1. A compound represented by Formula (I):
or a pharmaceutically acceptable salt or N-oxide thereof, wherein:
J is \u2014NR1R2 or \u2014OR1;
A is aryl, heteroaryl, cycloC3-10alkyl, heterocyclyl, cycloC3-10alkenyl, or heterocycloalkenyl, each of which is optionally substituted by 1-5 independent R4 substituents;
R1 is C1-6alkyl, aryl, heteroaryl, cycloC3-10alkyl, heterocyclyl, cycloC3-10alkenyl, heterocycloalkenyl, C2-6alkenyl, C2-6alkynyl, each of which is optionally substituted by 1-5 independent R41 substituents;
R2 is C0-6alkyl, aryl, heteroaryl, cycloC3-10alkyl, heterocyclyl, cycloC3-10alkenyl, heterocycloalkenyl, C2-6alkenyl, C2-6alkynyl, each of which is optionally substituted by 1-5 independent R42 substituents;
or R1 and R2, taken together with the N atom to which they are attached, form a heterocyclyl, heterocylcoalkenyl, or heteroaryl, each of which is optionally substituted with 1-4 independent R41 substituents; provided R1 and R2 taken together with the N atom to which they are attached do not form a pyrazolyl;
R3 is C0-6alkyl, halogen, C1-6alkyl, or haloalkyl;
R4, R41, and R42 each independently is C0-6alkyl, cycloC3-10alkyl, oxo, halogen, haloalkyl, cyanoC0-6alkyl, nitroC0-6alkyl, hydroxyC0-6alkyl, C0-6alkylaminoC0-6alkyl, aminoC1-6alkylamino, acylaminoC0-6alkylamino, acylC0-6alkyl, substituted acyl, guanidinoC0-6alkyl, hydroxyiminoC0-6alkyl, acylaminoC0-6alkyl, substituted acylamino, acyloxyC0-6alkyl, substituted acyloxy, arC0-6alkyl, substituted arC0-6alkyl, heteroarylC0-6alkyl, substituted heteroarylC0-6alkyl, heterocyclylC0-6alkyl, cyanoaminoC0-6alkyl, C0-6alkylhydrazino, heterocyclylamino, arC0-6alkylhydrazino, alkylsulfonylC0-6alkyl, arC0-6alkylsulfonylC0-6alkyl, alkylsulfinylC0-6alkyl, alkylsulfonamidoC0-6alkyl, arC0-6alkylsulfonamidoC0-6alkyl, aminoC0-6alkylsulfonyl, C0-6alkylaminosulfonyl, acylC1-6alkylsulfonyl, heterocyclylsulfonyl, aminoC0-6alkylsulfinyl, acylC1-6alkylsulfinyl, silyl, siloxy, alkenoxy, alkynoxy, C2-6alkenyl, acylC2-6alkenyl, C2-6alkynyl, acylC2-6alkynyl, hydroxyC2-6alkynyl, aminoC2-6alkynyl, C1-6alkoxyC0-6alkyl, C1-6alkylthioC0-6alkyl, hydroxyC1-6alkoxyC0-6alkyl, hydroxyC1-6alkylthioC0-6alkyl, acylC1-6alkoxyC0-6alkyl, acylC1-6alkylthioC0-6alkyl, C0-6alkylaminoC1-6alkoxyC0-6alkyl, C0-6alkylaminoC1-6alkylthioC0-6alkyl, acylaminoC1-6alkoxyC0-6alkyl, acylaminoC1-6alkylthioC0-6alkyl, arC0-6alkylaminoC0-6alkyl, arC0-6alkylthioC0-6alkyl, arC0-6alkoxyC0-6alkyl, arC0-6alkylamino, arC0-6alkylaminoC0-6alkyl, arC0-6alkylthio, substituted arC0-6alkoxy, substituted arC0-6alkylthio,or substituted arC0-6alkoxy; and
provided that the compound is not
N\u2032-(tert-butyl)-3-(quinolin-4-ylmethyl)aminothiophene-2-carbohydrazide or
N-morpholin-4-yl-3-(quinolin-4-ylmethyl)aminothiophene-2-carboxamide.
2. The compound according to claim 1 wherein J is \u2014NR1R2.
3. The compound according to claim 2 wherein R3 is hydrogen.
4. The compound according to claim 2 wherein A is heteroaryl.
5. The compound according to claim 2 wherein A is
6. The compound according to claim 1 wherein J is \u2014OR1.
7. The compound according to claim 6 wherein R3 is hydrogen.
8. The compound according to claim 6 wherein A is heteroaryl.
9. The compound according to claim 6 wherein A is
10. A composition comprising a compound according to claim 1, or a pharmaceutically acceptable salt or N-oxide thereof, and a pharmaceutically acceptable carrier.
