Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...
Patent
1982-09-16
1987-11-17
Brown, Johnnie R.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Nitrogen containing other than solely as a nitrogen in an...
514277, 514307, 514311, 514313, 514344, 514396, 514408, 514461, 514588, 514553, A61K 3117, A61K 3155, A61K 3147, A61K 3144
Patent
active
047074787
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention relates to a novel class of heterocyclic amidino substituted ureas and thioureas and their pharmaceutical use in methods for producing gastrointestinal, cardiovascular, and antiparasitic action, among others.
REPORTED DEVELOPMENTS
Phenylamidinoureas and their uses as antisecretory, antispasmodic, anti-ulcerogenic, anesthetic and antidiarrheal agents have been reported in Arzneimittel Forschung (Drug Research) 28 (II), 1433-1480 (1978), and U.S. Pat. Nos. 4,025,652, 4,058,557, 4,060,635, 4,088,785, 4,115,564, 4,115,647, 4,117,165, 4,147,804, 4,150,154, 4,169,155, 4,178,387, 4,204,000 and 4,220,658.
This invention relates to a class of heterocyclic amidino substituted urea and thiourea compounds which also possess valuable pharmaceutical properties.
SUMMARY OF THE INVENTION
This invention relates to the treatment of humans and animals afflicted with gastrointestinal disorders, spasmolytic disorders, ulcergenic disorders, cardiovascular disorders, diarrheal disorders, and parasitic infestations with compositions containing an effective amount of heterocylic amidino substituted urea or thiourea according to Formula I ##STR1## where: X is O or S; may include 1 to 4 hetero atoms of N, O or S; and containing a total of about 3 to about 20 carbon atoms; and the N- or S-oxides thereof; alkenyl, alkoxy or a heterocyclic group, or R.sub.5 and R.sub.6 together with the nitrogens to which they are attached form a 3 to 7 atom ring which may include 0 to 2 additional hetero atoms of N, O or S; and the nontoxic acid addition salts thereof.
DETAILED DESCRIPTION OF THE INVENTION
This invention also relates to novel compounds which are useful in these methods and include those according to Formula I where: to 3 hetero atoms of N, O or S; and N- and S-oxides thereof; lower alkoxy, or aralkyl or R.sub.5 and R.sub.6 together with the nitrogen to which they are attached form a 3 to 7 atom heterocycle.
This invention further relates to a novel class of compounds according to Formula I, which are useful in the above methods, in which R.sub.1 is one of the following heterocylic groups: 1-pyrrole, 2-pyrrole, 3-pyrrole, 2-furan, 3-furan, 2-thiophene, 3-thiophene, 2-tetrahydrothiophene, 3-tetrahydrothiophene, 2-imidazole, 2-imidazole, 4-imidazole, 5-imidazole, 2-oxazole, 4-oxazole, 2-thiazole, 4-thiazole, 5-thiazole, 1-pyrazole, 3-pyrazole, 4-pyrazole, 5-pyrazole, 1-pyrrolidine, 2-pyrrolidine, 3-pyrrolidine, 1-(3-pyrroline), 2-(3-pyrroline), 3-(3-pyrroline), 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidine, 4-pyrimidine, 5-pyrimidine, 6-pyrimidine, 2-purine, 6-purine, 8-purine, 9-purine, 2-quinoline, 3-quinoline, 4-quinoline, 5-quinoline, 6-quinoline, 7-quinoline, 8-quinoline, 1-isoquinoline, 3-isoquinoline, 4-isoquinoline, 5-isoquinoline, 6-isoquinoline, 7-isoquinoline, 8-isoquinoline, or carbazole.
The heterocylic groups above may be mono-, di-, tri- or tetra-substituted by ring substituents, such as, halogen, lower alkyl, lower alkenyl, aryl, lower alkynyl, aralkyl, nitro, cyano, sulfonyl, hydroxyl, carboxyl, lower alkanoyl, lower alkoxy, aryl lower alkoxy, halo lower alkoxy, amido, amino, lower alkyl acyloxy, alkylamino, lower alkoxyamino, and aralkoxyamino.
A preferred embodiment of this invention is a compound according to Formulae II-IV ##STR2## m is zero to four; n is zero, one, two or three; pyridyl nitrogen atom; and
Another preferred embodiment of this invention is a compound according to Formula V or VI ##STR3## where: m is zero to three thiophene sulfur atoms, such as, thiophenylsulfoxide and thiophenyl sulfone;
A particularly preferred embodiment of this invention is a compound according to Formula II, III, IV, V and VI, wherein X, m, n, R, and R.sub.2 are as described above, and one of R.sub.5 and R.sub.6 are phenyl or substituted phenyl. The most preferred substituted phenyl groups are those which are ortho- and diortho-substituted.
In any discussion of the true structure of an amidinourea, tautomerism must be considered. It should be clear to anyone skilled in the art that
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Dodson Stuart A.
Studt William L.
Zimmerman Harry K.
Barron Alexis
Brown Johnnie R.
Nicholson James A.
Rollins Jr. John W.
Rorer Pharmaceutical Corporation
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