1. An indane or dihydroindole compound of formula I
13
wherein A and B are independently O or S;
D is a methylene group optionally substituted with one or two C1-4 alkyl groups;
Y is a hydrocarbon group completing an indane ring, a group NR1 completing a dihydroindole ring, or a group N completing a dihydroindole ring attached via the 1-position;
W is a bond, and nm is 1, 2, 3, 4, 5, or 6;
W is CO, SO, or SO2, n is 2, 3, 4, or 5 and m is 0, 1, 2, or 3, provided that nm is not more than 6; or
W is O, S, n is 2, 3, 4, or 5 and m is 0, 1, 2, or 3, provided that nm is not more than 6, and
provided that when Y is N completing a dihydroindole ring attached via the 1-position then m is 2, or 3; and when Y is NR1 completing a dihydroindole ring linked via the 2-position then m is 1, 2, or 3;
the dotted line, emanating from X, indicates an optional bond; when it does not indicate a bond X is N, CH or COH; and when it indicates a bond X is C;
R1 is selected from
hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalk(en)yl, C3-8 cycloalk(en)yl-C1-6 alk(enyn)yl, aryl, heteroaryl, aryl- C1-6 alkyl, heteroaryl-C1-6 alkyl, acyl, thioacyl, C1-6 alkylsulfonyl, trifluoromethylsulfonyl, arylsulfonyl or heteroarylsulfonyl, or
R15VCO wherein V is O or S and R15 is C1-6 alkyl, C3-8 cycloalkyl, C3-8 cycloalkyl-C1-6 alkyl, aryl or heteroaryl, or
a group R16R17NCO or R16R17NCS wherein R16 and R17 are independently hydrogen, C1-6 alkyl, C3-8 cycloalkyl, C3-8 cycloalkyl-C1-6 alkyl, aryl or heteroaryl, or R16 and R17 together with the N-atom to which they are linked, form a pyrrolidinyl, piperidinyl or perhydroazepin group;
R2-R5 are independently selected from hydrogen, halogen, cyano, nitro, C1-6 alk(enyn)yl, C1-6 alkoxy, C1-6 alkylthio, hydroxy, C3-8 cycloalk(en)yl, C3-8 cycloalk(en)yl-C1-6 alk(enyn)yl, C1-6 alkylcarbonyl, phenylcarbonyl, halogen substituted phenylcarbonyl, trifluoromethyl, trifluoromethylsulfonyloxy and C1-6 alkylsulfonyl, one of R2-R5 alternatively being a group NR13R14 wherein R13 is selected from the R1 substituents;
R14 is hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalk(en)yl, C3-8 cycloalk(en)yl-C1-6 alk(enyn)yl, aryl, heteroaryl, aryl-C1-6 alkyl or heteroaryl-C1-6 alkyl, or
R13 and R14 together with the N-atom to which they are linked form a group
14
wherein Q is CO, CS or CH2; T is NH, S, O or CH2; and p is 1-4, inclusive; or two adjacent groups taken from R2-R5 may be joined and designate a (CH2)3 or CHCHNH thereby forming a fused 5-membered ring;
R6-R8 are independently hydrogen, halogen, cyano, nitro, C1-6-alk(enyn)yl, C1-6-alkoxy, C1-6-alkylthio, hydroxy, trifluoromethyl, or C1-6 alkylsulfonyl;
with the proviso that the substituent R3 or R4 in 6-position may not be NR13R14 when Y is CH2 and the ring is linked via the 1-position;
or a pharmaceutically acceptable acid addition salt thereof.
2. A compound of claim 1, characterized in that Y is CH2 and that the resulting indane ring is linked to the W(CH2)n group via the 1- or 2-position, preferably the 1-position.
3. A compound of claim 1, characterized in that Y is NR1 and that the resulting dihydroindole ring is linked to the W(CH2)n group via the 1- or 3-position.
4. A compound of claim 3, characterized in that R1 is hydrogen, C1-6 alkyl, or C1-6 alkylcarbonyl.
5. A compound of claims 1, 2, 3 or 4, characterized in that A and B are both O.
6. A compound of claims 1, 2, 3, 4 or 5, characterized in that D is methylene or methylene substituted with one or two methyl groups.
7. A compound of any of claims 1-6, characterized in that W is a bond and nm is 1, 2, 3 or 4.
8. A compound of claim 7, characterized in that nm is 1 or 2.
9. A compound of any of claims 1-8, characterized in that none of R2-R5 is a group NR13R14.
10. A compound of claim 9, characterized in that each of R2-R5 is selected from the group consisting of hydrogen, halogen or cyano.
11. A compound of any of claims 1-8, characterized in that at least one of R2-R5 is a group NR13R14.
12. A compound of claim 11, characterized in that R13 is acyl, C1-6 alkyl, C1-6 alkoxy or a group R16R17NCO wherein R16 is hydrogen, C1-6 alkyl, C3-8 cycloalkyl, cycloalkyl- C1-6 alkyl, aryl or heteroaryl and R17 is hydrogen or C1-6 alkyl or R16 and R17 together with the N-atom to which they are linked, form a pyrrolidinyl, piperidinyl or perhydroazepin group and R14 hydrogen or lower alkyl, preferably hydrogen or methyl.
13. A compound of claim 12, characterized in that R13 is formyl, acetyl, methylaminocarbonyl, methylaminothiocarbonyl, dimethylaminocarbonyl, dimethylaminothiocarbonyl, methylsulfonyl, aminocarbonyl, cyclopropylcarbonyl, methyl, pyrrolidinylcarbonyl or 4-fluorophenylaminocarbonyl.
