Development Finance Corporation of New Zealand

Cancer Research Technology Limited

Xenova Limited

Auckland Uniservices Limited

Cancer Research Campaign Technology Limited

Development Finance Corporation of New Zeland

Development of Finance Corporation of New Zealand

La Trobe University

Bruce Charles Baguley

William Alexander Denny

Graham John Atwell

Gordon William Rewcastle

Lai-Ming Ching

Graeme John Finlay

Philip Kestell

Julie Ann Spicer

Bruce F Cain, Deceased

Thomas Rodemann

Swarnalatha Akuritaya Gamage

James William Paxton

Liang-Chuan Steve Wang

Michael Leslie Rogers

Leslie William Deady

Martin Philpott

Liangli Zhao

The present invention relates to the use of compounds such as compounds of the xanthenone acetic acid class such as 5,6-dimethylxanthenone-4-acetic acid (DMXAA) for the treatment of cancer, wherein the compounds are administered gastrointestinally, preferably orally. More particularly, the invention is concerned with the use of such compounds, wherein the compound is delivered to the site of action in the patient to be treated in two or more doses.

Anti-cancer composition comprising DMXAA or related compound

Methods and compositions are provided for treating cancer, the methods including the step administering, either sequentially or simultaneously, (i) a compound of the xanthenone acetic acid group of compounds, and (ii) at least one compound selected from compounds which modulate TNF production and compounds which act on biochemical pathways leading to TNF synthesis. Compositions include a combination of (i) and (ii) above, together with acceptable pharmaceutical carriers and/or vehicles.

Cancer treatment by combination therapy

This invention relates to polycyclic carboxamide compounds of the formula (I) with cytotoxicity, processes for their preparation, pharmaceutical compositions containing them and their use in therapy, particularly I the treatment and/or prophylaxis of cellular proliferative disorders such a cancer. 

Anti-tumour polycyclic carboxamides

The present invention relates to synergistic combinations of the compounds of formula I such as compounds of the xanthenone acetic acid class such as 5,6-dimethylxanthenone-4-acetic acid (DMXAA) and NSAIDs, in particular diclofenac, which have anti-tumor activity. More particularly, the invention is concerned with the use of such combinations in the treatment of cancer and pharmaceutical compositions containing said combinations.

Anti-cancer combinations

Bis(acridinecarboxamide) and bis(phenazinecarboxamide) as antitumor

A new treatment schedule for administration of N-�2-(dimethylamino)ethyl!acridine-4-carboxamide and other related carboxamide anticancer drugs in which the drug is administered in a divided-dose schedule comprising two or more administrations at frequent intervals, for example every hour. Schedules to produce cyclic peaks/troughs in plasma levels are mentioned. The compounds can be used for circumventing multidrug resistance in cancers and may, for example, be used in combination with other cytotoxic drugs, especially non-topo II inhibitors. Treatment of melanoma and advanced colon cancer is included.

Treatment of cancers

The novel class of xanthenone-4-acetic acids represented by the general formula (I) ##STR1## where R.sub.1 represents up to two of the groups lower alkyl, halogen, CF.sub.3, CN, NO.sub.2, NH.sub.2, CH.sub.2 COOH, OR.sub.2, OH, NHCOR.sub.2, NHSO.sub.2 R.sub.2, SR.sub.2, SO.sub.2 R.sub.2, CH.sub.2 CONHR.sub.2 or NHR.sub.2 (where R.sub.2 is lower alkyl optionally substituted with hydroxy, amino or methoxy functions), at any of the positions 1-8 which are available, R.sub.1 may also represent the substitution of an aza (--N.dbd.) group for one or two of the methine (--CH.dbd.) groups in the carbocyclic rings and two of R.sub.1 on any two available adjacent positions may also represent the grouping --CH.dbd.CH--CH.dbd.CH-- to form an additional fused benzene ring; and basic addition salts thereof, possess antitumour and antibacterial properties.

