Bis-arylsulfones

Details Bis-arylsulfones Bis-arylsulfones

2001-10-02

2003-07-01

Coleman, Brenda (Department: 1624)

Organic compounds -- part of the class 532-570 series

Organic compounds

Unsubstituted hydrocarbyl chain between the ring and the -c-...

C382S131000, C424S009370, C424S009440

Reexamination Certificate

active

06586592

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to novel bis-arylsulfone derivatives, and more specifically, relates to bis-arylsulfone compounds of formula I described herein below. These compounds are 5-HT receptor ligands and are useful for treating diseases wherein modulation of 5-HT activity is desired.
BACKGROUND OF THE INVENTION
Serotonin has been implicated in a number of diseases and conditions that originate in the central nervous system. These include diseases and conditions related to sleeping, eating, perceiving pain, controlling body temperature, controlling blood pressure, depression, anxiety, schizophrenia, and other bodily states. Serotonin also plays an important role in peripheral systems, such as the gastrointestinal system, where it has been found to mediate a variety of contractile, secretory, and electrophysiologic effects.
As a result of the broad distribution of serotonin within the body, there is a tremendous interest in drugs that affect serotonergic systems. In particular, agonists, partial agonists and antagonists are of interest for the treatment of a wide range of disorders, including anxiety, depression, hypertension, migraine, obesity, compulsive disorders, schizophrenia, autism, neurodegenerative disorders (e.g. Alzheimer's disease, Parkinsonism, and Huntington's chorea), and chemotherapy-induced vomiting.
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 subtypes (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 is 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.
Generally, compounds of the present invention are 5-HT ligands. In particular, they can selectively bind to the 5-HT
6
receptor (e.g. receptor-specific agonists or antagonists). Thus, they are useful for treating diseases wherein modulation of 5-HT activity, specifically 5-HT
6
activity, is desired. Therefore, the compounds of this invention are useful for the treatment of diseases or disorders of the central nervous system. More specifically, for the treatment of psychosis, paraphrenia, psychotic depression, mania, schizophrenia, schizophreniform disorders, anxiety, migraine headache, drug addiction, convulsive disorders, personality disorders, post-traumatic stress syndrome, alcoholism, panic attacks, obsessive-compulsive disorders, and sleep disorders. The compounds of this invention are also useful to treat psychotic, affective, vegetative, and psychomotor symptoms of schizophrenia and the extrapyramidal motor side effects of other antipsychotic drugs. This last action will allow higher doses of antipsychotics to be used and thus greater antipsychotic efficacy to be obtained as a result of a reduction in side effects. The compounds of this invention are also useful in the modulation of eating behavior and thus are useful in treating excess weight and associated morbidity and mortality.
INFORMATION DISCLOSURE
U.S. Pat. No. 5,627,077 discloses aniline compounds useful in making mineral oils.
U.S. Pat. No. 4,851,423 discloses pharmaceutically active compounds having antiviral and antiinflammatory.
PCT International Publication WO 99/37623 discloses novel compounds having pharmacological activity for the treatment of CNS disorders.
PCT International Publication WO 99/47516 discloses 3-(2-pyrrolidinylmethyl)-indole compound having 5-HT6 affinity.
PCT International Publication WO 99/42465 discloses novel sulphonamide derivatives having CNS activity.
PCT International Publication WO 99/02502 discloses novel compounds having pharmacological activity for the treatment of CNS disorders.
PCT International Publication WO 93/17682 discloses angiotensin II receptor antagonists.
PCT International Publication WO 92/06683 discloses pharmaceutical compositions having anti-retrovirus activity.
PCT International Publication WO 92/20642 discloses bis or mono bicyclic aryl and/or heteroaryl compounds exhibiting protein tyrosine kinase inhibition activity.
Abstract of PCT International Publication WO 92/9408956A discloses compounds useful for depress blood lipid levels.
Abstract of JO 3056-431-a discloses diphenyl compounds having analgesic, anti-inflammatory, anti-rheumatic, and anti-nephritic activity.
Abstract of JP 07033735-A discloses diphenyl-sulphone compounds useful for treating inflammation, allergies and asthma.
Abstract of WO 9318035 discloses angiotensin II receptor containing fused heterocycle and two phenyl rings.
Abstract of WO 9707790 discloses compounds containing diphenyl for treating infectious infectious diseases such as malaria.
SUMMARY OF THE INVENTION
The present invention provides novel compounds of formula I:
Or a pharmaceutically acceptable salt thereof wherein
R
1
is H, C
1-12
alkyl, C
1-6
alkylaryl, or aryl; each R
2
is independently H, C
1-12
alkyl, C
1-12
alkenyl, halo, NO
2
, CN, CF
3
, or OR
1
; each R
3
is independently H, C
1-12
alkyl, C
1-12
alkenyl, or R
4
; R
4
is halo, NO
2
, CN, CF
3
, OR
1
, CON R
1
R
1
, NHSO
2
R
1
, NR
1
R
1
, NR
1
COR
1
, SO
2
N R
1
R
1
, C(═O)R
1
, CO
2
R
1
, or S(O)
i
R
1
; each R
5
is independently H, C
1-6
alkyl, C
1-6
alkylaryl, aryl, C(═O)R
1
, S(O)
2
R
1
, C(O)NR
1
R
1
, CO
2
R
1
, or CSR
1
; at each occurrence, alkyl, alkenyl, alkyaryl or aryl is optionally substituted with one or more R
4
;
i is 0, 1, or 2; m is 1, 2 or 3; and n is 1, 2, 3, 4, or 5.
The present invention further provides novel compounds of formula II:
Or a pharmaceutically acceptable salt thereof wherein R
6
is H, or C
1-4
alkyl; R
7
is H, halo, C
1-4
alkyl, or NR
6
R
6
; R
8
is H, halo, or C
1-4
alkyl; and; each R
9
is independently H, C
1-4
alkyl, C(═O)R
10
, S(O)
2
R
10
, C(O)NR
10
R
10
, CO
2
R
10
, or CSR
10
; and each R
10
is independently H, C
1-12
alkyl, C
1-6
alkylaryl, or aryl.
The present invention further provides a pharmaceutical composition comprising a compound of formula I or II, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. In preferred embodiments, the composition preferably comprises a therapeutically effective amount of a compound of formula I or a pharmaceutically acceptable salt thereof.
The present invention further provides a method for treating a disease or condition in a mammal wherein a 5-HT receptor is implicated and modulation of a 5-HT function is desired comprising administering to the mammal a therapeutically effective amount of a compound of formula III
or a pharmaceutically acceptable salt thereof wherein
R
1
is H, C
1-12
alkyl, C
1-6
alkylaryl, or aryl; each R
2
is independently H, C
1-12
alkyl, C
1-

Affiliated with

Also associated with

Rating

Bis-arylsulfones does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Bis-arylsulfones, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Bis-arylsulfones will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3047490