DE102006019589A1 - Inhibitors of the TASK-1 and Task-3 ion channel - Google Patents

Abstract

The This invention relates to the use of TASK-1 and TASK-3 inhibitors for the manufacture of a medicament for the therapy or prophylaxis of respiratory disorders, sleep-related respiratory disorders such as central and obstructive sleep apnea, Cheyne-Stokes respiration, Snoring, disturbed central respiratory drive, sudden Infant death, postoperative hypoxia and apnea, muscular-related Respiratory disorders, respiratory disorders after long-term ventilation, respiratory disorders in adaptation in high mountains, acute and chronic lung diseases with hypoxia and hypercapnia, neurodegenerative diseases, dementia, Alzheimer's disease, Parkinson's disease, Huntington's disease, cancer, Breast cancer, lung cancer, colon cancer and prostate cancer.

Description

und/oder pharmazeutisch verträglichen Salzen davon und die Verwendung von TASK-1 und TASK-3 Inhibitoren zur Herstellung eines Medikaments zur Therapie oder Prophylaxe von Atemstörungen, schlafbedingten Atemstörungen wie zentralen und obstruktiven Schlafapnoen, Cheyne-Stoke'sche Atmung, Schnarchen, gestörten zentralen Atemantrieb, plötzlicher Kindstod, postoperative Hypoxie und Apnoe, muskulär-bedingten Atemstörungen, Atemstörungen nach Langzeitbeatmung, Atemstörungen bei Adaptation im Hochgebirge, akute und chronische Lungenkrankheiten mit Hypoxie und Hyperkapnie, neurodegenerativen Erkrankungen, Demenz, Morbus Alzheimer, Morbus Parkinson, Morbus Huntington, Krebskrankheiten, Brustkrebs, Lungenkrebs, Kolonkrebs und Prostatakrebs.The invention relates to the blockade of the TASK-1 and TASK-3 ion channel by compounds of the formulas Ia, Ib, Ic, Id, Ie, If, Ig, Ih and / or Ij

and / or pharmaceutically acceptable salts thereof and the use of TASK-1 and TASK-3 inhibitors for the manufacture of a medicament for the therapy or prophylaxis of respiratory disorders, sleep-disordered breathing disorders such as central and obstructive sleep apnea, Cheyne-Stoke's respiration, snoring, disturbed central respiratory drive , sudden infant death syndrome, postoperative hypoxia and apnea, muscular respiratory disorders, respiratory disorders after long-term ventilation, respiratory disorders in high altitude adaptation, acute and chronic lung diseases with hypoxia and hypercapnia, neurodegenerative diseases, dementia, Alzheimer's disease, Parkinson's disease, Huntington's disease, cancer, breast cancer , Lung cancer, colon cancer and prostate cancer.

The Compounds of the formulas Ia-Ij and / or physiologically acceptable Salts thereof inhibit so-called TASK potassium channels, especially the subtypes TASK-1 and / or TASK-3.

Potassium channels are widespread membrane proteins that play an important role in many physiological processes because of their effects on cell membrane potentials. Within the diverse class of potassium channels one distinguishes 3 large groups due to their molecular structure, which are characterized by the number of transmembrane domains (2, 4 or 6). The group of potassium channels with 4 transmembrane segments is different from the other two in that their representatives each have 2 pore domains, which is why these channels are also referred to as K _2P channels [Coetzee WJ et al; Molecular diversity of K + channels; Ann. New York Acad. Sci. 1999 (868), 233-285]. Functionally, K _2P channels are characterized by the flow of so-called "leak" or "background" currents, which play an important role in the resting membrane potential and thus the excitability of nerve or muscle cells.

A particularly interesting family within the K _2P channels are the TASK channels, which were discovered only in the late 1990s, of which 5 are now TASK-1, TASK-2, TASK-3, TASK-4 and TASK-5, are described. Other common names in the literature for the underlying genes are KCNK3 or K2P3.1 (= TASK-1), KCNK5 or K2P5.1 (= TASK-2), KCNK9 or K2P9.1 (= TASK-3), KCNK15 or K2P15.1 (= TASK-5) and KCNK17 or K2P17.1 (= TASK-4, TALK-2). The largest homology within this family has the channels TASK-1 and TASK-3 with an amino acid identity greater than 50%. Dimerization of K _2P channels leads to the formation of functional potassium channels with a total of 4 pore units. The currents flowing through these channels are referred to in the literature as IKso current. In addition to homodimerization of z. B. two TASK-1 or two TASK-3 proteins, this is also a heterodimerization of TASK-1 and TASK-3 possible [Berg AP, Talley EM, Manger JP, Bayliss DA; Motoneuron's express Heteromeric TWIK-related acid-sensitive K + (TASK) channels containing TASK-1 (KCNK3) and TASK-3 (KCNK9) subunits; J. Neuroscience 2004 (24), 6693-6702].

The TASK channels are characterized in particular by their strong dependence on extracellular pH in the physiological range. The channels are inhibited at acidic pH and alkaline pH activated. Because of this pH dependence, the physiological function of a sensor that translates small changes in extracellular pH into corresponding cellular signals is attributed to the TASK channels [Duprat F., Lesage F., Fink M., Reyes R., Heurteaux C. , Lazdunski M .; TASK, a human background K + channel to sense external pH changes near physiological pH; EMBO J. 1997 (16), 5464-5471; Patel AJ, Honore E .; Properties and modulation of mammalian 2P domain K + channels; Trends Neurosci. 2001 (24), 339-346].

TASK-1 is in the brain as well as in dorsal root ganglia and some peripheral tissues expressed, such as pancreas, placenta, uterus, lung, Heart, kidney, small intestine and stomach. Furthermore was TASK-1 in the chemosensitive cells of the brainstem and the Karotiskörperchen and the motor neurons of the hypoglossal nerve. TASK-3 becomes main expressed in the cerebellum. [Medhurst A.D., Rennie G., Chapman C. G., Meadows H., Duckworth M.D., Kelsell R.E., Glober I.I., Pangalos M.N .; Distribution analysis of human two pore domain potassium channels in the tissues of the central nervous system and periphery; Mol. Brain Res. 2001 (86), 101-114].

Electrical currents caused by TASK-1 potassium channels were detected in motor neurons of the hypoglossal nerve (a motor cranial nerve that has the most important function for keeping the upper airway open) and locus coeruleus. It has been shown that TASK-1 channels in respiratory neurons of the brainstem, in carotid bodies and motor neurons of the hypoglossal nerve, as well as in neuroepithelial cells of the lung, are involved in respiratory regulation. Inadequate respiration (hypoxia, obstruction of respiration) and physical exertion lead either to an increase in the CO ₂ concentration and the resulting acidosis or acid metabolites (lactate) to a lowering of the pH value and thus to a blockage of the pH. dependent TASK-1 channels. This depolarizes the cells, resulting in activation of the neurons involved in respiratory regulation. [Buckler KJ, Williams BA, Honore E .; An oxygen-, acid- and anesthetics-sensitive TASK-like background potassium channel in rat arterial chemoreceptor cells; J. Physiol. 2000 (525), 135-142; Bayliss DA, Talley EM, Sirois JE, Lei Q .; TASK-1 is a highly modulated pH-sensitive 'leak' K + channel expressed in brainstem respiratory neurons; Respiration Physiology 2001 (129), 159-174].

A increase the activity chemosensitive neurons in conjunction with activation of the Motoneurone of the hypoglossal nerve through blockage of the TASK channel can stop breathing stimulate and simultaneously stabilize the upper respiratory tract and protect against collapse and closure. Furthermore can snore over the mechanism of stabilization of the upper respiratory tract can be inhibited. The blockade of TASK-1 ion channels may therefore be an application for the treatment of respiratory disorders, z. B. Sleep apnea.

TASK-1 channels are also in smooth muscle cells of mesenteric and pulmonary arteries available. In the latter it is possible that they are involved in acidosis-induced pulmonary vasoconstriction [Gurney A.M., Osipenko O.N., MacMillan D., McFarlane K.M., Tate R.J., Kempsill F.E .; Two-pore domain K channel, TASK-1, in pulmonary artery smooth muscle cells; Circ. Res. 2003 (93), 957-964].

Farther has been described as TASK channels in the zona glomerulosa of the adrenal cortex at the secretion of Adrenal hormones are involved [Czirjak G., Fischer T., Late A., Lesage F., Enyedi P .; TASK (TWIK-related acid-sensitive K + channel) is expressed in glomerulosa cells of rat adrenal cortex and inhibited by angiotensin II; Molecular Endocrinology 2000 (14), 863-874].

In Cultured granulosa cells of the cerebellum were shown to be genetic inactivation of TASK channels a neuroprotective effect [Lauritzen I., Zanzouri M., Honoré E., Duprat F., Ehrengruber M.U., Lazdunski M., Patel A.J .; K + -dependent cerebellar granule neuron apoptosis - Role of task leak K + channels; J. Biol. Chem. 2003 (278), 32068-32076]. Furthermore could be shown that TASK-1 channels in granulosa cells programmed for the Cell death (apoptosis) are responsible, and that through blockage TASK-3 can prevent cell death. It is therefore assumed that the development of specific inhibitors of TASK-1/3 channels a pharmacological strategy for the treatment of neurodegenerative diseases [Patel A.J., Lazdunski M., The 2P-domain K + channels: role in apoptosis and tumorigenesis, Pflugers Arch. 2004 (448), 261-273].

The TASK-3 gene is amplified and overexpressed in various human carcinoma tissues, such as breast, lung, colon and metastatic prostate cancer [Mu D., Chen L., Zhang X., et al., Genomic amplification and oncogenic properties of the KCNK9 potassium channel gene, Cancer Cell 2003 (3), 297-302]. It has been demonstrated that performing a point mutation on the TASK-3 is the Ka Switch off the function and simultaneously eliminates the tumor-forming function. It is therefore expected that TASK-3 antagonists may reduce the growth of various human carcinomas and thus represent a new family of anticancer agents [Pei L., Wiser O., Slavin A., Mu D., Powers S., Jan LY, Hoey T .; Oncogenic potential of TASK3 (Kcnk9) depends on K + channel function; Proc. Natl. Acad. Sci. USA 2003 (100), 7803-7807].

Despite the great physiological importance of the TASK channels, only a few pharmacological modulators of these channels are known in the literature so far. It has been described that activation of the TASK-1 channel is achieved by therapeutic concentrations of the inhaled anesthetics halothane and isoflurane [Patel AJ, Honore E., Lesage F., Fink M., Romey G., Lazdunski M .; Inhalational anesthesics activate two-pore-domain background K + channels; Nature Neurosci. 1999 (2), 422-426]. The only known direct blockers of TASK-1 are the arachindonic acid amides anandamides (an endogenous ligand of the cannabinoid receptor) and its homologue methanandamides, for which an IC-50 value of 0.7 μM has been described [Maingret F., Patel AJ, Lazdunski M. , Honore E .; The endocannabinoid anandamide is a direct and selective blocker of the background K + channel TASK-1; EMBO J. 2001 (20), 47-54], as well as the doxapram used to treat respiratory disorders, for which an IC-50 value of 0.4 μM has recently been described [Cotten JF, Keshavaprasad B., Vice MJ, Eger EI , Yost CS; The Ventilatory Stimulant Doxapram Inhibits TASK Tandem Pore (K _2P ) Potassium Channel Function but Does Not Affect Minimum Alveolar Anesthetic Concentration; Anesth. Analg. 2006 (102) 779-785].

It it has now been found that the compounds of the formulas Ia, Ib, Ic, Id, Ie, If, Ig, Ih, and Ij are potent blockers of TASK channels, in particular of subtypes TASK-1 and TASK-3. The connections were so far only as a blocker of Kv1.5 channels known to the group of potassium channels with 6 transmembrane domains and 1 pore domain belong (WO01 / 00573, WO01 / 025189, WO02 / 044137, WO02 / 046162, WO02 / 048131, WO02 / 087568, WO02 / 088073, WO02 / 100825). Given the large structural Differences between Kv1.5 and TASK channels was the effect of these compounds known as Kv1.5 blockers to the TASK-1 and TASK-3 channel surprising.

by virtue of TASK-1 and / or TASK-3-inhibitory properties are suitable the compounds of the formulas Ia to Ij and / or their pharmaceutically compatible Salts for prevention and treatment of diseases caused by activation or caused by an activated TASK-1 and / or TASK-3, as well as diseases secondary to TASK-1 and / or TASK-3-related damage caused.

The Compounds of the formulas Ia, Ib, Ic, Id, Ie, If, Ig, Ih and Ij and / or physiologically compatible Salts of it can also for treatment and prevention be used by diseases, the TASK-1 and / or TASK-3 is only partially inhibited, for example by using a lower dosage.

The Compounds of the formulas Ia to Ij can be used in particular are used for the therapy or prophylaxis of respiratory disorders, sleep-related respiratory disorders such as central and obstructive sleep apnea, Cheyne-Stoke's breathing, snoring, disturbed central respiratory drive, sudden Infant death, postoperative hypoxia and apnea, muscular Respiratory disorders, respiratory disorders after long-term ventilation, respiratory disorders in adaptation in high mountains, acute and chronic lung diseases with hypoxia and hypercapnia, neurodegenerative diseases, dementia, Alzheimer's disease, Parkinson's disease, Huntington's disease, cancer, Breast cancer, lung cancer, colon cancer and prostate cancer.

The The present invention relates to the use of Kv1.5 inhibitors for the manufacture of a medicament for the therapy or prophylaxis of Respiratory disorders, sleep-related respiratory disorders such as central and obstructive sleep apnea, Cheyne-Stoke's breathing, snoring, disturbed central respiratory drive, sudden Infant death, postoperative hypoxia and apnea, muscular-related Respiratory disorders, respiratory disorders after long-term ventilation, respiratory disorders with adaptation in high mountains, acute and chronic lung diseases with Hypoxia and hypercapnia, neurodegenerative diseases, dementia, Alzheimer's disease, Parkinson's disease, Huntington's disease, cancer, Breast cancer, lung cancer, colon cancer and prostate cancer.

wobei R(8) entweder für einen 1-Indanylrest der Formel II oder für einen 2-Indanylrest der Formel III steht,

und worin bedeuten:
R(1) und R(2)
unabhängig voneinander R(20)-C_rH_2r,
wobei eine CH₂-Gruppe der Gruppe C_rH_2r ersetzt sein kann durch -O-, -CH=CH-, -C≡C-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO₂-, -NR(21)- oder -CONR(21);
R(21) Wasserstoff oder Alkyl mit 1, 2 oder 3 C-Atomen;
R(20) H, CH₃, CH₂F, CHF₂, CF₃, C₂F₅, C₃F₇, Cycloalkyl mit 3, 4, 5, 6, 7 oder 8 C-Atomen, NR(22)R(23), -CONR(22)R(23), -OR(24), -COOR(24), Phenyl oder ein N-haltiger Heterocyclus mit 1, 2, 3, 4, 5, 6, 7, 8 oder 9 C-Atomen,
wobei Phenyl und der N-haltige Heterocyclus unsubstituiert sind oder substituiert mit 1 oder 2 Substituenten, ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, NO₂, CN, NH₂, OH, Methyl, Ethyl, Hydroxymethyl, Hydroxyethyl, Methoxy, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(22) und R(23)
unabhängig voneinander Wasserstoff oder Alkyl mit 1, 2, 3 oder 4 C-Atomen;
oder
R(22) und R(23)
gemeinsam eine Kette von 4 oder 5 Methylengruppen, von denen eine CH₂-Gruppe durch -O-, -S-, -NH-, -N(Methyl)- oder -N(Benzyl)- ersetzt sein kann;
R(24) Wasserstoff oder Alkyl mit 1, 2 oder 3 C-Atomen;
r Null, 1, 2, 3, 4, 5, 6, 7 oder 8;
oder
R(1) und R(2)
gemeinsam eine Kette von 4 oder 5 Methylengruppen, von denen eine CH₂-Gruppe durch -O-, -S-, -NH-, -N(Methyl)- oder -N(Benzyl)- ersetzt sein kann;
R(3), R(4), R(5) und R(6)
unabhängig voneinander Wasserstoff, F, Cl, Br, I, Alkyl mit 1, 2, 3, 4 oder 5 C-Atomen, Cycloalkyl mit 3, 4, 5, 6, 7 oder 8 C-Atomen, CN, CF₃, NO₂, OR(25) oder NR(26)R(27);
R(25) Wasserstoff, Alkyl mit 1, 2, 3 oder 4 C-Atomen, ein fluorierter Alkylrest der Formel -C_xH_2xCF_yH_3-y oder Phenyl,
das unsubstituiert ist oder substituiert mit 1 oder 2 Substituenten, ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, NO₂, CN, NH₂, OH, Methyl, Ethyl, Methoxy, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
x 0, 1, 2 oder 3;
y 1, 2 oder 3;
R(26) und R(27)
unabhängig voneinander Wasserstoff oder Alkyl mit 1, 2, 3 oder 4 C-Atomen;
oder
R(26) und R(27)
gemeinsam eine Kette von 4 oder 5 Methylengruppen, von denen eine CH₂-Gruppe durch -O-, -S-, -NH-, -N(Methyl)- oder -N(Benzyl)- ersetzt sein kann;
R(7) Wasserstoff oder Alkyl mit 1, 2, 3 oder 4 C-Atomen;
R(9) Wasserstoff, OR(28) oder OCOR(28); R(28) Wasserstoff oder Alkyl mit 1, 2, 3 oder 4 C-Atomen;
R(10) und R(11)
unabhängig voneinander Wasserstoff oder Alkyl mit 1, 2, 3 oder 4 C-Atomen;
R(12), R(13), R(14) und R(15)
unabhängig voneinander Wasserstoff, F, Cl, Br, I, Alkyl mit 1, 2, 3, 4 oder 5 C-Atomen, Cycloalkyl mit 3, 4, 5, 6, 7 oder 8 C-Atomen, -CN, -CF₃, -C₂F₅, -C₃F₇, -N₃, -NO₂, -Y-C_sH_2s-R(29), Phenyl, Thienyl, Furyl oder ein N-haltiger Heterocyclus mit 1, 2, 3, 4, 5, 6, 7, 8 oder 9 C-Atomen,
wobei Phenyl, Thienyl, Furyl und der N-haltige Heterocyclus unsubstituiert sind oder substituiert mit 1 oder 2 Substituenten, ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, NO₂, CN, NH₂, OH, Methyl, Ethyl, Methoxy, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
Y -O-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO₂-, -O-SO₂-, -SO₂NR(30)-, -CONR(30)- oder -NR(30)CO-, wobei die Verknüpfung mit dem Grundgerüst jeweils über das links stehende Atom erfolgt;
R(30) Wasserstoff oder Alkyl mit 1, 2 oder 3 C-Atomen;
s Null, 1, 2, 3, 4, 5 oder 6;
R(29) Wasserstoff, Methyl, CF₃, C₂F₅, C₃F₇, Cycloalkyl mit 3, 4, 5, 6, 7 oder 8 C-Atomen, -OR(31), -COOR(31), -NR(32)R(33), -CONR(32)R(33), Phenyl oder ein N-haltiger Heterocyclus mit 1, 2, 3, 4, 5, 6, 7, 8 oder 9 C-Atomen,
wobei Phenyl und der N-haltige Heterocyclus unsubstituiert sind oder substituiert mit 1 oder 2 Substituenten, ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, NO₂, CN, NH₂, OH, Methyl, Ethyl, Methoxy, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(31) Wasserstoff oder Alkyl mit 1, 2 oder 3 C-Atomen;
R(32) und R(33)
unabhängig voneinander Wasserstoff oder Alkyl mit 1, 2, 3 oder 4 C-Atomen;
oder
R(32) und R(33)
gemeinsam eine Kette von 4 oder 5 Methylengruppen, von denen eine CH₂-Gruppe durch -O-, -S-, -NH-, -N(CH₃)- oder -N(Benzyl)- ersetzt sein kann;
und/oder Verbindungen der Formel Ib

worin bedeuten:
R(1) C(O)OR(9), SO₂R(10), COR(11), C(O)NR(12)R(13) oder C(S)NR(12)R(13);
R(9) C_xH_2x-R(14);
x 0, 1, 2, 3 oder 4,
wobei x nicht 0 sein kann, wenn R(14) OR(15) oder SO₂Me bedeutet;
R(14) Alkyl mit 1, 2, 3, 4, 5 oder 6 C-Atomen, Cycloalkyl mit 3, 4, 5, 6, 7, 8, 9, 10 oder 11 C-Atomen, CF₃, C₂F₅, C₃F₇, CH₂F, CHF₂, OR(15), SO₂Me, Phenyl, Naphthyl, Biphenylyl, Furyl, Thienyl oder ein N-haltiger Heteroaromat mit 1, 2, 3, 4, 5, 6, 7, 8 oder 9 C-Atomen,
wobei Phenyl, Naphthyl, Biphenylyl, Furyl, Thienyl und der N-haltige Heteroaromat unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(15) Alkyl mit 1, 2, 3, 4 oder 5 C-Atomen, Cycloalkyl mit 3, 4, 5 oder 6 C-Atomen, CF₃ oder Phenyl,
das unsubstituiert ist oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(10), R(11) und R(12)
unabhängig von einander wie R(9) definiert;
R(13) Wasserstoff, Alkyl mit 1, 2, 3 oder 4 C-Atomen oder CF₃;
R(2) Wasserstoff, Alkyl mit 1, 2, 3 oder 4 C-Atomen oder CF₃;
R(3) C_yH_2y-R(16);
y 0, 1, 2, 3 oder 4,
wobei y nicht 0 sein kann, wenn R(16) OR(17) oder SO₂Me bedeutet;
R(16) Alkyl mit 1, 2, 3, 4, 5 oder 6 C-Atomen, Cycloalkyl mit 3, 4, 5, 6, 7, 8, 9, 10 oder 11 C-Atomen, CF₃, C₂F₅, C₃F₇, CH₂F, CHF₂, OR(17), SO₂Me, Phenyl, Naphthyl, Furyl, Thienyl oder ein N-haltiger Heteroaromat mit 1, 2, 3, 4, 5, 6, 7, 8 oder 9 C-Atomen, wobei Phenyl, Naphthyl, Furyl, Thienyl und der N-haltige Heteroaromat unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(17) Wasserstoff, Alkyl mit 1, 2, 3, 4 oder 5 C-Atomen, Cycloalkyl mit 3, 4, 5 oder 6 C-Atomen, CF₃, Phenyl oder 2-, 3- oder 4-Pyridyl,
wobei Phenyl oder 2-, 3- oder 4-Pyridyl unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
oder
R(3) CHR(18)R(19);
R(18) Wasserstoff oder C₂H_2z-R(16), wobei R(16) wie oben angegeben definiert ist;
z 0, 1, 2 oder 3;
R(19) COOH, CONH₂, CONR(20)R(21), COOR(22), CH₂OH;
R(20) Wasserstoff, Alkyl mit 1, 2, 3, 4 oder 5 C-Atomen, C_vH_2v-CF₃ oder C_wH_2w-Phenyl,
wobei der Phenylring unsubstituiert ist oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
v 0, 1, 2 oder 3;
w 0, 1, 2 oder 3;
R(21) Wasserstoff oder Alkyl mit 1, 2, 3, 4 oder 5 C-Atomen;
R(22) Alkyl mit 1, 2, 3, 4 oder 5 C-Atomen;
R(4) Wasserstoff, Alkyl mit 1, 2, 3, 4, 5 oder 6 C-Atomen oder CF₃;
oder
R(3) und R(4)
gemeinsam eine Kette von 4 oder 5 Methylengruppen, von denen eine Methylengruppe durch -O-, -S-, -NH-, -N(Methyl)- oder -N(Benzyl)- ersetzt sein kann;
R(5), R(6), R(7) und R(8)
unabhängig voneinander Wasserstoff, F, Cl, Br, I, CF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl oder Methylsulfonylamino;
R(30) und R(31)
unabhängig voneinander Wasserstoff oder Alkyl mit 1, 2 oder 3 C-Atomen;
oder
R(30) und R(31)
gemeinsam eine Kette von 2 Methylengruppen;
und/oder Verbindungen der Formel Ic