11. A composition comprising a compound according to claim 1, or a pharmaceutically acceptable salt or N-oxide thereof; and
an anti-neoplastic, anti-tumor, anti-angiogenic, or chemotherapeutic agent.
12. A composition comprising a compound according to claim 1, or a pharmaceutically acceptable salt or N-oxide thereof, and a cytotoxic cancer therapeutic agent.
13. A composition comprising a compound according to claim 1, or a pharmaceutically acceptable salt or N-oxide thereof, and an angiogenesis inhibiting cancer therapeutic agent.
14. A compound consisting of
N\u2032-(4-chlorophenyl)-3-(quinolin-4-ylmethyl)aminothiophene-2-carbohydrazide;
N-(tert-butoxy)-3-(quinolin-4-ylmethyl)aminothiophene-2-carboxamide;
N-piperidin-1-yl-3-(quinolin-4-ylmethyl)aminothiophene-2-carboxamide;
N\u2032-(4-bromophenyl)-3-(quinolin-4-ylmethyl)aminothiophene-2-carbohydrazide;
N-(4-methylpiperazin-1-yl)-3-(quinolin-4-ylmethyl)aminothiophene-2-carboxamide;
N\u2032-(3,4-dichlorophenyl)-3-(quinolin-4-ylmethyl)aminothiophene-2-carbohydrazide;
N-phenoxy-3-(quinolin-4-ylmethyl)aminothiophene-2-carboxamide;
N\u2032-methyl-N\u2032-phenyl-3-(quinolin-4-ylmethyl)aminothiophene-2-carbohydrazide;
N\u2032-(3-chlorophenyl)-3-(quinolin-4-ylmethyl)aminothiophene-2-carbohydrazide;
N\u2032-phenyl-3-(quinolin-4-ylmethyl)aminothiophene-2-carbohydrazide;
N\u2032-(4-cyanophenyl)-3-(quinolin-4-ylmethyl)aminothiophene-2-carbohydrazide;
3-(quinolin-4-ylmethyl)amino-N\u2032-4-(trifluoromethyl)phenylthiophene-2-carbohydrazide;
N\u2032-(4-methoxyphenyl)-3-(quinolin-4-ylmethyl)aminothiophene-2-carbohydrazide;
3-(quinolin-4-ylmethyl)amino-N\u2032-3-(trifluoromethyl)phenylthiophene-2-carbohydrazide;
N\u2032-(4-fluorophenyl)-3-(quinolin-4-ylmethyl)aminothiophene-2-carbohydrazide;
N-2,3-dihydro-1H-indol-1-yl-3-(quinolin-4-ylmethyl)aminothiophene-2-carboxamide
or a pharmaceutically acceptable salt, or N-oxide, 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. An aircraft telescopic in-flight refueling mast, comprising:
a metallic structural beam, electrically connected to the aircraft by flexible conductive means, having inside a fixed metallic tube and a metallic telescopic tube providing a fuel conduit, and, attached to said beam, flight control surfaces;
protection means against electric discharges including lightning strikes and electro-static discharges, said protection means including insulated means and low conductive means for reducing the lightning currents to a safe level and for draining static charge created during refueling, said low conductive means including a concentric liner between the fixed tube and the telescopic tube and a low conductive segment assembled at the beginning of the telescopic tube constituting a dynamic seal between both tubes, and conductive means providing a safe lightning current path and good electrical bonding for electro-static discharge.
2. An aircraft telescopic in-flight refueling mast comprising:
a metallic structural beam, electrically connected to the aircraft by flexible conductive means, having inside a fixed metallic tube and a metallic telescopic tube providing a fuel conduit, and, attached to said beam, flight control surfaces protection means against electric discharges including lightning strikes and electro-static discharges, said protection means including
insulating means which include an insulated pipe section in the connection interface between the fixed tube and the aircraft fuel system and insulated fittings in those elements susceptible to inject current inside the aircraft fuselage,
low conductive means which include a concentric liner between the fixed tube and the telescopic tube and a low conductive segment assembled at the beginning of the telescopic tube constituting a dynamic seal between both tubes, and
conductive means which include means providing electrical contact between the fixed tube and the telescopic tube, sliding electrical contacts between the flight control surfaces and the beam, and flexible electrical connections between the structural beam and the aircraft.
3. An aircraft telescopic in-flight refueling mast according to claim 2, wherein said non conductive segment is assembled between a first flange and a second flange connected by bolts.
4. An aircraft telescopic in-flight refueling mast according to claim 2, wherein said means providing electrical contact between the fixed tube and the telescopic tube comprise a sliding ring connected to the telescopic tube through flexible conductors.
5. An aircraft telescopic in-flight refueling mast according to claim 1, further comprising electro-static dischargers installed on the outer extremities of metallic structural beam and aerodynamic control surfaces.