In bronchial asthma or chronic obstructive pulmonary disease (COPD), bronchoconstriction, airway inflammation, mucus secretion, coughing, and the like increase. Substance P or neurokinin A is associated with an airway contracting effect, an inflammatory effect, coughing, and mucus secretion. A compound that antagonizes receptors of both substance P and neurokinin A (a neurokinin NK1 receptor and a neurokinin NK2 receptor) may suppress the above-mentioned physiological effects (Non-Patent Documents 1 and 2). Although nonpeptidic low-molecular weight compounds that antagonize both the neurokinin NK1 receptor and the neurokinin NK2 receptor have been disclosed (Patent Documents 1 and 2), the use of the compounds as pharmaceuticals has not been approved. Meanwhile, acetylcholine exhibits a potent airway contracting effect by acting on a muscarinic M3 receptor (Non-Patent Document 3). Compounds that antagonize the muscarinic M3 receptor have a bronchodilating effect (Patent Documents 3, 4, and 5) and are used as bronchodilating agents (Non-Patent Document 4). It has been described that a bronchodilating effect which is more potent than the bronchodilating effect exhibited by antagonizing each of the receptors individually is exhibited by antagonizing both the muscarinic M3 receptor and the neurokinin receptors (Patent Document 6). However, since no compound that antagonizes the neurokinin NK1 receptor and the neurokinin NK2 receptor has been marketed as a therapeutic agent for bronchial asthma or COPD, single agents cannot be used in combination. There has been demand for a single compound which has potent bronchodilating, anti-inflammatory, antiussive, and expectorant effects by antagonizing all of the neurokinin NK1 receptor, the neurokinin NK2 receptor, and the muscarinic M3 receptor.
USPTO Backgrounds
USPTO Backgrounds