worin bedeuten:
A1, A2, A3, A4, A5, A6, A7 und A8
unabhängig voneinander Stickstoff, CH oder CR5, wobei mindestens vier dieser Gruppen CH bedeuten;
R(1) C(O)OR(9), SO₂R(10), COR(11), C(O)NR(12)R(13) oder C(S)NR(12)R(13);
R(9), R(10), R(11) und R(12)
unabhängig voneinander C_xH_2x-R(14);
x 0, 1, 2, 3 oder 4,
wobei x nicht 0 sein kann, wenn R(14) OR(15) oder SO₂Me bedeutet;
R(14) Alkyl mit 1, 2, 3, 4, 5 oder 6 C-Atomen, Cycloalkyl mit 3, 4, 5, 6, 7, 8, 9, 10 oder 11 C-Atomen, CF₃, C₂F₅, C₃F₇, CH₂F, CHF₂, OR(15), SO₂Me, Phenyl, Naphthyl, Biphenylyl, Furyl, Thienyl oder ein N-haltiger Heteroaromat mit 1, 2, 3, 4, 5, 6, 7, 8 oder 9 C-Atomen,
wobei Phenyl, Naphthyl, Biphenylyl, Furyl, Thienyl und der N-haltige Heteroaromat unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(15) Alkyl mit 1, 2, 3, 4 oder 5 C-Atomen, Cycloalkyl mit 3, 4, 5 oder 6 C-Atomen, CF₃ oder Phenyl,
das unsubstituiert ist oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(13) Wasserstoff, Alkyl mit 1, 2, 3 oder 4 C-Atomen oder CF₃;
R(2) Wasserstoff, Alkyl mit 1, 2, 3 oder 4 C-Atomen oder CF₃;
R(3) C_yH_2y-R(16);
y 0, 1, 2, 3 oder 4,
wobei y nicht 0 sein kann, wenn R(16) OR(17) oder SO₂Me bedeutet;
R(16) Alkyl mit 1, 2, 3, 4, 5 oder 6 C-Atomen, Cycloalkyl mit 3, 4, 5, 6, 7, 8, 9, 10 oder 11 C-Atomen, CF₃, C₂F₅, C₃F₇, CH₂F, CHF₂, OR(17), SO₂Me, Phenyl, Naphthyl, Furyl, Thienyl oder ein N-haltiger Heteroaromat mit 1, 2, 3, 4, 5, 6, 7, 8 oder 9 C-Atomen,
wobei Phenyl, Naphthyl, Furyl, Thienyl und der N-haltige Heteroaromat unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino.The invention relates to the use of compounds of the formulas Ia

where R (8) is either a 1-indanyl radical of the formula II or a 2-indanyl radical of the formula III,

and wherein
R (1) and R (2)
independently, R (20) -C _r H _2r,
where one CH ₂ group of the group C _r H _2r may be replaced by -O-, -CH = CH-, -C≡C-, -CO-, -CO-O-, -O-CO-, -S -, -SO-, -SO ₂ -, -NR (21) - or -CONR (21);
R (21) is hydrogen or alkyl having 1, 2 or 3 C atoms;
R (20) H, CH ₃ , CH ₂ F, CHF ₂ , CF ₃ , C ₂ F ₅ , C ₃ F ₇ , cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms, NR (22) R (23), -CONR (22) R (23), -OR (24), -COOR (24), phenyl or an N-containing heterocycle having 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms,
where phenyl and the N-containing heterocycle are unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF _3, NO _2, CN, NH _2, OH, methyl, ethyl, hydroxymethyl Hydroxyethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (22) and R (23)
independently of one another hydrogen or alkyl having 1, 2, 3 or 4 C atoms;
or
R (22) and R (23)
together a chain of 4 or 5 methylene groups, of which one CH ₂ group may be replaced by -O-, -S-, -NH-, -N (methyl) - or -N (benzyl) -;
R (24) is hydrogen or alkyl having 1, 2 or 3 C atoms;
r is zero, 1, 2, 3, 4, 5, 6, 7 or 8;
or
R (1) and R (2)
together a chain of 4 or 5 methylene groups, of which one CH ₂ group may be replaced by -O-, -S-, -NH-, -N (methyl) - or -N (benzyl) -;
R (3), R (4), R (5) and R (6)
independently of one another hydrogen, F, Cl, Br, I, alkyl having 1, 2, 3, 4 or 5 C atoms, cycloalkyl having 3, 4, 5, 6, 7 or 8 C atoms, CN, CF ₃ , NO ₂ , OR (25) or NR (26) R (27);
R (25) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms, a fluorinated alkyl radical of the formula -C _x H _{2, 2} CF _y H _3-y or phenyl,
which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF _3, NO _2, CN, NH _2, OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
x 0, 1, 2 or 3;
y is 1, 2 or 3;
R (26) and R (27)
independently of one another hydrogen or alkyl having 1, 2, 3 or 4 C atoms;
or
R (26) and R (27)
together a chain of 4 or 5 methylene groups, of which one CH ₂ group may be replaced by -O-, -S-, -NH-, -N (methyl) - or -N (benzyl) -;
R (7) is hydrogen or alkyl having 1, 2, 3 or 4 C atoms;
R (9) is hydrogen, OR (28) or OCOR (28); R (28) is hydrogen or alkyl having 1, 2, 3 or 4 C atoms;
R (10) and R (11)
independently of one another hydrogen or alkyl having 1, 2, 3 or 4 C atoms;
R (12), R (13), R (14) and R (15)
independently of one another hydrogen, F, Cl, Br, I, alkyl having 1, 2, 3, 4 or 5 C atoms, cycloalkyl having 3, 4, 5, 6, 7 or 8 C atoms, -CN, -CF ₃ , -C ₂ F ₅ , -C ₃ F ₇ , -N ₃ , -NO ₂ , -YC _s H _2s -R (29), phenyl, thienyl, furyl or an N-containing heterocycle having 1, 2, 3, 4, 5, 6, 7, 8 or 9 carbon atoms,
wherein phenyl, thienyl, furyl and the N-containing heterocycle are unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl Ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
Y is -O-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO ₂ -, -O-SO ₂ -, -SO ₂ NR (30) -, -CONR (30) - or -NR (30) CO-, where the linkage to the backbone is in each case via the atom on the left;
R (30) is hydrogen or alkyl having 1, 2 or 3 C atoms;
s is zero, 1, 2, 3, 4, 5 or 6;
R (29) is hydrogen, methyl, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , cycloalkyl having 3, 4, 5, 6, 7 or 8 C atoms, -OR (31), -COOR (31), -NR (32) R (33), -CONR (32) R (33), phenyl or an N-containing heterocycle having 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms,
where phenyl and the N-containing heterocycle are unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF _3, NO _2, CN, NH _2, OH, methyl, ethyl, methoxy , Dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (31) is hydrogen or alkyl having 1, 2 or 3 C atoms;
R (32) and R (33)
independently of one another hydrogen or alkyl having 1, 2, 3 or 4 C atoms;
or
R (32) and R (33)
together a chain of 4 or 5 methylene groups, of which one CH ₂ group may be replaced by -O-, -S-, -NH-, -N (CH ₃ ) - or -N (benzyl) -;
and / or compounds of the formula Ib

in which mean:
R (1) C (O) OR (9), SO ₂ R (10), COR (11), C (O) NR (12) R (13) or C (S) NR (12) R (13) ;
R (9) C _x H _2x -R (14);
x 0, 1, 2, 3 or 4,
where x can not be 0 when R (14) is OR (15) or SO ₂ Me;
R (14) is alkyl having 1, 2, 3, 4, 5 or 6 C atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9, 10 or 11 C atoms, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , CH ₂ F, CHF ₂ , OR (15), SO ₂ Me, phenyl, naphthyl, biphenylyl, furyl, thienyl or an N-containing heteroaromatic 1, 2, 3, 4, 5, 6 , 7, 8 or 9 carbon atoms,
wherein phenyl, naphthyl, biphenylyl, furyl, thienyl and the N-containing heteroaromatic are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (15) is alkyl having 1, 2, 3, 4 or 5 C atoms, cycloalkyl having 3, 4, 5 or 6 C atoms, CF ₃ or phenyl,
which is unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF _3, NO _2, CN, COOMe, CONH _2, COMe, NH _2, OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (10), R (11) and R (12)
independently defined as R (9);
R (13) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms or CF ₃ ;
R (2) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms or CF ₃ ;
R (3) C _y H _2y -R (16);
y is 0, 1, 2, 3 or 4,
where y can not be 0 when R (16) is OR (17) or SO ₂ Me;
R (16) is alkyl having 1, 2, 3, 4, 5 or 6 C atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9, 10 or 11 C atoms, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , CH ₂ F, CHF ₂ , OR (17), SO ₂ Me, phenyl, naphthyl, furyl, thienyl or an N-containing heteroaromatic having 1, 2, 3, 4, 5, 6, 7 , 8 or 9 C-atoms, wherein phenyl, naphthyl, furyl, thienyl and the N-containing heteroaromatic are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, Methylsulfonyl and methylsulfonylamino;
R (17) is hydrogen, alkyl having 1, 2, 3, 4 or 5 C atoms, cycloalkyl having 3, 4, 5 or 6 C atoms, CF ₃ , phenyl or 2-, 3- or 4-pyridyl,
where phenyl or 2-, 3- or 4-pyridyl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
or
R (3) CHR (18) R (19);
R (18) is hydrogen or C ₂ H _2z- R (16) wherein R (16) is defined as above;
z is 0, 1, 2 or 3;
R (19) COOH, CONH ₂ , CONR (20) R (21), COOR (22), CH ₂ OH;
R (20) is hydrogen, alkyl having 1, 2, 3, 4 or 5 C atoms, C _v H _2v -CF ₃ or C _w H _2w-phenyl ,
wherein the phenyl ring is unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH , Alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
v is 0, 1, 2 or 3;
w is 0, 1, 2 or 3;
R (21) is hydrogen or alkyl having 1, 2, 3, 4 or 5 C atoms;
R (22) is alkyl having 1, 2, 3, 4 or 5 C atoms;
R (4) is hydrogen, alkyl having 1, 2, 3, 4, 5 or 6 C atoms or CF ₃ ;
or
R (3) and R (4)
together a chain of 4 or 5 methylene groups, of which one methylene group may be replaced by -O-, -S-, -NH-, -N (methyl) - or -N (benzyl) -;
R (5), R (6), R (7) and R (8)
independently of one another hydrogen, F, Cl, Br, I, CF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2 , 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl or methylsulfonylamino;
R (30) and R (31)
independently of one another hydrogen or alkyl having 1, 2 or 3 C atoms;
or
R (30) and R (31)
together a chain of 2 methylene groups;
and / or compounds of the formula Ic

in which mean:
A1, A2, A3, A4, A5, A6, A7 and A8
independently of one another nitrogen, CH or CR5, where at least four of these groups are CH;
R (1) C (O) OR (9), SO ₂ R (10), COR (11), C (O) NR (12) R (13) or C (S) NR (12) R (13) ;
R (9), R (10), R (11) and R (12)
independently C _x H _2x -R (14);
x 0, 1, 2, 3 or 4,
where x can not be 0 when R (14) is OR (15) or SO ₂ Me;
R (14) is alkyl having 1, 2, 3, 4, 5 or 6 C atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9, 10 or 11 C atoms, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , CH ₂ F, CHF ₂ , OR (15), SO ₂ Me, phenyl, naphthyl, biphenylyl, furyl, thienyl or an N-containing heteroaromatic 1, 2, 3, 4, 5, 6 , 7, 8 or 9 carbon atoms,
wherein phenyl, naphthyl, biphenylyl, furyl, thienyl and the N-containing heteroaromatic are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (15) is alkyl having 1, 2, 3, 4 or 5 C atoms, cycloalkyl having 3, 4, 5 or 6 C atoms, CF ₃ or phenyl,
which is unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF _3, NO _2, CN, COOMe, CONH _2, COMe, NH _2, OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (13) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms or CF ₃ ;
R (2) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms or CF ₃ ;
R (3) C _y H _2y -R (16);
y is 0, 1, 2, 3 or 4,
where y can not be 0 when R (16) is OR (17) or SO ₂ Me;
R (16) is alkyl having 1, 2, 3, 4, 5 or 6 C atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9, 10 or 11 C atoms, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , CH ₂ F, CHF ₂ , OR (17), SO ₂ Me, phenyl, naphthyl, furyl, thienyl or an N-containing heteroaromatic having 1, 2, 3, 4, 5, 6, 7 , 8 or 9 carbon atoms,
where phenyl, naphthyl, furyl, thienyl and the N-containing heteroaromatic are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino.

worin bedeuten:
A1, A2, A3, A4, A5, A6, A7 und A8 unabhängig voneinander Stickstoff, CH oder CR(5), wobei mindestens eine dieser Gruppen Stickstoff bedeutet und mindestens 4 dieser Gruppen CH bedeuten;
R(1) C(O)OR(9), SO₂R(10), COR(11), C(O)NR(12)R(13) oder C(S)NR(12)R(13);
R(9), R(10), R(11) und R(12)
unabhängig voneinander C_xH_2x-R(14);
x 0, 1, 2, 3 oder 4,
wobei x nicht 0 sein kann, wenn R(14) OR(15) oder SO₂Me bedeutet;
R(14) Alkyl mit 1, 2, 3, 4, 5 oder 6 C-Atomen, Cycloalkyl mit 3, 4, 5, 6, 7, 8, 9, 10 oder 11 C-Atomen, CF₃, C₂F₅, C₃F₇, CH₂F, CHF₂, OR(15), SO₂Me, Phenyl, Naphthyl, Biphenylyl, Furyl, Thienyl oder ein N-haltiger Heteroaromat mit 1, 2, 3, 4, 5, 6, 7, 8 oder 9 C-Atomen,
wobei Phenyl, Naphthyl, Biphenylyl, Furyl, Thienyl und der N-haltige Heteroaromat unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(15) Alkyl mit 1, 2, 3, 4 oder 5 C-Atomen, Cycloalkyl mit 3, 4, 5 oder 6 C-Atomen, CF₃ oder Phenyl, das unsubstituiert ist oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(13) Wasserstoff, Alkyl mit 1, 2, 3 oder 4 C-Atomen oder CF₃;
R(2) Wasserstoff, Alkyl mit 1, 2, 3 oder 4 C-Atomen oder CF₃;
R(3) C_yH_2y-R(16);
y 0, 1, 2, 3 oder 4,
wobei y nicht 0 sein kann, wenn R(16) OR(17) oder SO₂Me bedeutet;
R(16) Alkyl mit 1, 2, 3, 4, 5 oder 6 C-Atomen, Cycloalkyl mit 3, 4, 5, 6, 7, 8, 9, 10 oder 11 C-Atomen, CF₃, C₂F₅, C₃F₇, CH₂F, CHF₂, OR(17), SO₂Me, Phenyl, Naphthyl, Furyl, Thienyl oder ein N-haltiger Heteroaromat mit 1, 2, 3, 4, 5, 6, 7, 8 oder 9 C-Atomen,
wobei Phenyl, Naphthyl, Furyl, Thienyl und der N-haltige Heteroaromat unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(17) Wasserstoff, Alkyl mit 1, 2, 3, 4 oder 5 C-Atomen, Cycloalkyl mit 3, 4, 5 oder 6 C-Atomen, CF₃, Phenyl oder 2-, 3- oder 4-Pyridyl,
wobei Phenyl oder 2-, 3- oder 4-Pyridyl unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
oder
R(3) CHR(18)R(19);
R(18) Wasserstoff oder C_zH_2z-R(16), wobei R(16) wie oben angegeben definiert ist;
z 0, 1, 2 oder 3;
R(19) COOH, CONH₂, CONR(20)R(21), COOR(22) oder CH₂OH;
R(20) Wasserstoff, Alkyl mit 1, 2, 3, 4 oder 5 C-Atomen, C_vH_2v-CF₃ oder C_wH_2w-Phenyl,
wobei der Phenylring unsubstituiert ist oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
v 0, 1, 2 oder 3;
w 0, 1, 2 oder 3;
R(21) Wasserstoff oder Alkyl mit 1, 2, 3, 4 oder 5 C-Atomen;
R(22) Alkyl mit 1, 2, 3, 4 oder 5 C-Atomen;
R(4) Wasserstoff, Alkyl mit 1, 2, 3, 4, 5 oder 6 C-Atomen oder CF₃;
oder
R(3) und R(4)
gemeinsam eine Kette von 4 oder 5 Methylengruppen, von denen eine Methylengruppe durch -O-, -S-, -NH-, -N(Methyl)- oder -N(Benzyl)- ersetzt sein kann;
R(5) unabhängig voneinander F, Cl, Br, I, CF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl oder Methylsulfonylamino, wobei für den Fall, dass mehrere Reste A1 bis A8 die Bedeutung CR(5) haben, die Reste R(5) unabhängig voneinander definiert sind.
R(30) und R(31)
unabhängig voneinander Wasserstoff oder Alkyl mit 1, 2 oder 3 C-Atomen;
oder
R(30) und R(31)
gemeinsam Sauerstoff oder eine Kette von 2 Methylengruppen;
und/oder Verbindungen der Formel Ie oder If

worin bedeuten:
X Sauerstoff oder Schwefel;
R(1) C(O)OR(9), SO₂R(10), COR(11), C(O)NR(12)R(13) oder C(S)NR(12)R(13);
R(9), R(10), R(11) und R(12)
unabhängig voneinander C_xH_2x-R(14);
x 0, 1, 2, 3 oder 4,
wobei x nicht 0 sein kann, wenn R(14) OR(15) oder SO₂Me bedeutet;
R(14) Alkyl mit 1, 2, 3, 4, 5 oder 6 C-Atomen, Cycloalkyl mit 3, 4, 5, 6, 7, 8, 9, 10 oder 11 C-Atomen, CF₃, C₂F₅, C₃F₇, CH₂F, CHF₂, OR(15), SO₂Me, Phenyl, Naphthyl, Biphenylyl, Furyl, Thienyl oder ein N-haltiger Heteroaromat mit 1, 2, 3, 4, 5, 6, 7, 8 oder 9 C-Atomen,
wobei Phenyl, Naphthyl, Biphenylyl, Furyl, Thienyl und der N-haltige Heteroaromat unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(15) Alkyl mit 1, 2, 3, 4 oder 5 C-Atomen, Cycloalkyl mit 3, 4, 5 oder 6 C-Atomen, CF₃ oder Phenyl, das unsubstituiert ist oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(13) Wasserstoff, Alkyl mit 1, 2, 3 oder 4 C-Atomen oder CF₃;
R(2) Wasserstoff, Alkyl mit 1, 2, 3 oder 4 C-Atomen oder CF₃;
R(3) C_yH_2y-R(16);
y 0, 1, 2, 3 oder 4,
wobei y nicht 0 sein kann, wenn R(16) OR(17) oder SO₂Me bedeutet;
R(16) Alkyl mit 1, 2, 3, 4, 5 oder 6 C-Atomen, Cycloalkyl mit 3, 4, 5, 6, 7, 8, 9, 10 oder 11 C-Atomen, CF₃, C₂F₅, C₃F₇, CH₂F, CHF₂, OR(17), SO₂Me, Phenyl, Naphthyl, Furyl, Thienyl oder ein N-haltiger Heteroaromat mit 1, 2, 3, 4, 5, 6, 7, 8 oder 9 C-Atomen,
wobei Phenyl, Naphthyl, Furyl, Thienyl und der N-haltige Heteroaromat unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino.
R(17) Wasserstoff, Alkyl mit 1, 2, 3, 4 oder 5 C-Atomen, Cycloalkyl mit 3, 4, 5 oder 6 C-Atomen, CF₃, Phenyl oder 2-, 3- oder 4-Pyridyl,
wobei Phenyl oder 2-, 3- oder 4-Pyridyl unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
oder
R(3) CHR(18)R(19);
R(18) Wasserstoff oder C_zH_2z-R(16), wobei R(16) wie oben angegeben definiert ist;
z 0, 1, 2 oder 3;
R(19) COOH, CONH₂, CONR(20)R(21), COOR(22) oder CH₂OH;
R(20) Wasserstoff, Alkyl mit 1, 2, 3, 4 oder 5 C-Atomen, C_vH_2v-CF₃ oder C_wH_2w-Phenyl,
wobei der Phenylring unsubstituiert ist oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
v 0, 1, 2 oder 3;
w 0, 1, 2 oder 3;
R(21) Wasserstoff oder Alkyl mit 1, 2, 3, 4 oder 5 C-Atomen;
R(22) Alkyl mit 1, 2, 3, 4 oder 5 C-Atomen;
R(4) Wasserstoff, Alkyl mit 1, 2, 3, 4, 5 oder 6 C-Atomen oder CF₃;
oder
R(3) und R(4)
gemeinsam eine Kette von 4 oder 5 Methylengruppen, von denen eine Methylengruppe durch -O-, -S-, -NH-, -N(Methyl)- oder -N(Benzyl)- ersetzt sein kann;
R(5), R(6) und R(7)
unabhängig voneinander Wasserstoff, F, Cl, Br, I, CF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl oder Methylsulfonylamino.
R (17) is hydrogen, alkyl having 1, 2, 3, 4 or 5 C atoms, cycloalkyl having 3, 4, 5 or 6 C atoms, CF ₃ , phenyl or 2-, 3- or 4-pyridyl,
where phenyl or 2-, 3- or 4-pyridyl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
or
R (3) CHR (18) R (19);
R (18) is hydrogen or C _z H _2z -R (16) wherein R (16) is defined as above;
z is 0, 1, 2 or 3;
R (19) COOH, CONH ₂ , CONR (20) R (21), COOR (22) or CH ₂ OH;
R (20) is hydrogen, alkyl having 1, 2, 3, 4 or 5 C atoms, C _v H _2v -CF ₃ or C _w N _2w-phenyl ,
wherein the phenyl ring is unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
v is 0, 1, 2 or 3;
w is 0, 1, 2 or 3;
R (21) is hydrogen or alkyl having 1, 2, 3, 4 or 5 C atoms;
R (22) is alkyl having 1, 2, 3, 4 or 5 C atoms;
R (4) is hydrogen, alkyl having 1, 2, 3, 4, 5 or 6 C atoms or CF ₃ ;
or
R (3) and R (4)
together a chain of 4 or 5 methylene groups, of which one methylene group may be replaced by -O-, -S-, -NH-, -N (methyl) - or -N (benzyl) -;
R (5) F, Cl, Br, I, CF _3, NO _2, CN, COOMe, CONH _2, COMe, NH _2, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2 , 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl or methylsulfonylamino, wherein in the event that several radicals A1 to A8 have the meaning CR (5), the radicals R (5) are independently defined;
R (30) and R (31)
independently of one another hydrogen or alkyl having 1, 2 or 3 C atoms;
or
R (30) and R (31)
together a chain of 2 methylene groups;
and / or compounds of the formula Id

