1. In combination with a motorized grader having a wheeled frame with a movable grader blade mounted thereon, the blade having a heel and a toe, comprising:
a mount secured to the grader blade adjacent the heel thereof;
an elongated support having inner and outer ends;
said inner end of said elongated support being operably pivotally mounted to said mount whereby said outer end of said elongated support may be selectively moved between raised and lowered positions;
a weep hole blade operably secured to said elongated support for movement therewith between raised and lowered positions;
said weep hole blade, when moved from its said raised position to its said lowered position creating a weep hole in a ridge of road material created by the grader blade and moved outwardly of the heel thereof;
a motor operatively connected to said elongated support which moves said weep hole blade from its said raised position to its said lowered position;
and a spring operatively connected to said elongated support which returns said weep hole blade from its said lowered position to said raised position.
2. In combination with a motorized grader having a wheeled frame with a movable grader blade mounted thereon, the blade having a heel and a toe, comprising:
a mount secured to the grader blade adjacent the heel thereof;
an elongated support having inner and outer ends;
said inner end of said elongated support being operably pivotally mounted to said mount whereby said outer end of said elongated support may be selectively moved between raised and lowered positions;
a weep hole blade operably secured to said elongated support for movement therewith between raised and lowered positions;
said weep hole blade, when moved from its said raised position to its said lowered position creating a weep hole in a ridge of road material created by the grader blade and moved outwardly of the heel thereof;
said weep hole blade comprising an upper blade portion having a lower blade portion pivotally secured thereto about a generally horizontal axis.
3. The combination of claim 2 wherein said weep hole blade is selectively angularly movable, about a general vertical axis, with respect to the grader blade.
4. The combination of claim 2 wherein an electric motor is operatively connected to said elongated support which moves said elongated support and said weep hole blade from their said raised position to their said lowered position.
5. The combination of claim 2 wherein a spring interconnects said lower blade portion to said upper blade portion, said spring yieldably urging said lower blade portion to a position wherein it is generally in the same plane as said upper blade portion.
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 tetrahydroisoquinoline compound of the formula (I)
wherein
R is R1\u2014W-A1-Q-Y-A2-X\u2014;
R1 is hydrogen, C1-C6-alkyl, halogenated C1-C6-alkyl, hydroxy-C1-C4-alkyl, C1-C6-alkoxy-C1-C4-alkyl, amino-C1-C4-alkyl, C1-C6-alkylamino-C1-C4-alkyl, di-C1-C6-alkylamino-C1-C4-alkyl, C1-C6-alkylcarbonylamino-C1-C4-alkyl, C1-C6-alkyloxycarbonylamino-C1-C4-alkyl, C1-C6-alkylaminocarbonylamino-C1-C4-alkyl, di-C1-C6-alkylaminocarbonylamino-C1-C4-alkyl, C1-C6-alkylsulfonylamino-C1-C4-alkyl, (C6-C12-aryl-C1-C6-alkyl)amino-C1-C4-alkyl, optionally substituted C6-C12-aryl-C1-C4-alkyl, optionally substituted C3-C12-heterocyclyl-C1-C4-alkyl, C3-C12-cycloalkyl, C1-C6-alkylcarbonyl, halogenated C1-C6-alkylcarbonyl, C1-C6-alkoxycarbonyl, halogenated C1-C6-alkoxycarbonyl, C6-C12-aryloxycarbonyl, aminocarbonyl, C1-C6-alkylaminocarbonyl, (halogenated