2-aminobenzamide derivative

Abstract

Disclosed is a novel and excellent therapeutic or prophylactic agent for nociceptive pain, neuropathic pain, cancer pain, headache, bladder dysfunction or the like, which relies on a preventive activity on capsaicin receptor VR1 activation. It is found that a benzamide derivative having a benzene ring fused with a monocyclic ring on a nitrogen atom in the amide group and an amino group substituted by a lower alkylamino or cyclic group at a position adjacent to the amide group has a potent preventive activity on VR1 activation and an excellent pharmacological activity relying on the preventive activity, and therefore the derivative can be used as a good therapeutic or prophylactic agent for a VR1-related disease, such as nociceptive pain, neuropathic pain, cancer pain, headache and bladder dysfunction.

Description

technical field The present invention relates to a novel 2-aminobenzamide derivative or a salt thereof useful as a drug, especially as an activation inhibitor of capsaicin receptor VR1 (Vanilloid Receptor 1), and a drug thereof. Background technique VR1 is a receptor present on primary afferent sensory nerves (mainly C fibers), involved in pain in various diseases. This receptor is activated by capsaicin, which is the main component of tang xinzi, causing pain. It is known that in VR1-deficient mice, not only the pain response induced by capsaicin disappears, but also hyperalgesia during inflammation is attenuated [Nature 405: 183-187 (2000)]. It is known that capsaicin causes pain by activating VR1 as described above, but due to continuous activation desensitizes the afferent nerve, and inhibits subsequent activation, it shows analgesic effect [Pharmacol.Rev.51: 159-211 (1999 ); Drugs Aging 18:561-573 (2001)]. In fact, capsaicin cream is used in the treatment of neuroge...

AI Technical Summary

Problems solved by technology

However, each document discloses the inhibition of angiogenesis due to VEGF inhibition, etc., but there is no description about the VR1 receptor and no description about the application to pain.

In addition, none of the documents disclose a compound in which the amino group at the 2-position is directly bonded to a monocyclic ring without passing through an alkylene chain.

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