What is claimed is:
1. A compound selected from the group consisting of the following formulae:
17
wherein:
A is C(R8) or N (where R8 is hydrogen, alkyl or halo);
Z1 is O, N(R9), CH2O or S(O)n (where n is 0 to 2);
Z2 is O, N(R9), OCH2 or S(O)n (where n is 0 to 2);
R1 and R4 are each independently hydrogen, halo, alkyl, nitro, OR9, C(O)OR9, C(O)N(R9)R10, N(R9)R10, N(R9)C(O)R9, or N(H)S(O)2R11;
R2 is C(NH)NH2, C(NH)N(H)OR9, C(NH)N(H)C(O)OR11, C(NH)N(H)C(O)R9, C(NH)N(H)S(O)2R11, or C(NH)N(H)C(O)N(H)R9;
R3 is hydrogen, halo, alkyl, haloalkyl, nitro, ureido, guanidino, OR9, C(NH)NH2, C(NH)N(H)OR9, C(O)N(R9)R10, R12C(O)N(R9)R10, CH(OH)C(O)N(R9)R10, N(R9)R10, R12N(R9)R10, C(O)OR9, R12C(O)OR9, N(R9)C(O)R9, (1,2)-tetrahydropyrimidinyl (optionally substituted by alkyl), (1,2)-imidazolyl (optionally substituted by alkyl), or (1,2)-imidazolinyl (optionally substituted by alkyl);
R5 and R6 are independently hydrogen, halo, alkyl, haloalkyl, nitro, N(R9)R10, C(O)OR9, C(O)N(R9)R10, C(O)N(R9)CH2C(O)N(R9)R10, N(R9)C(O)N(R9)R10 N(R9)C(O)R10, N(R9)S(O)2R11, or N(R9)C(O)N(R9)CH2C(O)N(R9)R10;
R7 is XCH2C(R13)HpC(R13)H2 or XC(C(R13)HpC(R13)H2)2H where:
p is 0 to 5;
X is O, S(O)n (where n is 0 to 2), or N(R9);
and each R13 is independently C(OR9)HmCH2OR9 (where m is 1 to 4), CH2nOR9, CH2nSR9, CH2nN(R9)R10, CH2nOC(O)R9, CH2nSC(O)R9, CH2nN(R9)C(O)R9, CH2nOC(O)OR11, CH2nN(R9)C(O)OR11, CH2nOC(O)N(R9)R10, or CH2nN(R9)C(O)N(R9)R10 (where each n is independently 0 to 2);
or R7 is selected from the group consisting of the following formulae:
18
where
q is 0 to 4;
p is 0 to 5;
each R13 is independently C(OR9)HmCH2OR9 (where m is 1 to 4), CH2nOR9, CH2nSR9, CH2nN(R9)R10, (CH2)nOC(O)R9, CH2nSC(O) R9, CH2nN(R9)C(O)R9, CH2nOC(O)OR11, CH2nN(R9)C(O)OR11, CH2nOC(O)N(R9)R10, or CH2nN(R9)C(O)N(R9)R10 (where each n is independently 0 to 2); and
each R14 is XCH2r or XCH2C(R13)Hr, where:
each r is independently 0 to 5, and
each X is O, S(O)n (where n is 0 to 2), or N(R9); and
each R13 is independently CH(OR9)mCH2OR9 (where m is 1 to 4), CH2nOR9, CH2nSR9, CH2nN(R9)R10, CH2nOC(O)R9, CH2nSC(O)R9, CH2nN(R9)C(O)R9, CH2nOC(O)OR11, CH2nN(R9)C(O)OR11, CH2nOC(O)N(R9)R10, or CH2nN(R9)C(O)N(R9)R10 (where each n is independently 0 to 2);
each R9 and R10 is independently hydrogen, alkyl, aryl (optionally substituted by halo, alkyl, hydroxy, alkoxy, aralkoxy, amino, dialkylamino, monoalkylamino, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl), or aralkyl (optionally substituted by halo, alkyl, aryl, hydroxy, alkoxy, aralkyl, amino, dialkylamino, monoalkylamino, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl);
each R11 is alkyl, aryl (optionally substituted by halo, alkyl, hydroxy, alkoxy, aralkoxy, amino, dialkylamino, monoalkylamino, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl), or aralkyl (optionally substituted by halo, alkyl, aryl, hydroxy, alkoxy, aralkyl, amino, dialkylamino, monoalkylamino, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl); and
each R12 is independently an alkylene or alkylidene chain;
as a single stereoisomer or a mixture thereof; or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 selected from formula (I):
19
as a single stereoisomer or a mixture thereof; or a pharmaceutically acceptable salt thereof.
