1. A method of treating a microbial infection in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of Formula (I):
wherein:
n is an integer from 1 to 8;
p and q are each independently integers from 0 to 3;
X1 and X2 are each independently selected from the group consisting of O, S, and NR5, wherein R5 is selected from the group consisting of H, alkyl, aryl, alkoxyl, and aryloxyl;
R1 and R2 are each independently selected from the group consisting of alkyl, halo, hydroxyl, alkoxyl, aryloxyl, and aralkyloxyl; and
R3 and R4 are each independently selected from the group consisting of:
wherein:
R6, R7, R8, and R9 are each independently selected from the group consisting of H, alkyl, cycloalkyl, aryl, aralkyl, hydroxyl, alkoxyl, hydroxyalkyl, hydroxycycloalkyl, alkoxycycloalkyl, aminoalkyl, acyloxyl, alkylaminoalkyl, and alkoxycarbonyl; or
R6 and R7 together represent a C2 to C10 alkyl, C2 to C10 hydroxyalkyl, or C2 to C10 alkylene.
2. The method of claim 1, wherein the microbial infection is selected from the group consisting of a Mycobacterium tuberculosis infection, a Leishmania donovani infection, a Trypanosoma brucei rhodesiense infection, a Trypanosoma cruzi infection, a Plasmodium falciparum infection, a Candida albicans infection, an Aspergillus fumigatus infection, and a Cryptococcus neoformans infection.
3. The method of claim 1, wherein:
X1 and X2 are both O;
X1 is at one of the 3\u2032-position and 4\u2032-position of ring A;
X2 is at one of the 3\u2033-position and 4\u2033-position of ring B;
n is an integer from 3 to 6;
R3 and R4 are each
R3 is at one of the 5-position and 6-position of ring C; and
R4 is at one of the 1\u2033-position and 2\u2033-position of ring B.
4. The method of claim 1, wherein:
X1 and X2 are both O;
X1 is at one of the 3\u2032-position and 4\u2032-position of ring A;
X2 is at one of the 3\u2033-position and 4\u2033-position of ring B;
n is an integer from 3 to 6;
R3 and R4 are each
R3 is at one of the 5-position and 6-position of ring C; and
R4 is at one of the 1\u2033-position and 2\u2033-position of ring B.
5. The method of claim 1, wherein:
X1 and X2 are both O;
X1 is at one of the 3\u2032-position and 4\u2032-position of ring A;
X2 is at one of the 3\u2033-position and 4\u2033-position of ring B;
n is an integer from 3 to 6;
R3 and R4 are each
R3 is at one of the 5-position and 6-position of ring C; and
R4 is at one of the 1\u2033-position and 2\u2033-position of ring B.
6. The method of claim 1, wherein:
X1 and X2 are both O;
X1 is at one of the 3\u2032-position and 4\u2032-position of ring A;
X2 is at one of the 3\u2033-position and 4\u2033-position of ring B;
n is an integer from 3 to 6;
R3 and R4 are each
R3 is at one of the 5-position and 6-position of ring C; and
R4 is at one of the 1\u2033-position and 2\u2033-position of ring B.
7. The method of claim 1, wherein:
X1 and X2 are both O;
X1 is at one of the 3\u2032-position and 4\u2032-position of ring A;
X2 is in one the 3\u2033-position and 4\u2033-position of ring B;
n is an integer from 3 to 6;
R3 and R4 are each
R3 is at one of the 5-position and 6-position of ring C; and
R4 is at one of the 1\u2033-position and 2\u2033-position of ring B.
8. The method of claim 1, wherein the compound is selected from the group consisting of:
2-(3-(3-(4-Carbamimidoylphenoxy)propoxy)phenyl)benzofuran-5-carboxamidine;
2-(3-(3-(4-(N-Isopropylcarbamimidoyl)phenoxy)propoxy)phenyl)-N-isopropylbenzofuran-5-carboxamidine;
2-(2-(3-(3-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy)propoxy) phenyl)benzofuran-5-yl)-4,5-dihydro-1H-imidazole;
2-(3-(4-(4-Carbamimidoylphenoxy)butoxy)phenyl)benzofuran-5-carboxamidine;
2-(3-(4-(4-(N-Isopropylcarbamimidoyl)phenoxy)butoxy)phenyl)-N-isopropylbenzofuran-5-carboxamidine;
2-(2-(3-(4-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy)butoxy)phenyl)benzofuran-5-yl)-4,5-dihydro-1H-imidazole;
2-(3-(5-(4-Carbamimidoylphenoxy)pentyloxy)phenyl)benzofuran-5-carboxamidine;
2-(3-(5-(4-(N-Isopropylcarbamimidoyl)phenoxy)pentyloxy)phenyl)-N-isopropylbenzofuran-5-carboxamidine;
2-(2-(3-(5-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy)pentyloxy) phenyl)benzofuran-5-yl)-4,5-dihydro-1H-imidazole;
2-(3-(6-(4-Carbamimidoylphenoxy)hexyloxy)phenyl)benzofuran-5-carboxamidine;
2-(3-(6-(4-(N-Isopropylcarbamimidoyl)phenoxy)hexyloxy)phenyl)-N-isopropylbenzofuran-5-carboxamidine;
2-(2-(3-(6-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy) hexyloxy)phenyl)benzofuran-5-yl)-4,5-dihydro-1H-imidazole;
2-(4-(3-(4-Carbamimidoylphenoxy)propoxy)phenyl)benzofuran-5-carboxamidine;
2-(4-(3-(4-(N-isopropylcarbamimidoyl)phenoxy)propoxy)phenyl)-N-isopropylbenzofuran-5-carboxamidine;
2-(2-(4-(3-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy)propoxy) phenyl)benzofuran-5-yl)-4,5-dihydro-1H-imidazole;
2-(4-(4-(4-Carbamimidoylphenoxy)butoxy)phenyl)benzofuran-5-carboxamidine;
2-(4-(4-(4-(N-Isopropylcarbamimidoyl)phenoxy)butoxy)phenyl)-N-isopropylbenzofuran-5-carboxamidine;
2-(2-(4-(4-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy)butoxy)phenyl) benzofuran-5-yl)-4,5-dihydro-1H-imidazole;
2-(4-(5-(4-Carbamimidoylphenoxy)pentyloxy)phenyl)benzofuran-5-carboxamidine;
2-(4-(5-(4-(N-Isopropylcarbamimidoyl)phenoxy)pentyloxy)phenyl)-N-isopropylbenzofuran-5-carboxamidine;
2-(2-(4-(5-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy)pentyloxy)phenyl) benzofuran-5-yl)-4,5-dihydro-1H-imidazole;
2-(4-(6-(4-Carbamimidoylphenoxy)hexyloxy)phenyl)benzofuran-5-carboxamidine;
2-(4-(6-(4-(N-Isopropylcarbamimidoyl)phenoxy)hexyloxy)phenyl)-N-isopropylbenzofuran-5-carboxamidine;
2-(2-(4-(6-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy)hexyloxy)phenyl) benzofuran-5-yl)-4,5-dihydro-1H-imidazole;
2-(3-(3-(4-Carbamimidoylphenoxy)propoxy)phenyl)benzofuran-6-carboxamidine;
2-(3-(3-(4-(N-Isopropylcarbamimidoyl)phenoxy)propoxy)phenyl)-N-isopropylbenzofuran-6-carboxamidine;
2-(2-(3-(3-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy)propoxy)phenyl) benzofuran-6-yl)-4,5-dihydro-1H-imidazole;
2-(3-(4-(4-Carbamimidoylphenoxy)butoxy)phenyl)benzofuran-6-carboxamidine;
2-(3-(4-(4-(N-Isopropylcarbamimidoyl)phenoxy)butoxy)phenyl)-N-isopropylbenzofuran-6-carboxamidine;
2-(2-(3-(4-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy)butoxy)phenyl) benzofuran-6-yl)-4,5-dihydro-1H-imidazole;
