Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – Cyclic peptides
Reexamination Certificate
1999-02-11
2001-07-24
Davenport, Avis M. (Department: 1653)
Chemistry: natural resins or derivatives; peptides or proteins;
Peptides of 3 to 100 amino acid residues
Cyclic peptides
C514S009100, C514S011400
Reexamination Certificate
active
06265536
ABSTRACT:
TECHNICAL FIELD
The present invention relates to new polypeptide compound and a pharmaceutically acceptable salt thereof which are useful as a medicament.
BACKGROUND ART
In U.S. Pat. No. 5,376,634, there are disclosed the polypeptides compound and a pharmaceutically acceptable salt thereof, which have antimicrobial activities (especially antifungal activity).
DISCLOSURE OF INVENTION
The present invention relates to new polypeptide compound and a pharmaceutically acceptable salt thereof.
More particularly, it relates to new polypeptide compound and a pharmaceutically acceptable salt thereof, which have antimicrobial activities [especially, antifungal activities, in which the fungi may include Aspergillus, Cryptococcus, Candida, Mucor, Actinomyces, Histoplasma, Dermatophyte, Malassezia, Fusarium and the like.], inhibitory activity on &bgr;-1,3-glucan synthase, and further which are expected to be useful for the prophylactic and/or therapeutic treatment of
Pneumocystis carinii
infection (e.g.,
Pneumocystis carinii
pneumonia) in a human being or an animal, to a process for preparation thereof, to a pharmaceutical composition comprising the same, and to a method for the prophylactic and/or therapeutic treatment of infectious diseases including
Pneumocystis carinii
infection (e.g.
Pneumocystis carinii
pneumonia) in a human being or an animal.
The object polypeptide compound used in the present invention are new and can be represented by the following general formula [I] (SEQ ID NO:1):
wherein R
1
is lower alkanoyl substituted with unsaturated 6-membered heteromonocyclic group containing at least one nitrogen atom which may have one or more suitable substituent(s);
lower alkanoyl substituted with 1,2,3,4-tetrahydroisoquinoline which may have one or more suitable substituent(s);
lower alkanoyl substituted with unsaturated condensed heterocyclic group containing at least one oxygen atom which may have one or more suitable substituent(s);
lower alkanoyl substituted with unsaturated condensed heterocyclic group containing 1 to 3 sulfur atom(s) which may have one or more suitable substituent(s);
lower alkanoyl substituted with unsaturated condensed heterocyclic group containing 2 or more nitrogen atom(s) which may have one or more suitable substituent(s);
lower alkanoyl substituted with saturated 3 to 8 membered heteromonocyclic group containing at least one nitrogen atom which may have one or more suitable substituent(s);
ar(lower)alkenoyl substituted with aryl which may have one or more suitable substituent(s);
naphthyl(lower)alkenoyl which may have one or more higher alkoxy;
lower alkynoyl which may have one or more suitable substituent(s);
(C
2
-C
6
)alkanoyl substituted with naphthyl having higher alkoxy;
ar(C
2
-C
6
)alkanoyl substituted with aryl having one or more suitable subsitutent(s), in which ar(C
2
-C
6
)alkanoyl may have one or more suitable substituent(s);
aroyl substituted with heterocyclic group which may have one or more suitable substituent(s), in which aroyl may have one or more suitable substituent(s);
aroyl substituted with aryl having heterocyclic(higher)alkoxy, in which heterocyclic group may have one or more suitable substituent(s);
aroyl substituted with aryl having lower alkoxy(higher)alkoxy;
aroyl substituted with aryl having lower alkenyl(lower)alkoxy;
aroyl substituted with 2 lower alkoxy;
aroyl substituted with aryl having lower alkyl;
aroyl substituted with aryl having higher alkyl;
aryloxy(lower)alkanoyl which may have one or more suitable substituent(s);
ar(lower)alkoxy(lower)alkanoyl which may have one or more suitable substituent(s);
arylamino(lower)alkanoyl which may have one or more suitable substituent(s);
lower alkanoyl substituted with pyrazolyl which has lower alkyl and aryl having higher alkoxy;
lower alkoxy(higher)alkanoyl, in which higher alkanoyl may have one or more suitable substituent(s);
aroyl substituted with aryl having heterocyclicoxy, in which heterocyclicoxy may have one or more suitable substituent(s);
aroyl substituted with cyclo(lower)alkyl having lower alkyl;
indolylcarbonyl having higher alkyl; naphthoyl having lower alkyl; naphthoyl having higher alkyl; naphthoyl having lower alkoxy(higher)alkoxy;
aroyl substituted with aryl having lower alkoxy(lower)alkoxy(higher)alkoxy;
aroyl substituted with aryl having lower alkoxy(lower)alkoxy;
aroyl substituted with aryl which has aryl having lower alkoxy;
aroyl substituted with aryl which has aryl having lower alkoxy(lower)alkoxy;
aroyl substituted with aryl having heterocyclicoxy(higher)alkoxy;
aroyl substituted with aryl having aryloxy(lower)alkoxy;
aroyl substituted with aryl having heterocycliccarbonyl(higher)alkoxy;
lower alkanoyl substituted with oxazolyl which has aryl having higher alkoxy;
lower alkanoyl substituted with furyl which has aryl substituted with aryl having lower alkoxy;
lower alkanoyl substituted with triazolyl which has oxo and aryl having higher alkyl;
higher alkanoyl having hydroxy;
higher alkanoyl having ar(lower)alkyl and hydroxy;
3-methyl-tridecenoyl; or
(C
2
-C
6
)alkanoyl substituted with aryl having higher alkoxy, in which (C
2
-C
6
)alkanoyl may have amino or protected amino.
