Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
1994-03-23
2003-09-23
Spivack, Phyllis G. (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S444000, C514S456000
Reexamination Certificate
active
06624188
ABSTRACT:
FIELD OF THE INVENTION
The present invention is directed to methods of administering to mammals including humans, compounds which have retinoid like activity and which lack substantial teratogenic activity and have substantially reduced skin toxicity. The present invention is also directed to pharmaceutical compositions adapted for administering said compounds having retinoid like activity, reduced skin toxicity, and lacking substantial teratogenic activity. In some instances the present invention is also directed to novel compounds having said retinoid like activity, reduced skin toxicity, and lacking teratogenic activity.
BRIEF DESCRIPTION OF THE PRIOR ART
Compounds which have retinoid like activity are well known in the art, and are described in numerous United States and foreign patents and in scientific publications. It is generally known and accepted in the art that retinoid like activity is useful for treating animals of the mammalian species, including humans, for curing or alleviating the symptoms and conditions of numerous diseases and conditions. In other words, it is generally accepted in the art that pharmaceutical compositions having a retinoid like compound or compounds as the active ingredient are useful as regulators of cell proliferation and differentiation, and particularly as agents for treating dermatoses, such as acne, Darier's disease, psoriasis, icthyosis, eczema and atopic dermatitis, and for treating and preventing malignant hyperproliferative diseases such as epithelial cancer, breast cancer, prostatic cancer, head and neck cancer and myeloid leukemias, for reversing and preventing atherosclerosis and restenosis resulting from neointimal hyperproliferation, for treating and preventing other non-malignant hyperproliferative diseases such as endometrial hyperplasia, benign prostatic hypertrophy, proliferative vitreal retinopathy and dysplasias, for treating autoimmune diseases and immunological disorders (e.g. lupus erythematosus) for treating chronic inflammatory diseases such as pulmonary fibrosis, for treating and preventing diseases associated with lipid metabolism and transport such as dyslipidemias, for promoting wound healing, for treating dry eye syndrome and for reversing and preventing the effects of sun damage to skin.
The compounds developed in the prior art with retinoid like properties, are, however, not without disadvantages. Several such prior art compounds cause serious irritation when applied to the skin (which is an important mode of application for treatment of skin conditions) and cause skin toxicity when administered orally as well. Many of the prior art compounds having retinoid like activity are teratogenic. Teratogenecity or teratogenic activity can be defined as an undesirable effect of a drug on a developing fetus. It is generally accepted in the art that pregnant females, and even females who are not pregnant but in the child-bearing age should avoid teratogenic drugs.
In light of the foregoing, there is a significant need in the prior art for pharmaceutical compositions, methods of treatment and new chemical entitities which are effective as treatment of the diseases and conditions for which retinoid like compounds are usually applied, and which have reduced or no teratogenic activity and cause no significant irritation on the skin.
With respect to specific compounds or classes of compounds having retinoid like or other biological activity, the following examples are noted.
German Patent DE 3316-932 A describes 1-phenyl-2-chromanyl-propylene derivatives and sulphur and nitrogen analogs. Specific examples of this disclosure are ethyl p-[(E)-2-(4,4-dimethyl-6-chromanyl, thiochromanyl or 1,2,3,4-tetrahydro-6-quinolinyl)propenyl]-1-benzoate.
U.S. Pat. No. 4,826,984 describes benzopyranyl (chromanyl) and benzofuranyl-propenyl benzoic acids and esthers thereof, an example being ethyl-p-(2-(4,4-dimethyl chroman-6-yl)-propenyl benzoate.
European EP 130 795 A discloses 4,4-dimethyl-6-chromanyl alkenyl benzoic acid derivatives, thiochromanyl and tetrahydroquinolinyl analogs. The 2 and 7 positions of the chroman, thiochroman and tetrahydroquinoline ring moieties in these compounds are not substituted.
The publication WO 8500-806 A discloses 4,4.-dimethyl-chroman-6-yl and 4,4-dimethyl-thiochroman-6-yl-ethenyl and 4,4-dimethyl-chroman-6-yl and 4,4-dimethyl-thiochroman-6-yl- propenyl benzoic acid, its esters and the corresponding thiophencarboxylic acid and other heterocyclic acid analogs. The 2 position of the chroman or thiochroman ring is unsubstituted.
