HK1128154B

HK1128154B - Substituted tetrahydroisoquinoline compounds, their preparation and use in medicaments

Info

Publication number: HK1128154B
Application number: HK09105782.2A
Authority: HK
Inventors: JOVER Antonio TORRENS; Josep Mas Prio; Casamitjana Adriana Port; Helmut Heinrich Buschmann
Original assignee: Laboratorios Del Dr. Esteve, S.A.
Priority date: 2006-03-23
Filing date: 2007-03-23
Publication date: 2012-10-26

Abstract

The present invention relates to substituted tetrahydroisoquinoline compounds of general formulat I, a process for their preparation, medicaments comprising said substituted tetrahydroisoquinoline compounds as well as the use of said substituted tetrahydroisoquinoline compounds for the preparation of medicaments, which are particularly suitable for the prophylaxis and/or treatment of disorders or diseases that are at least partially mediated via 5-HT6 receptors.

Description

The present invention relates to substituted tetrahydroisoquinoline compounds of general formula I, a process for their preparation, medicaments comprising said substituted tetrahydroisoquinoline compounds as well as the use of said substituted tetrahydroisoquinoline compounds for the preparation of medicaments, which are particularly suitable for the prophylaxis and/or treatment of disorders or diseases that are at least partially mediated via 5-HT₆ receptors.

The superfamily of serotonin receptors (5-HT) includes 7 classes (5-HT₁-5-HT₇) encompassing 14 human subclasses [D. Hoyer, et al., Neuropharmacology, 1997, 36, 419]. The 5-HT₆ receptor is the latest serotonin receptor identified by molecular cloning both in rats [F.J. Monsma et al., Mol. Pharmacol., 1993, 43, 320; M. Ruat et al., Biochem. Biophys. Res. Commun., 1993, 193, 268] and in humans [R. Kohen, et al., J. Neurochem., 1996, 66, 47].

Compounds with 5-HT₆ receptor affinity are useful for the treatment of various disorders of the Central Nervous System and of the gastrointestinal tract, such as irritable intestine syndrome. Compounds with 5-HT₆ receptor affinity are also useful in the treatment of anxiety, depression and cognitive memory disorders [M. Yoshioka et al., Ann. NY Acad. Sci., 1998, 861, 244; A. Bourson et al., Br. J. Pharmacol. , 1998, 125, 1562; D.C. Rogers et al., Br. J. Pharmacol. Suppl., 1999, 127, 22P; A. Bourson et al., J. Pharmacol. Exp. Ther. , 1995, 274, 173; A.J. Sleight, et al., Behav. Brain Res. , 1996, 73, 245; T.A. Branchek et al., Annu. Rev. Pharmacol. Toxicol., 2000, 40, 319; C. Routledge et al., Br. J. Pharmacol. , 2000, 130, 1606]. It has been shown that typical and atypical antipsychotic drugs for treating schizophrenia have a high affinity for 5-HT₆ receptors [B.L. Roth et al., J. Pharmacol. Exp. Ther. , 1994, 268, 1403; C.E. Glatt et al., Mol. Med. 1995, 1, 398; F.J. Mosma,et al., Mol. Pharmacol. , 1993, 43, 320; T. Shinkai et al., Am. J. Med. Genet. , 1999, 88, 120]. Compounds with 5-HT₆ receptor affinity are useful for treating infant hyperkinesia (ADHD, attention deficit / hyperactivity disorder) [W.D. Hirst et al., Br. J. Pharmacol. , 2000, 130, 1597; C. Gérard et al., Brain Research , 1997, 746, 207; M.R. Pranzatelli, Drugs of Today , 1997, 33, 379].

Recently, it has been shown that the 5-HT₆ receptor also plays a role in food ingestion [Neuropharmacology, 41, 2001, 210-219].

Food ingestion disorders, particularly obesity, are a serious, fast growing threat to the health of humans of all age groups, since they increase the risk of developing other serious, even life-threatening diseases such as diabetes or coronary diseases as well.

Therefore an object of the present invention was to provide compounds that are particularly suitable as active ingredients in medicaments, especially in medicaments for the prophylaxis and/or treatment of disorders or diseases related to 5-HT₆ receptors such as food intake related disorders.

WO03095428 , W003068752 , W02004031181 and WO2005025576 are all related applications disclosing inter alia tetrahydrosioquinoline showing antipsychotic activity. However, in general terms these compounds are far removed from the ones of the present invention.

WO0132646 and W002100822 teaches some quinolines having affinity for 5HT6 receptors.

Some 1-(1-hydrosulfonylpiperidin-4-yl)-2,4-dihydro-1H-benzo[d][1,3]oxazines and indole sulphonamide were tested as good 5HT6 ligands by Holenz et al (J. Med. Chem. Am. Med. Soc., 2005, 48(6): 1781-1795).

DE10053799 describe tetrahydrosioquinoline sulphonamide but having the sulphonamide group inverted with respect to the compounds of the present invention.

Surprisingly, it has been found that the substituted tetrahydroisoquinoline compounds of general formula Ih given below show good to excellent affinity for 5-HT₆-receptors. These compounds are therefore particularly suitable as pharmacologically active agents in a medicament for the prophylaxis and/or treatment of disorders or diseases related to 5-HT₆-receptors such as food intake related disorders like obesity.

Thus, in one of its aspects the present invention relates to a medicament comprising a substituted tetrahydroisoquinoline compounds of general formula Ih.

A substituted tetrahydroisoquinoline compound of general formula Ih, wherein B represents a radical selected from the group consisting of

Ah: represents a hydrogen atom or a radical selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 2-butyl and tert-butyl;
Dh: represents an anion selected from the group consisting of chloride, bromide, iodide, fluoride, hydrogensulfate, nitrate, dihydrogenphosphate, thiocyanate, cyanate, acrylate, methanesulfonate, ethanesulfonate, toluenesulfonate and benzenesulfonate;
R1h: represents a radical selected from the group consisting of H, methyl, ethyl, -C(=O)-cyclopropyl, -C(=O)-O-tert-butyl and -CH2-cyclopropyl;
R2h , R3h, R4h and R5h,: independently of one another, each represents a hydrogen atom or a -N(R11h)-S(=O)2-R12h radical; with the proviso that at least one of the substituents R2h, R3h, R4h and R5h represents a -N(R11h)-S(=O)2-R12h moiety; R11h represents a radical selected from the group consisting of H, methyl and ethyl;
R12h: represents a radical selected from the group consisting of

which is unsubstituted or substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of H, F, Cl, methyl, ethyl, -NH₂, -N(CH₃)₂, oxo (=O), -O-CH₃, -O-CH₂-CH₃, -NH-(C=O)-CH₃, - C(=O)-O-CH₃, -C(=O)-CF₃; whereby the substitution can take place on any suitable position in the aforementioned radicals, including the heteroatom(s); or a substituted phenyl radical selected from the group consisting of: optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate, or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof, or a corresponding base thereof.

A further aspect of the present invention relates to a medicament comprising at least one substituted tetrahydroisoquinoline compound of general formula Ih, Ig or Ih optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate or in form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a physiologically acceptable salt thereof, or a corresponding solvate thereof, and optionally at least one physiologically acceptable auxiliary agent.

Said medicament is particularly suitable for 5-HT₆-receptor regulation and therefore for the prophylaxis and/or treatment of a disorder or a disease that is at least partially mediated via 5-HT₆-receptors.

Preferably said medicament is suitable for the prophylaxis and/or treatment of the prophylaxis and/or treatment of a disorder or disease related to food intake, preferably for the regulation of appetite, for the maintenance, increase or reduction of body weight, for the prophylaxis and/or treatment of obesity, bulimia, anorexia, cachexia, type II diabetes (non insulin dependent diabetes mellitus), preferably type II diabetes that is caused by obesity; for the prophylaxis and/or treatment of stroke; migraine; head trauma; epilepsy; irritable colon syndrome; irritable bowl syndrome; emesis; vertigo; disorders of the central nervous system; anxiety; panic attacks; depression; bipolar disorders; obsessive compulsory disorder; cognitive disorders; cognitive dysfunction associated with psychiatric diseases; memory disorders; senile dementia; mood disorders; sleep disorders; psychosis; neurodegenerative disorders, preferably selected from the group consisting of Morbus Alzheimer, Morbus Parkinson, Morbus Huntington and Multiple Sclerosis; schizophrenia; amnesia; autism; sexual dysfunction; gastric motility disorders; circadian rhythm disorders; chronic intermittent hypoxia; convulsions; or hyperactivity disorder (ADHD, attention deficit/hyperactivity disorder); for improvement of cognition (cognitive enhancement) or cognitive memory (cognitive memory enhancement); for the prophylaxis and/or treatment of drug addiction and/or withdrawal; for the prophylaxis and/or treatment of alcohol addiction and/or withdrawal, for the prophylaxis and/or treatment of nicotine addiction and/or withdrawal.

More preferably said medicament is suitable for the prophylaxis and/or treatment of a disorder or disease related to food intake, preferably for the regulation of appetite, for the maintenance, increase or reduction of body weight, for the prophylaxis and/or treatment of obesity, bulimia, anorexia, cachexia or type II diabetes (non insulin dependent diabetes mellitus), preferably type II diabetes that is caused by obesity.

More preferably said medicament is suitable for improvement of cognition (cognitive enhancement) or cognitive memory (cognitive memory enhancement).

Most preferably, said medicament is suitable for the prophylaxis and/or treatment of obesity and/or disorders or diseases related thereto.

In another aspect the present invention relates to the use of at least one substituted tetrahydroisoquinoline compound of general formula Ih given above, optionally in form of one of their stereoisomers, preferably enantiomers or diasteromers, a racemate or in form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a physiologically acceptable salt thereof, or a corresponding solvate thereof, for the preparation of a medicament suitable for 5-HT₆-receptor regulation, preferably for the prophylaxis and/or treatment of a disorder or a disease that is least partially mediated via 5-HT₆-receptors.

