Apoptosis inducing adamantyl derivatives and their usage as anti

Details Apoptosis inducing adamantyl derivatives and their usage as anti Apoptosis inducing adamantyl derivatives and their usage as anti

1999-04-14

2000-10-03

Lambkin, Deborah C.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Ester doai

514435, 514437, 514454, 514455, 514452, 514569, 560 59, 560100, 560102, 549 17, 549 26, 549360, 549361, 549386, 549388, 562490, 562492, A61K 31235, A61K 31385, A61K 3135, C07D33908, C07C 6336

Patent

active

061274151

DESCRIPTION:

BRIEF SUMMARY
This application is a 371 of PCT/US97/11564 Jul. 8, 1999.


TECHNICAL FIELD OF THE INVENTION

The invention relates to the discovery that specific adamantyl or adamantyl group derivative containing retinoid related compounds induce apoptosis of cancer cells and therefore may be used for the treatment of cancer, including advanced cancers. Also, the present invention relates to novel adamantyl or adamantyl group derivative containing retinoid related compounds and their use for the treatment and/or prevention of cancer, keratinization disorders, dermatological conditions and other therapies.


BACKGROUND OF THE INVENTION

Solid tumors are the leading cause of death attributable to cancers worldwide. Conventional methods of treating cancer include surgical treatments, the administration of chemotherapeutic agents, and recently immune based treatments which typically involve the administration of an antibody or antibody fragment which may be conjugated to a therapeutic moiety such as a radio-nuclide. However, to date, such treatments have been of limited success.
Surgical treatments are generally only successful if the cancer is detected at an early stage, i.e., before the cancer has infiltrated major organs and surgery becomes non-feasible. Chemotherapeutic treatments available today are also of limited usefulness because of their non-selective killing and/or toxicity to most cell types. Also, many tumor cells eventually become resistant against the chemotherapeutic agent, thus making treatment of solid tumors and other tumors non-feasible. For example, persons treated with cisplatin often develop tumors which are cisplatin resistant. Immune based treatments are also subject to numerous problems including difficulty in targeting antibodies to desired sites, e.g., solid tumors, and host immune reactions to the administered antibody, attributable to the fact that to date most therapeutic antibodies have been of murine origin.
The usage of retinoids for the prevention of cancer has also been reported. In contrast to most conventional chemotherapeutic agents, retinoids function via specific signal transduction pathways, activating defined receptors in the cell nucleus. These receptors, the RARs, and the RXRs bind to specific DNA sequences, retinoic acid response elements, or RAREs. In addition, retinoids interact with other transcription factors, in particular the activator protein-1 (AP-1).
It is believed that the selective action of certain synthetic retinoids is based on the ability of these molecules to selectively activate subclasses of RARs and/or RXRs in the context of specific DNA sequences and/or proteins. Because of this specificity, not all retinoids possess the same activities. Indeed, thousands of different retinoids have been synthesized with the object being the identification of retinoids having optimal therapeutic activity.
To date, most retinoids have been found to inhibit tumor progression or cell proliferation of certain cancers, but do not directly eliminate cancer cells. Consequently, retinoids have been considered predominantly for the prevention of cancer but not for direct treatment.
One special class of retinoids or retinoid related compounds comprises adamantyl retinoid derivatives. These compounds are aromatic heterocyclic retinoids which contain an adamantyl group or an adamantyl group derivative. In contrast to normal retinoids such as retinoic acid (all -trans, 9-cis or 13-cis) and their synthetic analogs and derivatives, the adamantyl retinoid derivatives exhibit enhanced activity against specific tumor cells both in vitro and in vivo.
Retinoids also comprise known usage in the treatment of keratinization disorders and other dermatological diseases. For example, the use of retinoic acid, vitamin D or analogues thereof for the topical treatment of various dermatological diseases and in the cosmetic field is well known.
However, notwithstanding the large number of retinoids which have been reported, the identification of retinoids or retinoid related compounds having enhanced proper

REFERENCES:
patent: 4347254 (1982-08-01), Katsube et al.
patent: 4391819 (1983-07-01), Thies et al.
patent: 5098929 (1992-03-01), Larkin et al.
patent: 5547983 (1996-08-01), Charpentier
patent: 5770382 (1998-06-01), Hwang et al.
patent: 5877342 (1999-03-01), Bernardon et al.
patent: 5888432 (1999-03-01), Chan
patent: 5919970 (1999-07-01), Song et al.

Affiliated with

Also associated with

Rating

Apoptosis inducing adamantyl derivatives and their usage as anti does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Apoptosis inducing adamantyl derivatives and their usage as anti, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Apoptosis inducing adamantyl derivatives and their usage as anti will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-196360