2-(3-(5-(4-Carbamimidoylphenoxy)pentyloxy)phenyl)benzofuran-6-carboxamidine;
2-(3-(5-(4-(N-Isopropylcarbamimidoyl)phenoxy)pentyloxy)phenyl)-N-isopropylbenzofuran-6-carboxamidine;
2-(2-(3-(5-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy)pentyloxy)phenyl) benzofuran-6-yl)-4,5-dihydro-1H-imidazole;
2-(3-(6-(4-Carbamimidoylphenoxy)hexyloxy)phenyl)benzofuran-6-carboxamidine;
2-(3-(6-(4-(N-Isopropylcarbamimidoyl)phenoxy)hexyloxy)phenyl)-N-isopropylbenzofuran-6-carboxamidine;
2-(2-(3-(6-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy)hexyloxy)phenyl)benzofuran-6-yl)-4,5-dihydro-1H-imidazole;
2-(4-(3-(4-Carbamimidoylphenoxy)propoxy)phenyl)benzofuran-6-carboxamidine;
2-(4-(3-(4-(N-Isopropylcarbamimidoyl)phenoxy)propoxy)phenyl)-N-isopropylbenzofuran-6-carboxamidine;
2-(2-(4-(3-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy)propoxy)phenyl) benzofuran-6-yl)-4,5-dihydro-1H-imidazole;
2-(4-(4-(4-Carbamimidoylphenoxy)butoxy)phenyl)benzofuran-6-carboxamidine;
2-(4-(4-(4-(N-Isopropylcarbamimidoyl)phenoxy)butoxy)phenyl)-N-isopropylbenzofuran-6-carboxamidine;
2-(2-(4-(4-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy)butoxy)phenyl) benzofuran-6-yl)-4,5-dihydro-1H-imidazole;
2-(4-(5-(4-Carbamimidoylphenoxy)pentyloxy)phenyl)benzofuran-6-carboxamidine;
2-(4-(5-(4-(N-Isopropylcarbamimidoyl)phenoxy)pentyloxy)phenyl)-N-isopropylbenzofuran-6-carboxamidine;
2-(2-(4-(5-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy)pentyloxy)phenyl) benzofuran-6-yl)-4,5-dihydro-1H-imidazole;
2-(4-(6-(4-Carbamimidoylphenoxy)hexyloxy)phenyl)benzofuran-6-carboxamidine;
2-(4-(6-(4-(N-Isopropylcarbamimidoyl)phenoxy)hexyloxy)phenyl)-N-isopropylbenzofuran-6-carboxamidine;
2-(2-(4-(6-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy)hexyloxy)phenyl) benzofuran-6-yl)-4,5-dihydro-1H-imidazole;
2-(4-(3-(4-(N-hydroxycarbamimidoyl)phenoxy)propoxy)phenyl)-N-hydroxybenzofuran-5-carboxamidine; and
2-(4-(5-(4-(N-hydroxycarbamimidoyl)phenoxy)pentyloxy)phenyl)-N-hydroxybenzofuran-5-carboxamidine.
9. The method of claim 1, wherein the compound of Formula I is administered in the form of a pharmaceutically acceptable salt.
10. The method of claim 8, wherein the pharmaceutically acceptable salt is a hydrochloride salt.
11. A method of treating a microbial infection in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of Formula (II):
wherein:
p and q are integers from 0 to 3;
R1 and R2 are each independently selected from the group consisting of alkyl, halo, hydroxyl, alkoxyl, aryloxyl, and aralkyloxyl; and
R3 and R4 are each independently selected from the group consisting of:
wherein:
R6, R7, R8, and R9 are each independently selected from the group consisting of H, alkyl, cycloalkyl, aryl, aralkyl, hydroxyl, alkoxyl, hydroxyalkyl, hydroxycycloalkyl, alkoxycycloalkyl, aminoalkyl, acyloxyl, alkylaminoalkyl, and alkoxycarbonyl; or
R6 and R7 together represent a C2 to C10 alkyl, C2 to C10 hydroxyalkyl, or C2 to C10 alkylene.
12. The method of claim 11, wherein the microbial infection is selected from the group consisting of a Mycobacterium tuberculosis infection, a Leishmania donovani infection, a Trypanosoma brucei rhodesiense infection, a Trypanosoma cruzi infection, a Plasmodium falciparum infection, a Candida albicans infection, an Aspergillus fumigatus infection, and a Cryptococcus neoformans infection.
13. The method of claim 11, wherein:
R3 and R4 are each
R3 is at one of the 5-position and 6-position of ring C; and
R4 is at one of the 3\u2032-position and 4\u2032-position of ring A.
14. The method of claim 11, wherein:
R3 and R4 are each
R3 is at one of the 5-position and 6-position of ring C; and
R4 is at one of the 3\u2032-position and 4\u2032-position of ring A.
15. The method of claim 11, wherein:
R3 and R4 are each
R3 is at one of the 5-position and 6-position of ring C; and
R4 is at one of the 3\u2032-position and 4\u2032-position of ring A.
16. The method of claim 11, wherein:
R3 and R4 are each
R3 is at one of the 5-position and 6-position of ring C; and
R4 is at one of the 3\u2032-position and 4\u2032-position of ring A.
17. The method of claim 11, wherein:
R3 and R4 are each
R3 is at one of the 5-position and 6-position of ring C; and
R4 is at one of the 3\u2032-position and 4\u2032-position of ring A.
18. The method of claim 11, wherein:
R3 and R4 are each
R3 is at one of the 5-position and 6-position of ring C;
R4 is at one of the 3\u2032-position and 4\u2032-position of ring A;
p is 1;
R1 is \u2014OCH3; and
R1 is in the 7-position of ring C.
19. The method of claim 11, wherein:
R3 and R4 are each
R3 is at one of the 5-position and 6-position of ring C;
R4 is at one of the 3\u2032-position and 4\u2032-position of ring A;
p is 1;
R1 is \u2014OCH3; and
R1 is in the 7-position of ring C.
20. The method of claim 11, wherein the compound is selected from the group consisting of:
2-(4-carbamimidoylphenyl)benzofuran-5-carboxamidine;
2-(4-(N-isopropylcarbamimidoyl)phenyl)-N-isopropylbenzofuran-5-carboxamidine;
2-(4-(5-(4,5-dihydro-1H-imidazol-2-yl)benzofuran-2-yl)phenyl)-4,5-dihydro-1H-imidazole;
2-(3-carbamimidoylphenyl)benzofuran-5-carboxamidine;
2-(3-(N-isopropylcarbamimidoyl)phenyl)-N-isopropylbenzofuran-5-carboxamidine;
2-(3-(5-(4,5-dihydro-1H-imidazol-2-yl)benzofuran-2-yl)phenyl)-4,5-dihydro-1H-imidazole;
2-(3-carbamimidoylphenyl)benzofuran-6-carboxamidine;
2-(3-(N-isopropylcarbamimidoyl)phenyl)-N-isopropylbenzofuran-6-carboxamidine;
2-(3-(6-(4,5-dihydro-1H-imidazol-2-yl)benzofuran-2-yl)phenyl)-4,5-dihydro-1H-imidazole;
2-(4-carbamimidoylphenyl)benzofuran-6-carboxamidine;
2-(4-(N-isopropylcarbamimidoyl)phenyl)-N-isopropylbenzofuran-6-carboxamidine;
2-(4-(6-(4,5-dihydro-1H-imidazol-2-yl)benzofuran-2-yl)phenyl)-4,5-dihydro-1H-imidazole;
2-(4-carbamimidoylphenyl)-7-methoxybenzofuran-5-carboxamidine;
2-(4-(5-(4,5-dihydro-1H-imidazol-2-yl)-7-methoxybenzofuran-2-yl)phenyl)-4,5-dihydro-1H-imidazole;
2-(4-(N-hydroxycarbamimidoyl)phenyl)-N-hydroxybenzofuran-5-carboxamidine;
2-(4-(N-methoxycarbamimidoyl)phenyl)-N-methoxybenzofuran-5-carboxamidine;
2-(3-(N-hydroxycarbamimidoyl)phenyl)-N-hydroxybenzofuran-6-carboxamidine; and
2-(4-(N-hydroxycarbamimidoyl)phenyl)-N-hydroxybenzofuran-6-carboxamidine.
21. The method of claim 11, wherein the compound of Formula II is administered in the form of a pharmaceutically acceptable salt.
