1. A pile connecting metal bracket adapted to be secured to a structure to be supported by a metal pile comprised by one or more hollow metal tubes, said pile connecting metal bracket comprising a pair of elongated straight vertical support flanges spaced-apart in parallel relationship, at least a pair of spaced-apart horizontal guide walls secured across said vertical support flanges, each said horizontal guide wall having an aperture therein dimensioned to receive a driven one of said one or more hollow metal tubes in close fit therethrough and between said pair of elongated straight vertical support flanges, attachment means for removably connecting a drive mechanism to said pile connecting metal bracket, attachment flanges connected to said vertical support flanges and provided with securement apertures for receiving fastener means to secure said pile connecting metal bracket to said structure, and connection means to immovably connect an uppermost portion of said one or more hollow metal tubes to said pile connecting metal bracket after said metal pile has been driven into soil to a position of rest.
2. A pile connecting bracket as claimed in claim 1 wherein there is further provided a foot plate attachment secured to a lowermost part of said pile connecting metal bracket for lifting engagement under said structure.
3. A pile connecting bracket as claimed in claim 2 wherein said foot plate attachment has a vertical reinforced connecting wall section and a lower transverse projecting support shoe adapted to engage under said structure adjacent a vertical wall of said structure to which said attachment flanges are to be secured, said vertical reinforced connecting wall section having opposed parallel spaced reinforcing walls to guide said one or more hollow metal tubes therebetween.
4. A pile connecting bracket as claimed in claim 3 wherein said reinforced connecting wall section is provided with connecting wings in an upper portion thereof for attachment to said pile connecting metal bracket.
5. A pile connecting bracket as claimed in claim 1 wherein there is further provided a foundation footing attachment adapted for securement to a lowermost part of said pile connecting metal bracket, said foundation footing attachment having a central attachment wall and a pair of horizontal connecting formations one on each side of said central attachment wall for securement to a foundation.
6. A pile connecting bracket as claimed in claim 5 wherein said central attachment wall is further provided with connecting wings in an upper portion thereof for attachment to said pile connecting metal bracket.
7. A pile connecting bracket as claimed in claim 1 wherein there is provided a pile connecting clamp assembly securable to a top end of said one or more hollow metal tubes after said pile has been driven to a position of rest in soil, an uppermost one of said horizontal guide walls having a horizontal attachment wall with extension fingers provided connecting bolt through bores and a large central bore for the passage of said hollow metal tubes, said horizontal attachment wall being secured on top of said guide walls, a cover top plate is also provided with connecting bolt through bores for alignment with the through bores of the horizontal attachment wall, said cover plate being secured over said top end of said hollow metal tubes by bolt fasteners extending through said aligned bolt through holes, thereby attaching said bracket to said pile.
8. A pile connecting bracket as claimed in claim 7 wherein said horizontal attachment wall has a central slot to receive a tube alignment insert having an extension foot for friction fit engagement in said top end of said hollow metal tubes, and means to secure said alignment insert to said horizontal attachment wall.
9. A pile connecting bracket as claimed in claim 1 wherein said connection means is a serrated clamp comprised by a clamping arcuate wall member secured between said guide walls in a top end rear section of said bracket, a clamping block having an arcuate serrated inner wall section, connecting means for removably securing said clamping block in facial relationship with said clamping arcuate wall member forwardly thereof with a section of said metal tube extending therebetween for clamping engagement therewith to secure said pile to said pile connecting metal bracket.
10. A pile connecting bracket as claimed in claim 9 wherein said clamping arcuate wall member is disposed between said pair of spaced-apart horizontal guide walls.
11. A pile connecting bracket as claimed in claim 1 wherein said connecting means comprises a tapered clamping cone having an inner serrated surface, said clamping cone being formed of at least two separated vertical wall sections intended to flex inward from a circular base by a clamping sleeve having an inner tapered face displaced downwardly thereabout, and displacement means to cause said downward displacement of said clamping sleeve.
