What is claimed:
1. A method of inhibiting plasminogen activator inhibitor-1 (PAI-1) in a mammal, the method comprising administering to a mammal in need thereof a pharmaceutically effective amount of a compound of the formula:
11
wherein
A is C or N;
B is O, S, N, or CHCH;
12
X is CO, CH(OH), CH2, or CHS-2-benzothiazole;
Y is hydrogen, alkyl of 1-6 carbon atoms, or halogen;
Z is O, S, or N;
R is hydrogen, nitro, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, or trifluoromethyl;
R1 is alkyl of 1-12 carbon atoms, aryl of 6-10 carbon atoms, aralkyl of 7-15 carbon atoms, halogen, Het-alkyl wherein the alkyl moiety contains 1-6 carbon atoms, or aryl mono-, di- or tri-substituted with a substituent selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, trifluoromethyl, and alkoxy of 1-6 carbon atoms;
Het is
13
G is O, S, or N;
R2 is hydrogen, halogen, alkyl of 1-6 carbon atoms, or OR5
R3 and R4 are each, independently, hydrogen, halogen, alkyl of 1-8 carbon atoms, aryl of 6-12 carbon atoms, nitro, amino, alkylsulfoamide, arylsulfoamide, cycloalkyl of 3-8 carbon atoms, heterocycle of 5 to 7 ring atom containing from 1 to 3 heteroatoms selected from oxygen, nitrogen, or sulfur, or aryl of 6-10 carbon atoms mono-, di- or tri-substituted with a substituent selected from the group consisting of halogen, alkyl of 1-6 carbon atoms, trifluoromethyl, alkoxy of 1-6 carbon atoms;
R5 is hydrogen, alkyl of 1-6 carbon atoms, CH(R7)R8, C(CH2)nCO2R9, C(CH3)2CO2R9, CH(R7)(CH2)nCO2R9, or CH(R7)C6H4CO2R9;
R6 is alkylene of 1-3 carbon atoms;
R7 is hydrogen, alkyl of 1-6 carbon atoms, aryl of 6-12 carbon atoms, aralkyl of 6-12 carbon atoms, cycloalkyl of 3-8 carbon atoms, phthalic acid, or Q-alkyl wherein the alkyl moiety contains 1-6 carbon atoms;
Q is
14
R8 is CO2R11, CONHR11, tetrazole, or PO3R11;
R9 is hydrogen, alkyl of 1-6 carbon atoms, aryl of 6-12 carbon atoms, or aralkyl of 7-15 carbon atoms;
W is O, N, or S;
R11 is hydrogen, alkyl of 1-6 carbon atoms, aryl of 6-12 carbon atoms, or aralkyl of 7-15 carbon atoms;
n1-6;
or a pharmaceutically acceptable salt or ester form thereof.
2. A method of claim 1 wherein the compound is selected from the group of:
6-(2-butyl-benzofuran-3-yl)-hydroxy-methyl-naphthalen-2-ol;
6-(2-butyl-benzofuran-3-ylmethyl)-naphthalen-2-ol;
1-bromo-6-(2-butyl-benzofuran-3-ylmethyl)-naphthalen-2-ol;
1-bromo-6-(2-butyl-benzofuran-3-ylmethyl)-naphthalen-2-yloxy-acetic acid; or
2-1-bromo-6-(2-butyl-benzofuran-3-ylmethyl)-naphthalen-2-yloxy-3-phenyl-propionic acid;
or a pharmaceutically acceptable salt or ester form thereof.