22. The method of claim 21, wherein the pharmaceutically acceptable salt is a hydrochloride salt.
23. A method of treating a microbial infection in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of Formula (III):
wherein:
n is an integer from 1 to 8;
p and q are integers from 0 to 3;
R1 and R2 are each independently selected from the group consisting of alkyl, halo, hydroxyl, alkoxyl, aryloxyl, and aralkyloxyl; and
R3 and R4 are each independently selected from the group consisting of:
wherein:
R6, R7, R8, and R9 are each independently selected from the group consisting of H, alkyl, cycloalkyl, aryl, aralkyl, hydroxyl, alkoxyl, hydroxyalkyl, hydroxycycloalkyl, alkoxycycloalkyl, aminoalkyl, acyloxyl, alkylaminoalkyl, and alkoxycarbonyl; or
R6 and R7 together represent a C2 to C10 alkyl, C2 to C10 hydroxyalkyl, or C2 to C10 alkylene.
24. The method of claim 23, wherein the microbial infection is selected from the group consisting of a Mycobacterium tuberculosis infection, a Leishmania donovani infection, a Trypanosoma brucei rhodesiense infection, a Trypanosoma cruzi infection, a Plasmodium falciparum infection, a Candida albicans infection, an Aspergillus fumigatus infection, and a Cryptococcus neoformans infection.
25. The method of claim 23, wherein:
n is an integer from 1 to 5;
R3 and R4 are each
R3 is at one of the 4-position, 5-position, and 6-position of ring C; and
R4 is at one of the 4\u2032-position, 5\u2032-position, and 6\u2032-position of ring C\u2032.
26. The method of claim 23, wherein:
n is an integer from 1 to 5;
R3 and R4 are each
R3 is at one of the 4-position, 5-position, and 6-position of ring C; and
R4 is at one of the 4\u2032-position, 5\u2032-position, and 6\u2032-position of ring C\u2032.
27. The method of claim 23, wherein:
n is an integer from 1 to 5;
R3 and R4 are each
R3 is at one of the 4-position, 5-position, and 6-position of ring C; and
R4 is at one of the 4\u2032-position, 5\u2032-position, and 6\u2032-position of ring C\u2032.
28. The method of claim 23, wherein:
n is an integer from 1 to 5;
R3 and R4 are each
R3 is at one of the 4-position, 5-position, and 6-position of ring C; and
R4 is at one of the 4\u2032-position, 5\u2032-position, and 6\u2032-position of ring C\u2032.
29. The method of claim 23, wherein:
n is an integer from 1 to 5;
R3 and R4 are each
R3 is at one of the 4-position, 5-position, and 6-position of ring C; and
R4 is at one of the 4\u2032-position, 5\u2032-position, and 6\u2032-position of ring C.
30. The method of claim 23, wherein the compound is selected from the group consisting of:
2-((4-Amidinobenzofuran-2-yl)methyl)benzofuran-4-carboxamidine;
2-((4-Amidinobenzofuran-2-yl)methyl)-N-isopropylbenzofuran-4-carboxamidine;
Bis(4-(4,5-dihydro-1H-imidazol-2-yl)benzofuran-2-yl)methane;
2-((5-Amidinobenzofuran-2-yl)methyl)benzofuran-5-carboxamidine;
2-((5-Amidinobenzofuran-2-yl)methyl)-N-isopropylbenzofuran-5-carboxamidine;
Bis(5-(4,5-dihydro-1H-imidazol-2-yl)benzofuran-2-yl)methane;
Bis(6-(4,5-dihydro-1H-imidazol-2-yl)benzofuran-2-yl)methane;
2-(2-(5-Amidinobenzofuran-2-yl)ethyl)benzofuran-5-carboxamidine;
2-(2-(5-Amidinobenzofuran-2-yl)ethyl)-N-isopropyl benzofuran-5-carboxamidine;
4,5-Dihydro-2-(2-(2-(5-(4,5-dihydro-1H-imidazol-2-yl)benzofuran-2-yl)ethyl)benzofuran-5-yl)-1H-imidazole;
2-(2-(6-Amidinobenzofuran-2-yl)ethyl)benzofuran-6-carboxamidine;
2-(2-(6-Amidinobenzofuran-2-yl)ethyl)-N-isopropylbenzofuran-6-carboxamidine;
4,5-dihydro-2-(2-(2-(6-(4,5-dihydro-1H-imidazol-2-yl)benzofuran-2-yl)ethyl)benzofuran-6-yl)-1H-imidazole;
2-(3-(5-Amidinobenzofuran-2-yl)propyl)benzofuran-5-carboxamidine;
2-(3-(5-Amidinobenzofuran-2-yl)propyl)-N-isopropylbenzofuran-5-carboxamidine;
4,5-Dihydro-2-(2-(3-(5-(4,5-dihydro-1H-imidazol-2-yl)benzofuran-2-yl)propyl)benzofuran-5-yl)-1H-imidazole;
2-(3-(6-Amidinobenzofuran-2-yl)propyl)benzofuran-6-carboxamidine;
2-(3-(6-Amidinobenzofuran-2-yl)propyl)-N-isopropylbenzofuran-6-carboxamidine;
4,5-Dihydro-2-(2-(3-(6-(4,5-dihydro-1H-imidazol-2-yl)benzofuran-2-yl)propyl)benzofuran-6-yl)-1H-imidazole;
2-(4-(5-Amidinobenzofuran-2-yl)butyl)benzofuran-5-carboxamidine;
2-(4-(5-Amidinobenzofuran-2-yl)butyl)-N-isopropylbenzofuran-5-carboxamidine;
4,5-Dihydro-2-(2-(4-(5-(4,5-dihydro-1H-imidazol-2-yl)benzofuran-2-yl)butyl)benzofuran-5-yl)-1H-imidazole;
2-(4-(6-Amidinobenzofuran-2-yl)butyl)benzofuran-6-carboxamidine;
2-(4-(6-Amidinobenzofuran-2-yl)butyl)-N-isopropylbenzofuran-6-carboxamidine;
4,5-Dihydro-2-(2-(4-(6-(4,5-dihydro-1H-imidazol-2-yl)benzofuran-2-yl)butyl)benzofuran-6-yl)-1H-imidazole;
2-(5-(5-Amidinobenzofuran-2-yl)pentyl)benzofuran-5-carboxamidine;
2-(5-(5-Amidinobenzofuran-2-yl)pentyl)-N-isopropylbenzofuran-5-carboxamidine;
4,5-Dihydro-2-(2-(5-(5-(4,5-dihydro-1H-imidazol-2-yl)benzofuran-2-yl)pentyl)benzofuran-5-yl)-1H-imidazole;
2-(5-(6-Amidinobenzofuran-2-yl)pentyl)benzofuran-6-carboxamidine;
2-(5-(6-Amidinobenzofuran-2-yl)pentyl)-N-isopropylbenzofuran-6-carboxamidine;
4,5-Dihydro-2-(2-(5-(6-(4,5-dihydro-1H-imidazol-2-yl)benzofuran-2-yl)pentyl)benzofuran-6-yl)-1H-imidazole;
2-(5-(6-(N-hydroxycarbamimidoyl)benzofuran-2-yl)pentyl)-N-hydroxybenzofuran-6-carboxamidine;
2-(3-(5-(N-hydroxycarbamimidoyl)benzofuran-2-yl)propyl)-N-hydroxybenzofuran-5-carboxamidine;
2-(4-(5-(N-hydroxycarbamimidoyl)benzofuran-2-yl)butyl)-N-hydroxybenzofuran-5-carboxamidine;
2-(5-(6-(N-methoxycarbamimidoyl)benzofuran-2-yl)pentyl)-N-methoxybenzofuran-6-carboxamidine;
2-(3-(5-(N-methoxycarbamimidoyl)benzofuran-2-yl)propyl)-N-methoxybenzofuran-5-carboxamidine;
2-(4-(5-(N-methoxycarbamimidoyl)benzofuran-2-yl)butyl)-N-methoxybenzofuran-5-carboxamidine;
2-(2-(5-(N-hydroxycarbamimidoyl)benzofuran-2-yl)ethyl)-N-hydroxybenzofuran-5-carboxamidine;
2-(2-(5-(N-methoxycarbamimidoyl)benzofuran-2-yl)ethyl)-N-methoxybenzofuran-5-carboxamidine;
2-(5-(5-(N-hydroxycarbamimidoyl)benzofuran-2-yl)pentyl)-N-hydroxybenzofuran-5-carboxamidine; and
2-(5-(5-(N-methoxycarbamimidoyl)benzofuran-2-yl)pentyl)-N-methoxybenzofuran-5-carboxamidine.
