Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1990-11-05
1992-12-29
Lee, Mary C.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
544333, 5483335, 548524, 548518, 548194, 548195, 548240, 548245, 5482644, 5483147, 5483127, 514402, 514400, 514371, 514378, 514380, 514383, 514399, 514340, 514341, 514256, 514397, 546275, 546276, C07D27704, C07D20730, C07D23354, A61K 3140, A61K 31415
Patent
active
051751828
DESCRIPTION:
BRIEF SUMMARY
The invention relates to acryloyl substituted pyrrole derivatives, to a process for their preparation and to pharmaceutical compositions containing them.
The pyrrole derivatives of the invention may be regarded as derivatives of Distamycin A which is a known compound having the following formula ##STR5## Literature referring to distamycin A includes, for examples Nature 203, 1064 (1964).
The invention provides acryloyl substituted pyrrole derivatives of the following formula (I) ##STR6## wherein n is an integer of 1 to 5; hydrogen, halogen, --CN, --NO.sub.2, C.sub.1 -C.sub.4 alkyl, or a group ##STR7## R.sub.3 is hydrogen, halogen, --CN, or --NO.sub.2 ; each R.sub.4 is, independently, hydrogen or C.sub.1 -C.sub.4 alkyl; ##STR8## or a group --NH--Het--CO--, wherein Het is a saturated or unsaturated pentatomic or hexatomic heteromonocyclic ring; and ##STR9## in which m is 1, 2 or 3 and each R.sub.5 is, independently, a C.sub.1 -C.sub.4 alkyl group.
The invention includes also the pharmaceutically acceptable salts of the compounds of formula (I) as well as the possible isomers covered by the formula (I), both separately and in mixture. In the above reported formula (I) ##STR10## or a group --NH--Het--CO--; B is preferably a group ##STR11## wherein m is preferably 1 and each R.sub.5 is methyl.
When A is a group --NH--Het--CO-- wherein Het represents a heteromonocyclic ring as defined above, this is, preferably, an unsaturated pentatomic or hexatomic heteromonocyclic ring containing at least one, preferably one or two, heteroatom chosen from O, S and N. Examples of said heteromonocyclics are thiophene, thiazole, pyridine, isoxazole, furane, triazole and imidazole.
When R.sub.1 and R.sub.2 are the same, they are, preferably, hydrogen.
When R.sub.1 and R.sub.2 are different, R.sub.1 is, preferably, hydrogen and R.sub.2 is, preferably, a halogen; the halogen is, preferably, chlorine or bromine.
When R.sub.3 is.halogen, it is, preferably, chlorine or bromine.
Preferably each group R.sub.4, independently, is C.sub.1 -C.sub.4 alkyl, in particular methyl and, most preferably, all groups R.sub.4 are methyl.
As already said, the invention includes also the pharmaceutically acceptable salts of the compounds of formula (I).
These salts are the salts with pharmaceutically acceptable acids, either inorganic acids such as e.g., hydrochloric, hydrobromic, nitric and sulfuric, or organic acids such as, e.g., citric, tartaric, maleic, fumaric, methanesulfonic and ethanesulfonic.
A preferred class of compounds under this invention is represented by the compounds of formula (I) wherein ##STR12## B is a group ##STR13## R.sub.1 and R.sub.2 are hydrogen; R.sub.3 is chlorine or bromine and R.sub.4 is methyl,
Specific examples of preferred compounds under this invention, especially in the form of salts with hydrochloric acid, are the following: lamido) pyrrole-2-carboxamido) pyrrole-2-carboxamido) pyrrole-2-carboxamido) pyrrole-2-carboxamido) propionamidine; mido) pyrrole-2-carboxamido) pyrrole-2-carboxamido) pyrrole-2-carboxamido) pyrrole-2-carboxamido) propionamidine; -bromoacrylamido) pyrrole-2-carboxamido) pyrrole-2-carboxamido) pyrrole-2-carboxamido) pyrrole-2-carboxamido) pyrrole-2-carboxamido) propionamidine; ) pyrrole-2-carboxamido) pyrrole-2-carboxamido) pyrrole-2-carboxamido) pyrrole-2-carboxamido) propyl-dimethylamine.
The compounds of formula (I) are prepared by a process comprising
A) reacting a compound of formula (II) ##STR14## wherein n, R.sub.4 and B are as defined above, or a salt thereof, with a compound of formula (III) ##STR15## wherein R.sub.1, R.sub.2, R.sub.3 and A are as defined above and X is hydroxy or a leaving group, so obtaining a compound of formula (I) or a salt thereof; or
B) reacting a compound of formula (IV) ##STR16## wherein Z is ##STR17## or H.sub.2 N--Het--CO--, and n, R.sub.4, B and Het are as defined above, or a salt thereof, with a compound of formula (V) ##STR18## wherein R.sub.1, R.sub.2, R.sub.3 and X are as defined above, so obtaining a compound of formula (I) wherein A is a group ##STR19##
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Biasoli Giovanni
Capolongo Laura
Mongelli Nicola
Pezzoni Gabriella
Farmitalia Carlo Erba Srl
Lee Mary C.
McKane Joseph K.
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