Nucana Plc

Hugh Griffith

Gordon Kennovin

Michaela Serpi

Christopher McGuigan

Valentina Ferrari

Magdalena Slusarczyk

Carmen Jimenez Antunez

Venkata Lakshmi Narasimha Rao Dammalapati

Mani Bushan Kotala

Fabrizio Pertusati

Chris Pepper

Chris McGuigan

Christopher Mcguigan

Chris Mcguigan

Christopher (deceased) Mcguigan

Samuele Di Ciano

This invention relates to pharmaceutical formulations and formulation strategies of protides (phosphoramidate derivatives of nucleosides) and, in particular, protides useful in the treatment of cancer such as NUC-3373 (5-fluoro-2'-deoxyuridine-5′-O-[1-naphthyl (benzoxy-L-alaninyl)] phosphate) and NUC-7738 (3′-deoxyadenosine-5′-O-[phenyl(benzyloxy-L-alaninyl)] phosphate). In particular, the invention relates to formulations which comprise a polar aprotic solvent, for example dimethyl acetamide (DMA).

Formulations of phosphoramidate derivatives of nucleoside drugs

The present invention relates to chemical compounds, the compounds for use in a method of treatment, particularly in a method of prophylaxis or treatment for cancer, a process for preparation of the compounds and pharmaceutical compositions comprising the compounds. The compounds may, in particular, be useful in the treatment of leukaemia, lymphoma and/or solid tumours in. The compounds are derivatives of cordycepin (3'-deoxyadenosine).

2' and/or 5′ amino-acid ester phosphoramidate 3′-deoxy adenosine derivatives as anti-cancer compounds

The present invention is a process for the preparation of certain 5'-phosphoramidate nucleotide diastereoisomers. The phosphoramidates include those useful in the treatment of cancer such as NUC-3373 (5-fluoro-2′-deoxyuridine-5′-O-[1-naphthyl(benzyloxy-L-alaninyl)]phosphate].

Synthesis of phosphate derivatives

This invention relates to pharmaceutical formulations and formulation strategies of protides (phosphoramidate derivatives of nucleosides) and, in particular, protides useful in the treatment of cancer such as NUC-3373 (5-fluoro-2'-deoxyuridine-5&#x2032;-O-[1-naphthyl (benzoxy-L-alaninyl)] phosphate) and NUC-7738 (3&#x2032;-deoxyadenosine-5&#x2032;-O-[phenyl(benzyloxy-L-alaninyl)] phosphate). In particular, the invention relates to formulations which comprise a polar aprotic solvent, for example dimethyl acetamide (DMA).

This invention relates to pharmaceutical formulations of gemcitabine-[phenyl-benzoxy-L-alaninyl)]-phosphate, a monophosphate derivative of the well-known oncology drug gemcitabine. In particular, the invention relates to formulations which comprise a polar aprotic solvent, preferably dimethyl acetamide (DMA). Formulations comprising these solvent provide therapeutically effective treatments of gemcitabine-[phenyl-benzoxy-L-alaninyl)]-phosphate. The invention also relates to methods of using said formulations and kits comprising said formulations.

Formulation comprising a gemcitabine-prodrug

This invention relates to a prodrug of the monophosphate nucleotide of the well-known oncology drug gemcitabine. Specifically, it relates to gemcitabine-[phenyl-benzoxy--alaninyl)]-phosphate when present as a single phosphate diastereoisomer and, in particular, it relates to the (S)-phosphate diastereoisomer which offers a remarkable and unexpected increase in solubility relative to the (R)-diastereoisomer. The (S)-phosphate epimer is also preferentially taken up into cyclodextrin solutions over the (R)-diastereoisomer.

Gemcitabine prodrugs

The present invention relates to compounds comprising a salt of a diphosphate phosphoramidate of a nucleoside drug, e.g. clofarabine. The compounds are useful in the treatment of cancer, e.g. leukemia.

Salts of diphosphate phosphoramidate of nucleosides as anticancer compounds

The present invention is a process for the preparation of certain 5'-phosphoramidate nucleotide diastereoisomers. The phosphoramidates include those useful in the treatment of cancer such as NUC-3373 (5-fluoro-2&#x2032;-deoxyuridine-5&#x2032;-O-[1-naphthyl(benzyloxy-L-alaninyl)]phosphate).

Provided are medical uses and methods for targeting cancer stem cells employing ProTide compounds, particularly in the prevention or treatment of cancer. The ProTide may be other than one selected from the group consisting of NUC-1031, a ProTide derived from cordycepin, and a ProTide derived from 8-chloroadenosine. The medical uses and methods for targeting cancer stem cells are particularly useful in the treatment of relapsed or refractory cancer in human patients. Also provided are methods of selecting patients who will benefit from prevention or treatment of cancer through the medical uses or methods of treatment of the invention.

Cancer treatments

This invention relates to a crystalline form of gemcitabine-[phenyl-(benzoxy-L-alaninyl)]-(S)-phosphate.

Crystalline form of gemcitabine

Disclosed are chemical compounds, the compounds for use in a method of treatment, particularly in a method of prophylaxis or treatment for cancer, a process for preparation of the compounds and pharmaceutical compositions comprising the compounds. The compounds may, in particular, be useful in the treatment of leukaemia, lymphoma and/or solid tumours in. The compounds are derivatives of cordycepin (3'-deoxyadenosine) having a 2&#x2032; and/or 5&#x2032;-amino-acid ester phosphoramidate moiety.

2' and/or 5&#x2032; amino-acid ester phosphoramidate 3&#x2032;-deoxy adenosine derivatives as anti-cancer compounds

This invention relates to derivatives of cladribine of Formula (I). The compounds are phosphoramidate derivatives in which the phosphoramidate moiety is situated on the 3'-hydroxyl group of cladribine. The invention also relates to pharmaceutical formulations of the cladribine derivatives and their use in methods of treatment. The compounds are useful in the treatment of cancer. 

Phosphoramidate nucleoside derivatives as anticancer agents

This invention relates to pharmaceutical formulations of gemcitabine-[phenyl-(benzoxy-L-alaninyl)]-phosphate, a monophosphate derivative of the well-known oncology drug gemcitabine. In particular, the invention relates to formulations which comprise a polar aprotic solvent, preferably dimethyl acetamide (DMA). Formulations comprising this solvent provide therapeutically effective treatments of gemcitabine-[phenyl-(benzoxy-L-alaninyl)]-phosphate. The invention also relates to methods of using said formulations and kits comprising said formulations.

Disclosed are methods of separating the diastereoisomers of gemcitabine-[phenyl-(benzoxy-L-alaninyl)]-phosphate (NUC-1031), or salts thereof, using crystallisation. In particular, crystallisation from isopropyl alcohol provides gemcitabine-[phenyl-(benzoxy-L-alaninyl)]-(S)-phosphate in high diastereoisomeric purity: Also disclosed is a crystalline form of gemcitabine-[phenyl-(benzoxy-L-alaninyl)]-(S)-phosphate. Disclosed are methods of isolating gemcitabine-[phenyl-(benzoxy-L-alaninyl)]-(R)-phosphate in high diastereoisomeric purity: 

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Edinburgh, United Kingdom

Hugh Griffith