3. A method of claim 1 wherein the compound is selected from the group of:
5-1-bromo-6-(2-butyl-benzofuran-3-ylmethyl)-naphthalen-2-yloxymethyl-1H-tetrazole;
6-(2-butyl-benzofuran-3-ylmethyl)-1-iodo-naphthalen-2-ol;
2–6-(2-butyl-benzofuran-3-ylmethyl)-1-iodo-naphthalen-2-yloxy-3-phenyl-propionic acid;
1-bromo-6-(2-butyl-benzofuran-3-yl)-hydroxy-methyl-naphthalen-2-ol;
1-bromo-6-(2-butyl-benzofuran-3-carbonyl)-naphthalen-2-yloxy-acetic acid; or a pharmaceutically acceptable salt or ester form thereof.
4. A method of claim 1 wherein the compound is selected from the group of:
2-1-bromo-6-(2-butyl-benzofuran-3-carbonyl)-naphthalen-2-yloxy-3-phenyl -propionic acid;
5-bromo-6-(1H-tetrazol-5-ylmethoxy)-naphthalen-2-yl-(2-butyl-benzofuran-3-yl) -methanone;
6-(2-benzyl-benzobthiophen-3-ylmethyl)-1-bromo-naphthalen-2-ol;
4-(2-butyl-benzofuran-3-yl)-hydroxy-methyl-biphenyl-4-ol; or
(2-butyl-benzofuran-3-yl)-(4-hydroxy-biphenyl-4-yl)-methanone;
or a pharmaceutically acceptable salt or ester form thereof.
5. A method of claim 1 wherein the compound is selected from the group of:
4-(2-butyl-benzofuran-3-ylmethyl-biphenyl-4-ol;
4-(2-butyl-benzofuran-3-ylmethyl-biphenyl-4-yloxy-acetic acid;
5-4-(2-butyl-benzofuran-3-ylmethyl)-biphenyl-4-yloxymethyl-1H-tetrazole;
4-(2-butyl-benzofuran-3-yl)-hydroxy-methyl-biphenyl-4-yloxy-acetic acid;
3,5-dibromo-4-(2-butyl-benzofuran-3-yl)-hydroxy-methyl-biphenyl-4-ol; or
4-(2-benzyl-benzobthiophen-3-yl)-hydroxy-methyl-biphenyl-4-ol;
or a pharmaceutically acceptable salt or ester form thereof.
6. A method of claim 1 wherein the compound is selected from the group of:
(2-butyl-benzofuran-3-yl)-5-(4-methoxy-phenyl)-oxazol-2-yl-methanol;
(2-butyl-benzofuran-3-yl)-5-(4-methoxy-phenyl)-oxazol-2-yl-methanone;
2-(2-butyl-benzofuran-3-ymethyl)-5-(4-methoxy-phenyl)-oxazole;
4-bromo-5-(4-methoxy-phenyl)-oxazol-2-yl-(2-butyl-benzofuran-3-yl)-methanone; or
4-bromo-5-(6-bromo-2-butyl-benzofuran-3-ylmethyl)-5-(4-methoxy-phenyl)-oxazole;
or a pharmaceutically acceptable salt or ester form thereof.
7. A method of claim 1 wherein the compound is selected from the group of:
6-(benzothiazol-2-ylsulfanyl)-(2-butyl-benzofuran-3-yl)-methyl-naphthalen-2-ol;
4-(2-butyl-benzofuran-3-yl)-(benzothiazol-2-ylsulfanyl)-methyl-biphenyl-4-ol;
2-1-(benzobthiophen-2-yl)-octylsulfanyl-benzothiazole;
2-(4-bromo-phenyl)-(2-butyl-benzofuran-3-yl)-methylsulfanyl-benzothiazole; or
2-(4-bromo-naphthalen-1-yl)-(2-butyl-benzofuran-3-yl)-methylsulfanyl-benzothiazole;
or a pharmaceutically acceptable salt or ester form thereof.
8. A method of claim 1 wherein the compound is selected from the group of:
2-(2-butyl-benzofuran-3-yl)-phenyl-methylsulfanyl-benzothiazole;
2,6-dibromo-4-(naphthalene-2-carbonyl)-phenoxy-acetic acid; or
5-2,6-dibromo-4-(naphthalen-2-ylmethyl)-phenoxymethyl-1H-tetrazole;
or a pharmaceutically acceptable salt or ester form thereof.
