Cytogen Corporation

Johnson Matthey Public Limited Company

Kempharm, Inc.

Daniel J Coughlin

Benjamin A Belinka, Jr

Vernon L Alvarez

John D Rodwell

Richard Wood

Da-Ming Gou

Thomas J McKearn

Chyi Lee

John W Goers

Robert D Radcliffe

Jeremy Clinton Wilt

H Dalton King

Anthony D Lopes

Hurley D King

Steven Collier

Mahmoud Mirmehrabi

Brian Heinrich

Benjamin A Belinka

Vernon Leon Alvarez

John Walter Goers

Hurley Dalton King

Richard Charles Siegel

John Dennies Rodwell

Thomas Joseph Mckearn

Anthony Dwight Lopes

Jeremy Wilt

A method of preparing purified decitabine comprises mixing crude decitabine with solvent, such as dimethylacetamide, to form a solution or suspension and forming the purified decitabine from the solution or suspension. The forming step comprises adding an anti-solvent, such as ethanol, to the solution or suspension. The forming step may further comprise after adding ethanol to provide a mixture of dimethylacetamide and ethanol: cooling the mixture; isolating the solid decitabine present in the cooled mixture; and evaporating residual dimethylacetamide and ethanol from the solid decitabine to provide the purified decitabine. The mixture of dimethylacetamide and ethanol may be heated. The purification method preferably results in decitabine having a ratio of the &#x3b2;-anomer of decitabine to the &#x3b1;-anomer of decitabine of at least about 99.9:0.1.

Method for the purification of decitabine

Novel processes, and intermediates, for making alkylated arylpiperazine and alkylated arylpiperidine compounds of the general formulas (I) and (VII), respectively wherein, Rand Rare individually selected from hydrogen, alkyl, substituted or alkyl; n=0, 1, or 2; Y=NRR, OR, or SR, where Rand Rare individually selected from acyl or sulfonyl, and where Ris aryl or heteroaryl, or heterocyclic; and Ar is an aryl, heteroaryl, or heterocyclic compound.

Processes for making alkylated arylpiperazine and alkylated arylpiperidine compounds including novel intermediates

Compositions comprising hydrocodone benzoic acid enol ester to form novel prodrugs including hydrocodone benzoic acid enol ester salts, and various polymorphs. Also provided are processes for the preparation of hydrocodone benzoic acid enol ester salts, and various polymorphs.

Pharmaceutically acceptable salts and polymorphic forms of hydrocodone benzoic acid enol ester and processes for making same

The invention relates to a method of treating a patient in need thereof, including a need for diagnosis or treatment, comprising the administration of a metal complex of a polypeptide construct. The construct comprises a compound of the formula (I): ##STR1## in which, 'B' is a hydrocarbon backbone,

Treatment methods using metal-binding targeted polypeptide constructs

This invention relates to the preparation and use of novel open-chain or cyclic polypeptide constructs in which two or more polypeptide chains, in an open-chain construct, or one or more chains, in a cyclic construct, are chemically derivatized such that the resulting construct exhibits both metal-binding capability and tissue-, organ- or cell-targeting selectivity. In particular, the polypeptide constructs of the present invention comprise compounds of the formula (I): ##STR1## in which, 'B' is a hydrocarbon backbone, 'P' is a polypeptide capable of targeting particular cells, tissues or organs of the body, 'A' may be the group --NR'--NR'-- or the group --NR'--NR'--L-- in which L may be an aliphatic or aromatic linker group, R, R', and R' may be the same or different and may be hydrogen or an aliphatic group, m is an integer.gtoreq.2, provided that the groups R, R', R', L and 'P' of a given chain may be the same or different from the groups R, R', R', L and 'P' of another chain, n is an integer.gtoreq.0; or a pharmaceutically acceptable salt thereof. The constructs of the present invention are capable of binding a variety of metallic species.

