Drug – bio-affecting and body treating compositions – Radionuclide or intended radionuclide containing; adjuvant... – In an organic compound
Reexamination Certificate
2002-08-01
2003-05-20
Jones, Dameron L. (Department: 1616)
Drug, bio-affecting and body treating compositions
Radionuclide or intended radionuclide containing; adjuvant...
In an organic compound
C424S001110, C424S001650, C424S001810, C424S001850, C424S009100, C424S009300, C424S009200, C548S400000, C548S414000, C548S416000, C514S183000, C514S410000
Reexamination Certificate
active
06565829
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to substituted 5-arylsulfonyl indoles and indolines which interact with serotonin receptors, such as 5-HT
6
receptors, and are useful for treating anxiety, depression, schizophrenia, stress-related disorders such as irritable bowel syndromes panic, a phobia, obsessive compulsive disorder, obesity, post-traumatic stress syndrome, epilepsy, and other central nervous system (CNS) disorders in humans and animals.
The major classes of serotonin receptors (5-HT
1-7
) contain fourteen to eighteen separate receptors that have been formally classified. See Glennon, et al., Neuroscience and Behavioral Reviews, 1990, 14, 35; and D. Hoyer, et al. Pharmacol. Rev. 1994, 46, 157-203. There is currently a need for pharmaceutical agents that are useful to treat diseases and conditions that are associated with 5-HT receptors. In particular, there is a need for agents that can selectively bind to individual receptor sub-types (e.g. receptor-specific agonists or antagonists); such agents would be useful as pharmaceutical agents, or would be useful to facilitate the study of the 5-HT receptor family, or to aid in the identification of other compounds that selectively bind to the specific 5-HT receptors.
For example, the 5-HT
6
receptor was identified in 1993 (Monsma et al. Mol. Pharmacol. 1993, 43, 320-327 and Ruat, M. et al. Biochem. Biophys. Res. Com. 1993, 193, 269-276). Several antidepressants and atypical antipsychotics bind to the 5-HT
6
receptor with high affinity and this binding may be a factor in their profile of activities (Roth et al. J. Pharm. Exp. Therapeut. 1994, 268, 1403-1410; Sleight et al. Exp. Opin. Ther. Patents 1998, 8, 1217-1224; Bourson et al. Brit. J. Pharm. 1998, 125, 1562-1566; Boess et al. Mol. Pharmacol. 1998, 54, 577-583; Sleight et al. Brit. J. Pharmacol. 1998, 124, 556-562). In addition, the 5-HT
6
receptor has been linked to generalized stress and anxiety states (Yoshioka et al. Life Sciences 1998, 17/18, 1473-1477). Together these studies and observations suggest that compounds that antagonize the 5-HT
6
receptor will be useful in treating disorders of the central nervous system, such as anxiety, depression, schizophrenia, stress-related disorders such as irritable bowel syndrome, panic, a phobia, obsessive compulsive disorder, obesity, post-traumatic stress syndrome, and epilepsy. In general, compounds of formula I exhibit selective inhibition of 5-HT
6
serotonin receptors relative to the inhibition of other 5-HT serotonin receptors.
General anxiety disorder (GAD) occurs when a person worries about things such as family, health, or work when there is no reason to worry and is unable not to worry. About 3 to 4% of the U.S. population has GAD during the course of a year. GAD most often strikes people in childhood or adolescence, but can begin in adulthood, too. It affects women more often than men. Currently, treatment involves cognitive-behavioral therapy, relaxation techniques, and biofeedback to control muscle tension and medications such as benzodiazepines, imipramine, and buspirone. These drugs are effective but all have side-effect liabilities. Therefore, there is a need of a pharmaceutical agent to address the symptoms with fewer side effects.
Depression is a mood disorder of varying lengths of normally several months to more than two years and of varying degrees of feelings involving sadness, despair, and discouragement. The heterocyclic antidepressants (HCA's) are currently the largest class of antidepressants, but monoamine oxidase inhibitors (MAOI's) are used in particular types of depression. Common side effects from HCA's are sedation and weight gain. In elderly patients with organic brain disease, the side effects from HCA's can also include seizures and behavioral symptoms. The main side effects from using MAOI's occur from dietary and drug interactions. Therefore, agents with fewer side effects would be useful.