In another aspect the present invention relates to the use of at least one substituted tetrahydroisoquinoline compound of general formula Ih given above, optionally in form of one of their stereoisomers, preferably enantiomers or diasteromers, a racemate or in form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a physiologically acceptable salt thereof, or a corresponding solvate thereof, for the preparation of a medicament for the prophylaxis and/or treatment of a disorder or disease related to food intake, preferably for the regulation of appetite; for the maintenance, increase or reduction of body weight; or for the prophylaxis and/or treatment of obesity, bulimia, anorexia, cachexia or type II diabetes (non insulin dependent diabetes mellitus), more preferably for the prophylaxis and/or treatment of obesity.

The present invention also relates to the use of at least one substituted tetrahydroisoquinoline compound of general formula Ih given above, optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate or in form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a physiologically acceptable salt thereof, or a corresponding solvate thereof, for the preparation of a medicament for the prophylaxis and/or treatment of stroke; migraine; head trauma; epilepsy; irritable colon syndrome; irritable bowl syndrome; emesis; vertigo; disorders of the central nervous system; anxiety; panic attacks; depression; bipolar disorders; obsessive compulsory disorder; cognitive disorders; cognitive dysfunction associated with psychiatric diseases; memory disorders; senile dementia; mood disorders; sleep disorders; psychosis; neurodegenerative disorders, preferably selected from the group consisting of Morbus Alzheimer, Morbus Parkinson, Morbus Huntington and Multiple Sclerosis; schizophrenia; amnesia; autism; sexual dysfunction; gastric motility disorders; circadian rhythm disorders; chronic intermittent hypoxia; convulsions; or hyperactivity disorder (ADHD, attention deficit/hyperactivity disorder).

The present invention also relates to the use of at least one substituted tetrahydroisoquinoline compound of general formula Ih given above, optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate or in form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a physiologically acceptable salt thereof, or a corresponding solvate thereof, for the manufacture of a medicament for the improvement of cognition (cognitive enhancement) and/or for the improvement of cognitive memory (cognitive memory enhancement).

The present invention also relates to the use of at least one substituted tetrahydroisoquinoline compound of general formula Ih given above, optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate or in form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a physiologically acceptable salt thereof, or a corresponding solvate thereof, for the manufacture of a medicament for the prophylaxis and/or treatment of drug addiction and/or withdrawal, preferably for the prophylaxis and/or treatment of addiction and/or withdrawal related to one or more of drugs selected from the group consisting of benzodiazepines, natural, semisynthetic or synthetic opioids like cocaine, ethanol and/or nicotine.

More preferred is the use of at least one substituted tetrahydroisoquinoline compound of general formula Ih as defined above, optionally in form of one of their stereoisomers, preferably enantiomers or diasteromers, a racemate or in form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a physiologically acceptable salt thereof, or a corresponding solvate thereof, for the preparation of a medicament for the maintenance, increase or reduction of body weight, for the prophylaxis and/or treatment of obesity, bulimia, anorexia, cachexia or type II diabetes (non insulin dependent diabetes mellitus), preferably type II diabetes that is caused by obesity.

More preferred is also the use of at least one substituted tetrahydroisoquinoline compound of general formula Ih as defined above, optionally in form of one of their stereoisomers, preferably enantiomers or diasteromers, a racemate or in form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a physiologically acceptable salt thereof, or a corresponding solvate thereof, for the preparation of a medicament for the improvement of cognition (cognitive enhancement) and/or for the improvement of cognitive memory (cognitive memory enhancement).

Any medicament according to the present invention may be in any form suitable for the application to humans and/or animals, preferably humans including infants, children and adults. The medicament can be produced by standard procedures known to those skilled in the art, e.g. from the table of contents of "Pharmaceutics: The Science of Dosage Forms", Second Edition, Aulton, M.E. (ED. Churchill Livingstone, Edinburgh (2002); "Encyclopedia of Pharmaceutical Technology", Second Edition, Swarbrick, J. and Boylan J.C. (Eds.), Marcel Dekker, Inc. New York (2002); "Modern Pharmaceutics", Fourth Edition, Banker G.S. and Rhodes C.T. (Eds.) Marcel Dekker, Inc. New York 2002 y "The Theory and Practice of Industrial Pharmacy", Lachman L., Lieberman H. And Kanig J. (Eds.), Lea & Febiger, Philadelphia (1986). The respective descriptions are hereby incorporated by reference and form part of the disclosure. The composition of the medicament may vary depending on the route of administration.

The medicament of the present invention may, for example, be administered parentally in combination with conventional injectable liquid carriers, such as water or suitable alcohols. Conventional pharmaceutical excipients for injection, such as stabilizing agents, solubilizing agents, and buffers, may be included in such injectable compositions. These medicaments may for example be injected intramuscularly, intraperitoneally, or intravenously.

Medicaments according to the present invention may also be formulated into orally administrable compositions containing one or more physiologically compatible carriers or excipients, in solid or liquid form. These compositions may contain conventional ingredients such as binding agents, fillers, lubricants, and acceptable wetting agents. The compositions may take any convenient form, such as tablets, pellets, granules, capsules, lozenges, aqueous or oily solutions, suspensions, emulsions, or dry powdered forms suitable for reconstitution with water or other suitable liquid medium before use, for immediate or retarded release. The multiparticulate forms, such as pellets or granules, may e.g. be filled into a capsule, compressed into tablets or suspended in a suitable liquid.

Suitable controlled release formulations, materials and methods for their preparation are are known from the prior art, e.g. from the table of contents of "Modified-Release Drug Delivery Technology", Rathbone, M.J. Hadgraft, J. and Roberts, M.S. (Eds.), Marcel Dekker, Inc., New York (2002); "Handbook of Pharmaceutical Controlled Release Technology", Wise, D.L. (Ed.), Marcel Dekker, Inc. New York, (2000); "Controlled Drug Delivery", Vol, I, Basic Concepts, Bruck, S.D. (Ed.), CRD Press Inc., Boca Raton (1983) y de Takada, K. and Yoshikawa, H., "Oral Drug Delivery", Encyclopedia of Controlled Drug Delivery, Mathiowitz, E. (Ed.), John Wiley & Sons, Inc., New York (1999), Vol. 2, 728-742; Fix, J., "Oral drug delivery, small intestine and colon", Encyclopedia of Controlled Drug Delivery, Mathiowitz, E. (Ed.), John Wiley & Sons, Inc., New York (1999), Vol. 2, 698-728. The respective descriptions are hereby incorporated by reference and form part of the disclosure.

Medicaments according to the present invention may also comprise an enteric coating, so that their dissolution is dependent on pH-value. Due to said coating the medicament can pass the stomach undissolved and the respective tetrahydroisoquinoline compound is liberated in the intestinal tract. Preferably the enteric coating is soluble at a pH value of 5 to 7.5. Suitable materials and methods for the preparation are are known from the prior art.

Typically, the medicaments according to the present invention may contain 1-60 % by weight of one or more substituted tetrahydroisoquinoline compounds as defined herein and 40-99 % by weight of one or more auxiliary substances (additives).

The liquid oral forms for administration may also contain certain additives such as sweeteners, flavoring, preservatives, and emulsifying agents. Non-aqueous liquid compositions for oral administration may also be formulated, containing edible oils. Such liquid compositions may be conveniently encapsulated in e.g., gelatin capsules in a unit dosage amount.

The compositions of the present invention may also be administered topically or via a suppository.

The daily dosage for humans and animals may vary depending on factors that have their basis in the respective species or other factors, such as age, sex, weight or degree of illness and so forth. The daily dosage for humans may preferably be in the range from 1 to 2000 mg, preferably 1 to 1000 mg, more preferably 1 to 500 mg, even more preferably 1 to 200 mg, of active substance to be administered during one or several intakes per day.