31. The method of claim 23, wherein the compound of Formula III is administered in the form of a pharmaceutically acceptable salt.
32. The method of claim 31, wherein the pharmaceutically acceptable salt is a hydrochloride salt.
33. A compound of Formula (I):
wherein:
n is an integer from 1 to 8;
p and q are integers from 0 to 3;
X1 and X2 are each independently selected from the group consisting of O, S, and NR5, wherein R5 is selected from the group consisting of H, alkyl, aryl, alkoxyl, and aryloxyl;
R1 and R2 are each independently selected from the group consisting of alkyl, halo, hydroxyl, alkoxyl, aryloxyl, and aralkyloxyl; and
R3 and R4 are each independently selected from the group consisting of:
wherein:
R6, R7, R8, and R9 are each independently selected from the group consisting of H, alkyl, cycloalkyl, aryl, aralkyl, hydroxyl, alkoxyl, hydroxyalkyl, hydroxycycloalkyl, alkoxycycloalkyl, aminoalkyl, acyloxyl, alkylaminoalkyl, and alkoxycarbonyl; or
R6 and R7 together represent a C2 to C10 alkyl, C2 to C10 hydroxyalkyl, or C2 to C10 alkylene.
34. The compound of claim 33, wherein:
X1 and X2 are both O;
X1 is at one of the 3\u2032-position and 4\u2032-position of ring A;
X2 is at one of the 3\u2033-position and 4\u2033-position of ring B;
n is an integer from 3 to 6;
R3 and R4 are each
R3 is at one of the 5-position and 6-position of ring C; and
R4 is at one of the 1\u2033-position and 2\u2033-position of ring B.
35. The compound of claim 33, wherein:
X1 and X2 are both O;
X1 is at one of the 3\u2032-position and 4\u2032-position of ring A;
X2 is at one of the 3\u2033-position and 4\u2033-position of ring B;
n is an integer from 3 to 6;
R3 and R4 are each
R3 is at one of the 5-position and 6-position of ring C; and
R4 is at one of the 1\u2033-position and 2\u2033-position of ring B.
36. The compound of claim 33, wherein:
X1 and X2 are both O;
X1 is at one of the 3\u2032-position and 4\u2032-position of ring A;
X2 is at one of the 3\u2033-position and 4\u2033-position of ring B;
n is an integer from 3 to 6;
R3 and R4 are each
R3 is at one of the 5-position and 6-position of ring C; and
R4 is at one of the 1\u2033-position and 2\u2033-position of ring B.
37. The compound of claim 33, wherein:
X1 and X2 are both O;
X1 is at one of the 3\u2032-position and 4\u2032-position of ring A;
X2 is at one of the 3\u2033-position and 4\u2033-position of ring B;
n is an integer from 3 to 6;
R3 and R4 are each
R3 is at one of the 5-position and 6-position of ring C; and
R4 is at one of the 1\u2033-position and 2\u2033-position of ring B.
38. The compound of claim 33, wherein:
X1 and X2 are both O;
X1 is at one of the 3\u2032-position and 4\u2032-position of ring A;
X2 is at one of the 3\u2033-position and 4\u2033-position of ring B;
n is an integer from 3 to 6;
R3 and R4 are each
R3 is at one of the 5-position and 6-position of ring C; and
R4 is at one of the 1\u2033-position and 2\u2033-position of ring B.
39. The compound of claim 33, wherein the compound is selected from the group consisting of:
2-(3-(3-(4-Carbamimidoylphenoxy)propoxy)phenyl)benzofuran-5-carboxamidine;
2-(3-(3-(4-(N-Isopropylcarbamimidoyl)phenoxy)propoxy)phenyl)-N-isopropylbenzofuran-5-carboxamidine;
2-(2-(3-(3-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy)propoxy) phenyl)benzofuran-5-yl)-4,5-dihydro-1H-imidazole;
2-(3-(4-(4-Carbamimidoylphenoxy)butoxy)phenyl)benzofuran-5-carboxamidine;
2-(3-(4-(4-(N-Isopropylcarbamimidoyl)phenoxy)butoxy)phenyl)-N-isopropylbenzofuran-5-carboxamidine;
2-(2-(3-(4-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy)butoxy)phenyl)benzofuran-5-yl)-4,5-dihydro-1H-imidazole;
2-(3-(5-(4-Carbamimidoylphenoxy)pentyloxy)phenyl)benzofuran-5-carboxamidine;
2-(3-(5-(4-(N-Isopropylcarbamimidoyl)phenoxy)pentyloxy)phenyl)-N-isopropylbenzofuran-5-carboxamidine;
2-(2-(3-(5-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy) pentyloxy)phenyl)benzofuran-5-yl)-4,5-dihydro-1H-imidazole;
2-(3-(6-(4-Carbamimidoylphenoxy)hexyloxy)phenyl)benzofuran-5-carboxamidine;
2-(3-(6-(4-(N-Isopropylcarbamimidoyl)phenoxy)hexyloxy)phenyl)-N-isopropylbenzofuran-5-carboxamidine;
2-(2-(3-(6-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy)hexyloxy)phenyl) benzofuran-5-yl)-4,5-dihydro-1H-imidazole;
2-(4-(3-(4-Carbamimidoylphenoxy)propoxy)phenyl)benzofuran-5-carboxamidine;
2-(4-(3-(4-(N-Isopropylcarbamimidoyl)phenoxy)propoxy)phenyl)-N-isopropylbenzofuran-5-carboxamidine;
2-(2-(4-(3-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy) propoxy)phenyl)benzofuran-5-yl)-4,5-dihydro-1H-imidazole;
2-(4-(4-(4-Carbamimidoylphenoxy)butoxy)phenyl)benzofuran-5-carboxamidine;
2-(4-(4-(4-(N-Isopropylcarbamimidoyl)phenoxy)butoxy)phenyl)-N-isopropylbenzofuran-5-carboxamidine;
2-(2-(4-(4-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy)butoxy)phenyl) benzofuran-5-yl)-4,5-dihydro-1H-imidazole;
2-(4-(5-(4-Carbamimidoylphenoxy)pentyloxy)phenyl)benzofuran-5-carboxamidine;
2-(4-(5-(4-(N-Isopropylcarbamimidoyl)phenoxy)pentyloxy)phenyl)-N-isopropylbenzofuran-5-carboxamidine;
2-(2-(4-(5-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy) pentyloxy)phenyl)benzofuran-5-yl)-4,5-dihydro-1H-imidazole;
2-(4-(6-(4-Carbamimidoylphenoxy)hexyloxy)phenyl)benzofuran-5-carboxamidine;
2-(4-(6-(4-(N-Isopropylcarbamimidoyl)phenoxy)hexyloxy)phenyl)-N-isopropylbenzofuran-5-carboxamidine;
2-(2-(4-(6-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy) hexyloxy)phenyl)benzofuran-5-yl)-4,5-dihydro-1H-imidazole;
2-(3-(3-(4-Carbamimidoylphenoxy)propoxy)phenyl)benzofuran-6-carboxamidine;
2-(3-(3-(4-(N-Isopropylcarbamimidoyl)phenoxy)propoxy)phenyl)-N-isopropylbenzofuran-6-carboxamidine;
2-(2-(3-(3-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy) propoxy)phenyl)benzofuran-6-yl)-4,5-dihydro-1H-imidazole;
2-(3-(4-(4-Carbamimidoylphenoxy)butoxy)phenyl)benzofuran-6-carboxamidine;
2-(3-(4-(4-(N-Isopropylcarbamimidoyl)phenoxy)butoxy)phenyl)-N-isopropylbenzofuran-6-carboxamidine;
2-(2-(3-(4-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy)butoxy)phenyl)benzofuran-6-yl)-4,5-dihydro-1H-imidazole;
2-(3-(5-(4-Carbamimidoylphenoxy)pentyloxy)phenyl)benzofuran-6-carboxamidine;
2-(3-(5-(4-(N-Isopropylcarbamimidoyl)phenoxy)pentyloxy)phenyl)-N-isopropylbenzofuran-6-carboxamidine;
