Cancer Research Technology Limited

Ucl Business Plc

University College London

Stephen Neidle

Lloyd Royston Kelland

Richard John Harrison

Sharon Michele Gowan

Martin Anthony Read

Anthony Reszka

Mekala Gunaratnam

Richard Angell

Gavin William Collie

Sally Oxenford

Aaron Grainger Dale

Gary N Parkinson

Stephan A Ohnmacht

Marialuisa Micco

Francisco Cuenca

Caterina Maria Lombardo

Sarah Welsh

Anthony Reskza

The present invention relates to naphthalene diimides, NDIs, and methods of synthesising them. The NDIs have DNA-quadruplex binding and stabilising activity, and potential in treatment of pancreatic, prostate, and other human cancers. The NDIs are a compound of Formula I. 

Substituted naphthalene diimides and their use

The invention relates to novel compounds which are naphthalene diimides of general formula (I):  The compounds are used in therapy, particularly in cancer treatment.

Diimide compounds

G-quadruplex stabilising agent

The invention relates to novel compounds which are naphthalene diimides of general formula (I). The compounds are used in therapy, particularly in cancer treatment.

Naphthalene diimide compounds

The present invention relates to a crystal structure of G-quadruplexes and its use. The invention provides a crystal of an intramolecular G-quadruplex structure having a hexagonal space group P6, and unit cell dimensions a=b=56.7 and c=42.1; &#x3b1;=&#x3b2;=90&#xb0;, &#x3b3;=120&#xb0; and a crystal of G-quadruplex having the three dimensional atomic coordinates of Table 1 or Table 2. These structures may be used in a computer-based method for the analysis of the interaction of a molecular structure with a G-quadruplex.

Crystal structure of G-quadruplex containing a potassium ion

The present invention pertains to acridone and acridine compounds of formula (I), wherein either: (a) K is &#x2550;O, L is &#x2014;H, alpha is a single bond, beta is a double bond, gamma is a single bond (acridones); or, (b) K is a 9-substituent, L is absent, alpha is a double bond, beta is a single bond, gamma is a double bond (acridines); and wherein: Jis a 2- or 3-substituent; Jis a 6- or 7-substituent; Jand Jare each independently a group of the formula &#x2014;NHCO(CH)NRR, wherein: n is an integer from 1 to 5; and, Rand Rare independently hydrogen, Calkyl, Cheterocyclyl, or Caryl, or Rand R, taken together with the nitrogen atom to which they are attached, form a heterocyclic ring having from 3 to 8 ring atoms; and wherein, when K is a 9-substituent, K is a group of the formula &#x2014;N(R)Q, wherein: Ris an amino substituent and is hydrogen, Calkyl, Cheterocyclyl, or Caryl; and, Q is Calkyl, Cheterocyclyl, or Caryl, and is optionally substituted; and pharmaceutically acceptable salts, esters, amides, solvates, hydrates and protected forms thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit telomerase, to regulate cell proliferation, and in the treatment of proliferative conditions, such as cancer.

Therapeutic acridone and acridine compounds

This invention pertains to certain acridone and acridine compounds of the formula which inhibit telomerase, regulate cell proliferation, etc., and/or treat cancer, proliferative conditions, etc.: wherein either: (a) K is &#x2550;O, L is &#x2014;H, alpha single bond, beta is a double bond, gamma is a single bond (acridones); or, (b) K is a 9-substituent, L is absent, alpha is a double bond, beta is a single bond, gamma is a double bond (acridines); and wherein: Jis a 2- or 3-substituent; Jis a 6- or 7-substituent; Jand Jare each a group of the formula &#x2014;N(R)&#x2014;W, wherein: Ris a nitrogen substituent and is hydrogen, Calkyl, Cheterocyclyl, or Caryl, and is optionally substituted; and, W is Calkyl, Cheterocyclyl, or Caryl, and is optionally substituted; and, wherein, when K is a 9-substituent, K is a group of the formula &#x2014;N(R)&#x2014;Q, wherein: Ris an amino substituent and is hydrogen, Calkyl, Cheterocyclyl, or Caryl; and, Q is Calkyl, Cheterocyclyl, or Caryl, and is optionally substituted; and pharmaceutically acceptable salts, esters, amides, solvates, hydrates, and protected forms thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit telomerase, to regulate cell proliferation, etc., and/or in the treatment of cancer, proliferative conditions, etc.

The present invention pertains to acridone and acridine compounds of formula (I), wherein either: (a) K is &#x2550;O, L is &#x2014;H, alpha single bond, beta is a double bond, gamma is a single bond (acridones); or, (b) K is a 9-substituent, L is absent, alpha is a double bond, beta is a single bond, gamma is a double bond (acridines); and wherein: Jis a 2- or 3-substituent; Jis a 6- or 7-substituent; Jand Jare each independently a group of the formula &#x2014;NHCO(CH)NRR, wherein: n is an integer from 1 to 5; and, Rand Rare independently hydrogen, Calkyl, Cheterocyclyl, or Caryl, or Rand R, taken together with the nitrogen atom to which they are attached, form a heterocyclic ring having from 3 to 8 ring atoms; and wherein, when K is a 9-substituent, K is a group of the formula &#x2014;N(R)Q, wherein: Ris an amino substituent and is hydrogen, Calkyl, Cheterocyclyl, or Caryl; and, Q is Calkyl, Cheterocyclyl, or Caryl, and is optionally substituted; and pharmaceutically acceptable salts, esters, amides, solvates, hydrates, and protected forms thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit telomerase, to regulate cell proliferation, and in the treatment of proliferative conditions, such as cancer.

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London, United Kingdom

Stephen Neidle