ANTICOAGULANT REVERSAL AGENTS
Novel anticoagulant reversal compounds are disclosed, as well as methods of making the compounds, pharmaceutical compositions including the compounds, methods of using the compounds to reverse the anticoagulant effects of coagulation inhibitors, and diagnostic assays comprising the compounds.
1 . A compound of formula I:
Y-M-X-L-A-L′-X′-M′-Y′ (I)
or a pharmaceutically acceptable salt thereof,
wherein:
A is a substituted or unsubstituted heterocyclic ring selected from the group consisting of benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzoxazolinyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazolinyl, carbazolyl, 4aH carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 2H,6H-1,5,2-dithiazinyl, dihydrofuro[2,3 b]tetrahydrofuran, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolenyl, indolinyl, indolizinyl, indolyl, 3H-indolyl, isatinoyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, methylenedioxyphenyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl, oxazolyl, oxindolyl, pyrimidinyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathinyl, phenoxazinyl, phthalazinyl, diketopiperazinyl, piperidinyl, piperidonyl, 4-piperidonyl, piperonyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazole, pyridoimidazole, pyridothiazole, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thiophenyl, and xanthenylor a linear moiety;
L and L′ are the same or different and are selected from a substituted or unsubstituted alkylene chain;
X and X′ are —NH—C(═O);
M and M′ are the same or different and are selected from a substituted alkylene chain; and
Y and Y′ are the same or different and are a moiety containing one or more cationic atoms or groups or one or more groups that become cationic under physiological conditions.
2 - 9 . (canceled)
10 . The compound of claim 1 , wherein L and L′ are each a substituted or unsubstituted C 1 to C 10 alkylene chain.
11 . The compound of claim 10 , wherein M and M′ are each a substituted C 1 to C 10 alkylene chain.
12 . The compound of claim 11 , wherein M and M′ are substituted by a substituent independently selected from the group consisting of alkyl, hydroxyl, hydroxyl alkyl, amino, amino alkyl, alkoxy, and alkyl alkoxy.
13 . The compound of claim 12 , wherein Y and Y′ are each a guanidine moiety.