2-(2-(3-(5-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy) pentyloxy)phenyl)benzofuran-6-yl)-4,5-dihydro-1H-imidazole;
2-(3-(6-(4-Carbamimidoylphenoxy)hexyloxy)phenyl)benzofuran-6-carboxamidine;
2-(3-(6-(4-(N-Isopropylcarbamimidoyl)phenoxy)hexyloxy)phenyl)-N-isopropylbenzofuran-6-carboxamidine;
2-(2-(3-(6-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy) hexyloxy)phenyl)benzofuran-6-yl)-4,5-dihydro-1H-imidazole;
2-(4-(3-(4-Carbamimidoylphenoxy)propoxy)phenyl)benzofuran-6-carboxamidine;
2-(4-(3-(4-(N-Isopropylcarbamimidoyl)phenoxy)propoxy)phenyl)-N-isopropylbenzofuran-6-carboxamidine;
2-(2-(4-(3-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy) propoxy)phenyl)benzofuran-6-yl)-4,5-dihydro-1H-imidazole;
2-(4-(4-(4-Carbamimidoylphenoxy)butoxy)phenyl)benzofuran-6-carboxamidine;
2-(4-(4-(4-(N-Isopropylcarbamimidoyl)phenoxy)butoxy)phenyl)-N-isopropylbenzofuran-6-carboxamidine;
2-(2-(4-(4-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy)butoxy)phenyl)benzofuran-6-yl)-4,5-dihydro-1H-imidazole;
2-(4-(5-(4-Carbamimidoylphenoxy)pentyloxy)phenyl)benzofuran-6-carboxamidine;
2-(4-(5-(4-(N-Isopropylcarbamimidoyl)phenoxy)pentyloxy)phenyl)-N-isopropylbenzofuran-6-carboxamidine;
2-(2-(4-(5-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy) pentyloxy)phenyl)benzofuran-6-yl)-4,5-dihydro-1H-imidazole;
2-(4-(6-(4-Carbamimidoylphenoxy)hexyloxy)phenyl)benzofuran-6-carboxamidine;
2-(4-(6-(4-(N-Isopropylcarbamimidoyl)phenoxy)hexyloxy)phenyl)-N-isopropylbenzofuran-6-carboxamidine;
2-(2-(4-(6-(4-(4,5-Dihydro-1H-imidazol-2-yl)phenoxy) hexyloxy)phenyl)benzofuran-6-yl)-4,5-dihydro-1H-imidazole;
2-(4-(3-(4-(N-hydroxycarbamimidoyl)phenoxy)propoxy)phenyl)-N-hydroxybenzofuran-5-carboxamidine; and
2-(4-(5-(4-(N-hydroxycarbamimidoyl)phenoxy)pentyloxy)phenyl)-N-hydroxybenzofuran-5-carboxamidine.
40. A pharmaceutically acceptable salt of a compound of claim 33.
41. The pharmaceutically acceptable salt of claim 40, wherein the salt is a hydrochloride salt.
42. A compound of Formula (II):
wherein:
p and q are integers from 0 to 3;
R1 and R2 are each independently selected from the group consisting of alkyl, halo, hydroxyl, alkoxyl, aryloxyl, and aralkyloxyl; and
R3 and R4 are each independently selected from the group consisting of:
wherein:
R6, R7, R8, and R9 are each independently selected from the group consisting of H, alkyl, cycloalkyl, aryl, aralkyl, hydroxyl, alkoxyl, hydroxyalkyl, hydroxycycloalkyl, alkoxycycloalkyl, aminoalkyl, acyloxyl, alkylaminoalkyl, and alkoxycarbonyl; or
R6 and R7 together represent a C2 to C10 alkyl, C2 to C10 hydroxyalkyl, or C2 to C10 alkylene.
43. The compound of claim 42, wherein:
R3 and R4 are each
R3 is at one of the 5-position and 6-position of ring C; and
R4 is at one of the 3\u2032-position and 4\u2032-position of ring A.
44. The compound of claim 42, wherein:
R3 and R4 are each
R3 is at one of the 5-position and 6-position of ring C; and
R4 is at one of the 3\u2032-position and 4\u2032-position of ring A.
45. The compound of claim 42, wherein:
R3 and R4 are each
R3 is at one of the 5-position and 6-position of ring C; and
R4 is at one of the 3\u2032-position and 4\u2032-position of ring A.
46. The compound of claim 42, wherein:
R3 and R4 are each
R3 is at one of the 5-position and 6-position of ring C; and
R4 is at one of the 3\u2032-position and 4\u2032-position of ring A.
47. The compound of claim 42, wherein:
R3 and R4 are each
R3 is at one of the 5-position and 6-position of ring C; and
R4 is at one of the 3\u2032-position and 4\u2032-position of ring A.
48. The compound of claim 42, wherein:
R3 and R4 are each
R3 is at one of the 5-position and 6-position of ring C;
R4 is at one of the 3\u2032-position and 4\u2032-position of ring A;
p is 1;
R1 is \u2014OCH3; and
R1 is in the 7-position of ring C.
49. The compound of claim 42, wherein:
R3 and R4 are each
R3 is at one of the 5-position and 6-position of ring C;
R4 is at one of the 3\u2032-position and 4\u2032-position of ring A;
p is 1;
R1 is \u2014OCH3; and
R1 is in the 7-position of ring C.
50. A pharmaceutically acceptable salt of a compound of claim 42.
51. The pharmaceutically acceptable salt of claim 50, wherein the salt is a hydrochloride salt.
52. A compound of Formula (III):
wherein:
n is an integer from 1 to 8;
p and q are integers from 0 to 3;
R1 and R2 are each independently selected from the group consisting of alkyl, halo, hydroxyl, alkoxyl, aryloxyl, and aralkyloxyl; and
R3 and R4 are each independently selected from the group consisting of:
wherein:
R6, R7, R8, and R9 are each independently selected from the group consisting of H, alkyl, cycloalkyl, aryl, aralkyl, hydroxyl, alkoxyl, hydroxyalkyl, hydroxycycloalkyl, alkoxycycloalkyl, aminoalkyl, acyloxyl, alkylaminoalkyl, and alkoxycarbonyl; or
R6 and R7 together represent a C2 to C10 alkyl, C2 to C10 hydroxyalkyl, or C2 to C10 alkylene.
53. The compound of claim 52, wherein:
n is an integer from 1 to 5;
R3 and R4 are each
R3 is at one of the 4-position, 5-position, and 6-position of ring C; and
R4 is at one of the 4\u2032-position, 5\u2032-position, and 6\u2032-position of ring C\u2032.
54. The compound of claim 52, wherein:
n is an integer from 1 to 5;
R3 and R4 are each
R3 is at one of the 4-position, 5-position, and 6-position of ring C; and
R4 is at one of the 4\u2032-position, 5\u2032-position, and 6\u2032-position of ring C\u2032.
55. The compound of claim 52, wherein:
n is an integer from 1 to 5;
R3 and R4 are each
R3 is at one of the 4-position, 5-position, and 6-position of ring C; and
R4 is at one of the 4\u2032-position, 5\u2032-position, and 6\u2032-position of ring C\u2032.
56. The compound of claim 52, wherein:
n is an integer from 1 to 5;
R3 and R4 are each
R3 is at one of the 4-position, 5-position, and 6-position of ring C; and
R4 is at one of the 4\u2032-position, 5\u2032-position, and 6\u2032-position of ring C\u2032.
57. The compound of claim 52, wherein:
n is an integer from 1 to 5;
R3 and R4 are each
R3 is at one of the 4-position, 5-position, and 6-position of ring C; and
R4 is at one of the 4\u2032-position, 5\u2032-position, and 6\u2032-position of ring C\u2032.