C1-C4-alkyl)aminocarbonyl, C6-C12-arylaminocarbonyl, C2-C6-alkenyl, C2-C6-alkynyl, optionally substituted C6-C12-aryl, hydroxy, C1-C6-alkoxy, halogenated C1-C6-alkoxy, C1-C6-alkylcarbonyloxy, C1-C6-hydroxyalkoxy, C1-C6-alkoxy-C1-C4-alkoxy, amino-C1-C4-alkoxy, C1-C6-alkylamino-C1-C4-alkoxy, di-C1-C6-alkylamino-C1-C4-alkoxy, C1-C6-alkylcarbonylamino-C1-C4-alkoxy, C6-C12-arylcarbonylamino-C1-C4-alkoxy, C1-C6-alkoxycarbonylamino-C1-C4-alkoxy, C6-C12-aryl-C1-C4-alkoxy, C1-C6-alkylsulfonylamino-C1-C4-alkoxy, (halogenated C1-C6-alkyl)sulfonylamino-C1-C4-alkoxy, C6-C12-arylsulfonylamino-C1-C4-alkoxy, (C6-C12-aryl-C1-C6-alkyl)sulfonylamino-C1-C4-alkoxy, C3-C12-heterocyclylsulfonylamino-C1-C4-alkoxy, C3-C12-heterocyclyl-C1-C4-alkoxy, C6-C12-aryloxy, C3-C12-heterocyclyloxy, C1-C6-alkylthio, halogenated C1-C6-alkylthio, C1-C6-alkylamino, (halogenated C1-C6-alkyl)amino, di-C1-C6-alkylamino, di-(halogenated C1-C6-alkyl)amino, C1-C6-alkylcarbonylamino, (halogenated C1-C6-alkyl)carbonylamino, C6-C12-arylcarbonylamino, C1-C6-alkylsulfonylamino, (halogenated C1-C6-alkyl)sulfonylamino, C6-C12-arylsulfonylamino or optionally substituted C3-C12-heterocyclyl;
W is \u2014NR8\u2014 or a bond;
A1 is optionally substituted C1-C4-alkylene or a bond;
Q is \u2014S(O)2\u2014 or \u2014C(O)\u2014;
Y is \u2014NR9\u2014 or a bond;
A2 is optionally substituted C1-C4-alkylene, C1-C4-alkylene-O\u2014C1-C4-alkylene, C1-C4-alkylene-NR10\u2014C1-C4-alkylene, optionally substituted C6-C12-arylene, optionally substituted C6-C12-heteroarylene or a bond;
X is \u2014O\u2014, \u2014NR11\u2014, \u2014S\u2014 or optionally substituted C1-C4-alkylene;
provided that X is optionally substituted C1-C4-alkylene if A2 is a bond;
R2 is hydrogen, halogen, C1-C6-alkyl, halogenated C1-C4-alkyl, hydroxy-C1-C4-alkyl, \u2014CN, C2-C6-alkenyl, C2-C6-alkynyl, optionally substituted C6-C12-aryl, hydroxy, C1-C6-alkoxy, halogenated C1-C6-alkoxy, C2-C6-alkenyloxy, C6-C12-aryl-C1-C4-alkoxy, C1-C6-alkylcarbonyloxy, C1-C6-alkylthio, C1-C6-alkylsulfinyl, C1-C6-alkylsulfonyl, aminosulfonyl, amino, C1-C6-alkylamino, C2-C6-alkenylamino or optionally substituted C3-C12-heterocyclyl;
R3 is hydrogen, halogen, C1-C6-alkyl or C1-C6-alkoxy, or two radicals R3 together with the carbon atom to which they are attached form a carbonyl group;
R4 is hydrogen, C1-C6-alkyl, halogenated C1-C4-alkyl, hydroxy-C1-C4-alkyl, C1-C6-alkoxy-C1-C4-alkyl, amino-C1-C4-alkyl, CH2CN, \u2014CHO, C1-C4-alkylcarbonyl, (halogenated C1-C4-alkyl)carbonyl, C6-C12-arylcarbonyl, C1-C6-alkylaminocarbonyl, C2-C6-alkenyl, \u2014C(\u2550NH)NH2, \u2014C(\u2550NH)NHCN, C1-C6-alkylsulfonyl, C6-C12-arylsulfonyl, amino, \u2014NO or C3-C12-heterocyclyl;
R5 is optionally substituted C1-C6-alkyl, C1-C6-alkylamino-C1-C4-alkyl, di-C1-C6-alkylamino -C1-C4-alkyl, C3-C12-heterocyclyl-C1-C6-alkyl, optionally substituted C6-C12-aryl or hydroxy;
R6 is hydrogen, optionally substituted C1-C6-alkyl or hydroxy, or
R5, R6 together are carbonyl or optionally substituted C1-C4-alkylene, wherein one \u2014CH2\u2014 of C1-C4-alkylene may be replaced by an oxygen atom or \u2014NR12\u2014;
R7 is optionally substituted C6-C12-aryl, optionally substituted C3-C12-cycloalkyl or optionally substituted C3-C12-heterocyclyl;
R8 is hydrogen or C1-C6-alkyl;
R9 is hydrogen, C1-C6-alkyl or amino-C1-C6-alkyl;
R10 is hydrogen, C1-C6-alkyl or C1-C6-alkylsulfonyl;
R11 is hydrogen or C1-C6-alkyl; or
R9, R11 together are C1-C4-alkylene; and
R12 is hydrogen or C1-C6-alkyl;
or a physiologically tolerated salt thereof.