in which mean:
A1, A2, A3, A4, A5, A6, A7 and A8 independently of one another nitrogen, CH or CR (5), where at least one of these groups is nitrogen and at least 4 of these groups are CH;
R (1) C (O) OR (9), SO ₂ R (10), COR (11), C (O) NR (12) R (13) or C (S) NR (12) R (13) ;
R (9), R (10), R (11) and R (12)
independently C _x H _2x -R (14);
x 0, 1, 2, 3 or 4,
where x can not be 0 when R (14) is OR (15) or SO ₂ Me;
R (14) is alkyl having 1, 2, 3, 4, 5 or 6 C atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9, 10 or 11 C atoms, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , CH ₂ F, CHF ₂ , OR (15), SO ₂ Me, phenyl, naphthyl, biphenylyl, furyl, thienyl or an N-containing heteroaromatic 1, 2, 3, 4, 5, 6 , 7, 8 or 9 carbon atoms,
wherein phenyl, naphthyl, biphenylyl, furyl, thienyl and the N-containing heteroaromatic are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (15) is alkyl having 1, 2, 3, 4 or 5 C atoms, cycloalkyl having 3, 4, 5 or 6 C atoms, CF ₃ or phenyl, which is unsubstituted or substituted by 1, 2 or 3 substituents from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (13) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms or CF ₃ ;
R (2) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms or CF ₃ ;
R (3) C _y H _2y -R (16);
y is 0, 1, 2, 3 or 4,
where y can not be 0 when R (16) is OR (17) or SO ₂ Me;
R (16) is alkyl having 1, 2, 3, 4, 5 or 6 C atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9, 10 or 11 C atoms, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , CH ₂ F, CHF ₂ , OR (17), SO ₂ Me, phenyl, naphthyl, furyl, thienyl or an N-containing heteroaromatic having 1, 2, 3, 4, 5, 6, 7 , 8 or 9 carbon atoms,
where phenyl, naphthyl, furyl, thienyl and the N-containing heteroaromatic are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (17) is hydrogen, alkyl having 1, 2, 3, 4 or 5 C atoms, cycloalkyl having 3, 4, 5 or 6 C atoms, CF ₃ , phenyl or 2-, 3- or 4-pyridyl,
where phenyl or 2-, 3- or 4-pyridyl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
or
R (3) CHR (18) R (19);
R (18) is hydrogen or C _z H _2z -R (16) wherein R (16) is defined as above;
z is 0, 1, 2 or 3;
R (19) COOH, CONH ₂ , CONR (20) R (21), COOR (22) or CH ₂ OH;
R (20) is hydrogen, alkyl having 1, 2, 3, 4 or 5 C atoms, C _v H _2v -CF ₃ or C _w H _2w-phenyl ,
wherein the phenyl ring is unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH , Alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
v is 0, 1, 2 or 3;
w is 0, 1, 2 or 3;
R (21) is hydrogen or alkyl having 1, 2, 3, 4 or 5 C atoms;
R (22) is alkyl having 1, 2, 3, 4 or 5 C atoms;
R (4) is hydrogen, alkyl having 1, 2, 3, 4, 5 or 6 C atoms or CF ₃ ;
or
R (3) and R (4)
together a chain of 4 or 5 methylene groups, of which one methylene group may be replaced by -O-, -S-, -NH-, -N (methyl) - or -N (benzyl) -;
R (5) independently of one another are F, Cl, Br, I, CF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1 , 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl or methylsulfonylamino, wherein in the event that several radicals A1 to A8 have the meaning CR (5), the radicals R (5) are defined independently of one another.
R (30) and R (31)
independently of one another hydrogen or alkyl having 1, 2 or 3 C atoms;
or
R (30) and R (31)
together oxygen or a chain of 2 methylene groups;
and / or compounds of the formula Ie or If

in which mean:
X oxygen or sulfur;
R (1) C (O) OR (9), SO ₂ R (10), COR (11), C (O) NR (12) R (13) or C (S) NR (12) R (13) ;
R (9), R (10), R (11) and R (12)
independently C _x H _2x -R (14);
x 0, 1, 2, 3 or 4,
where x can not be 0 when R (14) is OR (15) or SO ₂ Me;
R (14) is alkyl having 1, 2, 3, 4, 5 or 6 C atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9, 10 or 11 C atoms, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , CH ₂ F, CHF ₂ , OR (15), SO ₂ Me, phenyl, naphthyl, biphenylyl, furyl, thienyl or an N-containing heteroaromatic 1, 2, 3, 4, 5, 6 , 7, 8 or 9 carbon atoms,
wherein phenyl, naphthyl, biphenylyl, furyl, thienyl and the N-containing heteroaromatic are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (15) is alkyl having 1, 2, 3, 4 or 5 C atoms, cycloalkyl having 3, 4, 5 or 6 C atoms, CF ₃ or phenyl, which is unsubstituted or substituted by 1, 2 or 3 substituents from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (13) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms or CF ₃ ;
R (2) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms or CF ₃ ;
R (3) C _y H _2y -R (16);
y is 0, 1, 2, 3 or 4,
where y can not be 0 when R (16) is OR (17) or SO ₂ Me;
R (16) is alkyl having 1, 2, 3, 4, 5 or 6 C atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9, 10 or 11 C atoms, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , CH ₂ F, CHF ₂ , OR (17), SO ₂ Me, phenyl, naphthyl, furyl, thienyl or an N-containing heteroaromatic having 1, 2, 3, 4, 5, 6, 7 , 8 or 9 carbon atoms,
where phenyl, naphthyl, furyl, thienyl and the N-containing heteroaromatic are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino.
R (17) is hydrogen, alkyl having 1, 2, 3, 4 or 5 C atoms, cycloalkyl having 3, 4, 5 or 6 C atoms, CF ₃ , phenyl or 2-, 3- or 4-pyridyl,
where phenyl or 2-, 3- or 4-pyridyl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
or
R (3) CHR (18) R (19);
R (18) is hydrogen or C _z H _2z -R (16) wherein R (16) is defined as above;
z is 0, 1, 2 or 3;
R (19) COOH, CONH ₂ , CONR (20) R (21), COOR (22) or CH ₂ OH;
R (20) is hydrogen, alkyl having 1, 2, 3, 4 or 5 C atoms, C _v H _2v -CF ₃ or C _w H _2w-phenyl ,
wherein the phenyl ring is unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
v is 0, 1, 2 or 3;
w is 0, 1, 2 or 3;
R (21) is hydrogen or alkyl having 1, 2, 3, 4 or 5 C atoms;
R (22) is alkyl having 1, 2, 3, 4 or 5 C atoms;
R (4) is hydrogen, alkyl having 1, 2, 3, 4, 5 or 6 C atoms or CF ₃ ;
or
R (3) and R (4)
together a chain of 4 or 5 methylene groups, of which one methylene group may be replaced by -O-, -S-, -NH-, -N (methyl) - or -N (benzyl) -;
R (5), R (6) and R (7)
independently of one another hydrogen, F, Cl, Br, I, CF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2 , 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl or methylsulfonylamino.

worin bedeuten:
R(1) (CH₂)_x-R(8)
x 0, 1, 2, 3, 4 oder 5;
R(8) Phenyl, Thienyl oder Furanyl,
wobei Phenyl, Thienyl und Furanyl unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(2) Wasserstoff oder Alkyl mit 1, 2 oder 3 C-Atomen;
R(3) Wasserstoff oder Alkyl mit 1, 2 oder 3 C-Atomen;
R(4) Alkyl mit 3, 4, 5, 6 oder 7 C-Atomen, Cycloalkyl mit 3, 4, 5, 6 oder 7 C-Atomen, Phenyl, Naphthyl oder Heteroaryl,
wobei Phenyl und Heteroaryl unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₂, OCF₃, NO₂, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Methylsulfonyl und Methylsulfonylamino;
R(5), R(6) und R(7)
unabhängig voneinander F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
und/oder Verbindungen der Formel Ih

worin bedeuten:

A -C_nH_2n-;
n 0, 1, 2, 3, 4 oder 5;
O Sauerstoff;
D eine Bindung oder Sauerstoff;
E -C_mN_2m-;
m 0, 1, 2, 3, 4 oder 5;
R(8) Wasserstoff, Alkyl mit 1, 2, 3 oder 4 C-Atomen oder C_pH_2p-R(14);
p 0, 1, 2, 3, 4 oder 5;
R(14) Cycloalkyl mit 3, 4, 5 oder 6 C-Atomen, Aryl oder Heteroaryl, wobei Aryl und Heteroaryl unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(9) Wasserstoff oder Alkyl mit 1, 2, 3, 4, 5 oder 6 C-Atomen;
R(10) Wasserstoff, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Cycloalkyl mit 3, 4, 5 oder 6 C-Atomen, Aryl oder Heteroaryl,
wobei Aryl und Heteroaryl unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(11) Cycloalkyl mit 3, 4, 5 oder 6 C-Atomen, Phenyl, Naphthyl, Thienyl, Furyl, Pyridyl, Pyrazinyl, Pyridazinyl oder Pyrimidyl,
wobei Phenyl, Naphthyl, Thienyl, Furyl, Pyridyl, Pyrazinyl, Pyridazinyl und Pyrimidyl unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(12) Alkyl mit 1, 2, 3 oder 4 C-Atomen, Cycloalkyl mit 3, 4, 5 oder 6 C-Atomen, Aryl oder Heteroaryl,
wobei Aryl und Heteroaryl unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(13) C_pH_2p-R(14');
p 0, 1, 2, 3, 4 oder 5;
R(14') Cycloalkyl mit 3, 4, 5 oder 6 C-Atomen, Tetrahydrofuranyl, Tetrahydropyranyl, Aryl oder Heteroaryl, wobei Aryl und Heteroaryl unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(15) Cycloalkyl mit 3, 4, 5, 6, 7 oder 8 C-Atomen;
R(2) Wasserstoff oder Alkyl mit 1, 2, 3 oder 4 C-Atomen;
R(3) Alkyl mit 3, 4, 5, 6 oder 7 C-Atomen, Cycloalkyl mit 3, 4, 5 oder 6 C-Atomen, Phenyl oder Naphthyl,
wobei Phenyl oder Naphthyl unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(4), R(5), R(6) und R(7)
unabhängig voneinander Wasserstoff, F, Cl, Br, I, CF₃, OCF₃, OCHF₂, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
und oder Verbindungen der Formel Ij

worin bedeuten:

A -C_nH_2n-;
n = 0, 1, 2, 3, 4 oder 5;
D eine Bindung oder -O-;
E -C_mH_2m-;
m = 0, 1, 2, 3, 4 oder 5;
R(8) Wasserstoff, Alkyl mit 1, 2, 3 oder 4 C-Atomen oder C_pH_2p-R(14);
p 0, 1, 2, 3, 4 oder 5;
R(14) Phenyl, Naphthyl oder Heteroaryl,
wobei Phenyl, Naphthyl und Heteroaryl unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(9) Wasserstoff oder Alkyl mit 1, 2, 3, 4, 5 oder 6 C-Atomen;
R(10) Wasserstoff, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Phenyl, Naphthyl oder Heteroaryl,
wobei Phenyl, Naphthyl und Heteroaryl unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(11) Cycloalkyl mit 3, 4, 5 oder 6 C-Atomen, Phenyl, Naphthyl, Thienyl, Furyl, Pyridyl, Pyrazinyl, Pyrimidinyl, Pyridazinyl, Indolyl, Indazolyl, Chinolyl, Isochinolyl, Phthalazinyl, Chinoxalinyl, Chinazolinyl oder Cinnolinyl,
wobei Phenyl, Naphthyl, Thienyl, Furyl, Pyridyl, Pyrazinyl, Pyrimidinyl, Pyridazinyl, Indolyl, Indazolyl, Chinolyl, Isochinolyl, Phthalazinyl, Chinoxalinyl, Chinazolinyl oder Cinnolinyl unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(12) Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkinyl mit 1, 2, 3 oder 4 C-Atomen, Cycloalkyl mit 3, 4, 5 oder 6 C-Atomen, Phenyl, Naphthyl oder Heteroaryl,
wobei Phenyl, Naphthyl und Heteroaryl unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(13) C_pH_2p-R(14);
p 0, 1, 2, 3, 4 oder 5;
R(15) Cycloalkyl mit 3, 4, 5, 6, 7 oder 8 C-Atomen;
R(2) Wasserstoff oder Alkyl mit 1, 2, 3 oder 4 C-Atomen;
R(3) Heteroaryl,
wobei Heteroaryl unsubstituiert ist oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(4), R(5), R(6) und R(7)
unabhängig voneinander Wasserstoff, F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
und/oder physiologisch verträglicher Salze der Verbindungen der Formel Ia, Ib, Ic, Id, Ie, If, Ig, Ih oder Ij zur Herstellung eines Medikaments zur Therapie oder Prophylaxe von Atemstörungen, schlafbedingten Atemstörungen, zentralen und obstruktiven Schlafapnoen, Cheyne-Stoke'sche Atmung, Schnarchen, gestörten zentralen Atemantrieb, plötzlicher Kindstod, postoperative Hypoxie und Apnoe, muskulär-bedingten Atemstörungen, Atemstörungen nach Langzeitbeatmung, Atemstörungen bei Adaptation im Hochgebirge, akute und chronische Lungenkrankheiten mit Hypoxie und Hyperkapnie, neurodegenerativen Erkrankungen, Demenz, Morbus Alzheimer, Morbus Parkinson, Morbus Huntington, Krebskrankheiten, Brustkrebs, Lungenkrebs, Kolonkrebs und Prostatakrebs.
R (30) and R (31)
independently of one another hydrogen or alkyl having 1, 2 or 3 C atoms;
or
R (30) and R (31)
together oxygen or a chain of 2 methylene groups;
and / or compounds of the formula Ig

in which mean:
R (1) (CH ₂ ) _x -R (8)
x is 0, 1, 2, 3, 4 or 5;
R (8) is phenyl, thienyl or furanyl,
wherein phenyl, thienyl and furanyl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (2) is hydrogen or alkyl having 1, 2 or 3 C atoms;
R (3) is hydrogen or alkyl having 1, 2 or 3 C atoms;
R (4) alkyl having 3, 4, 5, 6 or 7 C atoms, cycloalkyl having 3, 4, 5, 6 or 7 C atoms, phenyl, naphthyl or heteroaryl,
where phenyl and heteroaryl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₂ , OCF ₃ , NO ₂ , COOMe, CONH ₂ , COMe, NH ₂ , OH, Alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, methylsulfonyl and methylsulfonylamino;
R (5), R (6) and R (7)
independently of one another F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
and / or compounds of the formula Ih

in which mean:

A -C _n H _2n -;
n is 0, 1, 2, 3, 4 or 5;
O oxygen;
D is a bond or oxygen;
E -C _m N _2m -;
m is 0, 1, 2, 3, 4 or 5;
R (8) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms or C _p H _2p- R (14);
p is 0, 1, 2, 3, 4 or 5;
R (14) cycloalkyl having 3, 4, 5 or 6 C atoms, aryl or heteroaryl, wherein aryl and heteroaryl unsubstituted or are substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF _3, OCF _3, NO _2, CN, COOMe, CONH _2, COMe, NH _2, OH, alkyl having 1 , 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (9) is hydrogen or alkyl having 1, 2, 3, 4, 5 or 6 C atoms;
R (10) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms, cycloalkyl having 3, 4, 5 or 6 C atoms, aryl or heteroaryl,
wherein aryl and heteroaryl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (11) cycloalkyl having 3, 4, 5 or 6 C atoms, phenyl, naphthyl, thienyl, furyl, pyridyl, pyrazinyl, pyridazinyl or pyrimidyl,
wherein phenyl, naphthyl, thienyl, furyl, pyridyl, pyrazinyl, pyridazinyl and pyrimidyl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (12) alkyl having 1, 2, 3 or 4 C atoms, cycloalkyl having 3, 4, 5 or 6 C atoms, aryl or heteroaryl,
wherein aryl and heteroaryl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (13) C _p H _2p- R (14 ');
p is 0, 1, 2, 3, 4 or 5;
R (14 ') is cycloalkyl having 3, 4, 5 or 6 C atoms, tetrahydrofuranyl, tetrahydropyranyl, aryl or heteroaryl, wherein aryl and heteroaryl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl , Br, I, CF _3, OCF _3, NO _2, CN, COOMe, CONH _2, COMe, NH _2, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (15) cycloalkyl having 3, 4, 5, 6, 7 or 8 C atoms;
R (2) is hydrogen or alkyl having 1, 2, 3 or 4 C atoms;
R (3) alkyl having 3, 4, 5, 6 or 7 C atoms, cycloalkyl having 3, 4, 5 or 6 C atoms, phenyl or naphthyl,
where phenyl or naphthyl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (4), R (5), R (6) and R (7)
independently hydrogen, F, Cl, Br, I, CF _3, OCF _3, OCHF _2, NO _2, CN, COOMe, CONH _2, COMe, NH _2, OH, alkyl having 1, 2, 3 or 4 carbon atoms Alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
and or compounds of formula Ij

in which mean:

A -C _n H _2n -;
n = 0, 1, 2, 3, 4 or 5;
D is a bond or -O-;
E -C _m H _2m -;
m = 0, 1, 2, 3, 4 or 5;
R (8) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms or C _p H _2p- R (14);
p is 0, 1, 2, 3, 4 or 5;
R (14) is phenyl, naphthyl or heteroaryl,
wherein phenyl, naphthyl and heteroaryl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (9) is hydrogen or alkyl having 1, 2, 3, 4, 5 or 6 C atoms;
R (10) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms, phenyl, naphthyl or heteroaryl,
wherein phenyl, naphthyl and heteroaryl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (11) cycloalkyl having 3, 4, 5 or 6 C atoms, phenyl, naphthyl, thienyl, furyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl or cinnolinyl,
wherein phenyl, naphthyl, thienyl, furyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl or cinnolinyl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F , Cl, Br, I, CF _3, OCF _3, NO _2, CN, COMe, NH _2, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms , Dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (12) is alkyl having 1, 2, 3 or 4 C atoms, alkynyl having 1, 2, 3 or 4 C atoms, cycloalkyl having 3, 4, 5 or 6 C atoms, phenyl, naphthyl or heteroaryl,
wherein phenyl, naphthyl and heteroaryl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (13) C _p H _2p- R (14);
p is 0, 1, 2, 3, 4 or 5;
R (15) cycloalkyl having 3, 4, 5, 6, 7 or 8 C atoms;
R (2) is hydrogen or alkyl having 1, 2, 3 or 4 C atoms;
R (3) heteroaryl,
where heteroaryl is unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, Alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (4), R (5), R (6) and R (7)
independently hydrogen, F, Cl, Br, I, CF _3, OCF _3, NO _2, CN, COOMe, CONH _2, COMe, NH _2, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
and / or physiologically acceptable salts of the compounds of the formula Ia, Ib, Ic, Id, Ie, If, Ig, Ih or Ij for the manufacture of a medicament for the therapy or prophylaxis of respiratory disorders, sleep-disordered breathing, central and obstructive sleep apnea, Cheyne-Stoke ' respiratory, snoring, disturbed central respiratory drive, sudden infant death syndrome, postoperative hypoxia and apnea, muscular respiratory disorders, respiratory disorders after long-term ventilation, respiratory disorders in high altitude adaptation, acute and chronic lung diseases with hypoxia and hypercapnia, neurodegenerative diseases, dementia, Alzheimer's disease, Morbus Parkinson's disease, Huntington's disease, cancer, breast cancer, lung cancer, colon cancer and prostate cancer.

Prefers is the use of compounds of the formulas Ia to Ij and / or a physiologically tolerable Salt thereof for the manufacture of a medicament for therapy or Prophylaxis of respiratory disorders, especially sleep apnea, and cancer diseases.