3. The compound of claim 2 wherein:
A is N;
Z1 is O, CH2O or S(O)n (where n is 1);
Z2 is O, OCH2 or S(O)n (where n is 1);
R1 and R4 are each independently hydrogen, halo, alkyl or OR9;
R2 is C(NH)NH2, C(NH)N(H)S(O)2R11 or C(NH)N(H)C(O)N(H)R9;
R3 is ureido, guanidino, N(R9)R10, N(R9)C(O)R9, (1,2)-tetrahydropyrimidinyl (optionally substituted by alkyl), (1,2)-imidazolyl (optionally substituted by alkyl) or (1,2)-imidazolinyl (optionally substituted by alkyl);
R5 and R6 are independently hydrogen, halo, alkyl or haloalkyl;
R7 is XCH2C(R13)HpC(R13)H2 where:
p is 0 to 5;
X is O, S(O)n (where n is 0 to 2), or N(R9);
and each R13 is independently C(OR9)HmCH2OR9 (where m is 1 to 4), CH2nOR9, CH2nSR9, CH2nN(R9)R10, CH2nOC(O)R9, CH2nSC(O)R9, CH2nN(R9)C(O)R9, CH2nOC(O)OR11, CH2nN(R9)C(O)OR11, CH2nOC(O)N(R9)R10, or CHnN(R9)C(O)N(R9)R10 (where each n is independently 0 to 2);
each R9 and R10 is independently hydrogen, alkyl, aryl (optionally substituted by halo, alkyl, hydroxy, alkoxy, aralkoxy, amino, dialkylamino, monoalkylamino, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl), or aralkyl (optionally substituted by halo, alkyl, aryl, hydroxy, alkoxy, aralkyl, amino, dialkylamino, monoalkylamino, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl); and
each R11 is alkyl, aryl (optionally substituted by halo, alkyl, hydroxy, alkoxy, aralkoxy, amino, dialkylamino, monoalkylamino, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl), or aralkyl (optionally substituted by halo, alkyl, aryl, hydroxy, alkoxy, aralkyl, amino, dialkylamino, monoalkylamino, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl).
4. The compound of claim 3 wherein:
A is N;
Z1 is O;
Z2 is O;
R1 is hydrogen or OR9;
R2 is C(NH)NH2;
R3 is (1,2)-tetrahydropyrimidinyl (optionally substituted by methyl), (1,2)-imidazolyl (optionally substituted by methyl) or (1,2)-imidazolinyl (optionally substituted by methyl);
R4 is hydrogen;
R5 and R6 are each halo;
R7 is XCH2C(R13)HpC(R13)H2 where:
p is 0 to 5;
X is O;
and each R13 is independently C(OR9)HmCH2OR9 (where m is 1 to 4), CH2nOR9, CH2nSR9, CH2nN(R9)R10, CH2nOC(O)R9, CH2nSC(O)R9, CH2nN(R9)C(O)R9, CH2nOC(O)OR11, CH2nN(R9)C(O)OR11, CH2nOC(O)N(R9)R10, or CH2nN(R9)C(O)N(R9)R10 (where each n is independently 0 to 2);
each R9 and R10 is independently hydrogen or alkyl; and
each R11 is alkyl or aryl (optionally substituted by halo, alkyl, hydroxy, alkoxy, aralkoxy, amino, dialkylamino, monoalkylamino, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl).