The publication EP 350 846 A discloses p-(2-(3,4-dihydro-4,4-dimethyl-dihydrochroman-7-yl)-propeneyl]benzoic acid ethyl ester and related compounds,
The publication WO 8504 652 A discloses certain diaryl substituted propenyl compounds, an example being ethyl (E)-4-[2-(4-isopropylphenyl)-propenylbenzoate.
European patent EP 206 751 A discloses 2-substituted phenyl-alkenyl-quinoline derivatives as inhibitors of leukotriene synthesis. An examples of a compound of this reference are (E)-4-(3-(2-(quinolin-2-yl)-1-methylethenylphenoxy)butyric acid.
Published European patent application 0 098 591 A1 describes rodenticidal disubstituted propenyl compounds, an example of which is ethyl p-[2-(4,5,6,7-tetrahydro-4,4,7,7-tetramethylbenzo[b]thien-2-yl)propenyl benzoate, and another example is ethyl 6-[(E)-2-(4,5,6,7-tetrahydro-4,4,7,7-tetramethylbenzo[b]thien-2-yl)propenyl]nicotinate.
Great Britain Patent GB 2190-378 describes tetramethyl-tetrahydronaphthylpropenylphenol compounds, examples of which are ortho, meta or para (E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl)phenol.
German Patent DE 3602-473 A discloses aralkenyl-phenol derivatives, examples of which are (E)-1-(4-hydroxyphenyl)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propene and (E)-1-(4-methoxyphenyl)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetrameth-yl-2-naphthyl)propene.
European Patent EP 176 033 A discloses isoxazolyl-vinyl indane and tetrahydronaphthalene derivatives, an example of which is (E)-5-[2-(3-fluoro-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)-1-propenyl]-isoxazole-3-carboxylic acid.
The publication EP 303 915 discloses indanyl and tetrahydronaphthyl and substituted phenyl propenes as retinoids, where the phenyl substituent is sulfur substitited. An example of the disclosed compounds is methyl 4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl(propenyl)phenylsulphone.
European patent EP 176 032 A discloses 6-styryl-tetrahydro-naphthalene derivatives, examples of which are (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-7-hydroxy-2-naphthalenyl)-1-propenyl]benzylalcohol, and E-4-[2-(5,8-dihydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid.
European Patent EP 315 071 discloses 1-benzocycloheptenyl-2-carboxy-phenyl ethylene derivatives, an example of which is ethyl p-(E)-2-(6,7,8,9-tetrahydro-7,7-dimethyl-5H-benzocycloheptene-2-yl)propenyl benzoate.
German Patent DE 3524-199-A discloses stilbene-4-carboxylic acid derivatives, examples of which are [E-2-(3,4-diisopropylphenyl)propenyl]benzoic acid, [E-2-(3-tert-butylphenyl)propenyl]benzoic acid.
European Patent EP 245 825 describes heterocyclyl-alkenyl benzene derivatives, examples of which are 3-(&bgr;-(4′-hydroxy-3′-methoxyphenyl)ethenyl)-5-methylpyrazole and 5-(&bgr;(4′-hydroxy-3′,5′-bis-(1,1-dimethylethyl)phenyl)-ethenyl)-5-methylpyrazole.
European Patent EP 210 929 A discloses certain 2-aryl-naphthalene derivatives useful in dermatological and ophthalmologycal medicaments. Intermediates leading to the synthesis of these compounds include certain arylethenyl benzene derivatives.
German Patent DE 3531 722 A discloses certain benzonorbornene derivatives which have vitamin A like activity.
Great Britain patent GB 2164-938 A discloses certain 2-styryl-naphthalene derivatives having retinoid like activity. An example of the compounds is 2-(4-methyl-&bgr;-methyl-styryl)naphthalene.
U.S. Pat.
Allergan Inc.
Baran Robert J.
Johnson Brent A.
Spivack Phyllis G.
Voet Martin A.
LandOfFree
Method of treatment with compounds having retinoid-like... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method of treatment with compounds having retinoid-like..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method of treatment with compounds having retinoid-like... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3038740