A use of compounds of the formulas Ia to Ij and / or a physiologically acceptable salt thereof consists in the preparation of a medicament for the therapy or prophylaxis of respiratory disorders, in particular sleep-related respiratory disorders such as central and obstructive sleep apnea, Cheyne-Stoke's respiration, snoring, a disturbed one central respiratory drive (sudden infantile death, postopera tive hypoxia and apnea), muscular respiratory disorders, respiratory disorders after long-term ventilation, respiratory disorders during adaptation in high mountains, acute and chronic lung diseases with hypoxia and hypercapnia.

A Further use of compounds of the formulas Ia to Ij and / or a physiologically tolerable Salt of it is in the preparation of a drug for therapy or prophylaxis of neurodegenerative diseases such as dementia, Alzheimer's disease, Parkinson's disease, Huntington's disease.

A Further use of compounds of the formulas Ia to Ij and / or a physiologically tolerable Salt of it is in the preparation of a drug for therapy or prophylaxis of cancer diseases, such as breast, lung, Colon and prostate cancer.

A -C_nH_2n-;
n 0, 1, 2 oder 3;
O Sauerstoff;
D eine Bindung oder Sauerstoff;
E -C_mH_2m-;
m 0, 1, 2 oder 3;
R(8) Wasserstoff oder Alkyl mit 1, 2, 3 oder 4 C-Atomen;
R(9) Wasserstoff oder Alkyl mit 1, 2, 3, 4, 5 oder 6 C-Atomen;
R(10) Wasserstoff, Alkyl mit 1, 2, 3 oder 4 C-Atomen oder Cycloalkyl mit 3, 4 oder 5 C-Atomen,
R(11) Cycloalkyl mit 3, 4, 5 oder 6 C-Atomen, Phenyl oder Pyridyl,
wobei Phenyl und Pyridyl unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, CF₃, OCF₃, NO₂, CN, COMe, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(12) Alkyl mit 1, 2, 3 oder 4 C-Atomen, Cycloalkyl mit 3, 4 oder 5 C-Atomen, Aryl oder Heteroaryl,
wobei Aryl und Heteroaryl unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(13) C_pH_2p-R(14');
p 0, 1, 2, 3, 4 oder 5;
R(14') Cycloalkyl mit 3, 4, 5 oder 6 C-Atomen, Tetrahydrofuranyl, Tetrahydropyranyl, Aryl oder Heteroaryl,
wobei Aryl und Heteroaryl unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(2) Wasserstoff oder Alkyl mit 1 oder 2 C-Atomen;
R(3) Alkyl mit 3, 4 oder 5 C-Atomen, Phenyl,
wobei Phenyl unsubstituiert ist oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, CF₃, OCF₃, NO₂, COOMe, CONH₂, COMe, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(4), R(5), R(6) und R(7)
unabhängig voneinander Wasserstoff, F, Cl, Br, CF₃, OCF₃, OCHF₂, NO₂, CN, COOMe, CONH₂, COMe, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
und/oder Verbindungen der Formel Ij, worin bedeuten:

A -C_nH_2n-;
n = 0, 1, 2, 3, 4 oder 5;
D eine Bindung oder -O-;
E -C_mH_2m-;
m = 0, 1, 2, 3, 4 oder 5;
R(8) Wasserstoff, Alkyl mit 1, 2, 3 oder 4 C-Atomen oder C_pH_2p-R(14);
p 0, 1, 2, 3, 4 oder 5;
R(14) Phenyl, Naphthyl oder Heteroaryl,
wobei Phenyl, Naphthyl und Heteroaryl unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(9) Wasserstoff oder Alkyl mit 1, 2, 3, 4, 5 oder 6 C-Atomen;
R(10) Wasserstoff, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Phenyl, Naphthyl oder Heteroaryl,
wobei Phenyl, Naphthyl und Heteroaryl unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(11) Cycloalkyl mit 3, 4, 5 oder 6 C-Atomen, Phenyl, Naphthyl, Thienyl, Furyl, Pyridyl, Pyrazinyl, Pyrimidinyl, Pyridazinyl, Indolyl, Indazolyl, Chinolyl, Isochinolyl, Phthalazinyl, Chinoxalinyl, Chinazolinyl oder Cinnolinyl,
wobei Phenyl, Naphthyl, Thienyl, Furyl, Pyridyl, Pyrazinyl, Pyrimidinyl, Pyridazinyl, Indolyl, Indazolyl, Chinolyl, Isochinolyl, Phthalazinyl, Chinoxalinyl, Chinazolinyl oder Cinnolinyl unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C- Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(12) Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkinyl mit 1, 2, 3 oder 4 C-Atomen, Cycloalkyl mit 3, 4, 5 oder 6 C-Atomen, Phenyl, Naphthyl oder Heteroaryl,
wobei Phenyl, Naphthyl und Heteroaryl unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(13) C_pH_2p-R(14);
p 0, 1, 2, 3, 4 oder 5;
R(15) Cycloalkyl mit 3, 4, 5, 6, 7 oder 8 C-Atomen;
R(2) Wasserstoff oder Alkyl mit 1, 2, 3 oder 4 C-Atomen;
R(3) Heteroaryl,
wobei Heteroaryl unsubstituiert ist oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
R(4), R(5), R(6) und R(7)
unabhängig voneinander Wasserstoff, F, Cl, Br, I, CF₃, OCF₃, NO₂, CN, COOMe, CONH₂, COMe, NH₂, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino;
und/oder physiologisch verträglicher Salze der Verbindungen der Formel Ia, Ib, Ic, Id, Ie, If, Ig, Ih oder Ij.In one embodiment, compounds of the formula Ia are used, in which
R (1) is hydrogen;
R (2) R (20) -C _r H _2r;
R (20) CH ₃ , CH ₂ F, CHF ₂ , CF ₃ , cycloalkyl having 3, 4, 5, 6, 7 or 8 C atoms, -CONR (22) R (23), -OR (24), -COOR (24) or phenyl,
which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, CF _3, NO _2, CN, OH, methyl, ethyl, hydroxymethyl, hydroxyethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino ;
R (22) and R (23)
independently of one another hydrogen or alkyl having 1, 2, 3 or 4 C atoms;
or
R (22) and R (23)
together form a chain of 4 or 5 methylene groups, of which one CH ₂ group is represented by -O-, -S-, -NH-, -N (methyl) -
or -N (benzyl) - may be replaced;
R (24) is hydrogen or alkyl having 1, 2 or 3 C atoms;
r is zero, 1, 2, 3, 4, or 5;
R (3), R (4), R (5) and R (6)
independently of one another hydrogen, F, Cl, Br, I, alkyl having 1, 2, 3, 4 or 5 C atoms, cycloalkyl having 3, 4, 5, 6, 7 or 8 C atoms, CN, CF ₃ , NO ₂ or OR (25);
R (25) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms, a fluorinated alkyl radical of the formula -C _x H _2x CF _y H _3-y or phenyl which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, CF _3, NO _2, CN, OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
x 0, 1, 2 or 3;
y is 1, 2 or 3;
R (7) is hydrogen or alkyl having 1, 2, 3 or 4 C atoms;
R (8) 1-indanyl radical of the formula II;
R (9) is hydrogen or OR (28);
R (28) is hydrogen or alkyl having 1, 2, 3 or 4 C atoms;
R (10) and R (11)
independently of one another hydrogen or alkyl having 1, 2, 3 or 4 C atoms;
R (12), R (13), R (14) and R (15)
independently of one another hydrogen, F, Cl, Br, I, alkyl having 1, 2, 3, 4 or 5 C atoms, cycloalkyl having 3, 4, 5, 6, 7 or 8 C atoms, CN, CF ₃ , - NO ₂ or -YC _s H _2s -R (29);
Y is -O-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO ₂ -, -O-SO ₂ -, -SO ₂ NR (30) -, -CONR (30) - or -NR (30) CO-, where the linkage to the backbone is in each case via the atom on the left; R (30) is hydrogen or alkyl having 1, 2 or 3 C atoms;
s is zero, 1, 2, 3, 4 or 5;
R (29) is hydrogen, methyl, CF ₃ , -OR (31), -COOR (31), -NR (32) R (33), -CONR (32) R (33) or phenyl,
which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, CF _3, NO _2, CN, OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (31) is hydrogen or alkyl having 1, 2 or 3 C atoms;
R (32) and R (33)
independently of one another hydrogen or alkyl having 1, 2, 3 or 4 C atoms;
or
R (32) and R (33)
together a chain of 4 or 5 methylene groups, of which one CH ₂ group may be replaced by -O-, -S-, -NH-, -N (CH ₃ ) - or -N (benzyl) -;
and / or compounds of the formula Ib, in which
R (1) C (O) OR (9), SO ₂ R (10), COR (11) or C (O) NR (12) R (13);
R (9) C _x H _2x -R (14);
x 0, 1, 2, 3 or 4,
where x can not be 0 when R (14) is OR (15);
R (14) is alkyl having 1, 2, 3 or 4 C atoms, cycloalkyl having 3, 4, 5, 6, 7, 8 or 9 C atoms, CF ₃ , C ₂ F ₅ , OR (15), phenyl , Furyl, thienyl or an N-containing heteroaromatic having 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms,
wherein phenyl, furyl, thienyl and the N-containing heteroaromatic are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (15) is alkyl having 1, 2, 3, 4 or 5 C atoms, cycloalkyl having 3, 4, 5 or 6 C atoms, CF ₃ or phenyl,
which is unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, CF _3, NO _2, CN, COOMe, CONH _2, COMe, OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (10), R (11) and R (12)
independently defined as R (9);
R (13) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms or CF ₃ ;
R (2) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms or CF ₃ ;
R (3) C _y H _2y -R (16);
y is 0, 1, 2, 3 or 4,
where y can not be 0 when R (16) is OR (17);
R (16) is alkyl having 1, 2, 3 or 4 C atoms, cycloalkyl having 3, 4, 5, 6, 7, 8 or 9 C atoms, CF ₃ , C ₂ F ₅ , OR (17), phenyl , Furyl, thienyl or an N-containing heteroaromatic having 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms,
wherein phenyl, furyl, thienyl and the N-containing heteroaromatic are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (17) is alkyl having 1, 2, 3, 4 or 5 C atoms, cycloalkyl having 3, 4, 5 or 6 C atoms, CF ₃ , phenyl or 2-, 3- or 4-pyridyl,
wherein phenyl or 2-, 3-, or 4-pyridyl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
or
R (3) CHR (18) R (19);
R (18) is hydrogen or C _z H _2z -R (16) wherein R (16) is defined as defined in claim 1 above;
z is 0, 1, 2 or 3;
R (19) CONH ₂ , CONR (20) R (21), COOR (22), CH ₂ OH;
R (20) is hydrogen, alkyl having 1, 2, 3, 4 or 5 C atoms, C _v H _2v -CF ₃ or C _w H _2w-phenyl ,
wherein the phenyl ring is unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, CF _3, OCF _3, NO _2, CN, COOMe, CONH _2, COMe, NH _2, OH, alkyl with 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
v is 0, 1, 2 or 3;
w is 0, 1, 2 or 3;
R (21) is hydrogen or alkyl having 1, 2, 3, 4 or 5 C atoms;
R (22) is alkyl having 1, 2, 3, 4 or 5 C atoms;
R (4) is hydrogen or alkyl having 1, 2, 3, 4, 5 or 6 C atoms, CF ₃ ;
R (5), R (6), R (7) and R (8)
independently of one another are hydrogen, F, Cl, Br, CF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl or methylsulfonylamino;
R (30) and R (31)
independently of one another hydrogen or alkyl having 1, 2 or 3 C atoms;
or
R (30) and R (31)
together a chain of 2 methylene groups;
and / or compounds of the formula Ic, in which
A1, A2, A3, A4, A5, A6, A7 and A8
independently of one another nitrogen, CH or CR (5), at most one of these groups being nitrogen and at least 5 of these groups being CH;
R (1) C (O) OR (9), SO ₂ R (10), COR (11) or C (O) NR (12) R (13);
R (9), R (10), R (11) and R (12)
independently of each other C _x H _2x -R (14);
x 0, 1, 2, 3 or 4;
R (14)
Alkyl having 1, 2, 3 or 4 C-atoms, cycloalkyl having 3, 4, 5, 6, 7, 8 or 9 C-atoms, CF ₃ , phenyl, naphthyl, biphenylyl, furyl, thienyl or an N-containing heteroaromatic with 1, 2, 3, 4, 5, 6, 7, 8 or 9 carbon atoms,
wherein phenyl, naphthyl, biphenylyl, furyl, thienyl and the N-containing heteroaromatic are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (13) is hydrogen;
R (2) is hydrogen or methyl;
R (3) C _y H _2y -R (16);
y is 0, 1, 2, 3 or 4;
where y can not be 0 when R (16) is OR (17);
R (16) is alkyl having 1, 2, 3, 4, 5 or 6 C atoms, cycloalkyl having 3, 4, 5, 6, 7, 8 or 9 C atoms, CF ₃ , OR (17), SO ₂ Me, phenyl, naphthyl, furyl, thienyl or an N-containing heteroaromatic having 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms,
where phenyl, naphthyl, furyl, thienyl and the N-containing heteroaromatic are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , OCF ₃ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (17) is hydrogen, alkyl having 1, 2, 3, 4 or 5 C atoms, cycloalkyl having 3, 4, 5 or 6 C atoms, CF ₃ , phenyl or 2-, 3- or 4-pyridyl,
where phenyl or 2-, 3- or 4-pyridyl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (4) is hydrogen, alkyl having 1 or 2 C atoms;
R (5) F, Cl, Br, I, CF _3, NO _2, CN, COOMe, CONH _2, COMe, NH _2, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2 , 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl or methylsulfonylamino;
R (30) and R (31)
independently of one another hydrogen or methyl;
and / or compounds of the formula Id, in which
A1, A2, A3, A4, A5, A6, A7 and A8 independently of one another nitrogen, CH or CR (5), where at least one and at most two of these groups are nitrogen and at least 4 of these groups are CH;
R (1) C (O) OR (9), SO ₂ R (10), COR (11) or C (O) NR (12) R (13) R (9), R (10), R (11 ) and R (12)
independently C _x H _2x -R (14);
x 0, 1, 2, 3 or 4;
where x can not be 0 when R (14) is OR (15);
R (14) alkyl having 1, 2, 3 or 4 C atoms, cycloalkyl having 3, 4, 5, 6, 7, 8 or 9 C atoms, CF ₃ , OR (15), phenyl, naphthyl, biphenylyl, Furyl, thienyl or an N-containing heteroaromatic having 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms,
wherein phenyl, naphthyl, biphenylyl, furyl, thienyl and the N-containing heteroaromatic are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (15) is alkyl having 1, 2, 3, 4 or 5 C atoms, cycloalkyl having 3, 4, 5 or 6 C atoms, CF ₃ or phenyl, which is unsubstituted or substituted by 1, 2 or 3 substituents from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (13) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms or CF ₃ ;
R (2) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms or CF ₃ ;
R (3) C _y H _2y -R (16);
y is 0, 1, 2, 3 or 4,
where y can not be 0 when R (16) is OR (17) or SO ₂ Me;
R (16) is alkyl having 1, 2, 3, 4, 5 or 6 C atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9, C atoms, CF ₃ , OR (17), SO ₂ Me, phenyl, naphthyl, furyl, thienyl or an N-containing heteroaromatic compound having 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms,
where phenyl, naphthyl, furyl, thienyl and the N-containing heteroaromatic are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (17) is hydrogen, alkyl having 1, 2, 3, 4 or 5 C atoms, cycloalkyl having 3, 4, 5 or 6 C atoms, CF ₃ , phenyl or 2-, 3- or 4-pyridyl,
where phenyl or 2-, 3- or 4-pyridyl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
or
R (3) CHR (18) R (19);
R (18) is hydrogen or C _z H _2z -R (16) wherein R (16) is defined as above;
z is 0, 1, 2 or 3;
R (19) CONH ₂ , CONR (20) R (21), COOR (22) or CH ₂ OH;
R (20) is hydrogen, alkyl having 1, 2, 3, 4 or 5 C atoms, C _v H _2v -CF ₃ or C _w H _2w-phenyl ,
wherein the phenyl ring is unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH , Alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
v is 0, 1, 2 or 3;
w is 0, 1, 2 or 3;
R (21) is hydrogen or alkyl having 1, 2, 3, 4 or 5 C atoms;
R (22) is alkyl having 1, 2, 3, 4 or 5 C atoms;
R (4) is hydrogen, alkyl having 1, 2, 3, 4, 5 or 6 C atoms or CF ₃ ;
R (5) independently of one another are F, Cl, Br, I, CF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1 , 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl or methylsulfonylamino;
R (30) and R (31)
independently of one another hydrogen or alkyl having 1, 2 or 3 C atoms;
or
R (30) and R (31)
a chain of 2 methylene groups;
and / or compounds of the formula Ie and If, in which
X oxygen or sulfur;
R (1) C (O) OR (9) or COR (11);
R (9) and R (11)
independently C _x H _2x -R (14);
x 0, 1, 2 or 3;
R (14) cycloalkyl having 5 or 6 C atoms or phenyl,
where phenyl is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , OH, alkyl having 1, 2, 3 or alkoxy having 1 or 2 C atoms;
R (2) is hydrogen;
R (3) C _y H _2y -R (16);
y is 0, 1 or 2;
R (16) alkyl having 1, 2 or 3 C atoms, cycloalkyl having 5 or 6 C atoms, phenyl or pyridyl,
where phenyl and pyridyl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, CF ₃ , alkyl having 1, 2 or 3 C atoms or alkoxy having 1 or 2 C atoms;
R (4) is hydrogen;
R (5), R (6) and R (7)
independently of one another hydrogen, F, Cl, alkyl having 1, 2 or 3 C atoms or alkoxy having 1, 2 C atoms;
R (30) and R (31)
Hydrogen;
and / or compounds of the formula Ig, in which
R (1) (CH ₂ ) _x -R (8)
x 1 or 2;
R (8) is phenyl, thienyl or furanyl
wherein phenyl, thienyl and furanyl are unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, CF _3, OCF _3, CN, COOMe, CONH _2, COMe, alkyl having 1, 2 or 3 C atoms, alkoxy having 1, 2 or 3 C-atoms, sulfamoyl , Methylsulfonyl and methylsulfonylamino;
R (2) is hydrogen or alkyl having 1 or 2 C atoms;
R (3) is hydrogen;
R (4) phenyl,
wherein phenyl is unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, CF ₃ , OCF ₃ , COMe, alkyl having 1, 2 or 3 C atoms, alkoxy having 1, 2 or 3 C atoms;
R (5), R (8) and R (7)
independently of one another F, Cl, Br, CF ₃ , OCF ₃ , CN, COOMe, CONH ₂ , COMe, alkyl having 1, 2 or 3 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl , Methylsulfonyl and methylsulfonylamino;
and / or compounds of the formula Ih, in which

A -C _n H _2n -;
n is 0, 1, 2 or 3;
O oxygen;
D is a bond or oxygen;
E -C _m H _2m -;
m is 0, 1, 2 or 3;
R (8) is hydrogen or alkyl having 1, 2, 3 or 4 C atoms;
R (9) is hydrogen or alkyl having 1, 2, 3, 4, 5 or 6 C atoms;
R (10) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms or cycloalkyl having 3, 4 or 5 C atoms,
R (11) cycloalkyl having 3, 4, 5 or 6 C atoms, phenyl or pyridyl,
wherein phenyl and pyridyl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, CF ₃ , OCF ₃ , NO ₂ , CN, COMe, OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (12) alkyl having 1, 2, 3 or 4 C atoms, cycloalkyl having 3, 4 or 5 C atoms, aryl or heteroaryl,
wherein aryl and heteroaryl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, OH, alkyl with 1 , 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (13) C _p H _2p- R (14 ');
p is 0, 1, 2, 3, 4 or 5;
R (14 ') cycloalkyl having 3, 4, 5 or 6 C atoms, tetrahydrofuranyl, tetrahydropyranyl, aryl or heteroaryl,
wherein aryl and heteroaryl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, OH, alkyl with 1 , 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (2) is hydrogen or alkyl having 1 or 2 C atoms;
R (3) alkyl having 3, 4 or 5 C atoms, phenyl,
wherein phenyl is unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, CF ₃ , OCF ₃ , NO ₂ , COOMe, CONH ₂ , COMe, OH, alkyl with 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (4), R (5), R (6) and R (7)
independently of one another are hydrogen, F, Cl, Br, CF ₃ , OCF ₃ , OCHF ₂ , NO ₂ , CN, COOMe, CONH ₂ , COMe, OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
and / or compounds of the formula Ij, in which

A -C _n H _2n -;
n = 0, 1, 2, 3, 4 or 5;
D is a bond or -O-;
E -C _m H _2m -;
m = 0, 1, 2, 3, 4 or 5;
R (8) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms or C _p H _2p- R (14);
p is 0, 1, 2, 3, 4 or 5;
R (14) is phenyl, naphthyl or heteroaryl,
wherein phenyl, naphthyl and heteroaryl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (9) is hydrogen or alkyl having 1, 2, 3, 4, 5 or 6 C atoms;
R (10) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms, phenyl, naphthyl or heteroaryl,
wherein phenyl, naphthyl and heteroaryl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (11) cycloalkyl having 3, 4, 5 or 6 C atoms, phenyl, naphthyl, thienyl, furyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl or cinnolinyl,
wherein phenyl, naphthyl, thienyl, furyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl or cinnolinyl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F , Cl, Br, I, CF _3, OCF _3, NO _2, CN, COMe, NH _2, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms , Dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (12) is alkyl having 1, 2, 3 or 4 C atoms, alkynyl having 1, 2, 3 or 4 C atoms, cycloalkyl having 3, 4, 5 or 6 C atoms, phenyl, naphthyl or heteroaryl,
wherein phenyl, naphthyl and heteroaryl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (13) C _p H _2p- R (14);
p is 0, 1, 2, 3, 4 or 5;
R (15) cycloalkyl having 3, 4, 5, 6, 7 or 8 C atoms;
R (2) is hydrogen or alkyl having 1, 2, 3 or 4 C atoms;
R (3) heteroaryl,
where heteroaryl is unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, Alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
R (4), R (5), R (6) and R (7)
independently hydrogen, F, Cl, Br, I, CF _3, OCF _3, NO _2, CN, COOMe, CONH _2, COMe, NH _2, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino;
and / or physiologically acceptable salts of the compounds of the formula Ia, Ib, Ic, Id, Ie, If, Ig, Ih or Ij.