58. The compound of claim 52, wherein the compound is selected from the group consisting of:
2-((4-Amidinobenzofuran-2-yl)methyl)benzofuran-4-carboxamidine;
2-((4-Amidinobenzofuran-2-yl)methyl)-N-isopropylbenzofuran-4-carboxamidine;
Bis(4-(4,5-dihydro-1H-imidazol-2-yl)benzofuran-2-yl)methane;
2-((5-Amidinobenzofuran-2-yl)methyl)benzofuran-5-carboxamidine;
2-((5-Amidinobenzofuran-2-yl)methyl)-N-isopropylbenzofuran-5-carboxamidine;
Bis(5-(4,5-dihydro-1H-imidazol-2-yl)benzofuran-2-yl)methane;
Bis(6-(4,5-dihydro-1H-imidazol-2-yl)benzofuran-2-yl)methane;
2-(2-(5-Amidinobenzofuran-2-yl)ethyl)benzofuran-5-carboxamidine;
2-(2-(5-Amidinobenzofuran-2-yl)ethyl)-N-isopropylbenzofuran-5-carboxamidine;
4,5-Dihydro-2-(2-(2-(5-(4,5-dihydro-1H-imidazol-2-yl)benzofuran-2-yl)ethyl)benzofuran-5-yl)-1H-imidazole;
2-(2-(6-Amidinobenzofuran-2-yl)ethyl)benzofuran-6-carboxamidine;
2-(2-(6-Amidinobenzofuran-2-yl)ethyl)-N-isopropylbenzofuran-6-carboxamidine;
4,5-dihydro-2-(2-(2-(6-(4,5-dihydro-1H-imidazol-2-yl)benzofuran-2-yl)ethyl)benzofuran-6-yl)-1H-imidazole;
2-(3-(5-Amidinobenzofuran-2-yl)propyl)benzofuran-5-carboxamidine;
2-(3-(5-Amidinobenzofuran-2-yl)propyl)-N-isopropylbenzofuran-5-carboxamidine;
4,5-Dihydro-2-(2-(3-(5-(4,5-dihydro-1H-imidazol-2-yl)benzofuran-2-yl)propyl)benzofuran-5-yl)-1H-imidazole;
2-(3-(6-Amidinobenzofuran-2-yl)propyl)benzofuran-6-carboxamidine;
2-(3-(6-Amidinobenzofuran-2-yl)propyl)-N-isopropylbenzofuran-6-carboxamidine;
4,5-Dihydro-2-(2-(3-(6-(4,5-dihydro-1H-imidazol-2-yl)benzofuran-2-yl)propyl)benzofuran-6-yl)-1H-imidazole;
2-(4-(5-Amidinobenzofuran-2-yl)butyl)benzofuran-5-carboxamidine;
2-(4-(5-Amidinobenzofuran-2-yl)butyl)-N-isopropylbenzofuran-5-carboxamidine;
4,5-Dihydro-2-(2-(4-(5-(4,5-dihydro-1H-imidazol-2-yl)benzofuran-2-yl)butyl)benzofuran-5-yl)-1H-imidazole;
2-(4-(6-Amidinobenzofuran-2-yl)butyl)benzofuran-6-carboxamidine;
2-(4-(6-Amidinobenzofuran-2-yl)butyl)-N-isopropylbenzofuran-6-carboxamidine;
4,5-Dihydro-2-(2-(4-(6-(4,5-dihydro-1H-imidazol-2-yl)benzofuran-2-yl)butyl)benzofuran-6-yl)-1H-imidazole;
2-(5-(5-Amidinobenzofuran-2-yl)pentyl)benzofuran-5-carboxamidine;
2-(5-(5-Amidinobenzofuran-2-yl)pentyl)-N-isopropylbenzofuran-5-carboxamidine;
4,5-Dihydro-2-(2-(5-(5-(4,5-dihydro-1H-imidazol-2-yl)benzofuran-2-yl)pentyl)benzofuran-5-yl)-1H-imidazole;
2-(5-(6-Amidinobenzofuran-2-yl)pentyl)benzofuran-6-carboxamidine;
2-(5-(6-Amidinobenzofuran-2-yl)pentyl)-N-isopropylbenzofuran-6-carboxamidine;
4,5-Dihydro-2-(2-(5-(6-(4,5-dihydro-1H-imidazol-2-yl)benzofuran-2-yl)pentyl)benzofuran-6-yl)-1H-imidazole;
2-(5-(6-(N-hydroxycarbamimidoyl)benzofuran-2-yl)pentyl)-N-hydroxybenzofuran-6-carboxamidine;
2-(3-(5-(N-hydroxycarbamimidoyl)benzofuran-2-yl)propyl)-N-hydroxybenzofuran-5-carboxamidine;
2-(4-(5-(N-hydroxycarbamimidoyl)benzofuran-2-yl)butyl)-N-hydroxybenzofuran-5-carboxamidine; and
2-(5-(6-(N-methoxycarbamimidoyl)benzofuran-2-yl)pentyl)-N-methoxybenzofuran-6-carboxamidine.
59. A pharmaceutically acceptable salt of a compound of claim 52.
60. The pharmaceutically acceptable salt of claim 59, wherein the salt is a hydrochloride salt.
61. A pharmaceutical formulation comprising:
(a) a compound of Formula (I); and
(b) a pharmaceutically acceptable carrier.
62. A pharmaceutical formulation comprising:
(a) a compound of Formula (II); and
(b) a pharmaceutically acceptable carrier.
63. A pharmaceutical formulation comprising:
(a) a compound of Formula (III); and
(b) a pharmaceutically acceptable carrier.
64. A method of preparing a compound of Formula (I):
wherein:
n is an integer from 1 to 8;
p and q are integers from 0 to 3;
X1 and X2 are each independently selected from the group consisting of O, S, and NR5, wherein R5 is selected from the group consisting of H, alkyl, aryl, alkoxyl, and aryloxyl;
R1 and R2 are each independently selected from the group consisting of alkyl, halo, hydroxyl, alkoxyl, aryloxyl, and aralkyloxyl;
R3 and R4 are each independently selected from the group consisting of:
wherein:
R6, R7, R8, and R9 are each independently selected from the group consisting of H, alkyl, cycloalkyl, aryl, aralkyl, hydroxyl, alkoxyl, hydroxyalkyl, hydroxycycloalkyl, alkoxycycloalkyl, aminoalkyl, acyloxyl, alkylaminoalkyl, and alkoxycarbonyl; or
R6 and R7 together represent a C2 to C10 alkyl, C2 to C10 hydroxyalkyl, or C2 to C10 alkylene;
the method comprising:
(a) mixing anhydrous 1,4-dioxane and an anhydrous alkyl alcohol to form a first reaction mixture;
(b) saturating the first reaction mixture with an anhydrous gaseous acid to form a second reaction mixture;
(c) adding a (cyanophenoxy)alkoxy)phenyl)benzofuran carbonitrile to the second reaction mixture to form a diimidate;
(d) suspending the diimidate in an anhydrous protic solvent to form a third reaction mixture; and
(e) saturating the third reaction mixture with an amine to form a compound of Formula (I).
65. The method of claim 64, wherein the (cyanophenoxy)alkoxy)phenyl)benzofuran carbonitrile is prepared by the method comprising:
(a) mixing a halogenated hydroxybenzonitrile and an alkoxybenzonitrile with a metal oxide in an anhydrous aprotic solvent to form a first reaction mixture;
(b) stirring the first reaction mixture for a period of time to form a (alkoxyphenyl)benzofuran carbonitrile;
(c) adding the (alkoxyphenyl)benzofuran carbonitrile to a melted pyridine hydrochloride to form a (hydroxyphenyl)benzofuran carbonitrile;
(d) mixing the (hydroxyphenyl)benzofuran carbonitrile with a carbonate salt in an anhydrous polar aprotic solvent to form a second reaction mixture; and
(e) adding a halogenated alkoxybenzonitrile to the second reaction mixture to form a (cyanophenoxy)alkoxy)phenyl)benzofuran carbonitrile.
