Inhibition of the binding human IgE to its receptor by tetracyclic compounds for the alleviation of IgE-mediated immune response
AssigneeHeska Corporation
InventorsY.-S. Edmond Cheng, Yuan Liu, John Chu, Jean-Pierre Kinet, Marie-Helene Jouvin, Yukio Sudo, Xiuqi Qian
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Abstract
Disclosed are chemical agents with unexpected activity to inhibit the interactions between human immunoglobulin E (IgE) and its receptor (Fc.epsilon.RI) which interactions are known to be involved in triggering allergic responses. The agents may be used to module the allergic response in the treatment of various clinical conditions, including rhinitis, asthma, urticaria, atopic dermatitis, and anaphylacric shock. The agents can be formulated for oral, topical or parenteral administration.
Claims24
A method of antagonizing the interaction between IgE and Fc.epsilon.RI on a surface of a mammalian cell bearing Fc.epsilon.RI comprising the step of contacting the cell with an IgE antagonizing amount of a compound having the formula:
- ##STR16## wherein the atom or group represented by each of R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6 is the same or different and is independently selected from the group consisting of hydrogen, hydroxyl, and a halogen;
- R.sup.7 is hydrogen, a pharmaceutically acceptable metal ion, an arylcarbonyl group or an alkylcarbonyl group having 1 to 6 carbon atoms;
- wherein the atom or group represented by each of R.sup.11, R.sup.12, R.sup.13, and R.sup.14 is the same or different and is independently selected from the group consisting of hydrogen, and a halogen;
- and
- R.sup.10 is independently selected from the group consisting of an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, an alkoxycarbonyl group having 1 to 6 carbon atoms, a carboxy group, an alkylcarbonyl group having 1 to 6 carbon atoms, an alkylsulfonyl group having 1 to 6 carbons atoms, sulfo;
- and salts thereof.
A method of antagonizing the interaction between IgE and Fc.epsilon.RI in vitro comprising the step of contacting said IgE and Fc.epsilon.RI with an IgE antagonizing amount of a compound having the formula:
- wherein the atom or group represented by each of R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.10, R.sup.11, R.sup.12, R.sup.13, and R.sup.14 is the same or different and is independently selected from the group consisting of hydrogen, hydroxyl, nitro, cyano, isothiocyano, a halogen, a sulfo group, a phospho group, an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, an alkoxycarbonyl group having 1 to 6 carbon atoms, a carboxy group, an alkylcarbonyl group having 1 to 6 carbon atoms, an aminocarbonyl group, an alkylaminocarbonyl group having 1 to 6 carbon atoms, an acylamino group, an alkylamino group having 1 to 6 carbon atoms, a dialkylamino group, an alkylurea group having 1 to 6 carbon atoms, an alkylsulfonyl group having 1 to 6 carbons atoms, an alkylsulfonylamino group having 1 to 6 carbon atoms, and salts thereof;
- and
- R.sup.7 is hydrogen, a pharmaceutically acceptable metal ion, an arylcarbonyl group or an alkylcarbonyl group having 1 to 6 carbon atoms.
Dependencies are inferred from the claim text.