5. The compound of claim 4 wherein:
A is N;
Z1 is O;
Z2 is O;
R1 is OR9;
R2 is C(NH)NH2;
R3 is (1,2)-imidazolyl (optionally substituted by methyl) or (1,2)-imidazolinyl (optionally substituted by methyl);
R4 is hydrogen;
R5 and R6 are both fluoro;
R7 is XCH2C(R13)HpC(R13)H2 where:
p is 0 to 5;
X is O;
and each R13 is independently C(OR9)HmCH2OR9 (where m is 1 to 4), CH2nOR9, CH2nSR9 or CH2nN(R9)R10 (where each n is independently 0 to 2); and
each R9 and R10 is independently hydrogen or alkyl.
6. The compound of claim 5 wherein:
R7is OCH2C(OH)HC(OH)H2.
7. The compound of claim 6, namely, 3-3,5-difluoro-6-(3-(1-methylimidazolin-2-yl)phenoxy)-4-(2,3-dihydroxypropoxy)pyridin-2-yloxy-4-hydroxybenzamidine.
8. The compound of claim 2 wherein:
A is N;
Z1 is O, CH2O or S(O)n (where n is 0 to 2);
Z2 is O, OCH2 or S(O)n (where n is 0 to 2);
R1 and R4 are each independently hydrogen, halo or OR9;
R2 is C(NH)NH2, C(NH)N(H)S(O)2R11 or C(NH)N(H)C(O)N(H)R9;
R3 is ureido, guanidino, N(R9)R10, N(R9)C(O)R9, (1,2)-tetrahydropyrimidinyl (optionally substituted by alkyl), (1,2)-imidazolyl (optionally substituted by alkyl), or (1,2)-imidazolinyl (optionally substituted by alkyl);
R5 and R6 are independently hydrogen, halo, alkyl or haloalkyl;
R7 is selected from the group consisting of the following formulae:
20
where
q is 0 to 4;
p is 0 to 5;
each R13 is independently C(OR9)HmCH2OR9 (where m is 1 to 4), CH2nOR9, CH2nSR9, CH2nN(R9)R10, (CH2)nOC(O)R9, CH2nSC(O)R9, CH2nN(R9)C(O)R9, CH2nOC(O)OR11, CH2nN(R9)C(O)OR11, CH2nOC(O)N(R9)R10, or CH2nN(R9)C(O)N(R9)R10 (where each n is independently 0 to 2); and
each R14 is XCH2r or XCH2C(R13)Hr where:
each r is independently 0 to 5, and
each X is O, S(O)n (where n is 0 to 2), or N(R9); and
each R13 is independently CH(OR9)mCH2OR9 (where m is 1 to 4), CH2nOR9, CH2nSR9, CH2nN(R9)R10, CH2nOC(O)R9, CH2nSC(O)R9, CH2nN(R9)C(O)R9, CH2nOC(O)OR11, CH2nN(R9)C(O)OR11, CH2nOC(O)N(R9)R10, or CH2nN(R9)C(O)N(R9)R10 (where each n is independently 0 to 2);
each R9 and R10 is independently hydrogen, alkyl, aryl (optionally substituted by halo, alkyl, hydroxy, alkoxy, aralkoxy, amino, dialkylamino, monoalkylamino, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl), or aralkyl (optionally substituted by halo, alkyl, aryl, hydroxy, alkoxy, aralkyl, amino, dialkylamino, monoalkylamino, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl);
each R11 is alkyl, aryl (optionally substituted by halo, alkyl, hydroxy, alkoxy, aralkoxy, amino, dialkylamino, monoalkylamino, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl), or aralkyl (optionally substituted by halo, alkyl, aryl, hydroxy, alkoxy, aralkyl, amino, dialkylamino, monoalkylamino, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl).