66. The method of claim 64, wherein the (cyanophenoxy)alkoxy)phenyl)benzofuran carbonitrile is prepared by the method comprising:
(a) mixing a halogenated hydroxybenzoate and a alkoxy benzonitrile with a metal oxide in an anhydrous aprotic solvent to form a first reaction mixture;
(b) stirring the first reaction mixture for a period of time to form a (alkoxyphenyl)benzofuran carboxylate;
(c) passing anhydrous NH3 through an anhydrous nonpolar aprotic solvent for a period of time to form a second reaction mixture;
(d) adding a solution of a metal alkyl in a nonpolar aprotic solvent to the second reaction mixture to form a third reaction mixture;
(e) passing NH3 through the third reaction mixture for a period of time to form a fourth reaction mixture;
(f) adding the (alkoxyphenyl)benzofuran carboxylate to the fourth reaction mixture to form a (alkoxyphenyl)benzofuran carbonitrile;
(g) adding the (alkoxyphenyl)benzofuran carbonitrile to a melted pyridine hydrochloride to form a (hydroxyphenyl)benzofuran carbonitrile;
(h) mixing the (hydroxyphenyl)benzofuran carbonitrile with a carbonate salt in an anhydrous polar aprotic solvent to form a fifth reaction mixture; and
(i) adding a halogenated alkoxybenzonitrile to the fifth reaction mixture to form a (cyanophenoxy)alkoxy)phenyl)benzofuran carbonitrile.
67. A method of preparing a compound of Formula (II):
wherein:
p and q are integers from 0 to 3;
R1 and R2 are each independently selected from the group consisting of alkyl, halo, hydroxyl, alkoxyl, aryloxyl, and aralkyloxyl;
R3 and R4 are each independently selected from the group consisting of:
wherein:
R6, R7, R8, and R9 are each independently selected from the group consisting of H, alkyl, cycloalkyl, aryl, aralkyl, hydroxyl, alkoxyl, hydroxyalkyl, hydroxycycloalkyl, alkoxycycloalkyl, aminoalkyl, acyloxyl, alkylaminoalkyl, and alkoxycarbonyl; or
R6 and R7 together represent a C2 to C10 alkyl, C2 to C10 hydroxyalkyl, or C2 to C10 alkylene;
the method comprising:
(a) mixing anhydrous 1,4-dioxane and an anhydrous alkyl alcohol to form a first reaction mixture;
(b) saturating the first reaction mixture with an anhydrous gaseous acid to form a second reaction mixture;
(c) adding a (cyanophenyl)benzofuran carbonitrile to the second reaction mixture to form a diimidate;
(d) suspending the diimidate in an anhydrous protic solvent to form a third reaction mixture; and
(e) saturating the third reaction mixture with an amine to form a compound of Formula (II).
68. The method of claim 67, wherein the (cyanophenyl)benzofuran carbonitrile is prepared by the method comprising:
(a) contacting a halogenated hydroxybenzonitrile and a alkynylbenzonitrile with a metal oxide in an anhydrous polar aprotic solvent to form a first reaction mixture; and
(b) stirring the first reaction mixture for a period of time to form a (cyanophenyl)benzofuran carbonitrile.
69. The method of claim 67, wherein the (cyanophenyl)benzofuran carbonitrile is prepared by the method comprising:
(a) contacting a halogenated hydroxybenzoate and an alkynylbenzoate with a metal oxide in an anhydrous polar aprotic solvent to form a first reaction mixture;
(b) stirring the first reaction mixture for a period of time to form a (alkyl-oxycarbonylphenyl)benzofuran carboxylate;
(c) passing anhydrous NH3 through an anhydrous nonpolar aprotic solvent for a period of time to form a second reaction mixture;
(d) adding a solution of a metal alkyl in a nonpolar aprotic solvent to the second reaction mixture to form a third reaction mixture;
(e) passing NH3 through the third reaction mixture for a period of time to form a fourth reaction mixture; and
(f) adding the (alkyl-oxycarbonylphenyl)benzofuran carboxylate to the fourth reaction mixture to form a (cyanophenyl)benzofuran carbonitrile.
70. The method of claim 67, wherein the (cyanophenyl)benzofuran carbonitrile is prepared by the method comprising:
(a) contacting a halogenated hydroxyalkoxybenzaldehyde and a alkynylbenzonitrile with a metal oxide in an anhydrous polar aprotic solvent to form a first reaction mixture;
(b) stirring the first reaction mixture for a period of time to form a ((cyanophenyl)alkoxy)benzofurancarbaldehyde;
(c) adding the ((cyanophenyl)alkoxy)benzofurancarbaldehyde and a hydroxylamine to a melted pyridine hydrochloride to form a formaldehyde oxime; and
(d) refluxing the formaldehyde oxime in a solution of an acid anhydride for a period of time to form a ((cyanophenyl)alkoxy)benzofuran carbonitrile.
71. A method of preparing compound of Formula (III):
wherein:
n is an integer from 1 to 8;
p and q are integers from 0 to 3;
R1 and R2 are each independently selected from the group consisting of alkyl, halo, hydroxyl, alkoxyl, aryloxyl, and aralkyloxyl;
R3 and R4 are each independently selected from the group consisting of:
wherein:
R6, R7, R8, and R9 are each independently selected from the group consisting of H, alkyl, cycloalkyl, aryl, aralkyl, hydroxyl, alkoxyl, hydroxyalkyl, hydroxycycloalkyl, alkoxycycloalkyl, aminoalkyl, acyloxyl, alkylaminoalkyl, and alkoxycarbonyl; or
R6 and R7 together represent a C2 to C10 alkyl, C2 to C10 hydroxyalkyl, or C2 to C10 alkylene;
the method comprising:
(a) mixing anhydrous 1,4-dioxane and an anhydrous alkyl alcohol to form a first reaction mixture;
(b) saturating the first reaction mixture with an anhydrous gaseous acid to form a second reaction mixture;
(c) adding a bis-benzofuran carbodinitrile to the second reaction mixture to form a diimidate;
(d) suspending the diimidate in an anhydrous protic solvent to form a third reaction mixture; and
(e) saturating the third reaction mixture with an amine to form a compound of Formula (III).
72. The method of claim 71, wherein n is an integer from 3 to 8 and the bis-benzofuran carbodinitrile is prepared from the method comprising
(a) contacting a halogenated alkyl-hydroxybenzoate and an alkadiyne with a metal halide and an alkylguanidine in the presence of a catalyst in an anhydrous aprotic solvent to form a first reaction mixture;
(b) stirring the first reaction mixture for a period of time to form a alkyl-((alkoxycarbonyl)benzofuran-2-yl)alkyl)benzofuran carboxylate;
(c) passing anhydrous NH3 through an anhydrous nonpolar aprotic solvent for a period of time to form a second reaction mixture;
(d) adding a solution of a metal alkyl in a nonpolar aprotic solvent to the second reaction mixture to form a third reaction mixture;
(e) passing NH3 through the third second reaction mixture for a period of time to form a fourth reaction mixture; and
(f) adding the alkyl-((alkoxycarbonyl)benzofuran-2-yl)alkyl) benzofuran carboxylate to the fourth reaction mixture to form a ((cyanobenzofuran-2-yl)alkyl)benzofuran carbonitrile.
73. The method of claim 71, wherein n is an integer from 3 to 8 and the bis-benzofuran carbodinitrile is prepared from the method comprising
(a) contacting a halogenated alkyl-hydroxybenzoate and an alkadiyne with a metal oxide in an anhydrous aprotic solvent to form a first reaction mixture;
(b) stirring the first reaction mixture for a period of time to form a alkyl-((alkoxycarbonyl)benzofuran-2-yl)alkyl)benzofuran carboxylate;
(c) passing anhydrous NH3 through an anhydrous nonpolar aprotic solvent for a period of time to form a second reaction mixture;
(d) adding a solution of a metal alkyl in a nonpolar aprotic solvent to the second reaction mixture to form a third reaction mixture;
(e) passing NH3 through the third second reaction mixture for a period of time to form a fourth reaction mixture; and
(f) adding the alkyl-((alkoxycarbonyl)benzofuran-2-yl)alkyl) benzofuran carboxylate to the fourth reaction mixture to form a ((cyanobenzofuran-2-yl)alkyl)benzofuran carbonitrile.