Metal-binding targeted polypeptide constructs

Substituted thioureas as bifunctional chelators

This invention relates to the preparation and use of novel open-chain or cyclic polypeptide constructs in which two or more polypeptide chains, in an open-chain construct, or one or more chains, in a cyclic construct, are chemically derivatized such that the resulting construct exhibits both metal-binding capability and tissue-, organ- or cell-targeting selectivity. In particular, the polypeptide constructs of the present invention comprise compounds of the formula (I): ##STR1## in which, 'B' is a hydrocarbon backbone, 'P' is a polypeptide capable of targeting particular cells, tissues or organs of the body, 'A' may be the group --NR'--NR'-- or the group --NR'-- NR'--L-- in which L may be an aliphatic or aromatic linker group, R, R', and R' may be the same or different and may be hydrogen or an aliphatic group, m is an integer.gtoreq.2, provided that the groups R, R', R', L and 'P' of a given chain may be the same or different from the groups R, R', R', L and 'P' of another chain, n is an integer.gtoreq.0; or a pharmaceutically acceptable salt thereof. The constructs of the present invention are capable of binding a variety of metallic species.

This invention relates to chelating agents useful for coupling metal ions to biologically active molecules. In particular, isothiocyanate derived thiocarbonyls for chelating metals such as technetium are provided that can be conjugated to a targeting molecule such as an antibody, a peptide or a protein.

Bifunctional isothiocyanate derived thiocarbonyls as ligands for metal

A process for the purification of aminophosphonic acids under non-alkaline conditions is described. In particular, aminophosphonic acids are slurred in neutral or acidic water, heated to reflux, cooled and then filtered. Product purities approaching 100% are thus obtained.

Non-alkaline purification of aminophosphonic acids

This invention relates to the preparation and use of novel open-chain or cyclic polypeptide constructs in which two or more polypeptide chains, in an open-chain construct, or one or more chains, in a cyclic construct, are chemically derivatized such that the resulting construct exhibits both metal-binding capability and tissue-, organ- or cell-targeting selectivity. In particular, the polypeptide constructs of the present invention comprise compounds of the formula (I): ##STR1## in which, 'B' is a hydrocarbon backbone, 'P' is a polypeptide capable of targeting particular cells, tissues or organs of the body, 'A' may be the group --NR'--NR'-- or the group --NR'--NR'--L-- in which L may be an aliphatic or aromatic linker group, R, R' and R' may be the same or different and may be hydrogen or an aliphatic group, m is an integer .gtoreq.2, provided that the groups R, R', R', L and 'P' of a given chain may be the same or different from the groups R, R', R', L and 'P' of another chain, n is an integer .gtoreq.0; or a pharmaceutically acceptable salt thereof. The constructs of the present invention are capable of binding a variety of metallic species.

Disclosed herein is a novel method for preparing a DPTA tripeptide-chelator. In particular, a method for preparing GYK-DTPA is described. The method disclosed herein is an improvement over the known methods of preparation based on the cost and labor savings of the present invention. The present invention utilizes t-butyloxycarbonyl (Boc) protecting groups to facilitate the polypeptide-chelator production.

Method for the preparation of GYK-DTPA

Novel antineoplastic amine-containing derivatives and methods for synthesizing such derivatives of anthracycline antibiotics are disclosed. The derivatives are useful to anthracycline antibiotic conjugates which retain substantial immunospecificity of the unconjugated antibody molecule. Using the conjugates, targeted delivery of the attached antibiotics is achieved in vivo. Such conjugates are thus therapeutically effective against a variety of neoplastic cellular disorders when administered in vivo. Methods for preparing the antibody conjugates and for use of the conjugates in vivo are also disclosed.

Amine derivatives of anthracycline antibodies

The invention relates to amine-containing porphyrin derivatives. Theporphyrins can be used as photosensitizers which are useful as therapeutic agents. Also described are methods for preparing conjugates in which a porphyrin derivative is covalently attached to an antibody or antibody fragment. In vivo therapeutic methods utilizing the conjugates are also desired.

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Robbinsville, NJ, United States of America

Daniel J Coughlin