9. The compound of claim 8 wherein:
A is N;
Z1 is O;
Z2 is O;
R1 is hydrogen or OR9;
R2 is C(NH)NH2;
R3 is (1,2)-tetrahydropyrimidinyl (optionally substituted by methyl), (1,2)-imidazolyl (optionally substituted by methyl), or (1,2)-imidazolinyl (optionally substituted by methyl);
R4 is hydrogen;
R5 and R6 are each halo;
R7 is selected from the group consisting of the following formulae:
21
where
q is 0 to 4;
p is 0 to 5;
each R13 is independently C(OR9)HmCH2OR9 (where m is 1 to 4), CH2nOR9, CH2nSR9, CH2nN(R9)R10, (CH2)nOC(O)R9, CH2nSC(O)R9, CH2nN(R9)C(O)R9, CH2nOC(O)OR11, CH2nN(R9)C(O)OR11, CH2nOC(O)N(R9)R10, or CH2nN(R9)C(O)N(R9)R10 (where each n is independently 0 to 2); and
each R14 is XCH2r or XCH2C(R13)Hr, where:
each r is independently 0 to 5, and
each X is O, S(O)n (where n is 0 to 2), or N(R9); and
each R13 is independently CH(OR9)mCH2OR9 (where m is 1 to 4), CH2nOR9, CH2nSR9, CH2nN(R9)R10, CH2nOC(O)R9, CH2nSC(O)R9, CH2nN(R9)C(O)R9, CH2nOC(O)OR11, CH2nN(R9)C(O)OR11, CH2nOC(O)N(R9)R10, or CH2rN(R9)C(O)N(R9)R10 (where each n is independently 0 to 2);
each R9 and R10 is independently hydrogen or alkyl; and
each R11 is independently alkyl or aryl (optionally substituted by halo, alkyl, hydroxy, alkoxy, aralkoxy, amino, dialkylamino, monoalkylamino, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl).
10. The compound of claim 9 wherein:
A is N;
Z1 is O;
Z2 is O;
R1 is OR9;
R2 is C(NH)NH2;
R3 is (1,2)-imidazolyl (optionally substituted by methyl), or (1,2)-imidazolinyl (optionally substituted by methyl);
R4 is hydrogen;
R5 and R6 are both fluoro;
R7 is selected from the group consisting of the following formulae:
22
where
q is 0 to 4;
p is 0 to 5;
each R13 is independently C(OR9)HmCH2OR9 (where m is 1 to 4), CH2nOR9, CH2nSR9 or CH2nN(R9)R10 (where each n is independently 0 to 2); and
each R14 is XCH2r or XCH2C(R13)Hr, where:
each r is independently 0 to 5, and
each X is independently O, S(O)n (where n is 0 to 2), or N(R9); and
each R13 is independently CH(OR9)mCH2OR9 (where m is 1 to 4), CH2nOR9, CH2nSR9 or CH2nN(R9)R10; and
each R9 and R10 is independently hydrogen or alkyl.
11. The compound of claim 10 wherein R7 is:
23
where
q is 0 to 4;
each R13 is independently C(OR9)HmCH2OR9 (where m is 1 to 4), CH2nOR9, CH2nSR9 or CH3nN(R9)R10 (where each n is independently 0 to 2); and
each R14 is XCH2r or XCH2C(R13)Hr, where:
each r is independently 0 to 5, and
each X is independently O, S(O)n (where n is 0 to 2), or N(R9); and
each R13 is independently CH(OR9)mCH2OR9 (where m is 1 to 4), CH2nOR9, CH2nSR9 or CH2nN(R9)R10; and
each R9 and R10 is independently hydrogen or alkyl.
12. The compound of claim 11 wherein R7 is:
24
where
q is 0 to 4;
each R13 is independently C(OR9)HmCH2OR9 (where m is 1 to 4), CH2nOR9, CH2nSR9 or CH2nN(R9)R10 (where each n is independently 0 to 2); and
each R14 is XCH2r where:
r is 0 to 5, and
X is O, S(O)n (where n is 0 to 2), or N(R9); and
each R9 and R10 is independently hydrogen or alkyl.
13. The compound of claim 12 wherein R7 is:
25
where
q is 0 to 4;
each R13 is independently C(OR9)HmCH2OR9 (where m is 1 to 4), CH2nOR9 or CH2nN(R9)R10 (where each n is independently 0 to 2); and
each R14 is XCH2r where:
r is 0 or 1, and
X is O; and
each R9 and R10 is independently hydrogen or alkyl.