74. The method of claim 71, wherein n is 1 and the bis-benzofuran carbodinitrile is prepared from the method comprising:
(a) contacting a halogenated hydroxybenzaldehyde with a dihalogenated ketone and a carbonate salt in an aprotic solvent to from a first reaction mixture;
(b) refluxing the first reaction mixture for a period of time to form a bis-benzofuranmethanone;
(c) dissolving a metal halide in an anhydrous nonpolar aprotic solvent to form a second reaction mixture;
(d) adding the second reaction mixture under an inert gas to a suspension of a metal hydride in an anhydrous nonpolar aprotic solvent to form a third reaction mixture;
(e) adding a bis-benzofuranmethanone to the third reaction mixture to form a fourth reaction mixture;
(f) adding an aqueous acid to the fourth reaction mixture to form a bis-benzofuranmethane;
(g) mixing the bis-benzofuranmethane and metal cyanide in anhydrous quinoline to form a sixth reaction mixture;
(h) refluxing the sixth reaction mixture for a period of time; and
(i) contacting the sixth reaction mixture with an aqueous acid solution to form a bis-benzofuranmethane carbodinitrile.
75. The method of claim 71, wherein n is 2 and the bis-benzofuran carbodinitrile is prepared from a method comprising:
(a) mixing a halogenated alkyl-hydroxybenzoate mixture with an alkynyl alcohol in an anhydrous aprotic solvent to form a first reaction mixture;
(b) contacting the first reaction mixture with a metal oxide in an anhydrous aprotic solvent to form a alkyl-(hydroxypropyl)benzofuran carboxylate;
(c) adding the alkyl-(hydroxypropyl)benzofuran carboxylate to a mixture of oxalyl chloride, a polar aprotic solvent and an anhydrous halogenated aprotic solvent to form a second reaction mixture;
(d) adding an alkylamine to the second reaction mixture to form a alkyl-(formylethyl)benzofuran carboxylate;
(e) adding the alkyl-(formylethyl)benzofuran carboxylate to a mixture of a dialkyl-diazo-oxopropylphosphonate and a carbonate salt in an anhydrous protic solvent to form a alkyl-(alkynyl)benzofuran carboxylate;
(f) adding the alkyl-(alkynyl)benzofuran carboxylate to a mixture of a halogenated alkyl-hydroxybenzoate and a metal oxide in an anhydrous aprotic solvent to form a alkyl-(alkoxycarbonyl)benzofuran-2-yl)alkyl)benzofuran carboxylate;
(g) passing anhydrous NH3 through an anhydrous nonpolar aprotic solvent for a period of time to form a third reaction mixture;
(h) adding a solution of a metal alkyl in a nonpolar aprotic solvent to the third reaction mixture to form a fourth reaction mixture;
(i) passing NH3 through the fourth reaction mixture for a period of time to form a fifth reaction mixture; and
(j) adding the alkyl-(alkoxycarbonyl)benzofuran-2-yl)alkyl)benzofuran carboxylate to the fifth reaction mixture to form a ((cyanobenzofuran-2-yl)alkyl)benzofuran carbonitrile.
76. A method of preparing a bis-amidoxime compound of any of Formula (I), (II) and (III), the method comprising:
(a) adding an alkali metal alcoholate to a solution of NH2OH.HCl in an anhydrous polar aprotic solvent to form a first reaction mixture;
(b) adding a benzofuran carbonitrile to the first reaction mixture to form a second reaction mixture;
(c) stirring the second reaction mixture for a period of time;
(d) pouring the second reaction mixture into ice water to form a precipitate;
(e) filtering the precipitate;
(f) washing the precipitate with a mixture of protic solvents;
(g) drying the washed precipitate; and
(h) recrystallizing the washed precipitate to form a bis-amidoxime.
77. A method for preparing a bis-alkylamidoxime of any of Formula (I), (II), and (III), the method comprising:
(a) adding an aqueous hydroxide solution to a stirred solution of a benzofuran carboxamidine in a polar aprotic solvent to form a first reaction mixture;
(b) cooling the first reaction mixture;
(c) adding a dialkyl sulfate to the cooled first reaction mixture to form a second reaction mixture;
(d) stirring the second reaction mixture for a period of time;
(e) diluting the second reaction mixture with a protic sovlent to form a residue;
(f) separating the residue;
(g) purifying the residue; and
(h) recrystallizing the residue from aqueous acid to form a bis-alkylamidoxime.
78. A method for preparing a bis-amidoxime of Formula (III), the method comprising:
(a) mixing anhydrous 1,4-dioxane and an anhydrous alkyl alcohol to form a first reaction mixture;
(b) saturating the first reaction mixture with an anhydrous gaseous acid to form a second reaction mixture;
(c) adding a bis-benzofuran carbodinitrile to the second reaction mixture to form a diimidate; and
(d) contacting the imidate with hydroxylamine in a solution of an alkali metal alcoholate in a protic solvent to form a bis-amidoxime of Formula (III).
79. A method for preparing a bis-alkylamidoxime of Formula (III), the method comprising:
(a) mixing anhydrous 1,4-dioxane and an anhydrous alkyl alcohol to form a first reaction mixture;
(b) saturating the first reaction mixture with an anhydrous gaseous acid to form a second reaction mixture;
(c) adding a benzofuran carbodinitrile to the second reaction mixture to form an imidate; and
(d) contacting the imidate with alkylhydroxylamine in a solution of an alkali metal alcoholate in a protic solvent to form a bis-alkylamidoxime of Formula (III).
The claims below are in addition to those above.
All refrences to claims which appear below refer to the numbering after this setence.
1. A system for provisioning data storage and runtime configuration in a telecommunications system or device, comprising:
a telecommunications platform including a decentralized revision control system, a data provisioning component communicably connected to the decentralized revision control system, and a client-server interface communicably connected to the data provisioning component, the client-server interface being communicably connectable to a user device,
wherein the decentralized revision control system includes a data repository operative to store, as one or more data objects, at least configuration data including real-time configuration data for the telecommunications system or device,
wherein the data provisioning component is operative to receive, from the user device via the client-server interface, at least one subscription message for subscribing to at least one of the data objects in the data repository of the decentralized revision control system, and
wherein the data provisioning component is further operative without being dependent upon network access:
to determine whether at least one characteristic of the at least one subscribed data object in the data repository of the decentralized revision control system has changed;
having determined that at least one characteristic of the at least one subscribed data object has changed, to generate at least one notification of the at least one changed characteristic of the at least one subscribed data object; and
to send the at least one notification of the at least one changed characteristic of the at least one subscribed data object to the client-user interface for notifying a user at the user device.
2. The system of claim 1 wherein the decentralized revision control system has a source code management (SCM) interface, and the data provisioning component is further operative to send at least one command to the decentralized revision control system over the SCM interface.
3. The system of claim 1 further comprising:
one or more application program components, at least one of the application program components being operative to register, with the data provisioning component, at least one application entity that requires access to the data objects stored in the data repository of the decentralized revision control system.
4. The system of claim 1 wherein the telecommunications platform is implementable as one of an access system, a network management system, a media switching center, a cross-connect, and a session border controller.
5. A method of provisioning data storage and runtime configuration in a telecommunications system or device, comprising:
providing a telecommunications platform including a decentralized revision control system, a data provisioning component communicably connected to the decentralized revision control system, and a client-server interface communicably connected to the data provisioning component, the decentralized revision control system including a data repository, the client-server interface being communicably connectable to a user device;
storing at least configuration data including real-time configuration data for the telecommunications system or device as one or more data objects in the data repository of the decentralized revision control system;
receiving, at the data provisioning component from the user device via the client-server interface, at least one subscription message for subscribing to at least one of the data objects in the data repository of the decentralized revision control system;
in a determining step, determining, by the data provisioning component, whether at least one characteristic of the at least one subscribed data object in the data repository of the decentralized revision control system has changed;
having determined that at least one characteristic of the at least one subscribed data object has changed, generating, by the data provisioning component, at least one notification of the at least one changed characteristic of the at least one subscribed data object; and
sending, by the data provisioning component, the at least one notification of the at least one changed characteristic of the at least one subscribed data object to the client-user interface for notifying a user at the user device,
wherein the determining step, the generating of the at least one notification, and the sending of the at least one notification are performed without being dependent upon network access.
6. The method of claim 5 further comprising:
registering, by one or more application program components with the data provisioning component, at least one application entity that requires access to the data objects stored in the data repository of the decentralized revision control system.
7. The method of claim 5 wherein the providing of the telecommunications platform includes implementing the telecommunications platform as one of an access system, a network management system, a media switching center, a cross-connect, and a session border controller.