2. The compound as claimed in claim 1, wherein R1 is C1-C6-alkyl, halogenated C1-C6-alkyl, C1-C6-alkoxy-C1-C4-alkyl, amino-C1-C4-alkyl, C1-C6-alkylamino-C1-C4-alkyl, di-C1-C6-alkylamino-C1-C4-alkyl, C1-C6-alkyloxycarbonylamino-C1-C4-alkyl, C1-C6-alkylaminocarbonylamino-C1-C4-alkyl, C6-C12-aryl-C1-C4-alkyl, C3-C12-cycloalkyl, optionally substituted C6-C12-aryl, hydroxy, C1-C6-alkylamino, (halogenated C1-C6-alkyl)amino, di-C1-C6-alkylamino or optionally substituted C3-C12-heterocyclyl.
3. The compound as claimed in claim 1 wherein A2 is optionally substituted C1-C4-alkylene or C1-C4-alkylene-NR10\u2014C1-C4-alkylene.
4. The compound as claimed in claim 1, wherein X is \u2014O\u2014 or \u2014NR11.
5. The compound as claimed in claim 1, wherein A2 is a bond and X is optionally substituted C1-C4-alkylene.
6. The compound as claimed in claim 1, wherein \u2014Y-A2-X\u2014 is \u2014NR9\u2014C1-C4-alkylene-O\u2014, \u2014C1-C4-alkylene-O\u2014, \u2014NR9\u2014C1-C4-alkylene-NH\u2014, \u2014NR9\u2014CH2CO\u2014NH\u2014, \u2014NR9\u2014C1-C4-alkylene-, \u2014NR9-1,4-phenylene-O\u2014, \u2014NR9-1,2-phenylene-O\u2014, \u2014NR9-2,5-pyridylene-O\u2014 or \u2014NR9-2,3-pyridylene-O\u2014.
7. The compound as claimed in claim 1, wherein \u2014Y-A2-X\u2014 has 2 to 6 atoms in the main chain.
8. The compound as claimed in claim 1, wherein R1\u2014W-A1-Q-Y-A2-X\u2014 is R1\u2014S(O)2\u2014NH-A2-X\u2014, R1\u2014NH\u2014S(O)2-A2-X\u2014, R1\u2014C(O)\u2014NH-A2-X\u2014 or R1\u2014NH\u2014C(O)-A2-X\u2014.
9. The compound as claimed in claim 1, having one of the formulae
wherein R1, W, A1, Q, Y, A2, X, R2, R3, R4, R5, R6, R7 are as defined in claim 1.
10. The compound as claimed in claim 1, wherein R2 is hydrogen, halogen or C1-C6-alkoxy.
11. The compound as claimed in claim 1, wherein R3 is hydrogen or C1-C6-alkyl.
12. The compound as claimed in claim 1, wherein R4 is hydrogen, C1-C6-alkyl, halogenated C1-C4-alkyl, amino-C1-C4-alkyl, CH2CN, C1-C4-alkylcarbonyl, (halogenated C1-C4-alkyl)carbonyl, \u2014C(\u2550NH)NH2, \u2014C(\u2550NH)NHCN, C1-C6-alkylsulfonyl, amino, \u2014NO or C3-C12-heterocyclyl.
13. The compound as claimed in claim 1, wherein R5 is C1-C6-alkyl and R6 is hydrogen or C1-C6-alkyl, or R5, R6 together are optionally substituted C1-C4-alkylene.