12. A pile connecting bracket as claimed in claim 11 wherein said displacement means is an actuating ring having a tapered lower edge disposed in frictional contact with a tapered top edge of said sleeve, said actuating ring and sleeve extending co-axially with one another; said actuating ring, said clamping sleeve and said clamping cone being disposed one on top of the other and retained captive between said pair of spaced-apart horizontal guide walls, and actuation means to displace said actuating ring in a horizontal plane for lateral displacement thereof causing said tapered lower edge thereof to apply a downward pushing force against said tapered top edge of said sleeve to cause said downward displacement of said clamping sleeve to displace said at least two separated vertical wall sections inwardly to apply a clamping arresting force on said hollow tube extending therethrough to interconnect said bracket to said hollow tube.
13. A pile connecting bracket as claimed in claim 12 wherein said actuation means is a threaded bolt threadably engaged in a transverse threaded bore of said actuating ring, said threaded bolt having a free end abutting on a side surface of said hollow tube extending therethrough.
14. A pile connecting bracket as claimed in claim 1 wherein said attachment means is constituted by elbow flanges removably connectable to a respective one of said vertical support flanges and extending in a common plane space d forwardly of said attachment flanges.
15. A pile connecting bracket as claimed in claim 1 wherein said connection means is constituted by a weld formed between at least one of said pair of horizontal guide wall and said uppermost portion of said one or more hollow metal tubes.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
What is claimed is:
1. A compound of formula (I),
24
or a pharmaceutically suitable salt or prodrug thereof, wherein
A is a member selected from the group consisting of
25
B and C are each independently a member selected from the group consisting of aryl, and heterocycle;
R1 is a member a member selected from the group consisting of alkyl, alkoxy, alkylSO2, trifluoroalkylSO2, trifluoroalkylNH, alkylSO2NH, carboxy, cyano, HONHcarbonyl, RaONHcarbonyl, nitro, RaOC(O), HO3S, H2NO2S, RaNHO2S, (HO)2(O)P, (HO)2(O)PCH2, (HO)2(O)PCHF, (HO)2(O)PCF2 and heterocycle, wherein said heterocycle is a member selected from the group consisting of:
26
R2, R3, R4, R5, R6 and R7 are each independently absent or are independently a member selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, aryl, arylcarbonyl, arylalkyl, carboxy, carboxyalkyl, cyano, cycloalkyl, cycloalkylalkyl, halo, haloalkyl, heterocycle, heterocyclecarbonyl, heterocyclealkyl, hydroxy, hydroxyalkyl, nitro, trihaloalkyl, RaRbN, RaRbNalkyl, RaRbNcarbonyl, RaRbNcarbonylalkyl, RaRbNNsulfonyl, RaRbNNsulfonylalkyl, wherein Ra and Rb are each independently a member selected from the group consisting of hydrogen, alkyl, alkoxycarbonyl, alkylcarbonyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heterocycle, and heterocyclealkyl;
L is GX1JX2K or a bond;
G, J and K are independently a member selected from the group consisting of a bond, alkyl, alkenyl, aryl and cycloalkyl, wherein said alkyl, alkenyl, aryl and cycloalkyl may be optionally substituted with a group consisting of alkoxy, alkyl, halogen, hydroxy, hydroxyalkyl, carboxy and RdReN, wherein Rd and Re are each independently a member selected from the group consisting of hydrogen, alkyl, alkoxycarbonyl, alkylcarbonyl and arylalkyl;
X1 and X2 are each independently a member selected from the group consisting of a bond, O, N(Rc), N(Rc)C(O), C(O)N(Rc), N(Rc)S(O)2, S(O)2N(Rc), and C(O), wherein Rc is a member selected from the group consisting of hydrogen, alkyl and arylalkyl; and
provided that if J is absent, then at least one of X1 and X2 must be absent.
