Hyperproliferative diseases

US patent 6,734,308, Crystal forms of 6-[(4-chloro-phenyl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-methyl]-4-(3-ethynyl-phenyl)-l-methyl-lH-quinolin-2-one, 2,3,-dihydroxy-butanedioate salts and method of production [108]. The invention relates to crystal forms of 6-[(4-chloro-phenyl)-hydroxy-(3-methyl-3H-imidazol-4-yl)-meth-yl]-4-(3-ethynyl-phenyl)-1 -methyl-lH-quinolin-2-one, 2,3-dihydroxy butanedioate salts, and to pharmaceutical compositions containing the above compound, methods of treating hyperproliferative diseases, such as cancers, in mammals, especially humans by administering the above compound, and to methods of preparing the crystal forms of the above compound and related compounds. 

Benzothiazole derivatives, (II), prepared by Scott (2) were useful as tyrosine inhibitor kinases and used in the treatment of hyperproliferative diseases, especially cancer. 

Photochemotherapy is an efficient way to treat hyperproliferative diseases. Especially the so-called PUVA therapy (psoralen + UVA light) is very common in which the psoralen is irradiated with UVA light to give rise to a covalent adduct with the pyrimidine bases of DNA by means of a photoaddition reaction. There are several undesired side effects for the patients as a result of this therapy, so the synthesis and photobiological evaluation of novel benzosporalen derivatives was undertaken by the research team of L.D. Via. The key step in their synthetic sequence was the von Pechman reaction of 2-methoxyresorcinol with ethyl 2-oxocyclohexanecarboxylate. 

One of the aptamers significantly reduced intradermal VEGF-induced vascular permeability in vivo. Thus, these nuclease-resistant molecules may be useful for the development of novel pharmaceutical lead compounds for epithelial hyperproliferative diseases. 

Recently, low humidity has been shown to stimulate epidermal DNA synthesis and to amplify the hyperproliferative response to barrier disruption.30,31 SC morphology was also influenced by a dry environment,32 and abnormal desquamation was observed under low humidity.33 These results suggest that this model system, that is, dry skin induced by dry environment, is also an important model for clinical research of skin diseases associated with skin surface dryness. 

Groves RW, Rauschmayr T, Nakamura K, et al. Inflammatory and hyperproliferative skin disease in mice that express elevated levels of the IL-l receptor... 

Retinoids are used in the treatment of diverse diseases and are effective in the treatment of inflammatory skin disorders, skin mahgnancies, hyperproliferative disorders, photoaging, and many other disorders. Topical retinoids can normalize disordered keratinization in sebaceous folhcles and reduce inflammation, and they may enhance the penetration of other topical medications. Specific retinoids and their uses in the treatment of dermatologic disorders are discussed below. 

It may at first appear paradoxical that diseases such as psoriasis and lamellar ichthyosis, which are characterized by a hyperproliferative epidermis, can benefit from dmgs such as the retinoids, which can stimulate epidermal proliferation under certain experimental conditions. However, when tested in patients with psoriasis, etretinate led to decreased ornithine decarboxylase activity, decreased levels of urinary and cutaneous polyamines, and decreased epidermal DNA synthesis (Kaplan et al., 1983). 

Thus bile acids, bacteria, food and chromic inflammatory disease could promote intestinal neoplasia by stimulating epithelial cell renewal. Indeed, hyperproliferative changes can be detected in premalignant colonic mucosa, both in rodents exposed to chemical carcinogens and in patients with familial polyposis coil[45,46]. 

The cutaneous phototoxicity of a-terthienyl was studied in guinea pig skin, both in vitro and in vivo 203). Effective penetration through the epidermis and superficial dermis produced cutaneous photosensitization comparable to that of intradermally administered a-terthienyl. Phototoxicity was accompanied by a corresponding inhibition of epidermal DNA synthesis in normal and hyperproliferative skin. The authors suggested that a-terthienyl might provide a selective and safer alternative to coal tar and furanocoumarin derivatives for the treatment of psoriasis and other cutaneous diseases by photosensitization. However, no clinical studies in this direction have yet been published. 

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