In yet another aspect the present invention relates to a substituted tetrahydroisoquinoline compound of general formula Ig, wherein R^1g represents a hydrogen atom; a radical selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, -CH₂-NH₂, -CH₂-NH-CH₃, -CH₂-N(CH₃)₂, -CH₂-N(C₂H₅)₂, -CH₂-NH-C₂H₅, -CH₂-CH₂-NH₂, -CH₂-CH₂-NH-CH₃, -CH₂-CH₂-N(CH₃)₂, -CH₂-CH₂-N(C₂H₅)₂, -CH₂-CH₂-NH-C₂H₅, -CH₂-CH₂-CH₂-NH-CH₃, -CH₂-CH₂-CH₂-N(CH₃)₂, -CH₂-CH₂-CH₂-N(C₂H₅)₂ and - CH₂-CH₂-CH₂-NH-C₂H₅; or a (hetero)cycloaliphatic radical selected from the group consisting of imidazolidinyl, aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, pyrazolidinyl and azepanyl, which may be bonded via a - (CH₂)_{1,2 or 3}- group and which may be unsubstituted or optionally substituted with 1, 2, 3, 4 or 5 substituent(s) independently selected from the group consisting of oxo (=O), thioxo (=S), methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, sec-butyl, isobutyl, - C(=O)-CH₃, -C(=O)-C₂H₅, -C(=O)-CH₂-CH₂-CH₃, -C(=O)-CH(CH₃)₂, -C(=O)-C(CH₃)₃, - C(=O)-NH₂, -C(=O)-NH-CH₃, -C(=O)-NH-C₂H₅, -C(=O)-N(CH₃)₂, -C(=O)-N(C₂H₅)₂ and - S(=O)₂-CH₃; R^2g, R^3g, R^4g and R^5g, independently of one another, each represent a hydrogen atom; F, Cl, Br, I, -NO₂; -NH₂; -SH; -OH; -CN; -C(=O)-OH; -C(=O)-H; -S(=O)₂-OH; - C(=O)-NH₂; -S(=O)₂-NH₂; -OR^8g; -SR^9g; -N(R^11g)-S(=O)₂-R^12g; a radical selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, vinyl, allyl, ethinyl, -CF₃, -CFH₂, -CF₂H, -CH₂-CF₃ and -CF₂-CF₃; or a radical selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; with the proviso that at least one of the substituents R^2g, R^3g, R^4g and R^5g represents a - N(R^11g)-S(=O)₂-R^12g moiety; R^8g and R^9g, independently of one another, each represent a radical selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, -CF₃, -CFH₂, -CF₂H, -CH₂-CF₃ and -CF₂-CF₃; a (hetero)cycloaliphatic radical selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; or an aryl or heteroaryl radical selected from the group consisting of phenyl, naphthyl, furyl (furanyl), thienyl (thiophenyl), pyrrolyl, and pyridinyl, which may be bonded via a - (CH₂)_{1, 2 or 3}-group and which may be unsubstituted or optionally substituted with 1, 2 or 3 substituent(s) independently selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, sec-butyl, isobutyl, -O-CH₃, -O-C₂H₅, -O-CH₂-CH₂-CH₃, -O-CH(CH₃)₂, -O-C(CH₃)₃, -S-CH₃, -S-C₂H₅, -S-CH₂-CH₂-CH₃, F, Cl, Br, I, -CN, - CF₃, -OCF₃, -SCF₃, -OH, -SH, -NH₂, -NO₂, -CHO, -CF₂H and -CFH₂; R^11g represents a hydrogen atom, -S(=O)₂-R^12g or an alkyl radical selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl and tert-butyl; R^12g represents a phenyl radical of general formula (Ag), wherein R^19g, R^20g, R^21g and R^22g, independently of one another, each represent a hydrogen atom; F, Cl, Br, I, -NO₂; -NH₂; -SH; -OH; -CN; -C(=O)-OH; -C(=O)-H; -S(=O)₂-OH; - C(=O)-NH₂; -S(=O)₂-NH₂; -C(=O)-R^23g; -S(=O)-R^24g; -S(=O)₂-R^24g; -OR^25g; -SR^26g; - C(=O)-OR^27g; methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, - CF₃, -CF₂H, -CFH₂, -CH₂-CF₃, -CF₂-CF₃, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; with the proviso that at least one of the substituents R^19g, R^20g, R^21g and R^22g is unlike hydrogen; or a naphthyl radical, which may be unsubstituted or optionally substituted with 1, 2, 3, 4 or 5 substituent(s) independently selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, sec-butyl, isobutyl, n-pentyl, -O-CH₃, -O-C₂H₅, -O-CH₂-CH₂-CH₃, -O-CH(CH₃)₂, -O-C(CH₃)₃, -S-CH₃, -S-C₂H₅, -S-CH₂-CH₂-CH₃, -S-CH(CH₃)₂, -S-C(CH₃)₃, F, Cl, Br, I, -CN, -CF₃, -OCF₃, -SCF₃, -OH, -SH, -NH₂, -NO₂, - CHO, -CF₂H and -CFH₂; R^23g and R^27g, independently of one another, each represent a radical selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, -CF₃, -CFH₂, -CF₂H, -CH₂-CF₃ and -CF₂-CF₃; or an aryl or heteroaryl radical selected from the group consisting of phenyl, naphthyl, furyl (furanyl), thienyl (thiophenyl), pyrrolyl, and pyridinyl, which may be bonded via a -(CH₂)_{1, 2 or 3}-group and which may be unsubstituted or optionally substituted with 1, 2 or 3 substituent(s) independently selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, sec-butyl, isobutyl, n-pentyl, -O-CH₃, -O-C₂H₅, -O-CH₂-CH₂-CH₃, F, Cl, Br, I, -CN, -CF₃, -OCF₃, -SCF₃, -OH, -SH, -NH₂-NO₂, -CHO, -CF₂H and -CFH₂; R^24g and R^26g, independently of one another, each represent a radical selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, vinyl, allyl, ethinyl, -CF₃, -CFH₂, -CF₂H, -CH₂-CF₃ and -CF₂-CF₃; or an aryl or heteroaryl radical selected from the group consisting of phenyl, naphthyl, furyl (furanyl), thienyl (thiophenyl), pyrrolyl, and pyridinyl, which may be unsubstituted or optionally substituted with 1, 2 or 3 substituent(s) independently selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, sec-butyl, isobutyl, n-pentyl, -O-CH₃, -O-C₂H₅, -O-CH₂-CH₂-CH₃, -O-CH(CH₃)₂, -O-C(CH₃)₃, F, Cl, Br, I, -CN, -CF₃, -OCF₃, -SCF₃, -OH, -SH, -NH₂, -NO₂, -CHO, -CF₂H and -CFH₂; R^25g represents a radical selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, -CF₃, -CFH₂, -CF₂H, -CH₂-CF₃ and -CF₂-CF₃ and R^37g represents a radical selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, fluorenyl, fluorenylmethyl, phenyl, benzyl and naphthyl.

Preferred is a substituted tetrahydroisoquinoline compound of general formula Ig, wherein R^1g represents a hydrogen atom; or a radical selected from the group consisting of methyl, ethyl, n-propyl, n-butyl, n-pentyl and n-hexyl; R^2g, R^3g, R^4g and R^5g, independently of one another, each represent a hydrogen atom or -N(R^11g)-S(=O)₂-R^12g; with the proviso that at least one of the substituents R^2g, R^3g, R^4g and R^5g represents a - N(R^11g)-S(=O)₂-R^12g moiety; R^11g represents a hydrogen atom, -S(=O)₂-R^12g or an alkyl radical selected from the group consisting of methyl, ethyl and n-propyl; R^12g represents a phenyl radical of general formula (Ag), wherein R^19g, R^20g, R^21g and R^22g, independently of one another, each represent a hydrogen atom; F, Cl, Br, I, -O-CH₃; -O-C₂H₅; -O-CF₃; -O-CFH₂; -O-CF₂H; -O-CH₂-CF₃; -O-CF₂-CF₃; methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl; with the proviso that at least one of the substituents R^19g, R^20g, R^21g and R^22g is unlike hydrogen; or a naphthyl radical, which may be unsubstituted or optionally substituted with 1, 2, 3, 4 or 5 substituent(s) independently selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, F, Cl and Br; and R^37g represents a radical selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, fluorenyl, fluorenylmethyl, phenyl, benzyl and naphthyl.

More preferred is a substituted tetrahydroisoquinoline compound of general formula Ig, wherein

[13] 6-(naphthalene-1-sulfonylamino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester,
[15] 6-(4-methyl-naphthalene-1-sulfonylamino)-3,4 -dihydro-1 H-isoquinoline-2-carboxylic acid tert-butyl ester,
[16] 6-(naphthalene-2-sulfonylamino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester and
[17] 6-(2-methoxy-5-methyl-benzenesulfonylamino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester.

If any of the substituents in any of the above defined formulae represents or comprises a 3- to 9-membered (hetero)cycloaliphatic radical, C_3-9 cycloalkyl radical or C_4-9 cycloalkenyl radical, said (hetero)cycloaliphatic radical, C_3-9 cycloalkyl radical or C_4-9 cycloalkenyl radical may - if not defined otherwise - be unsubstituted or substituted by one or more substituents, preferably unsubstituted or optionally substituted with 1, 2, 3, 4 or 5 substituent(s). Said substituent(s) may preferably be selected independently from the group consisting of oxo (=O), thioxo (=S), C_1-5-alkyl, -O-C_1-5-alkyl, -S-C_1-5-alkyl, - C(=O)-OH, -C(=O)-C_1-5-alkyl, -C(=O)-O-C_1-5-alkyl, -O-C(=O)-C_1-5-alkyl, F, Cl, Br, I, -CN, - CF₃, -OCF₃, -SCF₃, -OH, -SH, -NH₂, -NH(C_1-5-alkyl), -N(C_1-5-alkyl)₂, -NO₂, -CHO, -CF₂H, -CFH₂, -C(=O)-NH₂, -C(=O)-NH(C_1-5-alkyl), -C(=O)-N(C_1-5-alkyl)₂, -S(=O)₂-C_1-5-alkyl, - S(=O)₂-phenyl, phenyl, phenoxy and benzyl; whereby in each occurrence C_1-5-alkyl may be linear or branched and whereby said cyclic substituents may be unsubstituted or substituted by 1, 2 or 3 substituent(s) independently selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, F, Cl, Br, -CN, -CF₃, -OCF₃, - SCF₃, -OH, -SH, -NH₂ and -NO₂.

More preferably said substituents may be selected independently from the group consisting of oxo (=O), thioxo (=S), methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, sec-butyl, isobutyl, n-pentyl, -O-CH₃, -O-C₂H₅, -O-CH₂-CH₂-CH₃, -O-CH(CH₃)₂, -O-C(CH₃)₃, -S-CH₃, -S-C₂H₅, -S-CH₂-CH₂-CH₃, -S-CH(CH₃)₂, -S-C(CH₃)₃, -C(=O)-OH, - C(=O)-O-CH₃, -C(=O)-O-C₂H₅, -C(=O)-O-CH₃-CH₃-CH₃, -C(=O)-O-CH(CH₃)₂, -C(=O)-O-C(CH₃)₃, -C(=O)-CH₃, -C(=O)-C₂H₅, -C(=O)-CH₃-CH₃-CH₃, -C(=O)-CH(CH₃)₂, -C(=O)-C(CH₃)₃, F, Cl, Br, I, -CN, -CF₃, -OCF₃, -SCF₃, -OH, -SH, -NH₂, -NH-CH₃, -NH-C₂H₅, - NH-CH₂-CH₂-CH₃, -NH-CH(CH₃)₂, -NH-C(CH₃)₃, -N(CH₃)₂, -N(C₂H₅)₂, -NO₂, -CHO, - CF₂H, -CFH₂, -C(=O)-NH₂, -C(=O)-NH-CH₃, -C(=O)-NH-C₂H₅, -C(=O)-N(CH₃)₂, -C(=O)-N(C₂H₅)₂, -S(=O)₂-CH₃, -S(=O)₂-phenyl, phenyl, phenoxy and benzyl; whereby in each occurrence said cyclic substituents may be unsubstituted or substituted by 1, 2 or 3 substituent(s) independently selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, F, Cl, Br,-CN, -CF₃, -OCF₃, -SCF₃, -OH, -SH, -NH₂ and -NO₂.