The new polypeptides compound [I] and a pharmaceutically acceptable salt thereof can be prepared by the process as illustrated in the following reaction scheme or can be prepared by elimination reaction of amino protective group in R
1
.
wherein R
1
is as defined above.
Suitable pharmaceutically acceptable salts of the object polypeptide compound [I] are conventional non-toxic salts and may include a salt with a base or an acid addition salt such as a salt with an inorganic base, for example, an alkali metal salt (e.g., sodium salt, potassium salt, etc.), in alkaline earth metal salt (e.g., calcium salt, magnesium salt, etc.), an ammonium salt, a salt with an organic base, for example, an organic amine salt (e.g., triethylamine salt, pyridine salt, picoline salt, ethanolamine salt, triethanolamine salt, dicyclohexylamine salt, N,N′-dibenzylethylenediamine salt, etc.); an inorganic acid addition salt (e.g., hydrochloride, hydrobromide, sulfate, phosphate, etc.); an organic carboxylic sulfonic acid addition salt (e.g., formate, acetate, trifluoroacetate, maleate, tartrate, fumarate, methanesulfonate, benzenesulfonate, toluenesulfonate, etc.); a salt with a basic or acidic amino acid (e.g., arginine, aspartic acid, glutamic acid, etc.).
In the above and subsequent descriptions of the present specification, suitable examples and illustration of the various definitions which the present invention intends to include within the scope thereof are explained in detail as follows.
The term “lower” is used to intend a group having 1 to 6 carbon atom(s), unless otherwise provided.
The term “higher” is used to intend a group having 7 to 20 carbon atoms, unless otherwise provided.
Suitable example of “one or more” may be the number of 1 to 6, in which the preferred one may be the number of 1 to 3.
Suitable example of “lower alkanoyl” may include straight or branched one such as formyl, acetyl, 2-methylacetyl, 2,2-dimethylacetyl, propionyl, butyryl, isobutyryl, pentanoyl, 2,2-diemthylpropionyl, hexanoyl, and the like.
Suitable example of “suitable substituent(s)” in the groups such as “lower alkanoyl substituted with unsaturated 6-membered heteromonocyclic group containing at least one nitrogen atom which may have one or more suitable substituent(s)”, “lower alkanoyl substituted with 1,2,3,4-tetrahydroisoquinoline which may have one or more suitable substituent(s)”, etc. may include lower alkoxy as mentioned below, higher alkoxy as mentioned below, lower alkyl as mentioned below, higher alkyl as mentioned below, higher alkoxy(lower)alkyl, lower alkoxycarbonyl, oxo, aryl which may have one or more lower alkoxy, aryl which may have one or more higher alkoxy, aryl which may have one or more lower alkyl, aryl which may have one or more higher alkyl, aryl substituted with aryl which may have one or more lower alkoxy, aryl substituted with aryl whi
Ohki Hidenori
Takasugi Hisashi
Tomishima Masaki
Yamada Akira
Davenport Avis M.
Fujisawa Pharmaceutical Co. Ltd.
Oblon & Spivak, McClelland, Maier & Neustadt P.C.
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