14. The compound as claimed in claim 1, having the formula
wherein R1, W, A1, Q, Y, A2, X, R2, R3, R4, R5, R6 are as defined in claim 1, and
R13a, R13b, R13c, R13d, R13e
independently are hydrogen, halogen, optionally substituted C1-C6-alkyl, halogenated C1-C6-alkyl, CN, hydroxy, C1-C6-alkoxy, amino, C1-C6-alkylamino, di-C1-C6-alkylamino or C3-C12-heterocyclyl.
15. The compound as claimed in claim 1, having the formula
wherein R1, W, A1, Q, Y, A2, X, R2, R3, R4, R5, R6 are as defined in claim 1, and
R13b, R13c, R13d, R13e
independently are hydrogen, halogen, optionally substituted C1-C6-alkyl, halogenated C1-C6-alkyl, CN, hydroxy, C1-C6-alkoxy, amino, C1-C6-alkylamino, di-C1-C6-alkylamino or C3-C12-heterocyclyl.
16. The compound as claimed in claim 1, wherein
R1 is C1-C6-alkyl, halogenated C1-C6-alkyl, hydroxy-C1-C4-alkyl, C1-C6-alkoxy-C1-C4-alkyl, amino-C1-C4-alkyl, C1-C6-alkylamino-C1-C4-alkyl, di-C1-C6-alkylamino-C1-C4-alkyl, C1-C6- alkyloxycarbonylamino -C1-C4-alkyl, C1-C6-alkylaminocarbonylamino-C1-C4-alkyl, C6-C12-aryl-C1-C4-alkyl, C3-C12-heterocyclyl-C1-C4-alkyl, C3-C12-cycloalkyl, C1-C6-alkoxycarbonyl, C1-C6-alkylaminocarbonyl, C2-C6-alkenyl, optionally substituted C6-C12-aryl, hydroxy, C1-C6-alkylamino, di-C1-C6-alkylamino or optionally substituted C3-C12-heterocyclyl;
W is \u2014NR8\u2014 or a bond;
A1 is C1-C4-alkylene or a bond;
Q is \u2014S(O)2\u2014 or \u2014C(O)\u2014;
Y is \u2014NR9\u2014, C1-C4-alkylene or a bond;
A2 is C1-C4-alkylene, C6-C12-arylene or C6-C12-heteroarylene;
X is \u2014O\u2014, \u2014NR11\u2014 or C1-C4-alkylene;
R2 is hydrogen, halogen or C1-C6-alkoxy;
R3 is hydrogen or C1-C6-alkyl;
R4 is hydrogen, C1-C6-alkyl, halogenated C1-C4-alkyl, amino-C1-C4-alkyl, CH2CN, C1-C4-alkylcarbonyl, (halogenated C1-C4-alkyl)carbonyl, \u2014C(\u2550NH)NH2, \u2014C(\u2550NH)NHCN, C1-C6-alkylsulfonyl, amino, \u2014NO or C3-C12-heterocyclyl;
R5 is C1-C6-alkyl or optionally substituted C3-C12-aryl;
R6 is hydrogen, hydroxy or C1-C6-alkyl, or
R5, R6 together are optionally substituted C1-C4-alkylene;
R7 is optionally substituted C6-C12-aryl or optionally substituted C3-C12-heteroaryl;
R8 is hydrogen;
R9 is hydrogen or amino-C1-C6-alkyl;
R10 is hydrogen; and
R11 is hydrogen, or
R9, R11 together are C1-C4-alkylene.