If any of the substituents in any of the above defined formulae represents or comprises a cycloaliphatic radical, C_3-9 cycloalkyl radical or C_4-9 cycloalkenyl radical which contains one or more, preferably 1, 2 or 3 heteroatom(s) as ring member(s), unless defined otherwise, each of these heteroatom(s) may preferably be selected independently from the group consisting of N, O and S.

Suitable saturated or unsaturated, optionally at least one heteroatom as ring member containing cycloaliphatic radicals, C_3-9 cycloalkyl radicals or C_4-9 cycloalkenyl radicals may preferably be selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, pyrrolidinyl, piperidinyl, piperazinyl, homopiperazinyl, morpholinyl, aziridinyl, azetidinyl, imidazolidinyl, thiomorpholinyl, pyrazolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, azepanyl, diazepanyl, azocanyl, (2,5)-dihydrofuranyl, (2,5)-dihydrothiophenyl, (2,3)-dihydrofuranyl, (2,3)-dihydrofuranyl, (2,5)-dihydro-1H-pyrrolyl, (2,3)-dihydro-1H-pyrrolyl, tetrahydrothiopyranyl, tetrahydropyranyl, (3,4)-dihydro-2H-pyranyl, (3,4)-dihydro-2H-thiopyranyl, (1,2,3,6)-tetrahydropyridinyl, (1,2,3,4)-tetrahydropyridinyl, (1,2,5,6)-tetrahydropyridinyl, [1,3]-oxazinanyl, hexahydropyrimidinyl, (5,6)-dihydro-4H-pyrimidinyl, oxazolidinyl, (1,3)-dioxanyl, (1,4)-dioxanyl and (1,3)-dioxolanyl.

Suitable saturated or unsaturated, optionally at least one heteroatom as ring member containing cycloaliphatic radicals, C_3-9 cycloalkyl radicals or C_4-9 cycloalkenyl radicals which are condensed with an unsubstituted or at least mono-substituted mono- or bicyclic ring system may preferably be selected from the group consisting of indolinyl, isoindolinyl, decahydronaphthyl, (1,2,3,4)-tetrahydroquinolinyl, (1,2,3,4)-tetrahydroisoquinolinyl, (1,2,3,4)-tetrahydronaphthyl, octahydro-cyclopenta[c]pyrrolyl, (1,3,4,7,9a)-hexahydro-2H-quinolizinyl, (1,2,3,5,6,8a)-hexahydro-indolizinyl, decahydroquinolinyl, dodecahydrocarbazolyl, 9H-carbazolyl, decahydroisoquinolinyl, (6,7)-dihydro-4H-thieno[3,2-c]pyridinyl, (2,3)-dihydro-1H-benzo[de]isoquinolinyl, fluorenyl and (1,2,3,4)-tetrahydroquinoxazlinyl.

If any of the substituents in any of the above defined formulae represents an alkylene group, preferably an C_1-6 alkylene group, an alkenylene group, preferably an C_2-6 alkenylene group or an alkinylene group, preferably an C_2-6 alkinylene group, which may be substituted, said alkylene group, C_2-6alkylene group, alkenylene group, C_2-6 alkenylene group, alkinylene group or C_2-6alkinylene group may be unsubstituted or substituted by one or more substituents, preferably unsubstituted or optionally substituted with 1, 2 or 3 substituent(s). Said substituent(s) may preferably be selected independently from the group consisting of -O-C_1-5-alkyl, -S-C_1-5-alkyl, -F, Cl, Br, I, -CN, - CF₃, -OCF₃, -SCF₃, -OH, -SH, -NH₂, -NH(C_1-5-alkyl) and -N(C_1-5-alkyl)₂, whereby in each occurrence C_1-5-alkyl may be linear or branched. An alkenylene group comprises at least one carbon-carbon double bond, an alkinylene group comprises at least one carbon-carbon triple bond.

Suitable alkylene groups include -(CH₂)-, -CH(CH₃)-, -CH(phenyl), -(CH₂)₂-, -(CH₂)₃-,-(CH₂)₄-,-(CH₂)₅ and -(CH₂)₆-, suitable alkenylene groups include -CH=CH-, -CH₂-CH=CH- and -CH=CH-CH₂- and suitable alkinylene groups include -C≡C-, -CH₂-C≡C- and -C≡C-CH₂-.

If any of the substituents in any of the above defined formulae represents or comprises an aryl radical, including a 6-membered aryl radical such as phenyl or a 10-membered aryl radical such as naphthyl or a 14-membered aryl radical such as anthracenyl, said aryl radical may - if not defined otherwise - be unsubstituted or substituted by one or more substituents, preferably unsubstituted or substituted with 1, 2, 3, 4 or 5 substituent(s). Said substituent(s) may preferably be selected independently from the group consisting of C_1-5-alkyl, -O-C_1-5-alkyl, -S-C_1-5-alkyl, -C(=O)-OH, -C(=O)-C_1-5-alkyl, - C(=O)-O-C_1-5-alkyl, -O-C(=O)-C_1-5-alkyl, F, Cl, Br, I, -CN, -CF₃, -OCF₃, -SCF₃, -SH, -NH₂, -NH(C_1-5-alkyl), -N(C_1-5-alkyl)₂, -NO₂, -CHO, -CF₂H, -CFH₂, -C(=O)-NH₂, -C(=O)-NH(C_1-5-alkyl), -C(=O)-N(C_1-5-alkyl)₂, -S(=O)₂-C_1-5-alkyl, -S(=O)₂-phenyl, phenyl, phenoxy and benzyl; whereby in each occurrence C_1-5-alkyl may be linear or branched and whereby said cyclic substituent(s) may be unsubstituted or substituted by 1, 2 or 3 substituent(s) independently selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, F, Cl, Br, -CN, -CF₃, -OCF₃, -SCF₃, -OH, -SH, -NH₂ and -NO₂.

More preferably said substituents may be selected independently from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, sec-butyl, isobutyl, n-pentyl, -O-CH₃, -O-C₂H₅, -O-CH₂-CH₂-CH₃, -O-CH(CH₃)₂, -O-C(CH₃)₃, -S-CH₃, -S-C₂H₅, -S-CH₂-CH₂-CH₃, -S-CH(CH₃)₂, -S-C(CH₃)₃, -C(=O)-OH, -C(=O)-O-CH₃, -C(=O)-O-C₂H₅, -C(=O)-O-CH₃-CH₃-CH₃, -C(=O)-O-CH(CH₃)₂, -C(=O)-O-C(CH₃)₃, -C(=O)-CH₃, -C(=O)-C₂H₅, -C(=O)-CH₃-CH₃-CH₃, -C(=O)-CH(CH₃)₂, -C(=O)-C(CH₃)₃, F, Cl, Br, I, -CN, -CF₃, - OCF₃, -SCF₃, -OH, -SH, -NH₂, -NH-CH₃, -NH-C₂H₅, -NH-CH₂-CH₂-CH₃, -NH-CH(CH₃)₂, - NH-C(CH₃)₃, -N(CH₃)₂, -N(C₂H₅)₂, -NO₂, -CHO, -CF₂H, -CFH₂, -C(=O)-NH₂, -C(=O)-NH-CH₃, -C(=O)-NH-C₂H₅, -C(=O)-N(CH₃)₂, -C(=O)-N(C₂H₅)₂ and -S(=O)₂-CH₃.

Preferred aryl radicals, which may optionally be at least mono-substituted, are phenyl and naphthyl.

If any of the substituents in any of the above defined formulae represents or comprises a heteroaryl radical, including a monocyclic 5- or 6-membered heteroaryl radical or a bi- or tricyclic 8-, 9-, 10-, 11-, 12-, 13- or 14 membered heteroaryl radical, said heteroaryl radical may - if not defined otherwise - be unsubstituted or substituted by one or more substituents, preferably unsubstituted or substituted with 1, 2, 3, 4 or 5 substituent(s). Said substituent(s) may preferably be selected independently from the group consisting of C_1-5-alkyl, -O-C_1-5-alkyl, -S-C_1-5-alkyl, -C(=O)-OH, -C(=O)-C_1-5-alkyl, -C(=O)-O-C_1-5-alkyl, -O-C(=O)-C_1-5-alkyl, F, Cl, Br, I, -CN, -CF₃, -OCF₃, -SCF₃, -SH, -NH₂, -NH(C_1-5-alkyl), -N(C_1-5-alkyl)₂, -NO₂, -CHO, -CF₂H, -CFH₂, -C(=O)-NH₂, -C(=O)-NH(C_1-5-alkyl), - C(=O)-N(C_1-5-alkyl)₂, -S(=O)₂-C_1-5-alkyl, -S(=O)₂-phenyl, phenyl, phenoxy and benzyl; whereby in each occurrence C_1-5-alkyl may be linear or branched and whereby said cyclic substituent(s) may be unsubstituted or substituted by 1, 2 or 3 substituent(s) independently selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, F, Cl, Br, -CN, -CF₃, -OCF₃, -SCF₃, -OH, -SH, -NH₂ and -NO₂.