In a further embodiment Compounds of the formula Ia are used.

In a further embodiment Compounds of formula Ib are used.

In a further embodiment Compounds of the formula Ic are used.

In a further embodiment compounds of formula Id are used.

In a further embodiment Compounds of the formula Ie are used.

In a further embodiment compounds of formula If are used.

In a further embodiment compounds of the formula Ig are used.

In a further embodiment Compounds of the formula Ih are used.

In a further embodiment Compounds of the formula Ij are used.

Especially preference is given to the use of the compounds of the formula Ia, Ib, Id, Ie, If, Ih and Ij.

In an embodiment compounds of the formula Ia are preferred in which R (8) is a 1-indanyl radical of the formula II, for example a 1-indanyl radical of formula II wherein R9, R10, R11, R12, R13, R14 and R15 are hydrogen mean.

In a further embodiment compounds of the formula Ia are preferred in which R (1) is hydrogen is.

In another embodiment, compounds of the formula Ia are preferred in which R (2) R (20) -C _r H _2r, where R (20) CH _3, CH ₂ F, CHF _2, CF _3, cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms, -CONR (22) R (23), -OR (24), -COOR (24) or phenyl which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, CF _3, NO _2, CN, OH, methyl, ethyl, hydroxymethyl, hydroxyethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino and R is zero, 1, 2, 3, 4, or 5 is; particularly preferred are compounds of formula Ia in which R (2) R (20) -C _r H _2r, where R (20) is CH ₃ and R 4.

In a further embodiment, compounds of the formula Ia are preferred in which R (3), R (4), R (5) and R (6) independently of one another are hydrogen, F, Cl, Br, I, alkyl with 1, 2, 3, 4 or 5 C atoms, cycloalkyl having 3, 4, 5, 6, 7 or 8 C atoms, CN, CF ₃ , NO ₂ or OR (25); particular preference is given to compounds of the formula Ia in which R (3), R (4), R (5) and R (6) are, independently of one another, hydrogen or alkyl having 1, 2 or 3 C atoms, for example methyl; particular preference is given to compounds of the formula Ia in which R (3), R (4) and R (5) are hydrogen and R (6) is methyl.

In a further embodiment compounds of the formula Ia are preferred in which R (7) is hydrogen or alkyl having 1, 2, 3 or 4 C atoms, for example hydrogen is.

In one embodiment, preference is given to compounds of the formula Ib in which R (1) is C (O) OR (9) or COR (11), where R (9) and R (11) are C _x H _{2 2} -R (14) are with x is 0, 1, 2 or 3 and R (14) is cycloalkyl having 5 or 6 C atoms or phenyl, wherein phenyl is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, CF ₃ , OCF ₃ , alkyl of 1, 2 or 3 C atoms and alkoxy of 1 or 2 C atoms; Particular preference is given to compounds of the formula Ib in which R (1) is C (O) OR (9) or COR (11), where R (9) and R (11) are C _x H ₂ -X-R (14) x is 1 or 2 and R (14) is phenyl, wherein phenyl is unsubstituted or substituted with 1 substituent selected from the group consisting of alkoxy having 1 or 2 C atoms, for example methoxy.

In a further embodiment preference is given to compounds of the formula Ib in which R (2) is hydrogen is.

In a further embodiment, preference is given to compounds of the formula Ib in which R (3) is C _y H _2y -R (16), where y is 0, 1, 2 or 3 and R (16) is alkyl having 1, 2 or 3 C atoms, cycloalkyl having 5 or 6 C atoms, CF ₃ , OR 17 with R 17 is hydrogen, phenyl or pyridyl, where phenyl and pyridyl are unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, CF ₃ , OCF ₃ , alkyl having 1, 2 or 3 C atoms and alkoxy having 1 or 2 C atoms; particular preference is given to compounds of the formula Ib in which R (3) is C _y H _2y -R (16), where y is 1, 2 or 3 and R (16) OR 17 where R 17 is hydrogen, phenyl or pyridyl, Phenyl and pyridyl are unsubstituted or substituted with 2 substituents selected from the group consisting of F or Cl, for example F.

In a further embodiment compounds of the formula Ib are preferred in which R (4) is hydrogen or alkyl having 1 or 2 C atoms, for example hydrogen or methyl.

In a further embodiment, preference is given to compounds of the formula Ib in which R (5), R (6), R (7) and R (8) independently of one another are hydrogen, F, Cl, CF ₃ , alkyl having 1, 2 or 3 C atoms or alkoxy having 1 or 2 C atoms are; particular preference is given to compounds of the formula Ib in which R (5) is hydrogen or Cl and R (6), R (7) and R (8) are hydrogen.

In a further embodiment preference is given to compounds of the formula Ib in which R (30) and R (31) Are hydrogen.

In an embodiment compounds of the formula Ic are preferred in which A1, A2, A3, A4, A5, A6, A7 and A8 independent each other nitrogen, CH or CR (5), wherein at most one of these groups nitrogen and at least 5 of these groups are CH; especially preference is given to compounds of the formula Ic in which A1 denotes CR (5) where R (5) is alkyl having 1, 2 or 3 C atoms, for example methyl, and A2, A3, A4, A5, A6, A7 and A8 are CH.

In a further embodiment, preference is given to compounds of the formula Ic in which R (1) is C (O) OR (9) or COR (11), where R (9) and R (11) independently of one another are C _x H _2x -R (14) are with x is 0, 1, 2 or 3 and R (14) is cycloalkyl with 5 or 6 C atoms or phenyl, where phenyl is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, 1, CF ₃ , OCF ₃ , OH, alkyl having 1, 2, 3 C atoms or alkoxy having 1 or 2 C atoms; particular preference is given to compounds of the formula Ic in which R (1) is COR (11), where R (11) C _x H ₂ -R (14) where x is 2 and R (14) is phenyl, where phenyl is substituted is with 1 substituent selected from the group consisting of alkoxy having 1 or 2 C atoms, for example methoxy.

In a further embodiment compounds of the formula Ic are preferred in which R (2) is hydrogen is.

In another embodiment, preference is given to compounds of the formula Ic in which R (3) is C _y H _2y -R (16) where y is 0, 1, 2, 3 or 4 and R (16) is alkyl having 1, 2 or 3 C atoms, cycloalkyl having 5 or 6 C atoms, phenyl or pyridyl, wherein phenyl and pyridyl are unsubstituted or substituted with 1, 2 substituents selected from the group consisting of F, Cl, CF ₃ , OCF ₃ , alkyl with 1, 2 or 3 C atoms or alkoxy with 1 or 2 C atoms; particular preference is given to compounds of the formula Ic in which R (3) is C _y H _2y -R (16), where y is 4 and R (16) is alkyl having 1, 2 or 3 C atoms, for example methyl.

In a further embodiment compounds of the formula Ic are preferred in which R (4) is hydrogen is.

In a further embodiment preference is given to compounds of the formula Ic in which R (30) and R (31) Are hydrogen.

In an embodiment compounds of the formula Id are preferred in which one of A1, A4 and A7 denote nitrogen and the other of A1, A4 and A7 and A2, A3, A5, A6 and A8 are independently CH or CR (5) where at least 5 of these groups are CH; especially preference is given to compounds of the formula Id in which one of A1, A4 and A7 means nitrogen and the others of A1, A4 and A7 and A2, A3, A5, A6 and A8 are CH.

In a further embodiment, preference is given to compounds of the formula Id in which R (1) is C (O) OR (9) or COR (11), where R (9) and R (11) are each independently C _x H _2x -R (14) are with x is 0, 1, 2 or 3 and R (14) is cycloalkyl with 5 or 6 C atoms or phenyl, where phenyl is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , OH, alkyl having 1, 2 or 3 C atoms or alkoxy having 1 or 2 C atoms; Particular preference is given to compounds of the formula Id in which R (1) is C (O) OR (9) or COR (11), where R (9) and R (11) are each independently C _x H _{2 x} -R (14) are with x is 1, 2 or 3 and R (14) is phenyl.

In a further embodiment compounds of the formula Id are preferred in which R (2) is hydrogen is.

In another embodiment, preference is given to compounds of the formula Id in which R (3) is C _y H _2y -R (16), where y is 0, 1, 2, 3 or 4 and R (16) is alkyl having 1, 2 or 3 C atoms, cycloalkyl having 3, 4, 5 or 6 C atoms, phenyl or pyridyl, where phenyl and pyridyl are unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, CF ₃ , Alkyl having 1, 2, 3 C atoms and alkoxy having 1 or 2 C atoms; particular preference is given to compounds of the formula Id in which R (3) is C _y H _2y -R (16), where y is 1, 2 or 4 and R (16) is alkyl having 1, 2 or 3 C atoms, for example Methyl, cycloalkyl having 3 C atoms, phenyl or pyridyl, wherein phenyl and pyridyl are unsubstituted or substituted with 2 substituents selected from the group consisting of F or Cl, for example F.

In a further embodiment compounds of the formula Id are preferred in which R (4) is hydrogen is.

In a further embodiment preference is given to compounds of the formula Id in which R (30) and R (31) Are hydrogen.

In a further embodiment compounds of the formula Ie are preferred in which X is oxygen or sulfur, for example sulfur.

In a further embodiment, preference is given to compounds of the formula Ie in which R (1) is C (O) OR (9) or COR (11), where R (9) and R (11) are each independently C _x H _{2 x} -R (14) with x is 0, 1, 2, 3 or 4 and R (14) is alkyl with 1, 2 or 3 C atoms, cycloalkyl with 5 or 6 C atoms or phenyl, wherein phenyl are unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , OH, alkyl having 1, 2, 3 or alkoxy having 1 or 2 C atoms; particular preference is given to compounds of the formula Ie in which R (1) is COR (11), where R (11) C _x H _{2 is} -R (14) where x is 1 and R (14) is phenyl, where phenyl is substituted is with 1 substituent selected from the group consisting of alkoxy having 1 or 2 C atoms, for example methoxy.

In a further embodiment compounds of the formula Ie are preferred in which R (2) is hydrogen is.

In a further embodiment, preference is given to compounds of the formula Ie in which R (3) is C _y H _2y -R (16) where y is 0, 1 or 2 and R (16) is alkyl having 1, 2 or 3 C Atoms, cycloalkyl having 5 or 6 C atoms, phenyl or pyridyl, wherein phenyl and pyridyl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, CF ₃ , alkyl with 1, 2 or 3 C atoms or alkoxy having 1 or 2 C atoms; particular preference is given to compounds of the formula Ie in which R (3) is C _y H _2y -R (16), where y is 1 and R (16) is phenyl, where phenyl is substituted by 2 substituents selected from the group consisting of F and Cl, for example F.

In a further embodiment compounds of the formula Ie are preferred in which R (4) is hydrogen is.

In a further embodiment compounds of the formula Ie are preferred in which R (5), R (6) and R (7) are hydrogen.

In a further embodiment preference is given to compounds of the formula Ie in which R (30) and R (31) Are hydrogen.

In a further embodiment, preference is given to compounds of the formula If in which R (1) is C (O) OR (9) or COR (11), where R (9) and R (11) independently of one another are C _x H _2x -R (14) with x is 0, 1, 2, 3 or 4 and R (14) is alkyl with 1, 2 or 3 C atoms, cycloalkyl with 5 or 6 C atoms or phenyl, wherein phenyl are unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , OH, alkyl having 1, 2, 3 or alkoxy having 1 or 2 C atoms; particular preference is given to compounds of the formula If in which R (1) COR (11), where R (11) C _x H _{2 is} -R (14) where x is 1 and R (14) is phenyl, where phenyl is substituted is with 1 substituent selected from the group consisting of alkoxy having 1 or 2 C atoms, for example methoxy.

In a further embodiment compounds of the formula If are preferred in which R (2) is hydrogen is.

In another embodiment, preference is given to compounds of the formula If in which R (3) is C _y H _2y -R (16), where y is 0, 1, 2, 3 or 4 and R (16) is alkyl with 1, 2 or 3 C atoms, cycloalkyl having 5 or 6 C atoms, phenyl or pyridyl, wherein phenyl and pyridyl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, CF ₃ , alkyl 1, 2 or 3 C atoms or alkoxy having 1 or 2 C atoms; particular preference is given to compounds of the formula If in which R (3) is C _y H _2y -R (16), where y is 1 or 4 and R (16) is alkyl having 1, 2 or 3 C atoms, for example methyl, or phenyl, wherein phenyl is substituted with 2 substituents selected from the group consisting of F and Cl, for example F.

In a further embodiment, compounds of the formula If are preferred in which R (4) is hydrogen.

In a further embodiment compounds of the formula If are preferred in which R (5), R (6) and R (7) are hydrogen.

In a further embodiment preference is given to compounds of the formula If in which R (30) and R (31) Are hydrogen.

ist, wobei A -C_nH_2n- ist mit n ist 0, 1 oder 2, D eine Bindung oder Sauerstoff ist, E -C_mH_2m- ist mit m ist 0 oder 1, R(8) Wasserstoff oder Alkyl mit 1, 2, 3 oder 4 C-Atomen ist, R(9) Wasserstoff oder Alkyl mit 1, 2, 3 oder 4 C-Atomen ist, R(12) Alkyl mit 1, 2, 3 oder 4 C-Atomen oder Cyclopropyl ist und R(11) Phenyl oder Pyridyl ist, wobei Phenyl und Pyridyl unsubstituiert sind oder substituiert mit 1, 2 oder 3 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, CF₃, OCF₃, CN, COMe, OH, Alkyl mit 1, 2, 3 oder 4 C-Atomen, Alkoxy mit 1, 2, 3 oder 4 C-Atomen, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino; besonders bevorzugt sind Verbindungen R(1)

ist, wobei -C_nH_2n- ist mit n ist 0, D eine Bindung ist, E -C_mH_2m- ist mit m ist 0, R(8) und R(9) Wasserstoff sind, R(12) Alkyl mit 1, 2 oder 3 C-Atomen, beispielsweise Ethyl, ist und R(11) Phenyl oder Pyridyl ist, wobei Phenyl und Pyridyl unsubstituiert sind oder substituiert mit 1 Substituenten ausgewählt aus der Gruppe bestehend aus Alkoxy mit 1 oder 2 C-Atomen, beispielsweise Methoxy.In a further embodiment, compounds of the formula Ih are preferred in which R (1)

, wherein A is -C _n H _2n - where n is 0, 1 or 2, D is a bond or oxygen, E is -C _m H _2m - with m is 0 or 1, R (8) is hydrogen or alkyl 1, 2, 3 or 4 C atoms, R (9) is hydrogen or alkyl having 1, 2, 3 or 4 C atoms, R (12) alkyl having 1, 2, 3 or 4 C atoms or cyclopropyl and R (11) is phenyl or pyridyl, where phenyl and pyridyl are unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of F, Cl, CF _3, OCF _3, CN, COMe, OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; particularly preferred are compounds R (1)

where C _{n is} H _2n - where n is 0, D is a bond, E - C _m H _2m - where m is 0, R (8) and R (9) are hydrogen, R (12) is alkyl with 1, 2 or 3 C atoms, for example ethyl, and R (11) is phenyl or pyridyl, where phenyl and pyridyl are unsubstituted or substituted by 1 substituent selected from the group consisting of alkoxy having 1 or 2 C atoms, for example, methoxy.

In a further embodiment compounds of the formula Ih are preferred in which R (2) is hydrogen is.

In a further embodiment, preference is given to compounds of the formula Ih in which R (3) is alkyl having 3, 4 or 5 C atoms or phenyl, where phenyl is unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F , Cl, CF ₃ , OCF ₃ , COOMe, CONH ₂ , COMe, OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; Particular preference is given to compounds of the formula Ih in which R (3) is alkyl having 3, 4 or 5 C atoms, for example 4 C atoms, or phenyl, where phenyl is substituted by 1 substituent selected from the group consisting of alkoxy with 1 or 2 C atoms, for example methoxy.

In a further embodiment compounds of the formula Ih are preferred in which R (5) is hydrogen or methoxy and R (4), R (6) and R (7) are hydrogen.

ist, wobei A -C_nH_2n- ist mit n ist 0 oder 1, D eine Bindung oder -O- ist, E -C_mH_2m- ist mit m ist 0 oder 1, R(8) Wasserstoff oder Alkyl mit 1, 2 oder 3 C-Atomen ist, R(9) Wasserstoff, Ethyl oder Methyl ist, R(11) Phenyl, Naphthyl, Pyridyl, Pyrazinyl, Pyrimidinyl, Pyridazinyl, Indolyl, Indazolyl, Chinolyl, Isochinolyl, Phthalazinyl, Chinoxalinyl, Chinazolinyl oder Cinnolinyl ist, wobei Phenyl, Naphthyl, Pyridyl, Pyrazinyl, Pyrimidinyl, Pyridazinyl, Indolyl, Indazolyl, Chinolyl, Isochinolyl, Phthalazinyl, Chinoxalinyl, Chinazolinyl oder Cinnolinyl unsubstituiert sind oder substituiert mit 1 oder 2 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, CF₃, OCF₃, CN, COMe, Methoxy, Ethoxy, Dimethylamino, Sulfamoyl und Methylsulfonyl, und R(12) Alkyl mit 1, 2 oder 3 C-Atomen, Ethinyl, Cyclopropyl, Phenyl, Naphthyl oder Heteroaryl ist wobei Phenyl, Naphthyl und Heteroaryl unsubstituiert sind oder substituiert mit 1 oder 2 Substituenten ausgewählt aus der Gruppe bestehend aus F, Cl, CF₃, OCF₃, CN, COMe, Ethoxy, Dimethylamino, Sulfamoyl, Methylsulfonyl und Methylsulfonylamino; besonders bevorzugt sind Verbindungen der Formel Ih, in denen R(1)

ist, wobei -C_nH_2n- ist mit n ist 0, D eine Bindung ist, E -C_mH_2m- ist mit m ist 0, R(8) Wasserstoff ist, R(9) Wasserstoff ist, R(11) unsubstituiertes Phenyl ist und R(12) Alkyl mit 1, 2 oder 3 C-Atomen, beispielsweise Ethyl, ist.In a further embodiment, preference is given to compounds of the formula Ij in which R (1)

where A is C _n H _2n - where n is 0 or 1, D is a bond or -O-, E -C _m H _2m - with m is 0 or 1, R (8) is hydrogen or alkyl with 1, 2 or 3 C atoms, R (9) is hydrogen, ethyl or methyl, R (11) is phenyl, naphthyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl or cinnolinyl, wherein phenyl, naphthyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl or cinnolinyl are unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl , CF ₃ , OCF ₃ , CN, COMe, methoxy, ethoxy, dimethylamino, sulfamoyl and methylsulfonyl, and R (12) is alkyl having 1, 2 or 3 C atoms, ethynyl, cyclopropyl, phenyl, naphthyl or heteroaryl where phenyl, Naphthyl and heteroaryl are unsubstituted or substituted with 1 or 2 substituents selected from the group consisting from F, Cl, CF _3, OCF _3, CN, COMe, ethoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; Particular preference is given to compounds of the formula Ih in which R (1)

where C _{n is} H _2n - where n is 0, D is a bond, E - C _m H _2m - with m is 0, R (8) is hydrogen, R (9) is hydrogen, R (11 ) is unsubstituted phenyl and R (12) is alkyl having 1, 2 or 3 C atoms, for example ethyl.

In a further embodiment compounds of the formula Ij are preferred in which R (2) is hydrogen is.

In a further embodiment, preference is given to compounds of the formula Ij in which R (3) is heteroaryl, where heteroaryl is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, CF ₃ , OCF ₃ , CN, COMe Methyl, methoxy, ethoxy, dimethylamino, sulfamoyl and methylsulfonyl; particular preference is given to compounds of the formula Ih in which R (3) furanyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolyl, Isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl, cinnolinyl, for example quinolyl.

In a further embodiment compounds of the formula Ij are preferred in which R (5) is hydrogen or F, for example F, and R (4), R (6) and R (7) is hydrogen are.

Especially preferred is the use of compounds selected from the group:
2- (butyl-1-sulfonylamino) -N- [1 (R) - (6-methoxy-pyridin-3-yl) propyl] benzamide,
2- (butyl-1-sulfonylamino) -N- [1 (S) - (6-methoxy-pyridin-3-yl) propyl] benzamide,
2 '- {[2- (4-methoxy-phenyl) -acetylamino] methyl} biphenyl-2-carboxylic acid (2-pyridin-3-yl-ethyl) -amide,
(S) -5-fluoro-2- (quinoline-8-sulfonylamino) -N- (1-phenyl-propyl) -benzamide,
(S) -S-methoxy-2- (4-methoxy-benzenesulfonylamino) -N- (1-phenyl-propyl) -benzamide,
2 '- (α- (S) -methyl-benzyloxycarbonyl-aminomethyl) biphenyl-2-carboxylic acid 2- (2- (R) -hydroxy-propylamide)
5-chloro-2 '- {[2- (4-methoxy-phenyl) -acetylamino] methyl} biphenyl-2-carboxylic acid 2,4-difluoro-benzylamide,
{2 '- [methyl- (2-pyridin-2-yl-ethyl) -carbamoyl] -biphenyl-2-ylmethyl} -carbamic acid benzyl ester
3- (2 - {[2- (4-methoxy-phenyl) -acetylamino] -methyl} -phenyl) -thiophenes-2-carboxylic acid 2,4-difluoro-benzylamide,
5- (2 - {[2- (4-methoxy-phenyl) -acetylamino] -methyl} -phenyl) -furan-2-carboxylic acid 2,4-difluoro-benzylamide,
2- (2 - {[2- (4-methoxy-phenyl) -acetylamino] -methyl} -phenyl) -furan-3-carboxylic acid (3-methyl-butyl) -amide,
2- (2 - {[2- (4-methoxy-phenyl) -acetylamino] -methyl} -phenyl) -thiophenes-3-carboxylic acid 2,4-difluoro-benzylamide,
{2- [2- (2-pyridin-2-yl-ethylcarbamoyl) pyridin-3-yl] -benzyl} -carbamic acid (S) -1-phenylethyl ester,
3- {2 - [((R) -3-phenyl-butyrylamino) -methyl] -phenyl} -pyridin-2-carbonsäurecyclopropylmethyl-amide,
{2- [3- (2,4-Difluoro-benzylcarbamoyl) -pyridin-2-yl] -benzyl} -carbamic acid benzyl ester,
{4- [3- (3-methyl-butylcarbamoyl) -phenyl] -pyridin-3-ylmethyl} -carbamic acid benzyl ester,
2 '- {[3- (4-methoxy-phenyl) -propionylamino] -methyl} -6-methyl-biphenyl-3-carboxylic acid (3-methyl-butyl) -amide
and N-indan-1-yl-2-methyl-5- (3-methyl-butylsulfamoyl) -benzamide
and / or physiologically acceptable salts thereof.