17. The compound as claimed in claim 1, wherein
R1 is C1-C6-alkyl, halogenated C1-C6-alkyl, C1-C6-alkoxy-C1-C4-alkyl, amino-C1-C4-alkyl, C1-C6-alkylamino-C1-C4-alkyl, di-C1-C6-alkylamino-C1-C4-alkyl, C1-C6-alkyloxycarbonylamino-C1-C4-alkyl, C1-C6-alkylaminocarbonylamino-C1-C4-alkyl, C6-C12-aryl-C1-C4-alkyl, C3-C12-cycloalkyl, optionally substituted C6-C12-aryl, hydroxy, C1-C6-alkylamino, (halogenated C1-C6-alkyl)amino, di-C1-C6-alkylamino or Optionally substituted C3-C12-heterocyclyl;
W is \u2014NR8\u2014 or a bond;
A1 is a bond;
Q is \u2014S(O)2\u2014 or \u2014C(O)\u2014;
Y is \u2014NR9\u2014 or a bond;
A2 is C1-C4-alkylene;
X is \u2014O\u2014 or \u2014NR11\u2014;
R2 is hydrogen, halogen or C1-C6-alkoxy;
R3 is hydrogen or C1-C6-alkyl;
R4 is hydrogen, C1-C6-alkyl, halogenated C1-C4-alkyl, amino-C1-C4-alkyl, CH2CN, C1-C4-alkylcarbonyl, (halogenated C1-C4-alkyl)carbonyl, \u2014C(\u2550NH)NH2, \u2014C(\u2550NH)NHCN, C1-C6-alkylsulfonyl, amino, \u2014NO or C3-C12-heterocyclyl;
R5 is C1-C6-alkyl;
R6 is hydrogen or C1-C6-alkyl, or
R5, R6 together are optionally substituted C1-C4-alkylene;
R7 is optionally substituted C6-C12-aryl or optionally substituted C3-C12-heteroaryl; and
R8 is hydrogen;
R9 is hydrogen;
R10 is hydrogen;
R11 is hydrogen, or
R9, R11 together are C1-C4-alkylene.
18. A pharmaceutical composition which comprises a carrier and a compound of claim 1.
19. A method for treating a neurologic or psychiatric disorder in a mammalian patient in need thereof which comprises administering to the patient a therapeutically effective amount of the compound as claimed in claim 1, wherein the neurologic disorder is selected from the group consisting of dementia, cognitive impairment, and attention deficit disorder, and wherein the psychiatric disorder is selected from the group consisting of anxiety disorder, depression, bipolar disorder, schizophrenia, and psychosis.
20. A dihydroisoquinoline compound of the formula (II)
wherein
R is R1-W-A1-Q-Y-A2-X-;
R1 is hydrogen, C1-C6-alkyl, halogenated C1-C6-alkyl, hydroxy-C1-C4-alkyl, C1-C6-alkoxy-C1-C4 alkyl, amino C1 C4 alkyl, C1-C6-alkylamino-C1-C4-alkyl, di-C1 C6 – alkylamino C1 -C4-alkyl, C1-C6-alkylcarbonylamino-C1-C4-alkyl, C1-C6-alkyloxycarbonylamino-C1-C4-alkyl, C1-C6-alkylaminocarbonylamino-C1-C4-alkyl, di-C1-alkylaminocarbonylamino-C1-C4 -alkyl, C1-C6-alkylsulfonylamino-C1-C4-alkyl, (C6-C12-aryl-C1-C6-alkyl)amino-C1-C4-alkyl, optionally substituted C6-C12-aryl-C1-C4 -alkyl, optionally substituted C3-C12-heterocyclyl-C1-C4-alkyl, C3-C12-cycloalkyl, C1-C6-alkylcarbonyl, halogenated C1-alkylcarbonyl, C1-C6-alkoxycarbonyl, halogenated C1-C6-alkoxycarbonyl, C6-C12-aryloxycarbonyl, aminocarbonyl, C1-C6-alkylaminocarbonyl, (halogenated C1-C4-alkyl)aminocarbonyl, C6-C12 arylaminocarbonyl, C2-C6-alkenyl, C2-C6alkynyl, optionally substituted C6-C12-aryl, hydroxy, C1-C6-alkoxy, halogenated