The heteroatom(s), which are present as ring member(s) in the heteroaryl radical, may, unless defined otherwise, independently be selected from the group consisting of nitrogen, oxygen and sulphur. Preferably the heteroaryl radical comprises 1, 2, 3 or 4 heteroatom(s).

Suitable bi- or tricyclic heteroaryl radicals, which may optionally be at least mono-substituted, may preferably be selected from the group consisting of indolyl, isoindolyl, quinolinyl, isoquinolinyl, benzo[b]furanyl, benzo[b]thiophenyl, benzo[2,1,3]thiadiazolyl, [1,2,3]-benzothiadiazolyl, [2,1,3]-benzoxadiazolyl, [1,2,3]-benzoxadiazolyl, benzoxazolyl, benzothiazolyl, benzisoxazolyl, benzisothiazolyl, imidazo[2,1-b]thiazolyl, 2H-chromenyl, indazolyl and quinazolinyl.

Suitable mono-, bi- or tricyclic heteroaryl radicals, which are condensed with an unsubstituted or at least mono-substituted saturated or unsaturated mono- or bicyclic ring system, may preferably be selected from the group consisting of [1,3]-benzodioxolyl, [1,4]-benzodioxanyl, [1,2,3,4]-tetrahydronaphthyl, (2,3)-dihydro-1H-cyclopenta[b]indolyl, [1,2,3,4]-tetrahydroquinolinyl, [1,2,3,4]-tetrahydroisoquinolinyl, [1,2,3,4]-tetrahydroquinazolinyl and [3,4]-dihydro-2H-benzo[1,4]oxazinyl.

Suitable monocyclic heteroaryl radicals, which may optionally be at least mono-substituted, may preferably be selected from the group consisting of pyridinyl, furyl (furanyl), thienyl (thiophenyl), pyrrolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, triazolyl, pyridazinyl, pyrimidinyl, pyrazinyl and pyranyl.

A mono- or bicyclic ring system according to the present invention - if not defined otherwise - means a mono- or bicyclic hydrocarbon ring system that may be saturated, unsaturated or aromatic. Each of its different rings may show a different degree of saturation, i.e. it may be saturated, unsaturated or aromatic. Optionally each of the rings of the mono- or bicyclic ring system may contain one or more, preferably 1, 2 or 3, heteroatom(s) as ring member(s), which may be identical or different and which can preferably be selected from the group consisting of N, O and S. The rings of the mono-or bicyclic ring system are preferably 5-, 6- or 7-membered.

Preferably a mono-or bicyclic ring system according to the present invention is a phenyl or naphthyl ring system.

The term "condensed" according to the present invention means that a ring or ring system is attached to another ring or ring system, whereby the terms "annulated" or "annelated" are also used by those skilled in the art to designate this kind of attachment.

Such a mono- or bicyclic ring system may - if not defined otherwise - be unsubstituted or substituted by one or more substituents, preferably unsubstituted or substituted with 1, 2, 3, 4 or 5 substituent(s). Said substituents may preferably be selected independently from the group consisting of C_1-5-alkyl, -O-C_1-5-alkyl, -S-C_1-5-alkyl, -C(=O)-OH, oxo (=O), thioxo (=S), -C(=O)-O-C_1-5-alkyl, -O-C(=O)-C_1-5-alkyl, F, Cl, Br, I, -CN, -CF₃, -OCF₃, - SCF₃, -OH, -SH, -NH₂, -NH(C_1-5-alkyl), -N(C_1-5-alkyl)₂, -NO₂, -CHO, -CF₂H, -CFH₂, - C(=O)-NH₂, -C(=O)-NH(C_1-5-alkyl), -C(=O)-N(C_1-5-alkyl)₂, -S(=O)₂-C_1-5-alkyl, -S(=O)₂- phenyl, phenyl, phenoxy and benzyl; whereby in each occurrence C_1-5-alkyl may be linear or branched and whereby said cyclic substituents may be unsubstituted or substituted by 1, 2 or 3 substituent(s) independently selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, F, Cl, Br, -CN, -CF₃, -OCF₃, - SCF₃, -OH, -SH, -NH₂ and -NO₂.

More preferably said substituents may be selected from the group consisting of oxo (=O), thioxo (=S), methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, sec-butyl, isobutyl, n-pentyl, -O-CH₃, -O-C₂H₅, -O-CH₂-CH₂-CH₃, -O-CH(CH₃)₂, -O-C(CH₃)₃, -S-CH₃, -S-C₂H₅, -S-CH₂-CH₂-CH₃, -S-CH(CH₃)₂, -S-C(CH₃)₃, -C(=O)-OH, -C(=O)-O-CH₃, -C(=O)-O-C₂H₅, -C(=O)-O-CH₃-CH₃-CH₃, -C(=O)-O-CH(CH₃)₂, -C(=O)-O-C(CH₃)₃, -C(=O)-CH₃, -C(=O)-C₂H₅, -C(=O)-CH₃-CH₃-CH₃, -C(=O)-CH(CH₃)₂, -C(=O)-C(CH₃)₃, F, Cl, Br, I, -CN, -CF₃, -OCF₃, -SCF₃, -OH, -SH, -NH₂, -NH-CH₃, -NH-C₂H₅, -NH-CH₂-CH₂-CH₃, -NH-CH(CH₃)₂, -NH-C(CH₃)₃, -N(CH₃)₂, -N(C₂H₅)₂, -NO₂, -CHO, -CF₂H, -CFH₂, -C(=O)-NH₂, - C(=O)-NH-CH₃, -C(=O)-NH-C₂H₅, -C(=O)-N(CH₃)₂, -C(=O)-N(C₂H₅)₂, -S(=O)₂-CH₃, - S(=O)₂-phenyl, phenyl, phenoxy and benzyl; whereby in each occurrence said cyclic substituents may be unsubstituted or substituted by 1, 2 or 3 substituent(s) independently selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, F, Cl, Br, -CN, -CF₃, -OCF₃, -SCF₃, -OH, -SH, -NH₂ and -NO₂.

If any of the substituents in any of the above defined formulae represents a saturated or unsaturated aliphatic radical, i.e. an alkyl radical, preferably an C_1-10 alkyl radical; an alkenyl radical, preferably an C_2-10 alkenyl radical or an alkinyl radical, preferably an C_2-10 alkinyl radical; said aliphatic radical may - if not defined otherwise - be unsubstituted or substituted by one or more substituents, preferably unsubstituted or substituted with 1, 2, 3, 4 or 5 substituent(s). Said substituent(s) may preferably be selected independently from the group consisting of -O-C_1-5-alkyl, -S-C_1-5-alkyl, F, Cl, Br, I, -CN, -CF₃, -OCF₃, - SCF₃, -OH, -SH, -NH₂, -NH(C_1-5-alkyl) and -N(C_1-5-alkyl)₂, whereby in each occurrence C_1-5-alkyl may be linear or branched. More preferably said substituent(s) may preferably be selected independently from the group consisting of -O-CH₃, -O-C₂H₅, -O-CH₂-CH₂-CH₃, -O-CH(CH₃)₂, -O-C(CH₃)₃, -S-CH₃, -S-C₂H₅, -S-CH₂-CH₂-CH₃, -S-CH(CH₃)₂, -S-C(CH₃)₃, F, Cl, Br, I, -CN, -CF₃, -OCF₃, -SCF₃, -OH, -SH, -NH₂, NH-CH₃, -NH-C₂H₅, - NH-CH₂-CH₂-CH₃, -NH-CH(CH₃)₂, -NH-C(CH₃)₃, -N(CH₃)₂, -N(C₂H₅)₂.

An alkenyl radical comprises at least one carbon-carbon double bond, an alkinyl radical comprises at least one carbon-carbon triple bond.

Suitable alkyl radicals, which may be substituted by one or more substituents, may preferably be selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl and n-decyl.

Suitable alkenyl radicals, which may be substituted by one or more substituents, may preferably be selected from the group consisting of vinyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl and 3-butenyl.

Suitable alkinyl radicals, which may be substituted by one or more substituents, may preferably be selected from the group consisting of ethinyl, 1-propinyl, 2-propinyl, 1-butinyl, 2-butinyl and 3-butinyl.

In yet another aspect the present invention relates to a substituted tetrahydroisoquinoline compound of general formula Ih wherein B represents a radical selected from the group consisting of

Ah: represents a hydrogen atom or a radical selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 2-butyl and tert-butyl;
Dh: represents an anion selected from the group consisting of chloride, bromide, iodide, fluoride, hydrogensulfate, nitrate, dihydrogenphosphate, thiocyanate, cyanate, acrylate, methanesulfonate, ethanesulfonate, toluenesulfonate and benzenesulfonate;

R^1h represents a radical selected from the group consisting of H, methyl, ethyl, -C(=O)-cyclopropyl, -C(=O)-O-tert-butyl and -CH₂-cyclopropyl; R^2h, R^3h, R^4h and R^5h, independently of one another, each represents a hydrogen atom or a -N(R^11h)-S(=O)₂-R^12h radical; with the proviso that at least one of the substituents R^2h, R^3h, R^4h and R^5h represents a - N(R^11h-S(=O)₂-R^12h moiety; R^11h represents a radical selected from the group consisting of H, methyl and ethyl; R^12h represents a radical selected from the group consisting of which is unsubstituted or substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of H, F, Cl, methyl, ethyl, -NH₂, -N(CH₃)₂, oxo (=O), -O-CH₃, -O-CH₂-CH₃, -NH-(C=O)-CH₃, -C(=O)-O-CH₃, -C(=O)-CF₃, whereby the substitution can take place on any suitable position in the aforementioned radicals, including the heteroatom(s); or a substituted phenyl radical selected from the group consisting of: optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate, or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof, or a corresponding base thereof.