9. A method for treatment of thrombosis or fibrinolytic impairment in a mammal, the method comprising administering to a mammal in need thereof a pharmaceutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt or ester form thereof.
10. A method of claim 9 wherein the thrombosis or fibrinolytic impairment is associated with formation of atherosclerotic plaques, venous and arterial thrombosis, myocardial ischemia, atrial fibrillation, deep vein thrombosis, coagulation syndromes, pulmonary fibrosis, cerebral thrombosis, thromboembolic complications of surgery or peripheral arterial occlusion.
11. A method for the treatment of stroke associated with or resulting from atrial fibrillation in a mammal, comprising administering to a mammal in need thereof a pharmaceutically effective amount of a compound of claim 1.
12. A method for the treatment of deep vein thrombosis in a mammal, comprising administering to a mammal in need thereof a pharmaceutically effective amount of a compound of claim 1.
13. A method for the treatment of myocardial ischemia in a mammal, comprising administering to a mammal in need thereof a pharmaceutically effective amount of a compound of claim 1.
14. A method for the treatment of cardiovascular disease caused by noninsulin dependent diabetes mellitus in a mammal, comprising administering to a mammal in need thereof a pharmaceutically effective amount of a compound of claim 1.
15. A method for the treatment of the formation of atherosclerotic plaques in a mammal, comprising administering to a mammal in need thereof a pharmaceutically effective amount of a compound of claim 1.
16. A method for the treatment of chronic obstructive pulmonary disease in a mammal, comprising administering to a mammal in need thereof a pharmaceutically effective amount of a compound of claim 1.
17. A method for the treatment of renal fibrosis in a mammal, comprising administering to a mammal in need thereof a pharmaceutically effective amount of a compound of claim 1.
18. A method for the treatment of polycystic ovary syndrome in a mammal, comprising administering to a mammal in need thereof a pharmaceutically effective amount of a compound of claim 1.
19. A method for the treatment of Alzheimer’s disease in a mammal, comprising administering to a mammal in need thereof a pharmaceutically effective amount of a compound of claim 1.
20. A method for the treatment of cancer in a mammal, comprising administering to a mammal in need thereof a pharmaceutically effective amount of a compound of claim 1.
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 composition comprising:
a) at least one polydiorganosiloxane having at least two olefinically unsaturated groups as component (a),
b) at least one organohydrogenpolysiloxane as component (b),
c) at least one alkylsiloxane having at least one carbinol, carboxy or amino group as component (c),
d) at least one condensation cure compound as component (d) and
e) at least one addition cure precious metal catalyst as component (e);
wherein component (c) contains at least one compound of the formula:
R13Si\u2014O\u2014SiR12\u2014O\u2014aSiR12\u2014Y\u2014(O\u2014R2)d\u2014Xe\u2014(O\u2014R2)b\u2014OHc\u2003\u2003(II) or
HO\u2014(R2\u2014O)bc\u2014Xe\u2014(R2\u2014O)d\u2014Y\u2014SiR12\u2014O\u2014aSiR12\u2014Y\u2014(O\u2014R2)d\u2014Xe\u2014(O\u2014R2)b\u2014OHc\u2003\u2003(III) or
