Benzamidine derivatives
AssigneeAjinomoto Co., Inc.
InventorsMasaru Takayanagi, Kazuyuki Sagi, Tadakiyo Nakagawa, Masahiro Yamanashi, Takashi Kayahara, Shunji Takehana, Yumiko Fukuda, Mitsuo Takahashi, Masataka Shoji
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Abstract
Benzamidine derivatives of the following formulae or analogs thereof, i.e., pharmaceutically acceptable salts thereof, are provided. These compounds or salts thereof have a blood-coagulation inhibiting effect based on an excellent effect of inhibiting the action of activated blood coagulation factor X, and they are useful as anticoagulants
Claims32
A benzamidine compound of the formula (1) or a pharmaceutically acceptable salt thereof:
- wherein L represents a group of formula (2):
- wherein:
- W in formula (2) represents hydrogen or alkyl having 1 to 6 carbon atoms;
- X in formula (2) represents hydrogen methyl substituted by carboxyl;
- V represents phenyl or benzoyl, each of which is substituted;
- wherein the substituent for V is selected from the group consisting of carboxyl, carbamoyl, mono- or dialkylcarbamoyl having 2 to 7 carbon atoms, amidino, mono- or dialkylamidino having 2 to 7 carbon atoms, piperidyloxy, iminoalkylpiperidyloxy having 7 to 10 carbon atoms, pyrrolidyloxy, piperidylalkyl having 6 to 9 carbon atoms, pyrrolidinyl, pyrrolidinylcarbonyl, pyrrolidinylsulfonyl, and pyridinylethyl;
- Y represents a group of any of the following formulae (7), (8), (9), (10) and (11):
- wherein n in formula (7) and (8) represents an integer of 1 to 3;
- and
- Z represents a group of formula (12-2):
- wherein R5 represents hydrogen or alkyl having 1 to 6 carbon atoms.
A benzamidine compound or pharmaceutically acceptable salt thereof, which is selected from the group consisting of
- (3R)-3-(4-amidinobenzoylamino)-4-[5-amidino-2-(2-carboxy-2-oxoethyl)phenoxy]butanoic acid;
- (3R)-4-[5-amidino-2-(2-carboxy 2-oxoethyl)phenoxy]-3-(4-dimethylcarbamoylbenzoylamino)butanoic acid;
- (3R)-4-[5-amidino-2-(2-carboxy-2-oxoethyl)phenoxy]-3-(4-carboxybenzoylamino)butanoic acid;
- (3R)-4-[5-amidino-2-(2-carboxy-2-oxoethyl)phenoxy]-3-[4-(pyrrolidine-1-carbonyl)benzoylamino]butanoic acid;
- (3R)-4-[5-amidino-2-(2-carboxy-2-oxoethyl)phenoxy]-3-[4-(1-(1-iminoethyl)piperidyl-4-oxy)benzoylamino]butanoic acid;
- (3R)-4-[5-amidino-2-(2-carboxy-2-oxoethyl)phenoxy]-3-[4-pyrrolidine-1-sulfonyl)benzoylamino]butanoic acid;
- and
- pharmaceutically acceptable salts thereof.
A compound of the formula 3-[4-amidino-2-[2-[4-(1-acetimidoyl-4-piperidyloxy)benzoylamino]ethoxy]phenyl]-2-oxopropionic acid or a pharmaceutically acceptable salt thereof.
A benzamidine compound of the formula (1) or a pharmaceutically acceptable salt thereof:
- wherein L represents a group of formula (2):
- wherein:
- W in formula (2) represents hydrogen or alkyl having 1 to 6 carbon atoms;
- X in formula (2) represents hydrogen;
- V represents benzoyl, which is substituted;
- wherein the substituent for V is selected from the group consisting of carboxyl, carbamoyl, mono- or dialkylcarbamoyl having 2 to 7 carbon atoms, amidino, mono- or dialkylamidino having 2 to 7 carbon atoms, piperidyloxy, iminoalkylpiperidyloxy having 7 to 10 carbon atoms, piperidylalkyl having 6 to 9 carbon atoms, pyrrolidinyl, pyrrolidinylcarbonyl pyrrolidinylsulfonyl, and pyridinylethyl;
- Y represents a group of the formula —CH2—O—;
- and
- Z represents a group of formula (12-2):
- wherein R5 represents hydrogen or alkyl having 1 to 6 carbon atoms.
Dependencies are inferred from the claim text.