Alkyl radicals and alkylene radicals can be straight-chain or branched. This also applies to the alkylene radicals of the formulas C _r H _2r , C _x H _2x , C _s H _2s , C _y H _2y , C _z H _2z , C _v H _2v , C _w H _2w , C _n H _2n , C _m H _2m , C _p H _2p and (CH ₂ ) _x . Alkyl radicals and alkylene radicals can also be straight-chain or branched if they are substituted or are contained in other radicals, for example in fluoroalkyl radicals or alkoxy radicals. Examples of alkyl radicals are methyl, ethyl, n-propyl, isopropyl (= 1-methylethyl), n-butyl, isobutyl (= 2-methylpropyl), sec-butyl (= 1-methylpropyl), tert-butyl (= 1,1 -Dimethylethyl), n-pentyl, isopentyl, tert-pentyl, neopentyl, hexyl and heptyl. The divalent radicals derived from these radicals, for example methylene, 1,1-ethylene, 1,2-ethylene, 1,1-propylene, 1,2-propylene, etc. are examples of alkylene radicals. Preferred alkyl radicals are methyl, ethyl, n-propyl and isopropyl. In alkyl radicals, one or more, for example 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15, hydrogen atoms may be substituted by fluorine atoms. Examples of such fluoroalkyl radicals are trifluoromethyl, 2,2,2-trifluoroethyl and pentafluoroethyl. Substituted alkyl radicals may be substituted in any positions.

Alkynyl radicals can be straight-chain or branched. This also applies if they carry substituents, for example in Fluoralkinylresten. The alkynyl radicals may be unsaturated in different positions and also polyunsaturated. Examples of alkynyl radicals are ethynyl, n-prop-1-ynyl, n-prop-2-ynyl, n-but-1-ynyl, n-but-2-ynyl, n-but-3-ynyl, n-butanea 1,3-diynyl and sec-but-2-enyl (= 1-methylprop-2-enyl). In alkynyl radicals, one or more, for example, 1, 2, 3, 4, 5, 6, or 7, hydrogen atoms may be substituted by fluorine atoms be. Substituted alkynyl radicals may be substituted in any positions.

Examples for cycloalkyl radicals are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, Cyclooctyl, cyclononyl, cyclodecanyl and cycloundecanyl. In cycloalkyl radicals can one or more, for example 1, 2, 3, 4, 5, 6, 7 or 8 hydrogen atoms be substituted by fluorine atoms. Substituted cycloalkyl radicals can be substituted in any positions.

aryl stands for example Phenyl and 2- or 3-naphthyl.

phenyl can unsubstituted or simply or multiply, for example simply, two or three times, substituted by identical or different radicals be. When a phenyl radical is substituted, it preferably carries one or two identical or different substituents. This also applies to substituted phenyl radicals in groups such as phenylalkyl or phenyloxy. In monosubstituted Phenyl radicals may be the substituent in the 2-position, the 3-position or the 4-position are located. Doubly substituted phenyl may be in 2,3-position, 2,4-position, Be substituted 2,5-position, 2,6-position, 3,4-position or 3,5-position. In threefold substituted phenyl radicals, the substituents in 2,3,4-position, 2,3,5-position, 2,4,5-position, 2,4,6-position, 2,3,6-position or 3,4,5-position.

heteroaryl are aromatic ring compounds in which one or more ring atoms Oxygen atoms, sulfur atoms or nitrogen atoms are, for. B. 1, 2 or 3 nitrogen atoms, 1 or 2 oxygen atoms, 1 or 2 Sulfur atoms or a combination of different heteroatoms. The heteroaryl radicals can be over all Positions are connected, for example, via the 1-position, 2-position, 3-position, 4-position, 5-position, 6-position, 7-position or 8-position. heteroaryl can unsubstituted or simply or multiply, for example simply, two or three times, substituted by identical or different radicals be. This also applies to the heteroaryl radicals such as in the rest heteroarylalkyl. Heteroaryl means for example furanyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, Triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, Pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, Quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl and cinnolinyl.

When Heteroaryl radicals are especially 2- or 3-thienyl, 2- or 3-furyl, 1-, 2- or 3-pyrrolyl, 1-, 2-, 4- or 5-imidazolyl, 1-, 3-, 4- or 5-pyrazolyl, 1,2,3-triazole-1, -4- or -5-yl, 1,2,4-triazole-1, -3- or -5-yl, 1- or 5-tetrazolyl, 2-, 4- or 5-oxazolyl, 3-, 4- or 5-isoxazolyl, 1,2,3-oxadiazol-4 or 5-yl, 1,2,4-oxadiazol-3 or -5-yl, 1,3,4-oxadiazol-2-yl or -5-yl, 2-, 4- or 5-thiazolyl, 3-, 4- or 5-isothiazolyl, 1,3,4-thiadiazole-2-one or -5-yl, 1,2,4-thiadiazol-3-or-5-yl, 1,2,3-thiadiazol-4 or -5-yl, 2-, 3- or 4-pyridyl, 2-, 4-, 5- or 6-pyrimidinyl, 3- or 4-pyridazinyl, pyrazinyl, 1-, 2-, 3-, 4-, 5-, 6- or 7-indolyl, 1-, 2-, 4- or 5-benzimidazolyl, 1-, 3-, 4-, 5-, 6- or 7-indazolyl, 2-, 3-, 4-, 5-, 6-, 7- or 8-quinolyl, 1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolyl, 2-, 4-, 5-, 6-, 7- or 8-quinazolinyl, 3-, 4-, 5-, 6-, 7- or 8-cinnolinyl, 2-, 3-, 5-, 6-, 7- or 8-quinoxalinyl, 1-, 4-, 5-, 6-, 7- or 8-phthalazinyl. includes are still the corresponding N-oxides of these compounds, ie for example 1-oxy-2-, -3- or -4-pyridyl.

Especially the heteroaromatics are preferably 2- or 3-thienyl, 2- or 3-furyl, 1-, 2- or 3-pyrrolyl, 1-, 2-, 4- or 5-imidazolyl, 2-, 3-, 4-, 5-, 6-, 7- or 8-quinolyl, 1-, 3-, 4- or 5-pyrazolyl, 2-, 3- or 4-pyridyl, 2- or 3-pyrazinyl, 2-, 4-, 5- or 6-pyrimidinyl and 3- or 4-pyridazinyl.

N-containing Heterocycles are ring compounds in which one or more ring atoms Nitrogen atoms are, for. B. 1, 2 or 3 nitrogen atoms. The N-containing Heterocycles can be over all Positions are connected, for example, via the 1-position, 2-position, 3-position, 4-position, 5-position, 6-position, 7-position or 8-position. N-containing heterocycles can unsubstituted or simply or multiply, for example simply, two or three times, substituted by identical or different radicals be. As N-containing heterocycles having 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms are especially the aromatic systems 1-, 2- or 3-pyrrolyl, 1-, 2-, 4- or 5-imidazolyl, 1-, 3-, 4- or 5-pyrazolyl, 1,2,3-triazole-1, -4- or -5-yl, 1,2,4-triazole-1, -3- or -5-yl, 1- or 5-tetrazolyl, 2-, 4- or 5-oxazolyl, 3-, 4- or 5-isoxazolyl, 1,2,3-oxadiazol-4 or 5-yl, 1,2,4-oxadiazol-3 or -5-yl, 1,3,4-oxadiazol-2-yl or -5-yl, 2-, 4- or 5-thiazolyl, 3-, 4- or 5-isothiazolyl, 1,3,4-thiadiazol-2 or -5-yl, 1,2,4-thiadiazole-3 or -5-yl, 1,2,3-thiadiazol-4 or -5-yl, 2-, 3- or 4-pyridyl, 2-, 4-, 5- or 6-pyrimidinyl, 3- or 4-pyridazinyl, pyrazinyl, 1-, 2-, 3-, 4-, 5-, 6- or 7-indolyl, 1-, 2-, 4- or 5-benzimidazolyl, 1-, 3-, 4-, 5-, 6- or 7-indazolyl, 2-, 3-, 4-, 5-, 6-, 7- or 8-quinolyl, 1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolyl, 2-, 4-, 5-, 6-, 7- or 8-quinazolinyl, 3-, 4-, 5-, 6-, 7- or 8-cinnolinyl, 2-, 3-, 5-, 6-, 7- or 8-quinoxalinyl, 1-, 4-, 5-, 6-, 7- or 8-phthalazinyl. The N-containing heterocycles are particularly preferably pyrrolyl, imidazolyl, Quinolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl and pyridazinyl.

N-containing Heteroaromatics are aromatic ring compounds in which one or a plurality of ring atoms are nitrogen atoms, e.g. B. 1, 2 or 3 nitrogen atoms. The N-containing heteroaromatics can over all Positions are connected, for example, via the 1-position, 2-position, 3-position, 4-position, 5-position, 6-position, 7-position or 8-position. N-containing heteroaromatics can unsubstituted or simply or multiply, for example simply, two or three times, be substituted by identical or different radicals. As N-containing heteroaromatic compounds having 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms in particular 1-, 2- or 3-pyrrolyl, 1-, 2-, 4- or 5-imidazolyl apply, 1-, 3-, 4- or 5-pyrazolyl, 1,2,3-triazole-1, -4- or 5-yl, 1,2,4-triazole-1, -3- or -5-yl, 1- or 5-tetrazolyl, 2-, 4- or 5-oxazolyl, 3-, 4- or 5-isoxazolyl, 1,2,3-oxadiazole-4 or 5-yl, 1,2,4-oxadiazol-3 or 5-yl, 1,3,4-oxadiazol-2-yl or -5-yl, 2-, 4- or 5-thiazolyl, 3-, 4- or 5-isothiazolyl, 1,3,4-thiadiazol-2 or 5-yl, 1,2,4-thiadiazole-3 or -5-yl, 1,2,3-thiadiazol-4 or 5-yl, 2-, 3- or 4-pyridyl, 2-, 4-, 5- or 6-pyrimidinyl, 3- or 4-pyridazinyl, pyrazinyl, 1-, 2-, 3-, 4-, 5-, 6- or 7-indolyl, 1-, 2-, 4- or 5-benzimidazolyl, 1-, 3-, 4-, 5-, 6- or 7-indazolyl, 2-, 3-, 4-, 5-, 6-, 7- or 8-quinolyl, 1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolyl, 2-, 4-, 5-, 6-, 7- or 8-quinazolinyl, 3-, 4-, 5-, 6-, 7- or 8-cinnolinyl, 2-, 3-, 5-, 6-, 7- or 8-quinoxalinyl, 1-, 4-, 5-, 6-, 7- or 8-phthalazinyl. includes are still the corresponding N-oxides of these compounds, ie z. For example 1-oxy-2-, 3- or 4-pyridyl.

Especially the N-containing heterocycles are preferably pyrrolyl, imidazolyl, Quinolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl and pyridazinyl.

pyridyl stands for both 2-, 3- and 4-pyridyl. Thienyl stands for both 2- and also 3-thienyl. Furyl is both 2- and 3-furyl.

at Di- or multiple substitution of a radical may be the same substituents or be different.

Contain the compounds of the formula Ia, Ib, Ic, Id, Ie, If, Ig, Ih or Ij one or more acidic or basic groups or one or Several basic heterocycles, including the corresponding ones physiologically or toxicologically acceptable salts to the invention, in particular the pharmaceutically usable salts. So can the Compounds of the formula Ia, Ib, Ic, Id, Ie, If, Ig, Ih or Ij the sulfonamide be deprotonated and example as Alkali metal salts, preferably sodium or potassium salts, or as Ammonium salts, for example as salts with ammonia or organic Amines or amino acids, be used. Compounds of the formula Ia or Ib which have a Pyridine or quinoline substituent may also be in the form of their physiological acceptable Acid addition salts be used with inorganic or organic acids, for example as hydrochlorides, phosphates, sulfates, methanesulfonates, acetates, Lactates, maleinates, fumarates, malates, gluconates, etc. The compounds of formula Ia or Ib can but also present as trifluoroacetates.

The Compounds of the formula Ia, Ib, Ic, Id, Ie, If, Ig, Ih or Ij can in corresponding substitution in stereoisomeric forms. If the compounds of the formula Ia, Ib, Ic, Id, Ie, If, Ig, Ih or Ij one or more centers of asymmetry, so they can independently have the S configuration or the R configuration from each other. To the invention belong all possible Stereoisomers, for example enantiomers or diastereomers, and Mixtures of two or more stereoisomeric forms, for example Enantiomers and / or diastereomers, in any ratios. Enantiomers include, for example in enantiomerically pure form, both as left and as dextrorotatory antipodes, and also in the form of mixtures of the two Enantiomers in different ratios or in the form of racemates to the invention. The preparation of individual stereoisomers can if desired by separating a mixture by conventional methods or for example by using isomerically pure synthesis building blocks.

The The present invention includes all tautomeric forms of the compounds of the formula Ia, Ib, Ic, Id, Ie, If, Ig, Ih or Ij.

The Preparation of the compounds of the formulas Ia, Ib, Ic, Id, Ie, If, Ig, Ih or Ij can be done according to the manufacturing methods, in WO01 / 00573, WO01 / 025189, WO02 / 044137, WO02 / 046162, WO02 / 048131, WO02 / 087568, WO02 / 088073, WO02 / 100825.

The compounds of the formulas Ia, Ib, Ic, Id, Ie, If, Ig, Ih or Ij can be used alone or in admixture with one another or in the form of pharmaceutical preparations in humans or animals according to the invention for the therapy or prophylaxis of respiratory disorders, sleep-induced respiratory disorders, central and obstructive sleep apnea, Cheyne-Stoke's respiration, snoring, disturbed central respiratory drive, sudden child death, postoperative hypoxia and apnea, muscular respiratory disorders, respiratory disorders after long-term ventilation, respiratory disorders in high altitude adaptation, acute and chronic lung diseases with hypoxia and hypercapnia, neurodegenerative diseases such as dementia, Alzheimer's disease, Parkinson's disease, Huntington's disease, cancer, breast cancer, lung cancer , Colon cancer and prostate cancer are used.

pharmaceutical Preparations contain as active ingredient an effective dose at least one compound of the formula Ia, Ib, Ic, Id, Ie, If, Ig, Ih and / or Ij and / or a physiologically acceptable Salt of it beside usual, pharmaceutically acceptable carrier and excipients and optionally one or more others pharmacological agents. The pharmaceutical preparations usually contain from 0.1 to 90 percent by weight of the compounds of the formulas Ia to Ij and / or their physiologically tolerable Salts.

The Preparation of the pharmaceutical preparations can be known per se Done way. These are the active ingredients and / or their physiological acceptable Salts together with one or more solid or liquid galenic excipients and / or excipients in a suitable dosage form or dosage form then brought as medicines in human medicine or veterinary medicine can be used.

Drug, the compounds of the invention of the formulas Ia to Ij and / or their physiologically tolerable Salts may contain for example, orally, parenterally, intravenously, rectally, by inhalation or applied topically, with the preferred application depending on the individual case is.

Which Excipients for the desired Medicament formulation are suitable to those skilled in the reason his expertise. In addition to solvents, Gelling agents, suppository bases, tablet excipients and other drug carriers can for example, antioxidants, dispersants, emulsifiers, defoamers, flavoring agents, Preservatives, solubilizers, Means for obtaining a depot effect, buffers or dyes be used.

For an oral The active compounds are suitable for use with the appropriate ones Additives, such as carriers, Stabilizers or inert diluents, mixed and by the usual methods into suitable dosage forms, such as tablets, dragees, Plug capsules, watery, alcoholic or oily Solutions. As inert carrier can for example gum arabic, magnesia, magnesium carbonate, potassium phosphate, Lactose, glucose or starch, especially corn starch, be used. The preparation may be used both as dry as well as wet granules. As oily carriers or as a solvent For example, vegetable or animal oils may be considered like sunflower oil or cod liver oil. As a solvent for watery or alcoholic solutions for example, water, ethanol or sugar solutions or mixtures thereof, into consideration. Other excipients, also for other application forms, are, for example, polyethylene glycols and polypropylene glycols.

to subcutaneous, intramuscular or intravenous Application become the active compounds, if desired with the usual Substances such as solubilizers, Emulsifiers or other excipients, in solution, suspension or emulsion brought. As a solvent For example, water, physiological saline or Alcohols, for example ethanol, propanol, glycerol, into consideration, besides also sugar solutions like glucose or mannitol solutions, or mixtures of the various solvents mentioned.

When pharmaceutical formulation for administration in the form of aerosols or sprays are suitable for example solutions, Suspensions or emulsions of the active substances or their physiological acceptable Salts in a pharmaceutically acceptable solvent, in particular Ethanol or water, or a mixture of such solvents. The formulation may also contain other pharmaceuticals as needed Auxiliaries such as surfactants, emulsifiers and stabilizers as well as a Propellant gas included. Such a preparation usually contains the active substance in a concentration of about 0.1 to 10, especially about 0.3 to 3 weight percent.

The dosage of the active compounds to be administered according to the invention or of the physiologically tolerable salts thereof depends on the individual case and, as usual, must be adapted to the conditions of the individual case for optimum action. Of course, it depends on the frequency of administration and the potency and duration of action of each used for therapy or prophylaxis compounds, but also on the type and strength of the disease to be treated as well as gender, age, weight and individual Responsiveness of the person or animal to be treated and of whether acute or chronic therapy or prophylaxis is being carried out.

The Dosing of the TASK blocker of the formulas Ia, Ib, Ic, Id, Ie, If, Ig, Ih and / or Ij can usually be found in Range from 1 mg to 1 g per day and per human (at about 75 kg Body weight) vary, preferably from 5 to 750 mg per day and human. But it can also higher Cans be attached. The daily dose of the drug can be at once be administered or it can be applied to several, for example two, divided into three or four administrations.

Experimental part

List of abbreviations

• EDAC

  N-ethyl-N '- (3-dimethylaminopropyl) carbodiimide hydrochloride

  HOBT

  1-hydroxy-1H-benzotriazole

  THF

  tetrahydrofuran

Example 1: 2- (Butyl-1-sulfonylamino) -N- [1 (R) - (6-methoxypyridin-3-yl) -propyl] -benzamide and 2- (Butyl-1-sulfonylamino) -N- [1 (S) - (6-methoxy-pyridin-3-yl) propyl] benzamide

• a) 2- (Butyl-1-sulfonylamino) benzoic acid To a suspension of 20 g (146 mmol) 2-aminobenzoic acid in 250 ml ml of water was added 20 g (188 mmol) of sodium carbonate. Subsequently were Added dropwise 11.4 g (72.8 mmol) of butylsulfonyl chloride and the reaction mixture was stirred for 2 days at room temperature. It became more concentrated hydrochloric acid acidified Stirred for 3 hours at room temperature and sucked the failed product. After drying in vacuo 9.6 g of 2- (butyl-1-sulfonylamino) benzoic acid were obtained.
• b) 1- (6-methoxy-pyridin-3-yl) -propylamine To a solution of 10.2 ml of butyllithium (2.5 M solution in hexane; 25.5 mmol) in 50 ml of diethyl ether were added at -70 ° C 3 ml (23.2 mmol) of 5-bromo-2-methoxypyridine. After 10 minutes, 1.4 ml (19.5 mmol) of propionitrile. After 2 hours at -70 ° C was the Reaction mixture allowed to come slowly to room temperature. Then 2.2 g of sodium sulfate decahydrate was added and left stirring for 1 hour. After subsequent Addition of 5 g of magnesium sulfate was after brief stirring the salts were filtered off and the filtrate was concentrated. The residue was dissolved in 70 ml of methanol and at 0 ° C 1.1 g (28 mmol) of sodium borohydride was added. After stirring overnight, The reaction mixture was concentrated with concentrated hydrochloric acid pH 2 and concentrated on a rotary evaporator. The residue was added 10 ml of water and extracted once with diethyl ether. Subsequently became the aqueous phase saturated with sodium bicarbonate, concentrated in vacuo and the residue with ethyl acetate extracted. After drying and concentration of the ethyl acetate extracts were 1.4 g racemic 1- (6-methoxy-pyridin-3-yl) -propylamine obtained.
• c) 2- (Butyl-1-sulfonylamino) -N- [1 (R) - (6-methoxy-pyridin-3-yl) -propyl] -benzamide To a solution of 8.0 g (31.1 mmol) 2- (Butyl-1-sulfonylamino) benzoic acid in 250 ml of tetrahydrofuran were 4.4 g (32.7 mmol) of 1-hydroxy-1H-benzotriazole and 6.3 g (32.7 mmol) of N-ethyl-N ' - (3-dimethylaminopropyl) carbodiimide hydrochloride was added and the reaction mixture was stirred for 90 min. Then, a solution of 5.4 g (32.7 mmol) of racemic 1- (6-methoxypyridin-3-yl) -propylamine in 20 ml of tetrahydrofuran was added dropwise and stirred overnight. The reaction mixture was treated with 250 ml of water and extracted with 300 ml of ethyl acetate. The organic phase was extracted 5 times with 100 ml of saturated sodium bicarbonate solution and then dried over magnesium sulfate. 9.0 g of 2- (butyl-1-sulfonylamino) -N- [1- (6-methoxypyridin-3-yl) -propyl] -benzamide were obtained. The enantiomers were separated by preparative HPLC on a Chiralpak ADH column (250 x 4.6 mm); Eluent: heptane / etha nol / methanol 10: 1: 1; Temperature: 30 ° C; Flow rate: 1 ml / min. First, at a retention time of 5.9 minutes, 4.0 g of 2- (butyl-1-sulfonylamino) -N- [1 (R) - (6-methoxypyridin-3-yl) -propyl] -benzamide was eluted , After a mixed fraction, 3.0 g of 2- (butyl-1-sulfonylamino) -N- [1 (S) - (6-methoxypyridin-3-yl) -propyl] -benzamide were obtained at a retention time of 7.2 min receive.