2. A compound of formula (II),
27
or a pharmaceutically suitable salt or prodrug thereof, wherein
R1 is a member selected from the group consisting of alkyl, alkoxy, alkylSO2, trifluoroalkylSO2, trifluoroalkylNH, alkylSO2NH, carboxy, cyano, HONHcarbonyl, RaONHcarbonyl, nitro, RaOC(O), HO3S, H2NO2S, RaNHO2S, (HO)2(O)P, (HO)2(O)PCH2, (HO)2(O)PCHF, (HO)2(O)PCF2 and heterocycle, wherein said heterocycle is a member selected from the group consisting of:
28
R2, R3, R4, R5, R6 and R7 are each independently absent or are independently a member selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, aryl, arylcarbonyl, arylalkyl, carboxy, carboxyalkyl, cyano, cycloalkyl, cycloalkylalkyl, halo, haloalkyl, heterocycle, heterocyclecarbonyl, heterocyclealkyl, hydroxy, hydroxyalkyl, nitro, trihaloalkyl, RaRbN, RaRbNalkyl, RaRbNcarbonyl, RaRbNcarbonylalkyl, RaRbNNsulfonyl, RaRbNNsulfonylalkyl, wherein Ra and Rb are each independently a member selected from the group consisting of hydrogen, alkyl, alkoxycarbonyl, alkylcarbonyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heterocycle, and heterocyclealkyl;
L is GX1JX2K or a bond;
G, J and K are independently a member selected from the group consisting of a bond, alkyl, alkenyl, aryl and cycloalkyl, wherein said alkyl, alkenyl, aryl and cycloalkyl may be optionally substituted with a group consisting of alkoxy, alkyl, halogen, hydroxy, hydroxyalkyl, carboxy and RdReN, wherein Rd and Re are each independently a member selected from the group consisting of hydrogen, alkyl, alkoxycarbonyl, alkylcarbonyl and arylalkyl;
X1 and X2 are each independently a member selected from the group consisting of a bond, O, N(Rc), N(Rc)C(O), C(O)N(Rc), N(Rc)S(O)2, S(O)2N(Rc), and C(O), wherein Rc is a member selected from the group consisting of hydrogen, alkyl and arylalkyl; and
provided that if J is absent, then at least one of X1 and X2 must be absent.
3. The compound according to claim 2, wherein
G is a member selected from the group consisting of alkyl, alkenyl and cycloalkyl.
4. The compound according to claim 2, wherein
G is a member selected from the group consisting of alkyl, alkenyl and cycloalkyl; and
X1, J and K are a bond.
5. The compound according to claim 2, wherein
G is a member selected from the group consisting of alkyl, alkenyl and cycloalkyl; and
X1, J and K are a bond; and
R1 is CO2H.
6. The compound according to claim 5, a member selected from the group consisting of
5-(3-((1E)-3-(3-hydroxy-2-(methoxycarbonyl)phenoxy)prop-1-enyl)phenyl)isoxazole-3-carboxylic acid;
5-(3-(3-(3-hydroxy-2-(methoxycarbonyl)phenoxy)butyl)phenyl)isoxazole-3-carboxylic acid;
5-(3-((2-(3-hydroxy-2-(methoxycarbonyl)phenoxy)ethyl)amino)phenyl)isoxazole-3-carboxylic acid;
5-(3-(3-(3-hydroxy-2-(methoxycarbonyl)phenoxy)propyl)phenyl)isoxazole-3-carboxylic acid;
5-(2-fluoro-5-((1E)-3-(3-hydroxy-2-(methoxycarbonyl)phenoxy)prop-1-enyl)phenyl)isoxazole-3-carboxylic acid;
5-(3-((1E)-3-(3-hydroxy-2-nitrophenoxy)prop-1-enyl)phenyl)isoxazole-3-carboxylic acid;
5-(3-((1S,2S)-2-((3-hydroxy-2-(methoxycarbonyl)phenoxy)methyl)cyclopropyl)phenyl)isoxazole-3-carboxylic acid;
5-(3-(3-(3-hydroxy-2-(methoxycarbonyl)phenoxy)butyl)-4-methoxyphenyl)isoxazole-3-carboxylic acid;
5-(4-fluoro-3-(3-(3-hydroxy-2-(methoxycarbonyl)phenoxy)butyl)phenyl)isoxazole-3-carboxylic acid;
