Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing
Reexamination Certificate
2001-04-05
2003-07-01
Davis, Brian (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Amino nitrogen containing
C564S363000, C564S364000, C564S366000, C514S649000, C514S653000, C514S655000
Reexamination Certificate
active
06586633
ABSTRACT:
TECHNICAL FIELD
The present invention relates to novel amine derivatives exhibiting excellent antifungal activity.
BACKGROUND ART
These days, an increased number of victims suffer from superficial mycosis, led by athlete's foot. However, no reliable therapy or remedy therefor has yet been established. Thus, superficial mycosis is counted as a disease that has not yet been overcome by modern medicine. Extensive efforts have heretofore been made in an attempt toward discovery of remedies therefor, and numerous compounds have been screened for their potential antifungal action. Regrettably, not a few compounds that have been confirmed to exhibit activity in vitro or in animals are found unsatisfactory when used in actual clinical settings, and therefore, only a limited number of compounds yield satisfactory results.
In view of the foregoing, an object of the present invention is to provide novel compounds exhibiting excellent antifungal activity.
DISCLOSURE OF THE INVENTION
Under the above-described situation, the present inventors have performed extensive studies, and have found that amine derivatives represented by the below-described formula (1) exhibit excellent antifungal activity, leading to completion of the invention.
Accordingly, the present invention provides an amine derivative of formula (1):
(wherein R
1
represents a C1-C4 linear, branched, or cyclic alkyl group; R
2
represents a group represented by (i), (ii), or (iii);
R
3
represents a C1-C3 linear, branched, or cyclic alkyl group, a hydroxylated C1-C5 linear, branched, or cyclic alkyl group, a C1-C5 linear, branched, or cyclic acyl group, a C2-C5 linear, branched, or cyclic alkenyl group, or a halogen atom;
R
3
in the number of m may be identical to or different from one another; k, l, and m are each an integer of 1 to 4; and
R
4
represents a C1-C4 linear alkyl group or phenyl group) and a salt thereof.
The present invention also provides an antifungal agent comprising the amine derivative of formula (1) or a salt thereof.
The present invention also provides an antifungal composition comprising the amine derivative of formula (1) or a salt thereof.
The present invention also provides a drug comprising, as an active ingredient, the amine derivative of formula (1) or a salt thereof.
The present invention also provides a pharmaceutical composition comprising the amine derivative of formula (1) or a salt thereof, and a pharmaceutically acceptable carrier.
The present invention also provides use, as a drug, of the amine derivative of formula (1) or a salt thereof.
The present invention also provides a method for the treatment of a fungal infectious disease through administration of the amine derivative of formula (1) or a salt thereof to a patient in need thereof.
Best Mode for Carrying Out the Invention
The amine derivatives according to the present invention are represented by the aforementioned formula (1). In the formula, examples of R
1
representing a C1-C4 linear, branched, or cyclic alkyl group include, but are not limited to, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, a cyclopropyl group, an n-butyl group, a sec-butyl group, an isobutyl group, a tert-butyl group, and a cyclobutyl group. Of these groups, C1-C3 groups; particularly, methyl, ethyl, isopropyl, and cyclopropyl groups are preferred.
R
2
is a group represented by (i), (ii), or (iii), with (i) and (ii) being particularly preferred.
Of the groups represented by R
3
, examples of C1-C3 linear, branched, or cyclic alkyl groups include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, and a cyclopropyl group. Of these groups, a methyl group is preferred.
Examples of preferred hydroxylated C1-C5 linear, branched, or cyclic alkyl groups include a 1-hydroxy-1-methyl ethyl group, and a 1,2-dimethyl-1-hydroxypropyl group.
Examples of the C1-C5 linear, branched, or cyclic acyl groups include a formyl group and a C2-C5 alkanoyl group. Of these groups, a formyl group, an acetyl group, and a propionyl group are preferred.