Compounds having antitumor and antibacterial properties

The novel class of substituted quinolines represented by the general formula (I): ##STR1## where each of R.sub.1 and R.sub.2 separately represents H or up to three of the groups lower alkyl, halogen, CF.sub.3, CN, SO.sub.2 CH.sub.3, NO.sub.2, OH, NH.sub.2, NHSO.sub.2 R.sub.3, NHCOOR.sub.3, OR.sub.3, SR.sub.3, NHR.sub.3 or NR.sub.3 R.sub.3 (where R.sub.3 is lower alkyl optionally substituted with hydroxy, amino or ether functions), and each of R.sub.1 and R.sub.2 may additionally separately represent the substitution of an aza (--N.dbd.) group for one or two of the methine (--CH.dbd.) groups in each of the carbocyclic rings, and R.sub.1 may also represent, at positions 2', 3' or 4' only, a phenyl ring optionally further substituted with lower alkyl, halogen, CF.sub.3, CN, SO.sub.2 CH.sub.3, NO.sub.2, OH, NH.sub.2, NHCOR.sub.3, NHCOOR.sub.3, OR.sub.3, SR.sub.3, NHR.sub.3 or NR.sub.3 R.sub.3 (where R.sub.3 is lower alkyl optionally substituted with hydroxy, amino or ether functions);

Substituted quinoline derivatives and pharmaceutical compositions thereof

Compounds represented by the general formula (I): ##STR1## in which R.sub.1 represents ##STR2## A and B each represent H or a lower alkane optionally substituted with amino and/or hydroxyl functions, except that A and B are not both H; R.sub.3 represents H, OCH.sub.3, CH.sub.3, halogen, NH.sub.2, NO.sub.2, NHCH.sub.3, N.sub.3 (CH.sub.3).sub.2, N.sub.3, NHCOCH.sub.3, NHCOOCH.sub.3, N(CH.sub.3)COOCH.sub.3, CONH.sub.2 or CONHCH.sub.3 ; R.sub.4 represents H, alkyl, O-alkyl, CONH.sub.2, CONHCH.sub.3 or CONHCH.sub.2 CONHCH.sub.3, except that R.sub.3 and R.sub.4 taken together can represent --C.dbd.CH--CH.dbd.N--; R.sub.5 represents H, alkyl, O-alkyl, CONH.sub.2, CONHCH.sub.3 or CONH.sub.2 CH.sub.2 CONHCH.sub.3 ; R.sub.6 represents lower alkyl; R.sub.7 represents CH.sub.3 or C.sub.6 H.sub.5 (phenyl); R.sub.8 represents lower alkyl or C.sub.6 H.sub.5 (phenyl); R.sub.9 represents H, NHCOCH.sub.3, NH.sub.2 or N.dbd.CHN(CH.sub.3).sub.2 ; and R.sub.10 represents H or NH.sub.2 ; and the acid addition salts thereof, possess antibacterial and antitumour properties.

Substituted o-phenylenediamine acridine compounds having antitumor

4-Carboxamidoacridine compounds represented by the general formula (I), ##STR1## where R.sub.1 represents H, CH.sub.3 or NHR.sub.3, where R.sub.3 is H, COCH.sub.3, SO.sub.2 CH.sub.3, COPh, SO.sub.2 Ph or lower alkyl optionally substituted with hydroxyl and/or amino functions;

Acridinecarboxamide compounds

The novel class of compounds of the present invention represented by the general formula (I): ##STR1## in which R.sub.1 represents H or OCH.sub.3, R.sub.2 represents H, OCH.sub.3, CH.sub.3, halogen, NO.sub.2, NH.sub.2, NHCOCH.sub.3 or NHCOOCH.sub.3, and

Dimethylphosphoramidates

The novel class of compounds of the present invention represented by the general formula (I): ##STR1## in which R.sub.1 represents H or OCH.sub.3,

Certain acridinyl-phosphoramidate compounds

Compounds represented by the general formula (I) ##STR1## in which R represents an aniline substituted in the para position by either --NHSO.sub.2 CH.sub.3 or --NHCOOCH.sub.3 and bearing either an --H or --OCH.sub.3 in the ortho position, or an aniline substituted in the para position by --NHP(O)(OCH.sub.3).sub.2 and bearing an --H in the ortho position, and the acid addition salts thereof, have antitumor activity.

1,10[8,9-Benz]phenanthroline

3,5-Disubstituted-4'-(9-acridinylamino)-methane-sulfon-m-anisidide compounds represented by the general formula ##STR1## in which R.sup.2 and R.sup.3 represent, respectively, --CH.sub.3 and --CONHCH.sub.3, --CH.sub.3 and --CONHCH.sub.2 CONH.sub.2, --Cl and --CONHCH.sub.2 CONH.sub.2, --CONHCH.sub.3 and --CH.sub.3 ; and acid addition salts thereof have unexpectedly high antitumor activity in leukemic animals and low or no direct mutagenicity.

Growing community of inventors

Auckland, New Zealand

Bruce Charles Baguley