14. The compound of claim 13 wherein R7 is:
26
where R14 is O; q is 3 and one R13 is in the 4-position of the tetrahydrofuranyl ring and is hydroxy, the second R13 is in the 2-position of the tetrahydrofuranyl ring and is 2,3-dihydroxyethyl and the third R13 is in the 5-position of the tetrahydrofuranyl ring and is ethoxy.
15. The compound of claim 14, namely, 3-3,5-difluoro-6-(3 (1-methylimidazolin-2-yl)phenoxy)-4-2-(1,2-dihydoxyethyl)-4-hydroxy-5-ethoxytetrahydrofuran-3-yloxypyridin-2-yloxy-4-hydroxybenzamidine.
16. A pharmaceutical composition useful in treating a human having a disease-state characterized by thrombotic activity, which composition comprises a therapeutically effective amount of a compound selected from the group consisting of the following formulae:
27
wherein:
A is C(R8) or N (where R8 is hydrogen, alkyl or halo);
Z1 is O, N(R9), CH2O or S(O)n (where n is 0 to 2);
Z2 is O, N(R9), OCH2 or S(O)n (where n is 0 to 2);
R1 and R4 are each independently hydrogen, halo, alkyl, nitro, OR9, C(O)OR9, C(O)N(R9)R10, N(R9)R10, N(R9)C(O)R9, or N(H)S(O)2R11;
R2 is C(NH)NH2, C(NH)N(H)OR9, C(NH)N(H)C(O)OR11, C(NH)N(H)C(O)R9, C(NH)N(H)S(O)2R11, or C(NH)N(H)C(O)N(H)R9;
R3 is hydrogen, halo, alkyl, haloalkyl, nitro, ureido, guanidino, OR9, C(NH)NH2, C(NH)N(H)OR9, C(O)N(R9)R10, R12C(O)N(R9)R10, CH(OH)C(O)N(R9)R10, N(R9)R10, R12N(R9)R10, C(O)OR9, R12C(O)OR9, N(R9)C(O)R9, (1,2)-tetrahydropyrimidinyl (optionally substituted by alkyl), (1,2)-imidazolyl (optionally substituted by alkyl), or (1,2)-imidazolinyl (optionally substituted by alkyl);
R5 and R3 are independently hydrogen, halo, alkyl, haloalkyl, nitro, N(R9)R10, C(O)OR9, C(O)N(R9)R10, C(O)N(R9)CH2C(O)N(R9)R10, N(R9)C(O)N(R9)R10, N(R9)C(O)R10, N(R9)S(O)2R11, or N(R9)C(O)N(R9)CH2C(O)N(R9)R10;
R7 is XCH2C(R13)HpC(R13)H2 or XC(C(R13)HpC(R13)H2)2H where:
p is 0 to 5;
X is O, S(O)n (where n is 0 to 2), or N(R9);
and each R13 is independently C(OR9)HmCH2OR9 (where m is 1 to 4), CH2nOR9, CH2nSR9, CH2nN(R9)R10, CH2nOC(O)R9, CH2nSC(O)R9, CH2nN(R9)C(O)R9, CH2nOC(O)OR11, CH2nN(R9)C(O)OR11, CH2nOC(O)N(R9)R10, or CH2nN(R9)C(O)N(R9)R10 (where each n is independently 0 to 2);
or R7 is selected from the group consisting of the following formulae:
28
where
q is 0 to 4;
p is 0 to 5;
each R13 is independently C(OR9)HmCH2OR9 (where m is 1 to 4), CH2nOR9, CH2nSR9, CH2nN(R9)R10, (CH2)nOC(O)R9, CH2nSC(O)R9, CH2nN(R9)C(O)R9, CH2nOC(O)OR11, CH2nN(R9)C(O)OR11, CH2nOC(O)N(R9)R10, or CH2nN(R9)C(O)N(R9)R10 (where each n is independently 0 to 2); and
each R14 is XCH2r or XCH2C(R13)Hr, where:
each r is independently 0 to 5, and
each X is O, S(O)n (where n is 0 to 2), or N(R9); and
each R13 is independently CH(OR9)mCH2OR9 (where m is 1 to 4), CH2nOR9, CH2nSR9, CH2nN(R9)R10, CH2nOC(O)R9, CH2nSC(O)R9, CH2nN(R9)C(O)R9, CH2nOC(O)OR11, CH2nN(R9)C(O)OR11, CH2nOC(O)N(R9)R10, or CH2nN(R9)C(O)N(R9)R10 (where each n is independently 0 to 2);
each R9 and R10 is independently hydrogen, alkyl, aryl (optionally substituted by halo, alkyl, hydroxy, alkoxy, aralkoxy, amino, dialkylamino, monoalkylamino, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl), or aralkyl (optionally substituted by halo, alkyl, aryl, hydroxy, alkoxy, aralkyl, amino, dialkylamino, monoalkylamino, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl);
each R11 is alkyl, aryl (optionally substituted by halo, alkyl, hydroxy, alkoxy, aralkoxy, amino, dialkylamino, monoalkylamino, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl), or aralkyl (optionally substituted by halo, alkyl, aryl, hydroxy, alkoxy, aralkyl, amino, dialkylamino, monoalkylamino, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl); and
each R12 is independently an alkylene or alkylidene chain;
as a single stereoisomer or a mixture thereof; or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable excipient.