Schizophrenia is a disease having multiple aspects. Currently available drugs are generally aimed at controlling the positive aspects of schizophrenia, such as delusions. One drug, Clozapine, is aimed at a broader spectrum of symptoms associated with schizophrenia. This drug has many side effects and is thus not suitable for many patients. Thus, there is a need for a drug to treat the cognitive and attention deficits associated with schizophrenia. Similarly, there is a need for a drug to treat the cognitive and attention deficits associated with schizoaffective disorders, or similar symptoms found in the relatives of schizophrenic patients.
Post-traumatic stress disorder (PTSD) is a form of anxiety triggered by memories of a traumatic event that directly affected the patient or that the patient may have witnessed. The disorder commonly affects survivors of traumatic events including sexual assault, physical assault, war, torture, natural disasters, an automobile accident, an airplane crash, a hostage situation, or a death camp. The affliction also can affect rescue workers at an airplane crash or a mass shooting, someone who witnessed a tragic accident or someone who has unexpectedly lost a loved one. Treatment for PTSD includes cognitive-behavioral therapy, group psychotherapy, and medications such as Clonazepam, Lorazepam and selective serotonin-reuptake inhibitors such as Fluoxetine, Sertraline, Paroxetine, Citalopram and Fluvoxamine. These medications help control anxiety as well as depression. Various forms of exposure therapy (such as systemic desensitization and imaginal flooding) have all been used with PTSD patients. Exposure treatment for PTSD involves repeated reliving of the trauma, under controlled conditions, with the aim of facilitating the processing of the trauma. Therefore, there is a need for better pharmaceutical agents to treat post-traumatic stress disorder.
Stress may increase the release of epinephrine from the adrenal medulla and norepinephrine from adrenergic neurons activated by central nervous system (CNS) stimulation. High levels of circulating epinephrine mediate alpha-adrenergic effects including increases in heart rate and cardiac output. Epinephrine may also be taken up by beta
2
receptors on the presynaptic neuronal membrane and may enhance release of norepinephrine from storage granules. Transient epinephrine surges resulting from stress may produce considerably more prolonged vasoconstriction. Stress-induced activation of the sympathetic nervous system may lead to hypertension. Stress also can cause stress gastritis and affect the efficacy of medical treatment in some ulcer patients. There is a need for pharmaceutical agents to treat stress-related diseases.
Panic disorders, phobias, and obsessive compulsive behavior are forms of neurosis. They are all related to excessive anxiety. All humans experience fear and anxiety in response to an external threat, or a difficult situation. However, the neuroses noted above, are abnormal responses to ordinary situations. The causes of such neurotic disorders are not fully known.
Anxiety can arise suddenly, as in panic, or gradually over many minutes, hours, or even days. Anxiety may last for variable periods of time ranging from less than a minute to years. Brief panic attacks are common. However, most persons recover without treatment, and panic disorder is much less common.
Phobias are similar to panic attacks in that they involve anxiety. However, in the various phobias the anxiety is not the free-floating anxiety of panic disorder, but instead focuses on specific situations or stimuli. Persons who have a phobia often realize that their anxiety is excessive, but nonetheless, they tend to avoid the situations or stimuli that disturb them. If they must be exposed to such situations or stimuli they endure them with great distress. Some relatively commonly observed phobias include agoraphobia, that is, the fear of being trapped in closed places, fear of snakes, fear of heights, fear of the dark, fear of strangers, fear of storms, fear of water, heights,
Hosley Mary J.
Jones Dameron L.
Pharmacia & Upjohn Company
LandOfFree
5-arylsulfonyl indoles useful for treating disease does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with 5-arylsulfonyl indoles useful for treating disease, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and 5-arylsulfonyl indoles useful for treating disease will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3058602