C1-C6-alkoxy, C1-C6-alkylcarbonyloxy, C1-C6-hydroxyalkoxy, C1-C6-alkoxy-C1-C4-alkoxy, amino-C1-C4-alkoxy, C1-C6-alkylamino-C1-C4-alkoxy, di-C1-C6-alkylamino-C1-C4-alkoxy, C1-C6-alkylcarbonylamino-C1-C4-alkoxy, C6-C12-arylcarbonylamino-C1-C4-alkoxy, C1-C6-alkoxycarbonylamino-C1-C4-alkoxy, C6-C12 aryl-C1-C4-alkoxy, C1-C6-alkylsulfonylamino-C1-C4-alkoxy, (halogenated C1-C6-alkyl)sulfonylamino-C1-4-alkoxy, C6-C12-arylsulfonylamino-C1-C4-alkoxy, (C6-C12-aryl-C3-C6-alkyl)sulfonylamino-C1-C4-alkoxy, C3-C12-heterocyclylsulfonylamino-C1-C4-alkoxy, C3-C12-heterocyclyl-C1-C4alkoxy, C6-C12-aryloxy, C3-C12heterocyclyloxy, C1-C6-alkylthio, halogenated C1-C6-alkylthio, C1-C6-alkylamino, (halogenated C1-C6-alkyl)amino, di-C1-C6-alkylamino, di-(halogenated C1-C6-alkyl)amino, C1-C6-alkylcarbonylamino, (halogenated C1-C6-alkyl)carbonylamino, C6-C12-arylcarbonylamino,C1-C6-alkylsulfonylamino, (halogenated C1-C6-alkyl)sulfonylamino, C6-C12-arylsulfonylamino or optionally substituted C3-C12-heterocyclyl;
W is \u2014NR8\u2014 or a bond;
A1 is optionally substituted C1-C4-alkylene or a bond;
Q is \u2014S(O)2\u2014 or \u2014C(O)\u2014;
Y is \u2014NR9\u2014 or a bond;
A2 is optionally substituted C1-C4-alkylene, C1-C4-alkylene-O\u2014C1-C4-alkylene, C1-C4-alkylene-NR10\u2014C1-C4-alkylene, optionally substituted C6-C12-arylene, optionally substituted C6-C12-heteroarylene or a bond;
X is \u2014O\u2014, \u2014NR11\u2014, \u2014S\u2014 or optionally substituted C1-C4-alkylene;
provided that X is optionally substituted C1-C4-alkylene if A2 is a bond;
R2 is hydrogen, halogen, C1-C6-alkyl, halogenated C1-C4-alkyl, hydroxy-C1-C4-alkyl, \u2014CN, C2-C6-alkenyl, C2-C6-alkynyl, optionally substituted C6-C12-aryl, hydroxy, C1-C6-alkoxy, halogenated C1-C6-alkoxy, C2-C6-alkenyloxy, C6-C12-aryl-C1-C4-alkoxy, C1-C6-alkylcarbonyloxy, C1-C6-alkylthio, C1 -C6-alkylsulfinyl, C1-C6-alkylsulfonyl, aminosulfonyl, amino, C1-C6-alkylamino, C2-C6-alkenylamino or optionally substituted C3-C12-heterocyclyl:
R3 is hydrogen, halogen, C1-C6-alkyl or C1-C6-alkoxy, or two radicals R3 together with the carbon atom to which they are attached form a carbonyl group;
R5 is optionally substituted C1-C6-alkyl, C1-C6-alkylamino-C1-C4-alkyl, di-C1-C6-alkylamino-C1-C4-alkyl, C3-C12-heterocyclyl-C1-C6-alkyl, optionally substituted C6-C12-aryl or hydroxy;
R6 is hydrogen, optionally substituted C1-alkyl or hydroxy, or
R5, R6 together are carbonyl or optionally substituted C1-C4-alkylene, wherein one \u2014CH2\u2014 of C1-C4-alkylene may be replaced by an oxygen atom or \u2014NR12\u2014:
R7 is optionally substituted C6-C12-aryl, optionally substituted C3-C12-cycloalkyl or optionally substituted C3-C12-heterocyclyl:
R8 is hydrogen or C1-C6-alkyl;
R9 is hydrogen, C1-C6-alkyl or amino-C1-C6-alkyl;
R10 is hydrogen, C1-C6-alkyl or C1-C6-alkylsulfonyl;
R11 is hydrogen or C1-C6-alkyl: or
R9, R11 together are C1-C4-alkylene: and
R12 is hydrogen or C1-C6-alkyl.