Also preferred is a substituted tetrahydroisoquinoline compound of general formula Ih given above, wherein R^1h, R^2h, R^3h, R^4h, R^5h and R^11h have the meaning as defined above; with the proviso that at least one of the substituents R^2h, R^3h, R^4h and R^5h represents a - N(R^11h)-S(=O)₂-R^12h moiety; and R^12h represents a radical selected from the group consisting of optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate, or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof, or a corresponding base thereof.

Also preferred is a substituted tetrahydroisoquinoline compound of general formula Ih given above, wherein R^2h represents a -N(R^11h)-S(=O)₂-R^12h moiety; and B, A^h, D^h, R^1h, R^3h, R^4h, R^5h, R^11h and R^12h have the meaning as defined above; optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate, or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof, or a corresponding base thereof.

Also preferred is a substituted tetrahydroisoquinoline compound of general formula Ih given above, wherein R^3h represents a -N(R^11h)-S(=O)₂-R^12h moiety; and B, A^h, D^h, R^1h, R^2h, R^4h, R^5h, R^11h and R^12h have the meaning as defined above; optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate, or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof, or a corresponding base thereof.

Also preferred is a substituted tetrahydroisoquinoline compound of general formula Ih given above, wherein R^4h represents a -N(R^11h)-S(=O)₂-R^12h moiety; and B, A^h, D^h, R^1h, R^2h, R^3h, R^5h, R^11h and R^12h have the meaning as defined above; optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate, or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof, or a corresponding base thereof.

Also preferred is a substituted tetrahydroisoquinoline compound of general formula Ih given above, wherein R^5h represents a -N(R^11h)-S(=O)₂-R^12h moiety; and B, A^h, D^h, R^1h, R^2h, R^3h, R^4h, R^11h and R^12h have the meaning as defined above; optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate, or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof, or a corresponding base thereof.

Also preferred is a substituted tetrahydroisoquinoline compound selected from the group consisting of