17. A method of treating a human having a disease-state characterized by thrombotic activity, which method comprises administering to a human in need thereof a therapeutically effective amount of a compound selected from the group consisting of the following formulae:
29
wherein:
A is C(R8) or N (where R8 is hydrogen, alkyl or halo);
Z1 is O, N(R9), CH2O or S(O)n (where n is 0 to 2);
Z2 is O, N(R9), OCH2 or S(O)n (where n is 0 to 2);
R1 and R4 are each independently hydrogen, halo, alkyl, nitro, OR9, C(O)OR9, C(O)N(R9)R10, N(R9)R10, N(R9)C(O)R9, or N(H)S(O)2R11;
R2 is C(NH)NH2, C(NH)N(H)OR9, C(NH)N(H)C(O)OR11, C(NH)N(H)C(O)R9, C(NH)N(H)S(O)2R11, or C(NH)N(H)C(O)N(H)R9;
R3 is hydrogen, halo, alkyl, haloalkyl, nitro, ureido, guanidino, OR9, C(NH)NH2, C(NH)N(H)OR9, C(O)N(R9)R10, R12C(O)N(R9)R10, CH(OH)C(O)N(R9)R10, N(R9)R10, R12N(R9)R10, C(O)OR9, R12C(O)OR9, N(R9)C(O)R9, (1,2)-tetrahydropyrimidinyl (optionally substituted by alkyl), (1,2)-imidazolyl (optionally substituted by alkyl), or (1,2)-imidazolinyl (optionally substituted by alkyl);
R5 and R6 are independently hydrogen, halo, alkyl, haloalkyl, nitro, N(R9)R10, C(O)OR9, C(O)N(R9)R10, C(O)N(R9)CH2C(O)N(R9)R10, N(R9)C(O)N(R9)R10, N(R9)C(O)R10, N(R9)S(O)2R11, or N(R9)C(O)N(R9)CH2C(O)N(R9)R10;
R7 is XCH2C(R13)HpC(R13)H2 or XC(C(R13)HpC(R13)H2)2H where:
p is 0 to 5;
X is O, S(O)n (where n is 0 to 2), or N(R9);
and each R13 is independently C(OR9)HmCH2OR9 (where m is 1 to 4), CH2nOR9, CH2nSR9, CH2nN(R9)R10, CH2nOC(O)R9, CH2nSC(O)R9, CH2nN(R9)C(O)R9, CH2nOC(O)OR11, CH2nN(R9)C(O)OR11, CH2nOC(O)N(R9)R10, or CH2nN(R9)C(O)N(R9)R10 (where each n is independently 0 to 2);
or R7 is selected from the group consisting of the following formulae:
30
where
q is 0 to 4;
p is 0 to 5;
each R13 is independently C(OR9)HmCH2OR9 (where m is 1 to 4), CH2nOR9, CH2nSR9, CH2nN(R9)R10, (CH2)nOC(O)R9, CH2nSC(O)R9, CH2nN(R9)C(O)R9, CH2nOC(O)OR11, CH2nN(R9)C(O)OR11, CH2nOC(O)N(R9)R10, or CH2nN(R9)C(O)N(R9)R10 (where each n is independently 0 to 2); and
each R14 is XCH2r or XCH2C(R13)Hr where:
each r is independently 0 to 5, and
each X is O, S(O)n (where n is 0 to 2), or N(R9); and
each R13 is independently CH(OR9)mCH2OR9 (where m is 1 to 4), CH2nOR9, CH2nSR9, CH2nN(R9)R10, CH2nOC(O)R9, CH2nSC(O)R9, CH2nN(R9)C(O)R9, CH2nOC(O)OR11, CH2nN(R9)C(O)OR11, CH2nOC(O)N(R9)R10, or CH2nN(R9)C(O)N(R9)R10 (where each n is independently 0 to 2);
each R9 and R10 is independently hydrogen, alkyl, aryl (optionally substituted by halo, alkyl, hydroxy, alkoxy, aralkoxy, amino, dialkylamino, monoalkylamino, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl), or aralkyl (optionally substituted by halo, alkyl, aryl, hydroxy, alkoxy, aralkyl, amino, dialkylamino, monoalkylamino, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl);
each R11 is alkyl, aryl (optionally substituted by halo, alkyl, hydroxy, alkoxy, aralkoxy, amino, dialkylamino, monoalkylamino, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl), or aralkyl (optionally substituted by halo, alkyl, aryl, hydroxy, alkoxy, aralkyl, amino, dialkylamino, monoalkylamino, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, monoalkylaminocarbonyl, or dialkylaminocarbonyl); and
each R12 is independently an alkylene or alkylidene chain;
