Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Cyclopentanohydrophenanthrene ring system doai
Patent
1995-09-05
1997-07-08
Henley, III, Raymond
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Cyclopentanohydrophenanthrene ring system doai
552541, A61K 3158, C07J 900
Patent
active
056461380
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/CA93/0058 filed Dec. 21, 1993.
FIELD OF THE INVENTION
This invention relates to a new composition of matter, contignasterol, which is useful as an anti-inflammatory agent, an anti-allergen, as an agent used in the treatment of cardiovascular and haemodynamic disorders, and other diseases.
BACKGROUND OF THE INVENTION
Marine organisms have been the source of many steroids and a number of groups which have chemical and pharmacological activity.
An article in Journal Organic Chemistry, 1992, 57, 2996-2997, entitled "Two Unique Pentacyclic Steroids with Cis C/D Ring Junction from Xestospongia bergguistia Fromont, Powerful Inhibitors of Histamine Release", N. Shoji et al., discloses xestobergsterol A (1) (23S-16.beta., 23-cyclo-3.alpha., 6.alpha., 7.beta., 23-tetrahydroxy-5.alpha., 14.beta.-cholestan-15-one) and B (2) (23S-16.beta., 23-cyclo-1.beta., 2.beta., 3.alpha., 6.alpha., 7.beta., 23-hexahydroxy-5.alpha., 14.beta.-cholestan-15-one), potent inhibitors of histamine release from rat mast cells induced by anti-IgE, are the first report of steroids with both the C.sup.16 /C.sup.23 bond and cis C/D ring junction.
SUMMARY OF THE INVENTION
The invention relates to new compositions of matter, and the use of these compositions in the treatment of disease. The basic compound, contignasterol (1), as well as its related compounds, have a new chemical structure as drawn below. It belongs to the steroid class of natural products but it contains a unique set of functional groups attached to the basic cholestane steroid carbon skeleton. The combination of features which make the structure of contignasterol (1) unique are: i) the 3.alpha.-hydroxyl, ii) the 4.beta.-hydroxyl, iii) the 6.alpha.-hydroxyl, iv) the 7.beta.-hydroxyl, v) the 14.beta.-hydrogen configuration, vi) the 15-ketone functionality, and vii) the cyclic hemiacetal functionality in the steroid side chain which is formed between a hydroxyl functionality at C22 and an ethanol substituent (i.e. a methylene carbon at 28 and an aldehyde carbon at 29) attached at C24. Contignasterol (1) exists as a mixture of R and S stereoisomers at C29. Otherwise the stereochemistry is as drawn in 1. ##STR1##
In broad terms, the invention pertains to a novel group of contignasterol compounds having the following generic formula: ##STR2## contignasterol nucleus (ring C/D cis) where R= ##STR3## and the trans isomer ##STR4## 14-epicontignasterol nucleus (ring C/D trans) where R= ##STR5##
The compounds identified above (1 to 9) can be used to prevent inflammatory or allergic reaction when they are administered at a concentration in the range of 0.1 to 100 mg/l, and a pharmaceutically acceptable acid or salts thereof; and a pharmaceutically acceptable carrier.
The compounds identified above (1 to 9) can be used in the treatment of cardiovascular and haemodynamic disorders, when they are administered at 0.1 to 100 mg/l in a pharmaceutically acceptable carrier.
The invention also relates to a method of treating inflammation, asthma, allergic rhinitis, rashes, psoriasis, arthritis, thrombosis and hypotension or hypertension where platelets are involved in a mammal comprising treating the mammal with a therapeutic amount of any one or more of the compounds described above (1 to 9).
DETAILED DESCRIPTION OF THE INVENTION
Contignasterol (1) was isolated from extracts of specimens of the marine sponge Petrosia contignata which were collected by R. Andersen and T. Allen at Madang, Papua New Guinea. The details of the purification and structure elucidation of contignasterol (1) have been published in an article entitled "Conginasterol, Highly Oxygenated Steroid with the `Natural` 14.beta. Configuration from the Marine Sponge Petrosia Contignata Thiele, 1899", in the Journal of Organic Chemistry, Vol. 57, pgs. 525-528, which appeared on Jan. 17, 1992, the subject matter of which is incorporated herein by reference.
The sponge Petrosia contignata Thiele was identified by Dr. R. van Soest. A voucher specimens is deposited at the Zoological Museum of Ams
REFERENCES:
patent: 5079239 (1992-01-01), Sun et al.
Burgoyne et al., J. Org. Chem. 57, pp. 525-528. 1992.
Shoji et al., J. Org. Chem., 57, pp. 2996-2997. 1992.
Dissertation Abstract Online #AADNN-79757, Burgoyne "Chemical Studies of Metabolites from Pacific Ocean Marin Sponges and the Starfish Dermasterias Imbricata (Sponge Metabolites". 1992.
Allen Theresa M.
Andersen Raymond J.
Burgoyne David L.
Henley III Raymond
University of Alberta
University of British Columbia
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