R13Si\u2014O\u2014SiR12\u2014O\u2014aSiR12\u2014Y\u2014(O\u2014R2)d\u2014Xe-Zf-COOHc\u2003\u2003(IV) or
HOOC\u2014Zfc\u2014Xe\u2014(R2\u2014O)d\u2014Y\u2014SiR12\u2014O\u2014aSiR12\u2014Y\u2014(O\u2014R2)d\u2014Xe-Zf-COOHc\u2003\u2003(V) or
R13Si\u2014O\u2014{SiR12\u2014O\u2014nSiR1(\u2014Y\u2014(O\u2014R2)d\u2014Xe-Zf-COOHc)\u2014O\u2014m}\u2014SiR13\u2003\u2003(Va) or
R13Si\u2014O\u2014SiR12\u2014O\u2014aSiR12\u2014Y\u2014(O\u2014R2)d-Te-(O\u2014R2)b\u2014NHR3c\u2003\u2003(VI) or
R3HN\u2014(R2\u2014O)bc-Te-(R2\u2014O)d\u2014Y\u2014SiR12\u2014O\u2014aSiR12\u2014Y\u2014(O\u2014R2)d-Te-(O\u2014R2)b\u2014NHR3c\u2003\u2003(VII) or
R13Si\u2014O\u2014{SiR12\u2014O\u2014nSiR4(\u2014Y\u2014(O\u2014R2)d-Te-(O\u2014R2)b\u2014NHR3c)\u2014O\u2014m}\u2014SiR13\u2003\u2003(VIIa) or
wherein:
X is a linear or branched hydrocarbon or an aryl residue that may contain an oxygen atom andor an ether group with 6 to 14 C-atoms and a valency of c,
Y is a linear or branched alkylene group with 1 to 10 C-atoms or a cycloalkyl group with 4 to 14 C-atoms,
Z is a linear or branched alkylene or alkenylene or aryl group that may contain an ester group with 1 to 16 C-atoms,
T is a linear or branched hydrocarbon or an aryl residue that may contain an oxygen atom andor an ether group with 6 to 14 C-atoms and a valency of c,
for formulas II, III, IIIb, VI, VII, VIIa, and VIIb, R1 is a linear or branched alkyl or fluoroalkyl group with 1 to 8 C-atoms or a cycloalkyl or aryl group with 6 to 14 C-atoms,
for formulas IV, V, Va, and Vb, R1 is a linear or branched alkyl or fluoroalkyl group with 1 to 8 C-atoms or a cycloalkyl or aryl group with 4 to 14 C-atoms,
R2 is a linear or branched alkylene group that may contain a carbonyl group with 1 to 8 C-atoms,
D is R1 or \u2014Y\u2014(O\u2014R2)d\u2014Xe\u2014(O\u2014R2)b\u2014OHc with at least one residue \u2014Y\u2014(O\u2014R2)d\u2014Xe\u2014(O\u2014R2)b\u2014OHc per molecule,
E is R1 or \u2014Y\u2014(O\u2014R2)d\u2014Xe-Zf-COOHc with at least one residue \u2014Y\u2014(O\u2014R2)d\u2014Xe-Zf-COOHc per molecule,
F is R1 or \u2014Y\u2014(O\u2014R2)d-Te-(O\u2014R2)b\u2014NHR3c with at least one residue \u2014Y\u2014(O\u2014R2)d-Te-(O\u2014R2)b\u2014NHR3c per molecule,
R3 is a linear or branched alkyl or fluoroalkyl group with 1 to 8 C-atoms or a cycloalkyl or aryl group with 6 to 14 C-atoms or H,
R4 is R1 or methoxy or ethoxy,
1\u2266a\u226610,000,
for formulas II, III, IIIb, 0\u2266b\u2266500,
for formulas VI, VII, VIIa, and VIIb, 0\u2266b\u226610,000,
1\u2266c\u22666,
0\u2266d\u2266500,
e is 0 or 1,
f is 0 or 1,
0\u2266n\u2266500 and 0\u2266m\u2266100 where m+n exceeds 5,
x is 0, 1, 2, 3, 4, 5 or 6.
2. The composition according to claim 1 further comprising one or more adjuvants as component (f).
3. The composition according to claim 1 comprising the following components in the following amounts:
a) 2.5 to 40 weight percent of component (a),
b) 0.2 to 10 weight percent of component (b),
c) 0.5 to 8 weight percent of component (c),
d) 0.1 to 7 weight percent of component (d),
e) 0.05 to 4 weight percent of component (e), based on elemental Pt, and
f) 31 to 96.65 weight percent adjuvants as component (t),
wherein the components add up to 100 weight percent.
