1. A method of setting a parameter for an audio apparatus, the audio apparatus including: a delay processing unit which applies a delaying process and an amplifying process on an input audio signal in accordance with the set parameter and which outputs a processed audio signal; and an adding unit which adds the audio signal output from the delay processing unit to the input audio signal and which outputs an added audio signal to an outputting device that outputs, as sound, the audio signal output from the adding unit, the method comprising:
performing a measuring process including: causing the outputting device to output measurement sound; and measuring a first impulse response at a sound receiving point;
performing a specifying process including: analyzing the measured first impulse response; calculating a second impulse response at the sound receiving point when the outputting device outputs sound in case where a parameter is set in the audio apparatus and an audio signal indicative of the measurement sound is input to the audio apparatus; and specifying a parameter in accordance with the calculated second impulse response; and
performing a setting process of setting the specified parameter in the delay processing unit.
2. The method according to claim 1, wherein,
in the specifying process, a plurality of second impulse responses are calculated in case where a plurality of parameters, which have different values from each other, are respectively set in the audio apparatus, and one parameter is specified from the plurality of parameters in accordance with the plurality of second impulse responses.
3. The method according to claim 1, wherein
the audio apparatus further includes an extracting unit which performs, to the audio signal which is to be added to the input audio signal, a process of extracting and outputting a component of a frequency band that is equal to or lower than a predetermined frequency band.
4. The method according to claim 1, wherein,
in the specifying process, a parameter in which energy of the second impulse response in a predetermined period is smaller than energy of the first impulse response in the predetermined period is specified.
5. The method according to claim 1, wherein,
in the specifying process, a parameter in which a peak value of an absolute value of the second impulse response in a predetermined period is smaller than a peak value of an absolute value of the first impulse response in the predetermined period is specified.
6. An audio apparatus comprising:
a delay processing unit which applies a delaying process and an amplifying process on an input audio signal in accordance with a parameter being set so that a maximum delay time in the delaying process is 50 msec. or shorter and which outputs a processed audio signal; and
an adding unit which adds the audio signal output from the delay processing unit to the input audio signal and which outputs an added audio signal to an outputting device that outputs, as sound, the audio signal output from the adding unit.
7. The audio apparatus according to claim 6, further comprising:
an extracting unit which performs, to the audio signal which is to be added to the input audio signal, a process of extracting and outputting a component of a frequency band of 1 kHz or less.
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. 3-(Indolyl)- and 3-(azaindolyl)-4-phenylmaleimide compounds of formula I
wherein
R1 is \u2014H, C1-C6-alkyl, phenyl-C1-C4-alkyl or phenyl;
R2 is
wherein R4, R5 and R6 are C1-C6-alkoxy; and
R3 is selected from:
wherein
R7 is \u2014H, C1-C6-alkyl or phenyl;
R9 is \u2014H, C1-C6-alkyl, C1-C6-alkoxy, \u2014OH, halogen, \u2014NH2, C1-C6-alkylamino, di-C1-C6-alkylamino, heteroaryl with 5 or 6 ring atoms containing 1 or 2 heteroatoms which are independently selected from O, N, and S, or heterocyclyl with 5 or 6 ring atoms containing 1 or 2 heteroatoms which are independently selected from O, N, and S; and
R8 is \u2014C1-C8-alkyl-X1\u2014X2\u2014R10, \u2014C2-C8-alkenyl-X1\u2014X2\u2014R10 or \u2014C2-C8-alkynyl-X1\u2014X2\u2014R10, wherein
X1 is a single bond, \u2014(OCH2CH2)n\u2014, or \u2014(OCH2CH2CH2)n\u2014, wherein n is 1, 2 or 3;
X2 is \u2014OC(O)\u2014, \u2014NR11C(O)\u2014, \u2014C(O)O\u2014, \u2014C(O)NR11\u2014, \u2014OC(O)NR11\u2014, \u2014NR11C(O)O\u2014, \u2014NR12C(O)NR12\u2014, \u2014OS(O)2\u2014, \u2014S(O)2O\u2014, \u2014OS(O)2O\u2014, \u2014NR11\u2014, or
R10 is selected from
a) linear or branched C1-C6-alkyl substituted with one substituent selected from \u2014NHR11, \u2014OH, \u2014SH, \u2014C(O)OH and \u2014S(O)2OH, and optionally further substituted with one, two or three substituents independently selected from \u2014NHR13, \u2014OH, \u2014SR13, \u2014C(O)OH, \u2014S(O)2OH, \u2014C(O)NH2, \u2014NHC(NH)NH2, \u2014NHC(O)NH2, C3-C7-cycloalkyl, phenyl and 5- or 6-membered heteroaryl, said cycloalkyl being optionally substituted with one or two C1-C6-alkyl, and said phenyl and heterocyclyl being optionally substituted with one, two, three or four substituents independently selected from \u2014OH, C1-C6-alkyl and \u2014C(O)OH; or
b) a 5- or 6-membered saturated heterocyclyl, optionally substituted with one, two or three substituents independently selected from C1-C6-alkyl, \u2014OH and \u2014C(O)OH;
c) C1-C6-alkyl substituted with monocyclic or bicyclic heteroaryl, in particular with imidazolyl such as 5-imidazolyl, said aryl being optionally substituted with one, two, three or four substituents independently selected from \u2014OH, C1-C6-alkyl and \u2014C(O)OH;
d) monocyclic or bicyclic aryl, optionally substituted with one, two, three or four substituents independently selected from \u2014OH, C1-C6-alkyl and \u2014C(O)OH;
e) C3-C7-cycloalkyl optionally substituted with one or two C1-C6-alkyl;
f) monocyclic or bicyclic heteroaryl, optionally substituted with one, two, three or four substituents independently selected from \u2014OH, C1-C6-alkyl, and \u2014C(O)OH;
g) C1-C6-alkyl substituted with monocyclic or bicyclic aryl, in particular with phenyl, said aryl being optionally substituted with one, two or three substituents independently selected from \u2014OH, C1-C6-alkyl, and \u2014C(O)OH; and
h) \u2014(CH2CH2O)mH, \u2014(CH(CH3)CH2O)mH, or \u2014(CH2CH(CH3)O)mH, wherein m is 1 to 10;
R11 is selected from \u2014H, C1-C6-alkyl, phenyl and benzyl;
R12 is \u2014H or C1-C8-alkyl; and
R13 is selected from \u2014H, C1-C6-alkyl, phenyl and benzyl;
and the physiologically acceptable salts, solvates and solvates of the salts of the compounds of formula I.