2 g of the 2- (butyl-1-sulfonylamino) -N- [1 (R) - (6-methoxypyridin-3-yl) -propyl] -benzamide were dissolved in 9 ml of isopropanol in the heat, then became 8 ml of warm water was added and the reaction mixture allowed to cool slowly overnight. After filtration with suction at 0 ° C., 1.5 g of 2- (butyl-1-sulfonylamino) -N- [1 (R) - (6-methoxypyridin-3-yl) -propyl] -benzamide were obtained as colorless needle-shaped crystals ; Melting point 97 ° C. Example 2: 2 '- {[2- (4-Methoxy-phenyl) -acetylamino] -methyl} -biphenyl-2-carboxylic acid (2-pyridin-3-yl-ethyl) -amide

To a solution of 37.8 g (0.11 mol) of 2 '- (tert-butoxycarbonylamino-methyl) -biphenyl-2-carboxylic acid (Brandmeier, V .; Sauer, W.H.B .; Feigel, M .; Helv. Chim. Acta 1994, 77 (1), 70-85) in 550 ml of THF were added to 15.5 g (0.115 mol) HOBT and 21.9 g (0.115 mol) EDAC was added and the reaction mixture was 45 min at room temperature touched. Subsequently 14.0 g (0.115 mol) of 3- (2-aminoethyl) pyridine was added and it became overnight stirred at RT. After addition of 400 ml of water and 500 ml of ethyl acetate and intensive stirring, were the phases separated. The organic phase was washed once with 400 ml saturated Sodium chloride solution and 2 times with 400 ml of saturated sodium bicarbonate washed. After drying over Magnesium sulfate in the presence of activated carbon was filtered and concentrated on a rotary evaporator.

• a) 5-Fluor-2-(chinolin-8-sulfonylamino)-benzoesäure Eine Reaktionsmischung aus 10,0 g (64 mmol) 5-Fluor-2-amino-benzoesäure, 16,3 g (193 mmol) Natriumhydrogencarbonat und 16,3 g 8-Chinolinsulfonylchlorid in 325 ml Wasser und 325 ml Essigester wurde über Nacht bei Raumtemperatur gerührt. Die wässerige Phase wurde abgetrennt und einmal mit 50 ml Essigester extrahiert. Anschließend wurde die wässerige Phase mit konz. Salzsäure sauer gestellt und 2 h gerührt. Der ausgefallene Niederschlag wurde abgesaugt, im Vakuum getrocknet und man erhielt 19,5 g 5-Fluor-2-(chinolin-8-sulfonylamino)-benzoesäure.
• b) (S)-5-Fluor-2-(chinolin-8-sulfonylamino)-N-(1-phenyl-propyl)-benzamid Aus 5,5 g (15,9 mmol) 5-Fluor-2-(chinolin-8-sulfonylamino)-benzoesäure und 2,3 g (16,7 mmol) (S)-Phenylpropylamin wurden gemäß der Vorschrift in WO 02100825 5,7 g der Titelverbindung erhalten. Fp.: 163°C
• c) Zu einer Lösung von 5 g (S)-5-Fluor-2-(chinolin-8-sulfonylamino)-N-(1-phenyl-propyl)-benzamid in 120 ml Essigester wurden 2 ml einer 30-prozentigen Natriummethanolatlösung gegeben. Das ausgefallene Natriumsalz wurde abgesaugt und aus 25 ml Ethanol umkristallisiert und man erhielt 3,3 g (S)-5-Fluor-2-(chinolin-8-sulfonylamino)-N-(1-phenyl-propyl)-benzamid-Natriumsalz.

Beispiel 4: (S)-5-Methoxy-2-(4-methoxy-benzenesulfonylamino)-N-(1-phenyl-propyl)-benzamide

The resulting intermediate (40.7 g) was dissolved in 600 ml of methylene chloride and then 100 ml of trifluoroacetic acid was slowly added dropwise. After stirring overnight, the reaction mixture was concentrated in vacuo. The residue was treated with 250 ml of ethyl acetate and concentrated again to distill off excess trifluoroacetic acid. To the resulting crude product dissolved in 170 ml of methylene chloride, 72.8 ml (530 mmol) of triethylamine were added dropwise and 1 g of DMAP was added. Subsequently, at 5-10 ° C 18.7 g (100 mmol) of 4-Methoxyphenylessigsäurechlorid were added dropwise within 30 min, and the mixture was stirred overnight at room temperature. After addition of 150 ml of water and intensive stirring, the phases were separated and the organic phase was washed once with 100 ml of sodium chloride solution, once with 25 ml of 1 M hydrochloric acid and twice with 100 ml of saturated sodium bicarbonate solution. After drying over magnesium sulfate and charcoal, it was concentrated in vacuo. The resulting oil was dissolved in acetonitrile while hot and allowed to crystallize out slowly. There were 21.5 g of 2 '- {[2- (4-methoxy-phenyl) -acetylamino] -methyl} -biphenyl-2-carboxylic acid (2-pyridin-3-yl-ethyl) -amide, mp 116 ° C, received. Example 3: (S) -5-Fluoro-2- (quinoline-8-sulfonylamino) -N- (1-phenyl-propyl) -benzamide sodium salt

• a) 5-Fluoro-2- (quinoline-8-sulfonylamino) benzoic acid A reaction mixture of 10.0 g (64 mmol) of 5-fluoro-2-aminobenzoic acid, 16.3 g (193 mmol) of sodium bicarbonate and 16.3 g of 8-quinolinesulfonyl chloride in 325 ml of water and 325 ml of ethyl acetate was added overnight Room temperature stirred. The aqueous phase was separated and extracted once with 50 ml of ethyl acetate. Subsequently, the aqueous phase was acidified with conc. Hydrochloric acid and stirred for 2 h. The resulting precipitate was filtered off with suction, dried under reduced pressure, and 19.5 g of 5-fluoro-2- (quinoline-8-sulfonylamino) benzoic acid were obtained.
• b) (S) -5-Fluoro-2- (quinoline-8-sulfonylamino) -N- (1-phenyl-propyl) -benzamide From 5.5 g (15.9 mmol) of 5-fluoro-2- (quinoline 8-sulfonylamino) benzoic acid and 2.3 g (16.7 mmol) of (S) -phenylpropylamine were obtained according to the procedure in WO 02100825, 5.7 g of the title compound. Mp .: 163 ° C
• c) To a solution of 5 g of (S) -5-fluoro-2- (quinoline-8-sulfonylamino) -N- (1-phenyl-propyl) -benzamide in 120 ml of ethyl acetate was added 2 ml of a 30% sodium methoxide solution , The precipitated sodium salt was filtered off with suction and recrystallized from 25 ml of ethanol to give 3.3 g of (S) -5-fluoro-2- (quinoline-8-sulfonylamino) -N- (1-phenyl-propyl) -benzamide sodium salt.

Example 4: (S) -5-Methoxy-2- (4-methoxy-benzenesulfonylamino) -N- (1-phenyl-propyl) -benzamide

The compound was obtained according to the synthesis instructions given in WO02088073. Example 5: 2 '- (α- (S) -methyl-benzyloxycarbonyl-aminomethyl) -biphenyl-2-carboxylic acid 2- (2- (R) -hydroxy-propylamide)

The compound was obtained according to the synthesis instructions given in WO0125189. Example 6: 5-Chloro-2 '- {[2- (4-methoxy-phenyl) -acetylamino] -methyl} -biphenyl-2-carboxylic acid 2,4-difluoro-benzylamide

The compound was obtained according to the synthesis instructions given in WO0125189. Example 7: Benzyl {2 '- [methyl- (2-pyridin-2-yl-ethyl) -carbamoyl] -biphenyl-2-ylmethyl} -carbamate

The compound was obtained according to the synthesis instructions given in WO0125189. Example 8: 3- (2 - {[2- (4-Methoxy-phenyl) -acetylamino] -methyl} -phenyl) -thiophene-2-carboxylic acid-2,4-difluoro-benzylamide

The compound was obtained according to the synthesis instructions given in WO0248131. Example 9: 5- (2 - {[2- (4-Methoxy-phenyl) -acetylamino] -methyl} -phenyl) -furan-2-carboxylic acid-2,4-difluoro-benzylamide

The compound was obtained according to the synthesis instructions given in WO0248131. Example 10: 2- (2 - {[2- (4-Methoxy-phenyl) -acetylamino] -methyl} -phenyl) -furan-3-carboxylic acid (3-methyl-butyl) -amide

The compound was obtained according to the synthesis instructions given in WO0248131. Example 11: 2- (2 - {[2- (4-Methoxy-phenyl) -acetylamino] -methyl} -phenyl) -thiophene-3-carboxylic acid-2,4-difluoro-benzylamide

The compound was obtained according to the synthesis instructions given in WO0248131. Example 12: {2- [2- (2-Pyridin-2-yl-ethylcarbamoyl) -pyridin-3-yl] -benzyl} -carbamic acid (S) -1-phenylethyl ester

The compound was obtained according to the synthesis instructions given in WO 0246162. Example 13: 3- {2 - [((R) -3-Phenyl-butyrylamino) -methyl] -phenyl} -pyridine-2-carboxylic acid-cyclopropylmethyl-amide

The compound was obtained according to the synthesis instructions given in WO0246162. Example 14: {2- [3- (2,4-Difluoro-benzylcarbamoyl) -pyridin-2-yl] -benzyl} -carbamic acid benzyl ester

The compound was obtained according to the synthesis instructions given in WO0246162. Example 15: Benzyl {4- [3- (3-methyl-butylcarbamoyl) -phenyl] -pyridin-3-ylmethyl} -carbamate

The compound was obtained according to the synthesis instructions given in WO0246162. Example 16: 2 '- {[3- (4-Methoxy-phenyl) -propionylamino] -methyl} -6-methyl-biphenyl-3-carboxylic acid (3-methyl-butyl) -amide

The compound was obtained according to the synthesis instructions given in WO0244137. Example 17: N-Indan-1-yl-2-methyl-5- (3-methyl-butylsulfamoyl) -benzamide

The Compound was obtained according to the in WO01 / 00573 specified synthesis instructions.

pharmacological investigations

Determination of activity on the TASK-1 channel in Xenopus oocytes

TASK-1 mouse or human channels were expressed in Xenopus oocytes. For this purpose, oocytes from Xenopus laevis were first isolated and defolliculated. Subsequently, in these oocytes in vitro syn injected TASK-1 coding RNA injected. After 2 days of TASK-1 protein expression, TASK-1 currents were measured on the oocytes using the two-microelectrode voltage clamp technique. The TASK-1 channels were generally activated with 250 ms voltage jumps to 40 mV. The bath was rinsed with a solution of the following composition: NaCl 96 mM, KCl 2 mM, CaCl ₂ 1.8 mM, MgCl ₂ 1 mM, HEPES 5 mM (titrated to pH 7.4 with NaOH). These experiments were carried out at room temperature. For data collection and analysis, Geneclamp amplifiers (Axon Instruments, Foster City, USA) and MacLab D / A converters and software (AD Instruments, Castle Hill, Australia) were used. The substances according to the invention were tested by adding them to the bath solution in different concentrations. The effects of the substances were calculated as percent inhibition of the TASK-1 control current obtained when no substance was added to the solution. The data were then fitted to the Hill equation to determine the half-maximal inhibitory concentrations (IC ₅₀ values) for the respective substances.

In this way, the following IC ₅₀ values were determined for the compounds listed below:

Determination of activity on the TASK-1 channel with FLIPR technology

On CHO cells in which the human TASK-1 channel is expressed, the inhibition of the human TASK-1 current by the example compounds at a concentration of 10 μmol / l was measured by means of a FLIPR assay. Hereby, the following inhibition values were obtained:

Determination of activity on the TASK-3 channel through patch clamp tests

At CHO cells in which the human TASK-3 channel is expressed the inhibition of human TASK-3 with the help of the patch-clamp technique Current measured by the example compounds. For the production of the TASK-3 cell line was the human TASK-3 cDNA (Genbank, Accession Number AF248241) into the eukaryotic expression vector p658, which carries a DHFR (dihydrofolate reductase) resistance gene [Reference: Gene 1994 (149), 341-344, 1994]. CHO (Chinese Hamster Ovary) DHFR-minus cells were identified with the TASK-3 expression construct using the Fugene reagent (Roche Biochemicals) and according to the manufacturer's instructions transfected.

recombinant DHFR-positive cells were submerged in MEM (minimal essential medium) Addition of 10% dialyzed calf serum cultured. Resulting cell clones were generated using a fluorescence-based activity assay in the FlexStation (Molecular Devices) and with the membrane potential-sensitive Dye (Molecular Devices FMP Dye Kit) on the expression of TASK-3 checked out. A functional expression of TASK-3 was by the increase of the fluorescence signal after addition of 50 mM KCl to the cells showing a depolarization of the membrane potential corresponds, proved. TASK-3 positive cell clones were subsequently investigated for resulting potassium currents using the patch-clamp technique. The cell clone CHO-244-8-1 was used as a representative cell clone for subsequent Investigations selected.

To examine the substances, the cells were placed in a measuring chamber mounted on an inverted microscope. A micropipette drawn from borosilicate glass was gently pressed against a cell under optical control. By light suction, a high-resistance seal between glass pipette and cell was made. By briefly aspirating the membrane patch was ruptured and made a whole cell lead. By applying voltage jumps from -140 mV to +80 mV, the electric current under voltage clamping conditions with the help of an electronic Patch-Clamp amplifier (Axopatch-1D) registered. The effect of a substance was registered by adding in ascending concentrations in the bath solution. The concentration of the half-maximal inhibition of the current (IC ₅₀ value) was determined by curve fitting with the mathematical hill equation.

The following IC ₅₀ values were determined:

examination the effect on the respiration in the rabbit

One Respiratory arrest was due to infusion of the narcotic propofol, 10 mg / kg / min, in rabbits. The time from the start of the propofol infusion to respiratory arrest was detained. In the control of the respiratory arrest occurred about 2.92 min, after administration of 10 mg / kg i.v. the connection of the Example 1, the onset of respiratory arrest was delayed and occurred only 5.63 min after the start of the propofol infusion (p <0.001, n = 13).

Examination of compatibility and the effect on respiration in the rat

The Compound of Example 1 showed by oral administration of 1000 mg / kg in rats a significant stimulation of respiration (minute volume and respiratory rate) without other side effects being observed.

Claims (8)

Use of Kv1.5 inhibitors for production a drug for the therapy or prophylaxis of respiratory disorders, sleep-related respiratory disorders, central and obstructive sleep apnea, Cheyne-Stoke's breathing, snoring, disturbed central respiratory drive, sudden Infant death, postoperative hypoxia and apnea, muscular-related Respiratory disorders, respiratory disorders after long-term ventilation, respiratory disorders in adaptation in high mountains, acute and chronic lung diseases with hypoxia and hypercapnia, neurodegenerative diseases, dementia, Alzheimer's disease, Parkinson's disease, Huntington's disease, cancer, Breast cancer, lung cancer, colon cancer and prostate cancer. Use according to claim 1 of compounds of the formulas Ia

where R (8) is either a 1-indanyl radical of the formula II or a 2-indanyl radical of the formula III,

and in which: R (1) and R (2) R (20) -C _r H _2r, where a CH ₂ group of the group C _r H _2r may be independently replaced by -O-, -CH = CH- , -C≡C-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO ₂ -, -NR (21) - or -CONR (21); R (21) is hydrogen or alkyl having 1, 2 or 3 C atoms; R (20) H, CH ₃ , CH ₂ F, CHF ₂ , CF ₃ , C ₂ F ₅ , C ₃ F ₇ , cycloalkyl with 3, 4, 5, 6, 7 or 8 C atoms, NR (22) R (23), -CONR (22) R (23), -OR (24), -COOR (24), phenyl or an N-containing heterocycle having 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms, wherein phenyl and the N-containing heterocycle are unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH Methyl, ethyl, hydroxymethyl, hydroxyethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; R (22) and R (23) independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 C atoms; or R (22) and R (23) together form a chain of 4 or 5 methylene groups, of which one CH ₂ group is represented by -O-, -S-, -NH-, -N (methyl) - or -N (benzyl ) - can be replaced; R (24) is hydrogen or alkyl having 1, 2 or 3 C atoms; r is zero, 1, 2, 3, 4, 5, 6, 7 or 8; or R (1) and R (2) together form a chain of 4 or 5 methylene groups, of which one CH ₂ group is represented by -O-, -S-, -NH-, -N (methyl) - or -N (benzyl ) - can be replaced; R (3), R (4), R (5) and R (6) independently of one another are hydrogen, F, Cl, Br, I, alkyl having 1, 2, 3, 4 or 5 C atoms, cycloalkyl having 3, 4, 5, 6, 7 or 8 C atoms, CN, CF ₃ , NO ₂ , OR (25) or NR (26) R (27); R (25) is hydrogen, alkyl having 1, 2, 3 or 4 carbon atoms, a fluorinated alkyl radical of the formula -C _x H _2x CF _y H _3-y or phenyl, which is unsubstituted or substituted with 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF _3, NO _2, CN, NH _2, OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; x 0, 1, 2 or 3; y is 1, 2 or 3; R (26) and R (27) independently of one another are hydrogen or alkyl having 1, 2, 3 or 4 C atoms; or R (26) and R (27) together form a chain of 4 or 5 methylene groups, of which one CH ₂ group is represented by -O-, -S-, -NH-, -N (methyl) - or -N (benzyl ) - can be replaced; R (7) is hydrogen or alkyl having 1, 2, 3 or 4 C atoms; R (9) is hydrogen, OR (28) or OCOR (28); R (28) is hydrogen or alkyl having 1, 2, 3 or 4 C atoms; R (10) and R (11) independently of one another denote hydrogen or alkyl having 1, 2, 3 or 4 C atoms; R (12), R (13), R (14) and R (15) independently of one another are hydrogen, F, Cl, Br, I, alkyl having 1, 2, 3, 4 or 5 C atoms, cycloalkyl having 3, 4, 5, 6, 7 or 8 C atoms, -CN, -CF _3, -C ₂ F _5, -C ₃ F _7, -N _3, -NO _2, -YC _s H _2s -R (29), phenyl, thienyl , Furyl or an N-containing heterocycle having 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms, wherein phenyl, thienyl, furyl and the N-containing heterocycle are unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF _3, NO _2, CN, NH _2, OH, methyl, ethyl, methoxy, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; Y is -O-, -CO-, -CO-O-, -O-CO-, -S-, -SO-, -SO ₂ -, -O-SO ₂ -, -SO ₂ NR (30) -, -CONR (30) - or -NR (30) CO-, where the linkage to the backbone is in each case via the atom on the left; R (30) is hydrogen or alkyl having 1, 2 or 3 C atoms; s is zero, 1, 2, 3, 4, 5 or 6; R (29) is hydrogen, methyl, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , cycloalkyl having 3, 4, 5, 6, 7 or 8 C atoms, -OR (31), -COOR (31), -NR (32) R (33), -CONR (32) R (33), phenyl or an N-containing heterocycle having 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms, wherein Phenyl and the N-containing heterocycle are unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, NH ₂ , OH, methyl, ethyl, methoxy, Dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; R (31) is hydrogen or alkyl having 1, 2 or 3 C atoms; R (32) and R (33) independently of one another denote hydrogen or alkyl having 1, 2, 3 or 4 C atoms; or R (32) and R (33) together form a chain of 4 or 5 methylene groups, of which one CH ₂ group is represented by -O-, -S-, -NH-, -N (CH ₃ ) - or -N ( Benzyl) - may be replaced; and / or compounds of the formula Ib

wherein R (1) is C (O) OR (9), SO ₂ R (10), COR (11), C (O) NR (12) R (13) or C (S) NR (12) R (13); R (9) C _x H _2x -R (14); x is 0, 1, 2, 3, or 4, where x can not be 0 when R (14) is OR (15) or SO ₂ Me; R (14) is alkyl having 1, 2, 3, 4, 5 or 6 C atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9, 10 or 11 carbon atoms, CF _3, C ₂ F ₅ , C ₃ F ₇ , CH ₂ F, CHF ₂ , OR (15), SO ₂ Me, phenyl, naphthyl, biphenylyl, furyl, thienyl or an N-containing heteroaromatic 1, 2, 3, 4, 5, 6 , 7, 8 or 9 C atoms, wherein phenyl, naphthyl, biphenylyl, furyl, thienyl and the N-containing heteroaromatic are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I , CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, Dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; R (15) is alkyl having 1, 2, 3, 4 or 5 C atoms, cycloalkyl having 3, 4, 5 or 6 C atoms, CF ₃ or phenyl, which is unsubstituted or substituted by 1, 2 or 3 substituents from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; R (10), R (11) and R (12) are independently defined as R (9); R (13) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms or CF ₃ ; R (2) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms or CF ₃ ; R (3) C _y H _2y -R (16); y is 0, 1, 2, 3 or 4, where y can not be 0 if R (16) OR (17) or SO ₂ Me; R (16) is alkyl having 1, 2, 3, 4, 5 or 6 C atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9, 10 or 11 C atoms, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , CH ₂ F, CHF ₂ , OR (17), SO ₂ Me, phenyl, naphthyl, furyl, thienyl or an N-containing heteroaromatic with 1, 2, 3, 4, 5, 6, 7, 8 or 9 C atoms, wherein phenyl, naphthyl, furyl, thienyl and the N-containing heteroaromatic are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; R (17) is hydrogen, alkyl having 1, 2, 3, 4 or 5 C atoms, cycloalkyl having 3, 4, 5 or 6 C atoms, CF ₃ , phenyl or 2-, 3- or 4-pyridyl, wherein phenyl or 2-, 3- or 4-pyridyl are unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF _3, OCF _3, NO _2, CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; or R (3) CHR (18) R (19); R (18) is hydrogen or C _z H _2z -R (16) wherein R (16) is defined as above; z is 0, 1, 2 or 3; R (19) COOH, CONH ₂ , CONR (20) R (21), COOR (22), CH ₂ OH; R (20) is hydrogen, alkyl having 1, 2, 3, 4 or 5 C atoms, C _v H _2v -CF ₃ or C _w N _2w- phenyl, where the phenyl ring is unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF _3, OCF _3, NO _2, CN, COOMe, CONH _2, COMe, NH _2, OH, alkyl having 1, 2, 3 or 4 carbon atoms, Alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; v is 0, 1, 2 or 3; w is 0, 1, 2 or 3; R (21) is hydrogen or alkyl having 1, 2, 3, 4 or 5 C atoms; R (22) is alkyl having 1, 2, 3, 4 or 5 C atoms; R (4) is hydrogen, alkyl having 1, 2, 3, 4, 5 or 6 C atoms or CF ₃ ; or R (3) and R (4) together form a chain of 4 or 5 methylene groups, of which one methylene group is replaced by -O-, -S-, -NH-, -N (methyl) - or -N (benzyl) - can be; R (5), R (6) R (7) and R (8) independently of one another are hydrogen, F, Cl, Br, I, CF _3, NO _2, CN, COOMe, CONH _2, COMe, NH _2, OH , Alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl or methylsulfonylamino; R (30) and R (31) independently of one another are hydrogen or alkyl having 1, 2 or 3 C atoms; or R (30) and R (31) together form a chain of 2 methylene groups; and / or compounds of the formula Ic