4. The composition according to claim 3, wherein the adjuvant is selected from the group consisting of inert carrier materials, inhibitors, fillers, pigments or solvents.
5. A method for the preparation of the composition according to claim 1, said method comprising a step of thoroughly mixing the components in any order.
6. A method for the preparation of an impression of an object, wherein the surface of the object is brought into contact with the composition of claim 1.
7. The method according to claim 6, characterized in that the object is a surface within the oral cavity of a human.
8. The method according to claim 6, further comprising thoroughly mixing the components of claim 1 in any order to form the composition.
9. A dental filling or dental prosthesis, obtained from an impression taken with a composition of claim 1.
10. A two part system comprising parts A and B, wherein part A comprises:
a) at least one polydiorganosiloxane having at least two olefinically unsaturated groups as component (a),
b) at least one organohydrogenpolysiloxane as component (b), and
c) at least one alkylsiloxane having at least one carbinol, carboxy or amino group as component (c), wherein component (c) contains at least one compound of the formula:
R13Si\u2014O\u2014SiR12\u2014O\u2014aSiR12\u2014Y\u2014(O\u2014R2)d\u2014Xe\u2014(O\u2014R2)b\u2014OHc\u2003\u2003(II) or
HO\u2014(R2\u2014O)bc\u2014Xe\u2014(R2\u2014O)d\u2014Y\u2014SiR12\u2014O\u2014aSiR12\u2014Y\u2014(O\u2014R2)d\u2014Xe\u2014(O\u2014R2)b\u2014OHc\u2003\u2003(III) or
R13Si\u2014O\u2014{SiR12\u2014O\u2014nSiR1(\u2014Y\u2014(O\u2014R2)d\u2014Xe\u2014(O\u2014R2)b\u2014OHc)\u2014O\u2014m}\u2014SiR13\u2003\u2003(IIIa) or
R13Si\u2014O\u2014SiR12\u2014O\u2014aSiR12\u2014Y\u2014(O\u2014R2)d\u2014Xe-Zf-COOHc\u2003\u2003(IV) or
HOOC\u2014Zfc\u2014Xe\u2014(R2\u2014O)d\u2014Y\u2014SiR12\u2014O\u2014aSiR12\u2014Y\u2014(O\u2014R2)d\u2014Xe-Zf-COOHc\u2003\u2003(V) or
R13Si\u2014O\u2014{SiR12\u2014O\u2014nSiR1(\u2014Y\u2014(O\u2014R2)d\u2014Xe-Zf-COOHc)\u2014O\u2014m}\u2014SiR13\u2003\u2003(Va) or
R13Si\u2014O\u2014SiR12\u2014O\u2014aSiR12\u2014Y\u2014(O\u2014R2)d-Te-(O\u2014R2)b\u2014NHR3c\u2003\u2003(VI) or
R3HN\u2014(R2\u2014O)bc-Te-(R2\u2014O)d\u2014Y\u2014SiR12\u2014O\u2014aSiR12\u2014Y\u2014(O\u2014R2)d-Te-(O\u2014R2)b\u2014NHR3c\u2003\u2003(VII) or
R13Si\u2014O\u2014{SiR12\u2014O\u2014nSiR4(\u2014Y\u2014(O\u2014R2)d-Te-(O\u2014R2)b\u2014NHR3c)\u2014O\u2014m}\u2014SiR13\u2003\u2003(VIIa) or
wherein:
X is a linear or branched hydrocarbon or an aryl residue that may contain an oxygen atom andor an ether group with 6 to 14 C-atoms and a valency of c,
Y is a linear or branched alkylene group with 1 to 10 C-atoms or a cycloalkyl group with 4 to 14 C-atoms,
Z is a linear or branched alkylene or alkenylene or aryl group that may contain an ester group with 1 to 16 C-atoms,
T is a linear or branched hydrocarbon or an aryl residue that may contain an oxygen atom andor an ether group with 6 to 14 C-atoms and a valency of c,