[1] N-(1,2,3,4-tetrahydroisoquinolin-6-yl)naphthalene-1-sulfonamide hydrochloride,
[2] 2,2-dimethyl-6-(N-methylnaphthalene-1-sulfonamido)-1,2,3,4-tetrahydroisoquinolinium iodide,
[3] N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-6-yl)naphthalene-1-sulfonamide hydrochloride,
[4] 5-chloro-3-methyl-N-(1,2,3,4-tetrahydroisoquinolin-6-yl)benzo[b]thiophene-2-sulfonamide hydrochloride,
[5] 5-chloro-3-methyl-N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-6-yl)benzo[b]thiophene-2-sulfonamide hydrochloride,
[6] 4-methyl-N-(1,2,3,4-tetrahydroisoquinolin-6-yl)naphthalene-1-sulfonamide hydrochloride,
[7] 4-methyl-N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-6-yl)naphthalene-1-sulfonamide hydrochloride,
[8] N-(1,2,3,4-tetrahydroisoquinolin-6-yl)naphthalene-2-sulfonamide hydrochloride,
[9] N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-6-yl)naphthalene-2-sulfonamide hydrochloride,
[10] 6-chloro-N-(1,2,3,4-tetrahydroisoquinolin-6-yl)imidazo[2,1-b]thiazole-5-sulfonamide hydrochloride,
[11] 2-methoxy-5-methyl-N-(1,2,3,4-tetrahydroisoquinolin-6-yl)benzenesulfonamide hydrochloride,
[12] N-(1,2,3,4-tetrahydroisoquinolin-6-yl)pyridine-3-sulfonamide dihydrochloride,
[13] 6-(naphthalene-1-sulfonylamino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester,
[14] 6-(5-chloro-3-methyl-benzo[b]thiophene-2- sulfonylamino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester,
[15] 6-(4-methyl-naphthalene-1-sulfonylamino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester,
[16] 6-(naphthalene-2-sulfonylamino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester,
[17] 6-(2-methoxy-5-methyl-benzenesulfonylamino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester
[18] 6-(pyridine-3-sulfonylamino)-3,4-dihydro-1H-isoquinoline-2carboxylic acid tert-butyl ester;
[19] 6-Chloro-imidazo[2,1-b]thiazole-5-sulfonic acid (2-methyl-1,2,3,4tetrahydro-isoquinolin-6-yl)-amide hydrochloride
[20] 6-(6-Chloro-imidazo[2,1-b]thiazole-5-sulfonylamino)-3,4-dihydro-1Hisoquinoline-2-carboxylic acid tert-butyl ester
[21] 4-Methyl-3,4-dihydro-2H-benzo[1,4]oxazine-7-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride
[23] Benzo[1,2,5]thiadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride
[24] Benzo[b]thiophene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride
[25] 7-Chloro-benzo[1,2,5] oxadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin - 6-yl)-amide hydrochloride
[26] Benzo[1,2,5]oxadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride
[27] 5-Methyl-benzo[1,2,5] thiadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoqui- nolin-6-yl)-amide hydrochloride
[28] 7-Methyl-benzo[1,2,5]thiadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoqui- nolin-6-yl)-amide hydrochloride
[29] Benzo[b]thiophene-3-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-6-yl) -amide hydrochloride
[30] 4-Fluoro-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride
[31] 4-Chloro-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride
[32] 5-Dimethylaminonaphtha- lene-1-sulfonic acid (1,2,3,4 -tetrahydro-isoquinolin -6-yl)-amide hydrochloride
[33] 2-Oxo-4a,8a-dihydro-2H-chromene-6-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride
[34] 2-Methyl-benzothiazole-6-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-6-yl)-amide hydrochloride
[35] 5-Ethyl-2-methoxy-N-(1,2,3,4-tetrahydro- isoquinolin-6-yl)-benzene sulfonamide hydrochloride
[36] 6-Methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride
[37] N-[4-Ethoxy-3-(1,2,3,4-tetrahydro-isoquinolin-6-ylsulfamoyl)-phenyl]-acetamide hydrochloride
[38] 4-Methoxy-3-(1,2,3,4-tetrahydro-isoquinolin-6-yl sulfamoyl)-benzoic acid methyl ester hydrochloride
[39] 2-(2,2,2-Trifluoro-acetyl)-1,2,3,4-tetrahydro-isoquinoline-7-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride
[40] 1,2,3,4-Tetrahydro-isoquino line-7-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide dihydrochloride
[41] 5-Amino-2-ethoxy-N-(1,2,3,4-tetrahydro-isoquinolin-6-yl)-benzenesulfonamide dihydrochloride
[42] 5-Chloro-naphthalene-1-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-6-yl)-amide hydrochloride
[43] 1,2-Dimethyl-1H-imidazole-4-sulfonic acid (1 ,2,3,4-tetrahydro-isoquinolin- 6-yl)-amide hydrochloride
[44] N-[4-Methyl-5-(1,2,3,4-tetrahydro-isoquinolin-6- ylsulfamoyl)-thiazol-2-yl] - acetamide hydrochloride
[45] 1,3,5-Trimethyl-1H-pyrazole -4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl) - amide hydrochloride
[46] N-[5-(1,2,3,4-Tetrahydro-isoquinolin-6-ylsulfamoyl) -naphthalen-1-yl]-acetamide hydrochloride
[47] 2-Naphthalen-1-yl-ethanesulfonic acid (1,2,3,4 -tetrahydro-isoquinolin-6-yl) - amide hydrochloride
[48] Dibenzofuran-2-sulfonic acid (1,2,3,4-tetrahydro- isoquinolin-6-yl)-amide hydrochloride
[49] 2,5-Dimethoxy-N-(1,2,3,4-tetrahydro-isoquinolin -6-yl)-benzenesulfonamide hydrochloride
[50] 5-Chloro-2-methoxy-N-(1,2,3,4-tetrahydro-iso quinolin-6-yl)-benzene sulfonamide hydrochloride
[51] 2,5-Dimethyl-N-(1,2,3,4-tetrahydro-isoquinolin-6-yl)-benzenesulfonamide hydrochloride
[52] 2-Fluoro-5-methyl-N-(1,2,3,4-tetrahydro-isoquinolin-6-yl)-benzene sulfonamide hydrochloride
[53] 6-Chloro-imidazo[2,1-b]thiazole-5-sulfonic acid (2-methyl-1,2,3,4-tetrahydro - isoquinolin-7-yl)-amide hydrochloride
[54] 6-Chloro-imidazo[2,1-b]thiazole-5-sulfonic acid (1,2,3,4-tetrahydro-iso- quinolin-7-yl)-amide hydrochloride
[55] 4-Methyl-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride
[56] 4-Methyl-naphthalene-1-sulfonic acid (2-methyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride
[57] 5-Chloro-naphthalene-2-sulfonic acid (2-methyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride
[58] 5-Chloro-naphthalene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl) -amide hydrochloride
[59] 4-Methyl-3,4-dihydro-2H-benzo[1,4]oxazine-7-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride
[60] 5-Chloro-3-methyl-benzo[b]thiophene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin -7-yl)-amide hydrochloride
[61] Naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro- isoquinolin-7-yl)-amide hydrochloride
[63] 2,3-Dihydro-benzo[1,4] dioxine-6-sulfonic acid (1,2,3,4-tetrahydro-iso- quinolin-7-yl)-amide hydrochloride
[64] 5-Fluoro-3-methyl-benzo[b] thiophene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin -7-yl)-amide hydrochloride
[65] 3-Methyl-quinoline-8-sulfonic acid (1,2,3,4-tetra hydro-isoquinolin-7-yl)-amide hydrochloride
[66] Naphthalene-2-sulfonic acid (1,2,3,4-tetrahydro -isoquinolin-7-yl)-amide hydrochloride
[67] Benzo[1,2,5]thiadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl) - amide hydrochloride
[68] 1,4-Dimethyl-2,3-dioxo-1,2,3,4-tetrahydro-quino xaline-6-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride
[69] Benzo[b]thiophene-2-sulfonic acid (1,2,3,4-tetrahydro -isoquinolin-7-yl)-amide hydrochloride
[71] 7-Chloro-benzo[1,2,5] oxadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride
[72] Benzo[1,2,5]oxadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride
[73] 2-Oxo-2,3-dihydro-benzo thiazole-6-sulfonic acid (1,2,3,4-tetrahydro-isoqui- nolin-7-yl)-amide hydro- chloride
[74] 2-Oxo-2,3-dihydro-benzo oxazole-6-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride
[76] 5-Methylbenzo[1,2,5] thiadiazole -4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride
[77] 7-Methyl-benzo[1,2,5] thiadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride
[78] Benzo[b]thiophene-3-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-7-yl) -amide hydrochloride
[79] Isoquinoline-5-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride
[80] 4-Fluoro-naphthalene-1-sulfonic acid (1,2,3,4 -tetrahydro-isoquinolin-7-yl) -amide hydrochloride
[81] 4-Chloro-naphthalene-1-sulfonic acid (1,2,3,4 -tetrahydro-isoquinolin-7-yl) -amide hydrochloride
[82] 2,2-Dimethyl-chroman-6-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-7-yl) -amide hydrochloride
[83] 5-Dimethylamino-naphtha lene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl) -amide hydrochloride
[84] 2-Oxo-2H-chromene-6-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)- amide hydrochloride
[85] 2-Methyl-benzothiazole-6-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl) - amide hydrochloride
[86] 5-Ethyl-2-methoxy-N-(1,2,3,4-tetrahydro-isoquinolin-7-yl)-benzenesulfonamide hydrochloride
[87] 6-Methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine- 5-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride
[88] 6-Chloro-imidazo[2,1-b] thiazole-5-sulfonic acid ethyl-(2-ethyl-1,2,3,4-tetrahydro-isoquinolin-5-yl) -amide hydrochloride
[89] 6-Chloro-imidazo[2,1-b] thiazole-5-sulfonic acid (2-ethyl-1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride
[90] 6-Chloro-imidazo[2,1-b] thiazole-5-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride
[91] 5-Methyl-naphthalene-1-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-5-yl) -amide hydrochloride
[92] Naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro- isoquinolin-5-yl)-amide hydrochloride
[93] 5-Chloro-naphthalene-2-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-5-yl) -amide hydrochloride
[94] 4-Methyl-3,4-dihydro-2H-benzo[1,4]oxazine-7- sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride
[95] 5-Chloro-3-methyl-benzo[b] thiophene-2-sulfonic acid ethyl-(2-ethyl-1 ,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride
[96] 5-Chloro-3-methyl-benzo[b] thiophene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride
[98] 2,3-Dihydro-benzo[1,4] dioxine-6-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride
[99] 5-Fluoro-3-methyl-benzo[b] thiophene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride
[100] 3-Methyl-quinoline-8-sulfonic acid ethyl-(2-ethyl -1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride
[101] 3-Methyl-quinoline-8-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-5-yl) -amide hydrochloride
[102] Naphthalene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquino lin-5-yl)-amide hydrochloride
[103] Benzo[1,2,5]thiadiazole-4-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-5-yl) - amide hydrochloride
[104] Benzo[b]thiophene-2-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-5-yl) -amide hydrochloride
[105] Benzo[1,2,5]oxadiazole-4-sulfonic acid (1,2,3,4-tetra hydro-isoquinolin-5-yl)-amide hydrochloride
[106] 7-Chlorobenzo[1,2,5]oxa diazole -4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride
[107] 2-Oxo-2,3-dihydro-benzooxazole-6-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl) -amide hydrochloride
[108] 5-Methyl-benzo[1,2,5] thiadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride
[109] 7-Methyl-benzo[1,2,5] thiadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride
[110] Benzo[b]thiophene-3-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-5-yl) -amide hydrochloride
[111] Isoquinoline-5-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide dihydrochloride
[112] 4-Fluoro-naphthalene-1-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-5-yl) -amide hydrochloride
[113] 4-Chloro-naphthalene-1-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-5-yl) -amide hydrochloride
[114] 2,2-Dimethyl-chroman-6-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-5-yl) -amide hydrochloride
[115] 5-Dimethylamino-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride
[116] 2,2,5,7,8-Pentamethyl-chroman-6-sulfonic acid (1,2,3,4-tetrahydro-isoquino lin-5-yl)-amide hydrochloride
[117] 2-Oxo-2H-chromene-6-sulfonic acid (1,2,3,4-tetrahy dro-isoquinolin-5-yl) -amide hydrochloride
[118] 5-Ethyl-2-methoxy-N(1,2, 3,4-tetrahydro-isoquinolin-5-yl)-benzenesulfonamide hydrochloride
[119] N-[4-Ethoxy-3-(1,2,3,4-tetrahydro-isoquinolin-5-yl sulfamoyl)-phenyl]-acetamide hydrochloride
[120] 2-Methoxy-5-methyl-N-(1,2,3,4-tetrahydro-isoquinolin-5-yl)-benze nesulfonamide hydrocloride
[121] 5-Chloro-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl) -amide hydrochloride
[122] 2-Methoxy-5-methyl-N-(1,2,3,4-tetrahydro-isoquinolin-5-yl)-benzenesulfonamide hydrocloride
[123] Quinoline-8-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin -5-yl)-amide hydrochloride
[124] Dibenzofuran-2-sulfonic acid (1,2,3,4-tetrahydro- isoquinolin-5-yl)-amide hydrochloride
[125] 6-Chloro-imidazo[2,1-b] thiazole-5-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide hydrochloride
[126] 6-chloro-N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-8-yl)imidazo[2,1-b]thiazole-5-sulfonamide hydrochloride
[127] Benzo[b]thiophene-2-sulfonic acid (1,2,3,4-tetra hydro-isoquinolin-8-yl) -amide hydrochloride
[128] Benzo[b]thiophene-2-sulfonic acid (2-methyl- 1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide hydrochloride
[129] Benzo[b]thiophene-3-sulfonic acid (2-methyl- 1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide hydrochloride
[130] Benzo[b]thiophene-3-sulfonic acid (1,2,3,4-tetra hydro-isoquinolin-8-yl) -amide hydrochloride
[131] 5-Chloro-3-methyl-benzo[b]thiophene-2-sulfonic acid (2-methyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide hydrochloride
[132] 5-Chloro-3-methyl-benzo[b]thiophene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin -8-yl) -amide hydrochloride
[133] Naphthalene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide hydrochloride
[134] Naphthalene-2-sulfonic acid (2-methyl-1 ,2,3,4-tetrahydro-isoquinolin-8-yl) -amide hydrochloride
[137] Naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide hydrochloride
[138] Naphthalene-1-sulfonic acid (2-methyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide Hydrochloride
[139] 4-Methyl-naphthalene-1-sulfonic acid (2-methyl- 1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide Hydrochloride
[140] 4-Methyl-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide Hydrochloride
[141] 4-Chloro-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-8-yl)- amide Hydrochloride
[142] 4-Chloro-naphthalene-1-sulfonic acid (2-methyl -1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide Hydrochloride
[143] 5-Chloro-naphthalene-1-sulfonic acid (2-methyl -1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide Hydrochloride
[144] 5-Chloro-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-8-yl)- amide Hydrochloride
[145] 5-Chloro-naphthalene-2-sulfonic acid (1 ,2,3,4-tetrahydro-isoquinolin-8-yl)- amide Hydrochloride
[146] 5-Chloro-naphthalene-2-sulfonic acid (2-methyl -1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide Hydrochloride
[147] 4-Methyl-3,4-dihydro-2H-benzo[1,4]oxazine-7- sulfonic acid (2-methyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide Hydrochloride
[148] 4-Methyl-3,4-dihydro-2H-benzo[1,4]oxazine-7- sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide Hydrochloride
[149] 5-Ethyl-2-methoxy-N-(1,2,3,4-tetrahydro- isoquinolin-8-yl)-benzenesulfonamide Hydrochloride
[150] 5-Ethyl-2-methoxy-N-(2-methyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-benzene sulfonamide Hydrochloride
[151] 5-Methyl-benzo[1,2,5] thiadiazole-4-sulfonic acid (2-methyl-1,2,3,4-tetrahydro - isoquinolin-8-yl)-amide Hydrochloride
[152] 5-Methyl-benzo[1,2,5] thiadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide Hydrochloride
[153] Naphthalene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide and
[154] 5-Chloro-naphthalene-1-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-7-yl)-amide Hydrochloride
[155] Naphthalene-2-sulfonic acid (2-cyclopropanecarbonyl- 1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide
[156] Naphthalene-2-sulfonic acid (2-cyclopropylmethyl- 1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide Hydrochloride
[157] 6-Chloro-imidazo[2,1-b] thiazole-5-sulfonic acid (2-cyclopropanecarbonyl- 1,2,3,4-tetrahydro-isoquino lin-6-yl)-amide and
[158] 6-Chloro-imidazo[2,1-b] thiazole-5-sulfonic acid (2-cyclopropylmethyl-1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride;

optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a salt thereof, or a corresponding solvate thereof.