wherein: A1, A2, A3, A4, A5, A6, A7 and A8 independently of one another denote nitrogen, CH or CR ₅ , at least four of these groups being CH; R (1) C (O) OR (9), SO ₂ R (10), COR (11), C (O) NR (12) R (13) or C (S) NR (12) R (13) ; R (9), R (10), R (11) and R (12) independently of one another are C _x H _2x -R (14); x 0, 1, 2, 3 or 4, where x can not be 0 when R (14) is OR (15) or SO ₂ Me; R (14) is alkyl having 1, 2, 3, 4, 5 or 6 C atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9, 10 or 11 C atoms, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , CH ₂ F, CHF ₂ , OR (15), SO ₂ Me, phenyl, naphthyl, biphenylyl, furyl, thienyl or an N-containing heteroaromatic 1, 2, 3, 4, 5, 6 , 7, 8 or 9 C atoms, wherein phenyl, naphthyl, biphenylyl, furyl, thienyl and the N-containing heteroaromatic are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I , CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, Dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; R (15) is alkyl having 1, 2, 3, 4 or 5 C atoms, cycloalkyl having 3, 4, 5 or 6 C atoms, CF ₃ or phenyl, which is unsubstituted or substituted by 1, 2 or 3 substituents from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; R (13) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms or CF ₃ ; R (2) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms or CF ₃ ; R (3) C _y H _2y -R (16); y is 0, 1, 2, 3 or 4, where y can not be 0 if R (16) OR (17) or SO ₂ Me; R (16) is alkyl having 1, 2, 3, 4, 5 or 6 C atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9, 10 or 11 C atoms, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , CH ₂ F, CHF ₂ , OR (17), SO ₂ Me, phenyl, naphthyl, furyl, thienyl or an N-containing heteroaromatic having 1, 2, 3, 4, 5, 6, 7 , 8 or 9 C-atoms, wherein phenyl, naphthyl, furyl, thienyl and the N-containing heteroaromatic are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, Methylsulfonyl and methylsulfonylamino. R (17) is hydrogen, alkyl having 1, 2, 3, 4 or 5 C atoms, cycloalkyl having 3, 4, 5 or 6 C atoms, CF ₃ , phenyl or 2-, 3- or 4-pyridyl, wherein Phenyl or 2-, 3- or 4-pyridyl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; or R (3) CHR (18) R (19); R (18) is hydrogen or C _z H _2z -R (16) wherein R (16) is defined as above; z is 0, 1, 2 or 3; R (19) COOH, CONH ₂ , CONR (20) R (21), COOR (22) or CH ₂ OH; R (20) is hydrogen, alkyl having 1, 2, 3, 4 or 5 carbon atoms, C _v H _2v -CF ₃ or C _w H _2w -phenyl, where the phenyl ring is unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1 , 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; v is 0, 1, 2 or 3; w is 0, 1, 2 or 3; R (21) is hydrogen or alkyl having 1, 2, 3, 4 or 5 C atoms; R (22) is alkyl having 1, 2, 3, 4 or 5 C atoms; R (4) is hydrogen, alkyl having 1, 2, 3, 4, 5 or 6 C atoms or CF ₃ ; or R (3) and R (4) together form a chain of 4 or 5 methylene groups, of which one methylene group is replaced by -O-, -S-, -NH-, -N (methyl) - or -N (benzyl) - can be; R (5) F, Cl, Br, I, CF _3, NO _2, CN, COOMe, CONH _2, COMe, NH _2, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2 , 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl or methylsulfonylamino, wherein in the event that several radicals A1 to A8 have the meaning CR (5), the radicals R (5) are independently defined; R (30) and R (31) independently of one another are hydrogen or alkyl having 1, 2 or 3 C atoms; or R (30) and R (31) together form a chain of 2 methylene groups; and / or compounds of the formula Id

in which: A1, A2, A3, A4, A5, A6, A7 and A8 independently of one another denote nitrogen, CH or CR (5), where at least one of these groups is nitrogen and at least 4 of these groups are CH; R (1) C (O) OR (9), SO ₂ R (10), COR (11), C (O) NR (12) R (13) or C (S) NR (12) R (13) ; R (9), R (10), R (11) and R (12) independently of one another are C _x H _2x -R (14); x 0, 1, 2, 3 or 4, where x can not be 0 if R (14) OR (15) or SO ₂ Me; R (14) is alkyl having 1, 2, 3, 4, 5 or 6 C atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9, 10 or 11 C atoms, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , CH ₂ F, CHF ₂ , OR (15), SO ₂ Me, phenyl, naphthyl, biphenylyl, furyl, thienyl or an N-containing heteroaromatic 1, 2, 3, 4, 5, 6 , 7, 8 or 9 C atoms, wherein phenyl, naphthyl, biphenylyl, furyl, thienyl and the N-containing heteroaromatic are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I , CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, Dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; R (15) is alkyl having 1, 2, 3, 4 or 5 C atoms, cycloalkyl having 3, 4, 5 or 6 C atoms, CF ₃ or phenyl, which is unsubstituted or substituted by 1, 2 or 3 substituents from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; R (13) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms or CF ₃ ; R (2) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms or CF ₃ ; R (3) C _y H _2y -R (16); y is 0, 1, 2, 3 or 4, where y can not be 0 when R (16) is OR (17) or SO ₂ Me; R (16) is alkyl having 1, 2, 3, 4, 5 or 6 C atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9, 10 or 11 C atoms, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , CH ₂ F, CHF ₂ , OR (17), SO ₂ Me, phenyl, naphthyl, furyl, thienyl or an N-containing heteroaromatic having 1, 2, 3, 4, 5, 6, 7 , 8 or 9 C-atoms, wherein phenyl, naphthyl, furyl, thienyl and the N-containing heteroaromatic are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, Methylsulfonyl and methylsulfonylamino; R (17) is hydrogen, alkyl having 1, 2, 3, 4 or 5 C atoms, cycloalkyl having 3, 4, 5 or 6 C atoms, CF ₃ , phenyl or 2-, 3- or 4-pyridyl, wherein Phenyl or 2-, 3- or 4-pyridyl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH _2, COMe, NH _2, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; or R (3) CHR (18) R (19); R (18) is hydrogen or C _z H _2z -R (16) wherein R (16) is defined as above; z is 0, 1, 2 or 3; R (19) COOH, CONH ₂ , CONR (20) R (21), COOR (22) or CH ₂ OH; R (20) is hydrogen, alkyl having 1, 2, 3, 4 or 5 C atoms, C _v H _2v -CF ₃ or C _w H _2w- phenyl, where the phenyl ring is unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, Alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; v is 0, 1, 2 or 3; w is 0, 1, 2 or 3; R (21) is hydrogen or alkyl having 1, 2, 3, 4 or 5 C atoms; R (22) is alkyl having 1, 2, 3, 4 or 5 C atoms; R (4) is hydrogen, alkyl having 1, 2, 3, 4, 5 or 6 C atoms or CF ₃ ; or R (3) and R (4) together form a chain of 4 or 5 methylene groups, of which one methylene group is replaced by -O-, -S-, -NH-, -N (methyl) - or -N (benzyl) - can be; R (5) independently of one another are F, Cl, Br, I, CF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1 , 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl or methylsulfonylamino, wherein in the event that several radicals A1 to A8 have the meaning CR (5), the radicals R (5) are defined independently of one another. R (30) and R (31) independently of one another are hydrogen or alkyl having 1, 2 or 3 C atoms; or R (30) and R (31) together represent oxygen or a chain of 2 methylene groups; and / or compounds of the formula Ie or If

wherein X is oxygen or sulfur; R (1) C (O) OR (9), SO ₂ R (10), COR (11), C (O) NR (12) R (13) or C (S) NR (12) R (13) ; R (9), R (10) R (11) and R (12) independently of one another C _x H _2x -R (14); x is 0, 1, 2, 3, or 4, where x can not be 0 when R (14) is OR (15) or SO ₂ Me; R (14) is alkyl having 1, 2, 3, 4, 5 or 6 C atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9, 10 or 11 C atoms, CF ₃ , C ₂ F ₅ , C ₃ F ₇ , CH ₂ F, CHF ₂ , OR (15), SO ₂ Me, phenyl, naphthyl, biphenylyl, furyl, thienyl or an N-containing heteroaromatic 1, 2, 3, 4, 5, 6 , 7, 8 or 9 C atoms, wherein phenyl, naphthyl, biphenylyl, furyl, thienyl and the N-containing heteroaromatic are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I , CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, Dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; R (15) is alkyl having 1, 2, 3, 4 or 5 C atoms, cycloalkyl having 3, 4, 5 or 6 C atoms, CF ₃ or phenyl, which is unsubstituted or substituted by 1, 2 or 3 substituents from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; R (13) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms or CF ₃ ; R (2) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms or CF ₃ ; R (3) C _y H _2y -R (16); y is 0, 1, 2, 3 or 4, where y can not be 0 when R (16) is OR (17) or SO ₂ Me; R (16) is alkyl having 1, 2, 3, 4, 5 or 6 C atoms, cycloalkyl having 3, 4, 5, 6, 7, 8, 9, 10 or 11 C atoms, CF ₃ , C ₂ F _5, C ₃ F _7, CH ₂ F, CHF _2, oR (17), SO ₂ Me, phenyl, naphthyl, furyl, thienyl or an N-containing heteroaromatic having 1, 2, 3, 4, 5, 6, 7 , 8 or 9 C-atoms, wherein phenyl, naphthyl, furyl, thienyl and the N-containing heteroaromatic are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, Methylsulfonyl and methylsulfonylamino. R (17) is hydrogen, alkyl having 1, 2, 3, 4 or 5 C atoms, cycloalkyl having 3, 4, 5 or 6 C atoms, CF _3, phenyl or 2-, 3- or 4-pyridyl, where Phenyl or 2-, 3- or 4-pyridyl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, Alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; or R (3) CHR (18) R (19); R (18) is hydrogen or C _z H _2z -R (16) wherein R (16) is defined as above; z is 0, 1, 2 or 3; R (19) COOH, CONH ₂ , CONR (20) R (21), COOR (22) or CH ₂ OH; R (20) is hydrogen, alkyl having 1, 2, 3, 4 or 5 C atoms, C _v H _2v -CF ₃ or C _w N _2w- phenyl, where the phenyl ring is unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1 , 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; v is 0, 1, 2 or 3; w is 0, 1, 2 or 3; R (21) is hydrogen or alkyl having 1, 2, 3, 4 or 5 C atoms; R (22) is alkyl having 1, 2, 3, 4 or 5 C atoms; R (4) is hydrogen, alkyl having 1, 2, 3, 4, 5 or 6 C atoms or CF ₃ ; or R (3) and R (4) together form a chain of 4 or 5 methylene groups, of which one methylene group is replaced by -O-, -S-, -NH-, -N (methyl) - or -N (benzyl) - can be; R (5), R (6) and R (7) independently of one another are hydrogen, F, Cl, Br, I, CF ₂ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl with 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl or methylsulfonylamino. R (30) and R (31) independently of one another are hydrogen or alkyl having 1, 2 or 3 C atoms; or R (30) and R (31) together represent oxygen or a chain of 2 methylene groups; and / or compounds of the formula Ig

wherein: R (1) is (CH ₂ ) _x -R (8) x 0, 1, 2, 3, 4 or 5; R (8) is phenyl, thienyl or furanyl, where phenyl, thienyl and furanyl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH _2, COMe, NH _2, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; R (2) is hydrogen or alkyl having 1, 2 or 3 C atoms; R (3) is hydrogen or alkyl having 1, 2 or 3 C atoms; R (4) is alkyl having 3, 4, 5, 6 or 7 C atoms, cycloalkyl having 3, 4, 5, 6 or 7 C atoms, phenyl, naphthyl or heteroaryl, where phenyl and heteroaryl are unsubstituted or substituted by 1 , 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl with 1, 2, 3 or 4 C. Atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino, methylsulfonyl and methylsulfonylamino; R (5), R (6) and R (7) independently of one another are F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, OH, alkyl with 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; and / or compounds of the formula Ih

in which mean:

A -C _n H _2n -; n is 0, 1, 2, 3, 4 or 5; O oxygen; D is a bond or oxygen; E -C _m H _2m -; m is 0, 1, 2, 3, 4 or 5; R (8) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms or C _p H _2p- R (14); p is 0, 1, 2, 3, 4 or 5; R (14) cycloalkyl having 3, 4, 5 or 6 C atoms, aryl or heteroaryl, where aryl and heteroaryl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF _3, OCF _3, NO _2, CN, COOMe, CONH _2, COMe, NH _2, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, dimethylamino Sulfamoyl, methylsulfonyl and methylsulfonylamino; R (9) is hydrogen or alkyl having 1, 2, 3, 4, 5 or 6 C atoms; R (10) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms, cycloalkyl having 3, 4, 5 or 6 C atoms, aryl or heteroaryl, where aryl and heteroaryl are unsubstituted or substituted by 1, 2 or 3 Substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C-atoms Alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; R (11) cycloalkyl having 3, 4, 5 or 6 C atoms, phenyl, naphthyl, thienyl, furyl, pyridyl, pyrazinyl, pyridazinyl or pyrimidyl, wherein phenyl, naphthyl, thienyl, furyl, pyridyl, pyrazinyl, pyridazinyl and pyrimidyl unsubstituted or are substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF _3, OCF _3, NO _2, CN, COMe, NH _2, OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; R (12) alkyl having 1, 2, 3 or 4 C atoms, cycloalkyl having 3, 4, 5 or 6 C atoms, aryl or heteroaryl, wherein aryl and heteroaryl are unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy with 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; R (13) C _p H _2p- R (14 '); p is 0, 1, 2, 3, 4 or 5; R (14 ') is cycloalkyl having 3, 4, 5 or 6 C atoms, tetrahydrofuranyl, tetrahydropyranyl, aryl or heteroaryl, wherein aryl and heteroaryl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl , Br, I, CF _3, OCF _3, NO _2, CN, COOMe, CONH _2, COMe, NH _2, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; R (15) cycloalkyl having 3, 4, 5, 6, 7 or 8 C atoms; R (2) is hydrogen or alkyl having 1, 2, 3 or 4 C atoms; R (3) alkyl having 3, 4, 5, 6 or 7 carbon atoms, cycloalkyl having 3, 4, 5 or 6 carbon atoms, phenyl or naphthyl, wherein phenyl or naphthyl are unsubstituted or substituted by 1, 2 or 3 Substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C-atoms Alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; R (4), R (5), R (6) and R (7) independently of one another are hydrogen, F, Cl, Br, I, CF ₃ , OCF ₃ , OCHF ₂ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; and or compounds of formula Ij

in which mean:

A -C _n H _2n -; n = 0, 1, 2, 3, 4 or 5; D is a bond or -O-; E -C _m H _2m -; m = 0, 1, 2, 3, 4 or 5; R (8) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms or C _p H _2p- R (14); p is 0, 1, 2, 3, 4 or 5; R (14) is phenyl, naphthyl or heteroaryl, where phenyl, naphthyl and heteroaryl are unsubstituted or substituted with 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF _3, OCF _2, NO _2, CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; R (9) is hydrogen or alkyl having 1, 2, 3, 4, 5 or 6 C atoms; R (10) is hydrogen, alkyl having 1, 2, 3 or 4 C atoms, phenyl, naphthyl or heteroaryl, where phenyl, naphthyl and heteroaryl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; R (11) cycloalkyl having 3, 4, 5 or 6 C atoms, phenyl, naphthyl, thienyl, furyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl or cinnolinyl, wherein Phenyl, naphthyl, thienyl, furyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, quinolyl, isoquinolyl, phthalazinyl, quinoxalinyl, quinazolinyl or cinnolinyl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF _3, OCF _3, NO _2, CN, COMe, NH _2, OH, alkyl having 1, 2, 3 or 4 carbon atoms, alkoxy having 1, 2, 3 or 4 carbon atoms, Dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; R (12) alkyl having 1, 2, 3 or 4 C atoms, alkynyl having 1, 2, 3 or 4 C atoms, cycloalkyl having 3, 4, 5 or 6 C atoms, phenyl, naphthyl or heteroaryl, wherein Phenyl, naphthyl and heteroaryl are unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe, NH ₂ , OH, Alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; R (13) C _p H _2p- R (14); p is 0, 1, 2, 3, 4 or 5; R (15) cycloalkyl having 3, 4, 5, 6, 7 or 8 C atoms; R (2) is hydrogen or alkyl having 1, 2, 3 or 4 C atoms; R (3) heteroaryl, wherein heteroaryl is unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of F, Cl, Br, I, CF ₃ , OCF ₃ , NO ₂ , CN, COOMe, CONH ₂ , COMe , NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; R (4), R (5), R (6) and R (7) independently of one another are hydrogen, F, Cl, Br, I, CF _3, OCF _3, NO _2, CN, COOMe, CONH _2, COMe, NH ₂ , OH, alkyl having 1, 2, 3 or 4 C atoms, alkoxy having 1, 2, 3 or 4 C atoms, dimethylamino, sulfamoyl, methylsulfonyl and methylsulfonylamino; and / or physiologically acceptable salts of the compounds of the formula Ia, Ib, Ic, Id, Ie, If, Ig, Ih or Ij. Use according to claim 1 and / or 2 for the manufacture of a medicament for therapy or Prophylaxis of respiratory disorders, sleep-related respiratory disorders, central and obstructive sleep apnea, Cheyne-Stoke's breathing, snoring, disturbed central respiratory drive, sudden Infant death, postoperative hypoxia and apnea, muscular-related Respiratory disorders, respiratory disorders after long-term ventilation, respiratory disorders with adaptation in high mountains and acute and chronic lung diseases with hypoxia and hypercapnia. Use according to one or more of the claims 1 to 3 for the preparation of a medicament for therapy or prophylaxis of sleep apnea. Use according to one Claims 1 and / or 2 for the manufacture of a medicament for therapy or Prophylaxis of neurodegenerative diseases, dementia, Alzheimer's disease, Parkinson's disease and Huntington's disease. Use according to claim 1 and / or 2 for the manufacture of a medicament for therapy or Prophylaxis of cancer, breast cancer, lung cancer, colon cancer and prostate cancer. Use according to one or more of the claims 1 to 6 of the compounds of the formulas Ia, Ib, Ic, Id, Ie, If, Ih and Ij. Use according to one or more of the claims 1 to 6 of compounds selected from the group 2- (butyl-1-sulfonylamino) -N- [1 (R) - (6-methoxy-pyridin-3-yl) propyl] benzamide, 2- (butyl-1-sulfonylamino) -N- [1 (S) - (6-methoxy-pyridin-3-yl) -propylj-benzamide, 2 '- {[2- (4-methoxy-phenyl) -acetylamino] methyl} biphenyl-2-carboxylic acid (2-pyridin-3-yl-ethyl) -amide, (S) -5-fluoro-2- (quinoline-8-sulfonylamino) -N- (1-phenyl-propyl) -benzamide, (S) -5-methoxy-2- (4-methoxy-benzenesulfonylamino) -N- (1-phenyl-propyl) -benzamide, 2 '- (α- (S) -methyl-benzyloxycarbonyl-aminomethyl) biphenyl-2-carboxylic acid 2- (2- (R) -hydroxy-propylamide) 5-chloro-2 '- {[2- (4-methoxy-phenyl) -acetylamino] methyl} biphenyl-2-carboxylic acid 2,4-difluoro-benzylamide, {2 '- [methyl- (2-pyridin-2-yl-ethyl) -carbamoyl] -biphenyl-2-ylmethyl} -carbamic acid benzyl ester 3- (2 - {[2- (4-methoxy-phenyl) -acetylamino] -methyl} -phenyl) -thiophenes-2-carboxylic acid 2,4-difluoro-benzylamide, 5- (2 - {[2- (4-methoxy-phenyl) -acetylamino] -methyl} -phenyl) -furan-2-carboxylic acid 2,4-difluoro-benzylamide, 2- (2 - {[2- (4-methoxy-phenyl) -acetylamino] -methyl} -phenyl) -furan-3-carboxylic acid (3-methyl-butyl) -amide, 2- (2 - {[2- (4-methoxy-phenyl) -acetylamino] -methyl} -phenyl) -thiophenes-3-carboxylic acid 2,4-difluoro-benzylamide, {2- [2- (2-pyridin-2-yl-ethylcarbamoyl) pyridin-3-yl] -benzyl} -carbamic acid (S) -1-phenylethyl ester, 3- {2 - [((R) -3-phenyl-butyrylamino) -methyl] -phenyl} -pyridin-2-carbonsäurecyclopropylmethyl-amide, {2- [3- (2,4-Difluoro-benzylcarbamoyl) -pyridin-2-yl] -benzyl} -carbamic acid benzyl ester, {4- [3- (3-methyl-butylcarbamoyl) -phenyl] -pyridin-3-ylmethyl} -carbamic acid benzyl ester, 2 '- {[3- (4-methoxy-phenyl) -propionylamino] -methyl} -6-methyl-biphenyl-3-carboxylic acid (3-methyl-butyl) -amide and N-indan-1-yl-2-methyl-5- (3-methyl-butylsulfamoyl) benzamide and or physiologically compatible Salts thereof.