for formulas II, III, IIIa, IIIb, VI, VII, VIIa, and VIIb, R1 is a linear or branched alkyl or fluoroalkyl group with 1 to 8 C-atoms or a cycloalkyl or aryl group with 6 to 14 C-atoms,
for formulas IV, V, Va, and Vb, R1 is a linear or branched alkyl or fluoroalkyl group with 1 to 8 C-atoms or a cycloalkyl or aryl group with 4 to 14 C-atoms,
R2 is a linear or branched alkylene group that may contain a carbonyl group with 1 to 8 C-atoms,
D is R1 or \u2014Y\u2014(O\u2014R2)d\u2014Xe\u2014(O\u2014R2)b\u2014OHc with at least one residue \u2014Y\u2014(O\u2014R2)d\u2014Xe\u2014(O\u2014R2)b\u2014OHc per molecule,
E is R1 or \u2014Y\u2014(O\u2014R2)d\u2014Xe-Zf-COOHc with at least one residue \u2014Y\u2014(O\u2014R2)d\u2014Xe-Zf-COOHc per molecule,
F is R1 or \u2014Y\u2014(O\u2014R2)d-Te-(O\u2014R2)b\u2014NHR3c with at least one residue \u2014Y\u2014(O\u2014R2)d-Te-(O\u2014R2)b\u2014NHR3c per molecule,
R3 is a linear or branched alkyl or fluoroalkyl group with 1 to 8 C-atoms or a cycloalkyl or aryl group with 6 to 14 C-atoms or H,
R4 is R1 or methoxy or ethoxy,
1\u2266a\u226610,000,
for formulas II, III, IIIa, IIIb, 0\u2266b\u2266500,
for formulas VI, VII, VIIa, and VIIb, 0\u2266b\u226610,000,
1\u2266c\u22666,
0\u2266d\u2266500,
e is 0 or 1,
f is 0 or 1,
0\u2266n\u2266500 and 0\u2266m\u2266100 where m+n exceeds 5,
x is 0, 1, 2, 3, 4, 5 or 6
and part B comprises:
d) at least one condensation cure component as component (d) and
e) at least one addition cure precious metal catalyst as component (e).
11. The system according to claim 10, wherein part A contains the following components in the following amounts:
i) 8 to 25% by weight of component (a),
ii) 1 to 10 weight percent of component (b),
iii) 0.5 to 10 weight percent of component (c) and
iv) 55 to 90.5 weight percent of adjuvants,
wherein the components add up to 100 weight percent.
12. The system according to claim 11, wherein the adjuvant is selected from the group consisting of inert carrier materials, inhibitors, fillers, pigments or solvents.
13. The system according to claim 10, wherein part B contains the following components in the following amounts:
i) 0.5 to 10 weight percent of component (d),
ii) 0.1 to 5 weight percent of component (e), based on elemental Pt, and
iii) 85 to 99.4 weight percent of adjuvants,
wherein the components add up to 100 weight percent.
14. A method for the preparation of the two-part system according to claim 10, said method comprising a step of thoroughly mixing the components of part A in any order, and a step of thoroughly mixing the components of part B.
15. A method for the preparation of an impression of an object, wherein the surface of the object is brought into contact with a mixture of part A and part B of the two-part system of claim 10.
16. The method according to claim 15, characterized in that the object is a surface within the oral cavity of a human.
17. The method according to claim 15, further comprising thoroughly mixing the components of each of part A and part B of claim 10, and combining part A and part B to form a mixture.
18. A dental filling or dental prosthesis, obtained from an impression taken with a two-part system of claim 10.