Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1993-03-11
1994-07-12
Rotman, Alan L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
546273, 546309, A61K 3144, C07D40112
Patent
active
053289226
DESCRIPTION:
BRIEF SUMMARY
This invention relates to compounds having pharmacological activity, to a process for their preparation, to compositions containing them and to their use in the treatment of mammals.
P. Fludzinski et. al., J. Med. Chem. 1986 29 2415-2418 describes N-(1,2-dimethyl-3-ethyl-1H-indol-5-yl)-N'-(3-trifluoromethylphenyl)urea which shows selectivity for the rat stomach fundus serotonin receptor.
A class of compounds has now been discovered, which compounds have been found to have 5HT.sub.1C receptor antagonist activity. 5HT.sub.1C receptor antagonists are believed to be of potential use in the treatment of CNS disorders such as anxiety, depression, obsessive compulsive disorders, migraine, anorexia, Alzheimers disease, sleep disorders, bulimia, panic attacks, withdrawal from drug abuse and/or schizophrenia.
Accordingly, the present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof: ##STR1## wherein:
R.sub.1, R.sub.2 and R.sub.3 are independently hydrogen or C.sub.1-6 alkyl;
R.sub.4 is hydrogen, C.sub.1-6 alkyl, halogen, hydroxy or NR.sub.8 R.sub.9 where
R.sub.8 and R.sub.9 are independently hydrogen or C.sub.1-6 alkyl;
R.sub.5 and R.sub.6 are independently hydrogen or C.sub.1-6 alkyl; and
R.sub.7 is hydrogen, C.sub.1-6 alkyl or halogen; and wherein the urea moiety is attached at the 4-, 5- or 6-position of the indole ring.
Alkyl moieties within the variables R.sub.1 to R.sub.9 are preferably C.sub.1-3 alkyl, such as methyl, ethyl, n- and iso- propyl, most preferably methyl, ethyl and n-propyl.
Suitable R.sub.4 and R.sub.7 halogens include chloro and bromo.
Examples of R.sub.1 include hydrogen, methyl, ethyl and n-propyl, preferably methyl. R.sub.2 is preferably methyl or hydrogen and R.sub.3 is hydrogen, methyl, ethyl, n-propyl, iso-propyl or n-hexyl.
Preferably R.sub.4 is hydrogen, chloro, hydroxy or dimethylamino, most preferably hydrogen.
Preferably R.sub.5, R.sub.6 and R.sub.7 are independently hydrogen or methyl.
The urea moiety may be attached at the 2-, 3-, 4-, 5- or 6-position of the pyridine ring, preferably the 3-, 4- or 5-position.
The urea moiety is preferably attached at the 4- or 5-position of the indole ring.
The compounds of the formula (I) can form acid addition salts with acids, such as conventional pharmaceutically acceptable acids, for example maleic, hydrochloric, hydrobromic, phosphoric, acetic, fumaric, salicylic, citric, lactic, mandelic, tartaric and methanesulphonic.
Compounds of formula (I) may also form solvates such as hydrates, and the invention also extends to these forms. When referred to herein, it is understood that the term `compound of formula (I)` also includes solvates thereof. When R.sub.5 and/or R.sub.6 are hydrogen or when R.sub.4 is 2- or 4-hydroxy or NR.sub.8 R.sub.9 and at least one of R.sub.8 and R.sub.9 are hydrogen the compounds of formula (I) may exist tautomerically in more than one form. The invention extends to each of these forms and mixtures thereof.
Certain compounds of formula (I) are capable of existing in stereoisomeric forms including enantiomers and the invention extends to each of these stereoisomeric forms and to mixtures thereof including racemates. The different stereoisomeric forms may be separated one from the other by the usual methods, or any given isomer may be obtained by stereospecific or asymmetric synthesis.
The present invention also provides a process for the preparation of a compound of formula (I) or a pharmaceutically acceptable salt thereof, which process comprises
(a) the coupling of a compound of formula (II); ##STR2## with a compound of formula (III); wherein B is attached at the 4-, 5- or 6-position of the indole ring and A and B contain the appropriate functional group(s) necessary to form the moiety --NR.sub.5 'CONR.sub.6 '- when coupled, wherein R.sub.5 ' and R.sub.6 ' are R.sub.5 and R.sub.6 as defined in formula (I) or groups convertible thereto, and the variables R.sub.1 ', R.sub.2 ', R.sub.3 ', R.sub.4 ' and R.sub.7 ' are R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.7 respectively, as d
REFERENCES:
patent: 4273782 (1981-06-01), Cross et al.
patent: 4346093 (1982-08-01), Friebe et al.
P. Fludinski et al., J. Med. Chem., 1986, 29, 2415.
Forbes Ian T.
Martin Roger T.
Beecham Group p.l.c.
Hall Linda E.
Lentz Edward T.
Rotman Alan L.
Suter Stuart R.
LandOfFree
Indole ureas as 5 ht receptor antagonist does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Indole ureas as 5 ht receptor antagonist, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Indole ureas as 5 ht receptor antagonist will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-396724