2. The compounds of claim 1
(a) having formula Ia:
wherein R1, R7, R8 and R9 are as defined in claim 1 and R4, R5 and R6 are C1-C6-alkoxy;
(b) having formula Ib:
wherein R1, R7, R8 and R9 are as defined in claim 1 and R4, R5 and R6 are C1-C6-alkoxy;
(c) having formula Ic:
wherein R1, R7, R8 and R9 are as defined in claim 1 and R4, R5 and R6 are C1-C6-alkoxy;
(d) having formula Id:
wherein R1, R7, R8 and R9 are as defined in claim 1 and R4, R5 and R6 are C1-C6-alkoxy; or
(e) having formula Ie:
wherein R1, R7, R8 and R9 are as defined in claim 1 and R4, R5 and R6 are C1-C6-alkoxy; and the physiologically acceptable salts, solvates and solvates of the salts of said compounds.
3. The compounds of claim 1, wherein R1 and R7 are \u2014H, and R9 is \u2014H, C1-C6-alkyl or halogen; and the physiologically acceptable salts, solvates and solvates of the salts thereof.
4. The compounds of claim 1, wherein R8 is \u2014C1-C8-alkyl-X1\u2014OC(O)\u2014R10, \u2014C1-C8-alkyl-X1\u2014NR11C(O)\u2014R10, \u2014C1-C8-alkyl-X1\u2014C(O)NR11\u2014R10, \u2014C1-C8-alkyl-X1\u2014OC(O)NR11\u2014R10 or \u2014C1-C8-alkyl-X1\u2014NR12C(O)NR12\u2014R10; and the physiologically acceptable salts, solvates and solvates of the salts thereof.
5. The compounds of claim 1, wherein R10 is selected from
a) linear or branched C1-C6-alkyl substituted with one residue selected from \u2014NHR11, \u2014OH, \u2014SH and \u2014C(O)OH, and optionally further substituted with one, two or three residues independently selected from \u2014NHR13, \u2014OH, \u2014SR13, \u2014C(O)OH, \u2014C(O)NH2, \u2014NHC(NH)NH2, \u2014NHC(O)NH2, phenyl, hydroxyphenyl, indolyl and imidazolyl, said indolyl or imidazolyl being optionally substituted with one, two, three or four substituents independently selected from \u2014OH, C1-C6-alkyl and \u2014C(O)OH;
b) 5- or 6-membered saturated heterocycloalkyl, optionally substituted with one or two substituents independently selected from C1-C6-alkyl, \u2014OH and \u2014C(O)OH; and
c) C1-C6-alkyl substituted with imidazolyl; and the physiologically acceptable salts, solvates and solvates of the salts thereof.
6. The compounds of claim 1, wherein R10 is 2-(1H-imidazol-5-yl)ethyl, or a residue of an amino acid that is derived from said amino acid by removal of an \u2014COOH, \u2014NH2 or \u2014OH group; and the physiologically acceptable salts, solvates and solvates of the salts thereof.
7. The compounds of claim 6, wherein the amino acid is selected from isoleucine, alanine, leucine, asparagine, lysine, aspartic acid, methionine, cysteine, phenylalanine, histidine, tryptophan, glutamic acid, threonine, glutamine, glycine, valine, serine, tyrosine, arginine, proline, ornithine and citrulline; and the physiologically acceptable salts, solvates and solvates of the salts thereof.
8. The compounds of claim 6, wherein said amino acid is an \u03b1-amino acid; and the physiologically acceptable salts, solvates and solvates of the salts thereof.
9. The compounds of claim 6, wherein the residue is derived from said amino acid by removal of the \u2014COOH group comprising the C1 atom of the amino acid; and the physiologically acceptable salts, solvates and solvates of the salts thereof.
10. The compounds of claim 6, wherein the residue is derived from said amino acid by removal of the \u2014NH2 group from the C2 atom of the amino acid; and the physiologically acceptable salts, solvates and solvates of the salts thereof.
11. The compounds of claim 6, wherein the absolute stereoconfiguration at the C2 atom of the amino acid is L-configuration; and the physiologically acceptable salts, solvates and solvates of the salts thereof.
12. The compounds of claim 1 having a formula selected from
and the physiologically acceptable salts, solvates and solvates of the salts thereof.
13. A pharmaceutical composition comprising at least one compound of formula I according to claim 1, and the physiologically acceptable salts, solvates and solvates of the salts of the compounds of formula I and a pharmaceutically acceptable excipient, and, optionally, further comprising an additional chemotherapeutic agent.
14. The composition of claim 13, wherein the additional chemotherapeutic agent is selected from antineoplastic agents, multidrug resistance reversing agents; and biological response modifiers, and combinations thereof.
15. A method of treating tumors comprising administering a compound of formula I according to claim 1 and the physiologically acceptable salts, solvates and solvates of the salts of the compounds of formula I.
16. The method of claim 15 further comprising administering an additional chemotherapeutic agent.