime;-oligoadenylate and antiviral uses thereof

Base-modified derivatives of 2&prime;,5&prime;-oligoadenylate and antiviral uses thereof

The invention relates to nucleo-side derivatives with photo-unstable protective groups of the general formula (I) ##STR1## in which R.sup.1 is H, NO.sub.2, CN, OCH.sub.3, halogen, alkyl or alkoxyalkyl with 1 to 4 C atoms, R.sup.2 is H, OCH.sub.3, R.sup.3 is H, F, Cl, Br, NO.sub.2 or an aliphatic acyl radical with 2 to 5 C atoms, R.sup.4 is H, halogen, OCH.sub.3, an alkyl radical with 1 to 4 C atoms or a possibly substituted aryl radical, R.sup.5 is H or a conventional functional group for producing oligonucleotides, R.sup.6 is H, OH, halogen or XR.sup.8, where X is O or S and R.sup.8 is a conventional protective group in nucleotide chemistry, B is adenine, cytosin, guanine, thymine, uracil, 2,6-diaminopurin-9-yl, hypoxanthin-9-yl, 5-methylcytosin-1-yl, 5-amino-4-imidazol carboxylic acid amid-1-yl or 5-amino-4-imidazol carboxylic acid amide-3-yl, where, if B is adenine, cytosin or guanine, the primary amino function may have a permanent protective group. These derivatives may be used for the light-controlled synthesis of oligonucleotides on a DNA chip.

A process for the chemical synthesis of oligonucleotides Use of a dansylethoxycarbonyl group as base-labile 5'-hydroxyl protective group in the chemical synthesis of DNA and RNA and suitable synthetic processes. The ease of detection of the dansyl protective group and the ease of elimination from the sugar residue of the nucleotide without side reactions make oligonucleotide synthesis possible with high yields in very small quantities.

Process for the chemical synthesis of oligonucleotides

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Constance, Germany

Wolfgang Pfleiderer