Examples of preferred ones of the C2-C5 linear, branched, or cyclic alkenyl groups include a vinyl group, an isopropenyl group, a 2-methyl-1-propenyl group, a 1-ethylvinyl group, a 1-methyl-1-propenyl group, and a 1-isopropylvinyl group.
Examples of the halogen atoms include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
Preferred examples of R
3
include, among others, a methyl group, a 1-hydroxy-1-methylethyl group, a 1,2-dimethyl-1-hydroxypropyl group, a 1-hydroxypropyl group, a formyl group, an acetyl group, a propionyl group, a vinyl group, an isopropenyl group, a 2-methyl-1-propenyl group, a 1-ethylvinyl group, a 1-methyl-1-propenyl group, a 1-isopropyl vinyl group, a fluorine atom, and a bromine atom.
R
3
groups appearing in the number of m may be identical to or different from one another.
Of the R
3
groups, at least one group is preferably a C2-C5 linear, branched, or cyclic alkenyl group; particularly, a vinyl group, an isopropenyl group, a 2-methyl-1-propenyl group, a 1-ethylvinyl group, a 1-methylpropenyl group, or a 1-isopropylvinyl group.
k, l, and m are each independently an integer of 1 to 4. Preferably, k is 1, l is 1, and m is 1-3.
R
4
represents a C1-C4 linear alkyl group or phenyl group. Particularly, a methyl group and a phenyl group are preferred.
Specific examples of preferred amine derivatives of formula (1) include the following.
Trans-3′-[N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methylaminomethyl]acetophenone,
Trans-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-(3-isopropenylbenzyl)amine,
Cis-3′-[N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methylaminomethyl]acetophenone,
Cis-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-(3-isopropenylbenzyl)amine,
Trans-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-(3-bromobenzyl)amine,
Trans-3-[N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methylaminomethyl]benzaldehyde,
Trans-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-(3-vinylbenzyl)amine,
Trans-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-[3-(2-methyl-1-propenyl)benzyl]amine,
Trans-3′-[N-cyclopropyl-N-(6,6-dimethyl-2-hepten-4-ynyl)aminomethyl]acetophenone,
Trans-N-cyclopropyl-N-(6,6-dimethyl-2-hepten-4-ynyl)-(3-isopropenylbenzyl)amine,
Trans-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-(3-bromo-5-methylbenzyl)amine,
2-[3-{N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methylaminomethyl}-5-methylphenyl]-2-propanol,
Trans-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-(3-isopropenyl-5-methylbenzyl)amine,
2-[3-{N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methylaminomethyl}phenyl]-3-methyl-2-butanol,
Trans-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-[3-(1-isopropylvinyl)benzyl]amine,
Trans-3′-[N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methylaminomethyl]propiophenone,
Trans-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-[3-(1-ethylvinyl)benzyl]amine,
Trans,cis-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-[3-(1-methyl-1-propenyl)benzyl]amine,
Trans-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-(3-bromo-4-fluorobenzyl)amine,
Trans-2-[2-fluoro-5-{N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methylaminomethyl}phenyl]-2-propanol,
Trans-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-(4-fluoro-3-isopropenylbenzyl)amine,
Trans-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-(5-bromo-2-methylbenzyl)amine,
Trans-2-[3-{N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methylaminomethyl}-4-methylphenyl]-2-propanol,
Trans-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-(5-isopropenyl-2-methylbenzyl)amine,
Trans-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-(2-bromobenzyl)amine,
2-[3-{N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methylaminomethyl}phenyl]-2-propanol,
Trans-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-(2-isopropenylbenzyl)amine,
Trans-3′-[N-(6,6-dimethyl-2-hepten-4-ynyl)-N-isopropylaminomethyl]acetophenone,
Trans-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-isopropyl-(3-isopropenylbenzyl)amine,
Trans-3′-[N-(6,6-dimethyl-2-hepten-4-ynyl)-N-ethylaminomethyl]acetophenone
Itoh Takao
Kawazu Yukio
Majima Toshiro
Nakashima Takuji
Nozawa Akira
Davis Brian
Pola Chemical Industries Inc.
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