5-(3-(3-(3-hydroxy-2-(methoxycarbonyl)phenoxy)pentyl)phenyl)isoxazole-3-carboxylic acid;
5-(3-((1E)-3-(3-hydroxy-2-propionylphenoxy)prop-1-enyl)phenyl)isoxazole-3-carboxylic acid;
5-(3-((1E)-4-hydroxy-3-(3-hydroxy-2-(methoxycarbonyl)phenoxy)but-1-enyl)phenyl)isoxazole-3-carboxylic acid;
5-(1-(2-(3-hydroxy-2-(methoxycarbonyl)phenoxy)ethyl)-1H-indol-6-yl)isoxazole-3-carboxylic acid;
5-(3-((1E)-3-(2-(acetylamino)-3-hydroxyphenoxy)prop-1-enyl)phenyl)isoxazole-3-carboxylic acid;
5-(3-((1E)-3-(2-((benzylamino)carbonyl)-3-hydroxyphenoxy)prop-1-enyl)phenyl)isoxazole-3-carboxylic acid;
5-(3-((1E)-3-(3-hydroxy-2-(methoxycarbonyl)-4-nitrophenoxy)prop-1-enyl)phenyl)isoxazole-3-carboxylic acid;
4-amino-5-(3-((1E)-3-(3-hydroxy-2-(methoxycarbonyl)phenoxy)prop-1-enyl)phenyl)isoxazole-3-carboxylic acid;
5-(3-((1E)-3-((3,5-dihydroxy-4-(methoxycarbonyl) 1,1-biphenyl-3-yl)oxy)prop-1-enyl)phenyl)isoxazole-3-carboxylic acid; and
5-(3-(1E)-3-(3-hydroxy-2-(methoxycarbonyl)phenoxy)prop-1-enylphenyl)-4-(hydroxymethyl)isoxazole-3-carboxylic acid.
7. The compound according to claim 2, wherein
X1 is a member selected from the group consisting of NH and NHC(O).
8. The compound according to claim 2, wherein
X1 is a member selected from the group consisting of NH and NHC(O); and
G and K are a bond.
9. The compound according to claim 2, wherein X1 is a member selected from the group consisting of NH and NHC(O);
G and K are a bond; and
R1 is CO2H.
10. The compound according to claim 9, a member selected from the group consisting of
5-(3-(((1-acetylpiperidin-4-yl)carbonyl)amino)phenyl)isoxazole-3-carboxylic acid;
5-(3-((2-(3-hydroxy-2-((methylamino)carbonyl)phenoxy)ethyl)amino)phenyl)isoxazole-3-carboxylic acid; and
5-(3-((1E)-3-(3-hydroxy-2-((methylamino)carbonyl)phenoxy)prop-1-enyl)phenyl)isoxazole-3-carboxylic acid.
11. The compound according to claim 2 wherein
L is a bond.
12. The compound according to claim 2 wherein
L is a bond; and
R1 is CO2H.
13. The compound according to claim 12 that is
5-3-(3-(carboxy)isoxazol-5-yl)-1,1-biphenyl-3-ylisoxazole-3-carboxylic acid.
14. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 in combination with a pharmaceutically suitable carrier.
15. A method of selectively inhibiting protein tyrosine phosphatase 1B comprising administering a therapeutically effective amount of a compound of claim 1 in combination with a pharmaceutically suitable carrier.
16. A method of treating disorders caused by overexpressed or altered protein tyrosine phosphatase 1B comprising administering a therapeutically effective amount of a compound of claim 1 in combination with a pharmaceutically suitable carrier.
17. A method of treating type I and type II diabetes, impaired glucose tolerance and insulin resistance, comprising administering a therapeutically effective amount of a compound of claim 1 in combination with a pharmaceutically suitable carrier.
18. A method of treating obesity comprising administering a therapeutically effective amount of a compound of claim 1 in combination with a pharmaceutically suitable carrier.
19. A method of treating autoimmune disorders, acute and chronic inflammatory disorders, osteoporosis, cancer, malignant disorders comprising administering a therapeutically effective amount of a compound of claim 1 in combination with a pharmaceutically suitable carrier.