as a single stereoisomer or a mixture thereof; or a pharmaceutically acceptable salt thereof.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A device for use for forming an aperture in structure formed from unsolidified material that is capable of solidifying to a hard state, comprising:
a strand of flexible material that is helically coiled in the form of a preformed elongated member having adjacent coils between opposite ends of said preformed member removably bonded together and having a given outside diameter such that said preformed member may be embedded in unsolidified material with one of said ends extending at least close to a surface of said material such that when said material solidifies, said one end of said strand may be pulled to break the bonds between adjacent coils of said strand to remove said strand from said solidified material to form an aperture in said solidified material from the surface.
2. The device of claim 1, wherein:
said strand is formed of flexible plastic material helically coiled to form said preformed member.
3. The device of claim 1, wherein:
said preformed member has an aperture extending from said one end through the other of said ends with a cap coupled to said one end of said strand partially covering said aperture at said one end.
4. The device of claim 3, comprising:
gripping means coupled to said cap to facilitate removal of said preformed member from said solidified material.
5. The device of claim 3, wherein:
said strand is formed of flexible plastic material helically coiled to form said preformed member.
6. The device of claim 4, wherein:
said strand is formed of flexible plastic material helically coiled to form said preformed member.
7. The device of claim 1, wherein:
said strand is helically coiled to form said preformed member with an aperture extending from said one end to the other of said ends with said aperture at said other end being closed.
8. A method of forming an aperture into structure formed from unsolidified material that is capable of solidifying to a hard state comprising the steps of:
embedding an elongated preformed member having two opposite ends, in said unsolidified material with one of said ends located close to a surface of said material,
said preformed member comprises a strand of flexible material that is helically coiled and has adjacent coils which are removably bonded together and having a given outside diameter,
after said material solidifies, pulling said one end of said strand to separate the bonds between adjacent coils of said strand to remove said strand from said solidified material to form an aperture in said solidified material from said surface.
9. The method of claim 8, wherein:
said preformed member is embedded in said material when in an unsolidified state by pushing the other of said ends of said preformed member into said unsolidified material until said one end of said preformed member is located close to said surface of said material.
10. The method of claim 8, wherein:
said preformed member is embedded in said material when in an unsolidified state by attaching said preformed member to a support member, and
placing said unsolidified material around said preformed member with said one end located close to said surface of said material.
11. The method of claim 8, wherein:
said material of said structure comprises concrete.