The treatment of pain conditions is of great importance in medicine. There is currently a world-wide need for additional pain therapy. The pressing requirement for a specific treatment of pain conditions is documented in the large number of scientific works that have appeared recently in the field of applied analgesics.
PAIN is defined by the International Association for the Study of Pain (IASP) as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” (IASP, Classification of chronic pain, 2nd Edition, IASP Press (2002), 210). Although it is a complex process influenced by both physiological and psychological factors and is always subjective, its causes or syndromes can be classified. Pain can be classified based on temporal, aetiological or physiological criteria. When pain is classified by time, it can be acute or chronic. Aetiological classifications of pain are malignant or non-malignant. A third classification is physiological, which includes nociceptive pain (results from detection by specialized transducers in tissues attached to A-delta and C-fibres), that can be divided into somatic and visceral types of pain, and neuropathic pain (results from irritation or damage to the nervous system), that can be divided into peripheral and central neuropathic pain. Pain is a normal physiological reaction of the somatosensory system to noxious stimulation which alerts the individual to actual or potential tissue damage. It serves a protective function of informing us of injury or disease, and usually remits when healing is complete or the condition is cured. However, pain may result from a pathological state characterized by one or more of the following: pain in the absence of a noxious stimulus (spontaneous pain), increased duration of response to brief stimulation (ongoing pain or hyperpathia), reduced pain threshold (allodynia), increased responsiveness to suprathreshold stimulation (hyperalgesia), spread of pain and hyperalgesia to uninjured tissue (referred pain and secondary hyperalgesia), and abnormal sensations (e.g., dysesthesia, paresthesia).
WO2006021462 and WO2007098953 describe pyrazole-containing compounds useful in the therapy of pain, in general, and, more particularly, in treatment of neuropathic pain or allodynia. These compounds have the following chemical structure:

On another front, opioids and opiates are potent analgesics widely used in clinical practice. Opiates refer to alkaloids extracted from poppy pods (Opium Poppy; Papaver Somniferum) and their semi-synthetic counterparts which bind to the opioid receptors. Basically to be called an opiate one has to either be a natural opioid receptor agonist or start the refining process with one of the natural alkaloid molecules. Once chemically altered, such as the process of converting morphine into heroin, the drug is then labeled as a semi-synthetic opiate or semi-synthetic opioid—the terms can be used interchangeably. Semi-synthetic opiates (or semi-synthetic opioids) include heroin (diamorphine), oxycodone, hydrocodone, dihydrocodiene, hydromorphone, oxymorphone, buprenorphine and etorphine. In contrast, opioid is a blanket term used for any drug which binds to the opioid receptors. Opioids include all of the opiates as well as any synthesized drug that bind to opioid receptors. Synthetic opioids include methadone, pethidine, fentanyl, alfentanil, sufentanil, remifentanil, carfentanyl, tramadol, tapentadol and loperamide.
Opioid analgesics are recommended for the management of moderate to severe pain including that which occurs following surgery and trauma and in many patients with cancer.
In spite of this background, there is still a need in the art to provide alternative compounds useful in the therapy of pain, in general, and more particularly, in the treatment of neuropathic pain or allodynia. Likewise, it would be highly desirable to dispose of new compounds which potentiate the analgesic effect of opioids and opiates.
USPTO Backgrounds
USPTO Backgrounds