14. A compound of claim 11, characterized in that R13 and R14 are linked together to form a 5-7 membered unsubstituted lactam ring or a pyrrolidinyl, piperidinyl or perhydroazepin.
15. A compound of claim 2, characterized in that wherein Y is CH2 the resulting indane ring being linked via the 2-position, A and B are both O and D is optionally substituted methylene.
16. A compound of claim 2, characterized in that Y is CH2 the resulting indane ring being linked via the 1-position, A and B are both O and D is optionally substituted methylene.
17. A compound of claim 3, characterized in that Y is NR1 the dihydroindole ring being linked via the 3- or 1-position, preferably the 3-position, A and B are both O, D is optionally substituted methylene.
18. A compound of any of claims 15-17, characterized in that W is a bond.
19. A compound of any of claims 15-18, characterized in that nm is 1 or 2, and R1-R5 are all hydrogen.
20. A compound of any of claims 15-19, characterized in that X is N.
21. A compound of claim 1, characterized in that it is selected from the following compounds:
1-(1-Indanylmethyl)-4-(3,4-methylendioxyphenyl)piperazine,
1-(6-Bromo-1-indanylmethyl-4-(3,4-methylendioxyphenyl)piperazine,
1-2-4-(3,4-methylenedioxyphenyl)-piperazine-1-ylethyl-indane,
2,3-Dihydro-3-4-4-(3,4-methylendioxyphenyl)piperazine-1-ylbutyl-1-oxo-1H-indole,
1-Acetyl-2,3-dihydro-3-2-4-(3,4-methylendioxyphenyl)piperazine-1-ylethyl-1H-indole or
1-(2-Indanylmethyl)-4-(3,4-methylendioxyphenyl)piperazine.
22. Use of a compound of any of claims 1-21 for the manufacture of a medicament useful in the treatment of positive and negative symptoms of schizophrenia, other psychoses, anxiety disorders, such as generalised anxiety disorder, panic disorder, and obsessive compulsive disorder, depression, alcohol abuse, impulse control disorders, aggression, side effects induced by conventional antipsychotic agents, ischaemic disease states, migraine, senile dementia and cardiovascular disorders and in the improvement of sleep.
23. Pharmaceutical composition characterized in that it comprises a compound of any of claims 1-21 in a therapeutically effective amount together with one or more pharmaceutically acceptable carriers or diluents.
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 method of regulating coolant pump inlet pressure of an internal combustion engine, the method comprising the steps of:
producing pressurized air by way of a mechanism; and
directing a portion of said pressurized air coming from said mechanism to a coolant system of the internal combustion engine.
2. The method of claim 1, wherein said directing step includes the step of regulating a pressure of said portion of pressurized air going to said coolant system.
3. The method of claim 1, wherein said mechanism is a turbocharger.
4. The method of claim 3, further comprising the step of passing air from said turbocharger through a cooling device before carrying out said directing step.
5. The method of claim 3, further comprising the step of limiting a flow of air from said turbocharger to become said portion of air.
6. The method of claim 5, further comprising the step of regulating air pressure in said coolant system.
7. The method of claim 6, wherein said step of regulating air pressure is carried out by way of a pressure regulator that regulates a pressure of said portion of air before said portion of air arrives at a surge tank of said coolant system.
8. The method of claim 6, wherein said step of regulating air pressure is carried out by way of a pressure regulator that bleeds air from a surge tank of said coolant system to thereby regulate air pressure in said coolant system.
9. A vehicle using an internal combustion engine, comprising:
a chassis coupled to the engine, the engine having a cooling system;
an air pressurizing device configured to compress air; and
a surge tank fluidly coupled to said cooling system, said surge tank coupled to said air pressurizing device to thereby receive a portion of the compressed air.
10. The vehicle of claim 9, wherein the portion of the compressed air is sent to said surge tank at a predetermined regulated pressure.
11. The vehicle of claim 9, wherein said air pressurizing device is a turbocharger.
12. The vehicle of claim 11, further comprising a pressure regulator positioned downstream from said turbocharger, said pressure regulator being fluidly coupled to said surge tank, said pressure regulator being positioned one of upstream from said surge tank and downstream from said surge tank.
13. The vehicle of claim 12, further comprising a flow limiting device fluidly coupled to said turbocharger downstream from said turbocharger, said flow limiting device being upstream of said pressure regulator.
14. The vehicle of claim 11, further comprising an air cooling device coupled to said turbocharger downstream from said turbocharger, the portion of the compressed air being directed to said surge tank after traversing said air cooling device.
15. An internal combustion engine, comprising:
a cooling system;
an air pressurizing device configured to compress air; and
a surge tank fluidly coupled to said cooling system, said surge tank coupled to said air pressurizing device to thereby receive a portion of the compressed air.
16. The internal combustion engine of claim 15, wherein the portion of the compressed air is sent to said surge tank at a predetermined regulated pressure.
17. The internal combustion engine of claim 15, wherein said air pressurizing device is a turbocharger.
18. The internal combustion engine of claim 17, further comprising a pressure regulator positioned downstream from said turbocharger, said pressure regulator being fluidly coupled to said surge tank, said pressure regulator being positioned one of upstream from said surge tank and downstream from said surge tank.
19. The internal combustion engine of claim 18, further comprising a flow limiting device fluidly coupled to said turbocharger downstream from said turbocharger, said flow limiting device being upstream of said pressure regulator.
20. The internal combustion engine of claim 17, further comprising an air cooling device coupled to said turbocharger downstream from said turbocharger, the portion of the compressed air being directed to said surge tank after traversing said air cooling device.