In still another aspect the present invention relates to a process for the preparation of a substituted tetrahydroisoquinoline compound of general formula Ih, wherein at least one compound of general formula IVh, wherein R^12h has the meaning given above and X represents a leaving group, preferably a halogen atom, particularly preferably a chlorine atom, is reacted with at least one compound of general formula VhA, wherein R^1h to R^5h have the meaning given above, with the proviso that at least one substituent of the group consisting of R^2h, R^3h, R^4h and R^5h represents a -N(H)(R^11h) moiety, wherein R^11e has the meaning given above, or a protected derivative thereof, in a reaction medium, preferably in a reaction medium selected from the group consisting of pyridine, chloroform, dichloromethane, tetrahydrofurane and mixtures thereof, preferably in the presence of at least one base, more preferably in the presence of at least one base selected from the group consisting of triethylamine, diisopropylethylamine and diethylisopropylamine, preferably at a temperature between 0 °C and 30 °C.

If the substituted tetrahydroisoquinoline compounds of general formula Ih are obtained in form of a mixture of stereoisomers, particularly enantiomers or diastereomers, said mixtures may be separated by standard procedures known to those skilled in the art, e.g. chromatographic methods or crystallization with chiral reagents.

Compounds of general formula IV and/or IVhA are in most cases commercially available or may be prepared by processes known to those skilled in the art.

Compounds of general formula V and/or VhA are in most cases commercially available or may be prepared by processes known to those skilled in the art.

In particular, 1,2,3,4-tetrahydroisoquinoline compounds with an amino group in position 5 can be prepared starting from 5-nitro-1,2,3,4-tetrahydroisoquinoline compounds. A process for the preparation of the latter compounds is described in K. V. Rao et al., Journal of Heterocyclic Chemistry, 1973, 10, 213 to 215.

In particular, 1,2,3,4-tetrahydroisoquinoline compounds with an amino group in position 6 are commercially available or can be prepared starting from 6-nitro-1,2,3,4-tetrahydroisoquinoline compounds. A process for the preparation of the latter compounds is described in G. J. Quallich, Journal of Organic Chemistry, 1998, 63, 4116 to 4119.

1,2,3,4-tetrahydroisoquinoline compounds with a nitro group in position 6 or 8 may be prepared by established procedures described in M. Tercel, Journal of Medicinal Chemistry, 1996, 39, 1084 to 1094.

In particular, 1,2,3,4-tetrahydroisoquinoline compounds with an amino group in position 7 are commercially available or can be prepared starting from 7-nitro-1,2,3,4-tetrahydroisoquinoline compounds. A process for the preparation of the latter compounds is described in J. F. Ajao et al., Journal of Heterocyclic Chemistry, 1985, 22, 329 to 331.

The N-methyl-8-amino-substituted 1,2,3,4-tetrahydroisoquinoline compounds were prepared by bromination and nitration of the corresponding 1,2,3,4-tetrahydroisoquinolines followed by two-step standard reduction conditions as described in M. Rey, Helvetica Chimica Acta, 1985, 66, 1828 to 1834.

In all the following schemes 1 to 7 protecting groups for the nitrogen atom may be used. Some examples include cyclic imide derivatives, such as maleimides or succinimides, a variety of carbamates, such as tert-butoxy-carbonyl (BOC) and fluorenylmethyloxycarbonyl (Fmoc)m a variety of amides, such as acetamides, and alkyl and aryl amine derivatives, such as N-benzyl or N-allyl amines. Additional examples of nitrogen protecting groups can be found in reference books such as Protective groups in Organic Chemistry, ed. J. F. W. McOmie, Plenum Press, 1973; and T.W. Greene & P.G.M. Wuts, Protective Groups in Organic Chemistry, John Wiley & sons, 1999.

Preparation of substituted tetrahydroisoquinoline compounds of general formula Ia (scheme 1 and 2)

Preparation of substituted tetrahydroisoquinoline compounds of general formula Ib (scheme 3)

Preparation of substituted tetrahydroisoquinoline compounds of general formula Ic (scheme 4, 5 and 6)

Preparation of substituted tetrahydroisoquinoline compounds of general formula Id (scheme 7)

In still another aspect the present invention relates to a process for the preparation of a salt of a substituted tetrahydroisoquinoline compound of general formula Ih, wherein at least one compound of general formula VIhA, wherein R^1h to R^5h have the meaning given above, preferably with the proviso that at least one substituent of the group consisting of R^2h, R^3h, R^4h and R^5h represents a - NR^11h-S(=O)₂-R^12h moiety, wherein R^11h and R^12h have the meaning given above, is reacted with at least one compound of general formula A^h-D^h, wherein A^h and D^h have the meaning given above, in a reaction medium, preferably in a reaction medium selected from the group consisting of acetone, tetrahydrofurane, water, ethyl acetate, chloroform, acetonitrile, dichloromethane and mixtures thereof, to yield at least one salt of general formula Ih, wherein A^h, D^h and R^1h to R^5h have the meaning given above with the proviso that at least one substituent of the group consisting of R^2h, R^3h, R^4h and R^5h represents a - NR^11h-S(=O)₂-R^12h moiety, wherein R^11h and R^12h have the meaning given above.

The term "salt" is to be understood as meaning any form of the substituted tetrahydroisoquinoline compounds of general formula I in which they assume an ionic form or are charged and are coupled with a counter-ion (a cation or anion) or are in solution. By this are also to be understood complexes of the active compound with other molecules and ions, in particular complexes which are complexed via ionic interactions.

The term "physiologically acceptable salt" is understood in particular, in the context of this invention, as salt (as defined above) formed either with a physiologically tolerated acid, that is to say salts of the particular active compound with inorganic or organic acids which are physiologically tolerated - especially if used on humans and/or mammals - or with at least one, preferably inorganic, cation which are physiologically tolerated - especially if used on humans and/or mammals. Examples of physiologically tolerated salts of particular acids are salts of: hydrochloric acid, hydrobromic acid, sulfuric acid, hydrobromide, monohydrobromide, monohydrochloride or hydrochloride, methiodide, methanesulfonic acid, formic acid, acetic acid, oxalic acid, succinic acid, malic acid, tartaric acid, mandelic acid, fumaric acid, lactic acid, citric acid, glutamic acid, hippuric acid picric acid and/or aspartic acid. Examples of physiologically tolerated salts of particular bases are salts of alkali metals and alkaline earth metals and with NH₄.

Solvates, preferably hydrates, of the substituted tetrahydroisoquinoline compounds of general formula I or in each case of corresponding stereoisomers may also be obtained by standard procedures known to those skilled in the art.

The term "solvate" according to this invention is to be understood as meaning any form of the substituted tetrahydroisoquinoline compounds of general formula I in which they have attached to it via non-covalent binding another molecule (most likely a polar solvent) especially including hydrates and alcoholates, e.g. methanolate.

In the following methods for determining the pharmacological activity of the substituted tetrahydroisoquinoline compounds are described.

Pharmacological Methods: I) BINDING TO SEROTONIN RECEPTOR 5-HT₆

Cell membranes of HEK-293 cells expressing the 5HT₆-human recombinant receptor were supplied by Receptor Biology. In said membranes the receptor concentration is 2.18 pmol/mg protein and the protein concentration is 9.17 mg/ml. The experimental protocol follows the method of B. L. Roth et al. [B. L. Roth, S. C. Craigo, M. S. Choudhary, A. Uluer, F. J. Monsma, Y. Shen, H. Y. Meltzer, D. R. Sibley: Binding of Typical and Atypical Antipsychotic Agents to 5-Hydroxytryptamine-6 and Hydroxytryptamine-7 Receptors. The Journal of Pharmacology and Experimental Therapeutics, 1994, 268, 1403] with the following slight changes. The respective part of the literature description is hereby incorporated by reference and forms part of the disclosure.

The commercial membrane is diluted (1:40. dilution) with the binding buffer: 50 mM Tris-HCl, 10 mM MgCl₂, 0.5 mM EDTA (pH 7.4). The radioligand used is [³H]-LSD at a concentration of 2.7 nM with a final volume of 200 µl. Incubation is initiated by adding 100 µl of membrane suspension, (≈ 2.9 µg membrane protein), and is prolonged for 60 minutes at a temperature of 37 ºC. The incubation is ended by fast filtration in a Brandel Cell Harvester through fiber glass filters made by Schleicher & Schuell GF 3362 pretreated with a solution of polyethylenimine at 0.5 %. The filters are washed three times with three milliliters of buffer Tris-HCl 50 mM pH 7.4. The filters are transferred to flasks and 5 ml of Ecoscint H liquid scintillation cocktail are added to each flask. The flasks are allowed to reach equilibrium for several hours before counting with a Wallac Winspectral 1414 scintillation counter. Non-specific binding is determined in the presence of 100 µM of serotonin. Tests were made in triplicate. The inhibition constants (K_i, nM) were calculated by non-linear regression analysis using the program EBDA/LIGAND described in Munson and Rodbard, Analytical Biochemistry, 1980, 107, 220, the respective part of which is hereby incorporated by reference and forms part of the disclosure.

II.) FOOD INTAKE MEASUREMENT (BEHAVIOURAL MODEL):

Male W rats (200-270 g) obtained from Harlan, S.A. are used. The animals are acclimatized to the animal facility for at least 5 days before they are subjected to any treatment. During this period the animals are housed (in groups of five) in translucid cages and provided with food and water ad libitum. At least 24 hours before the treatment starts, the animals are adapted to single-housing conditions.

The acute effect of the substituted tetrahydroisoquinoline compounds according to the present invention in fasted rats is then determined as follows:

The rats were fasted for 23 hours in their single homecages. After this period, the rats are orally or intraperitoneally dosed with a composition comprising a substituted tetrahydroisoquinoline compound or a corresponding composition (vehicle) without said substituted tetrahydroisoquinoline compound. Immediately afterwards, the rat is left with preweighed food and cumulative food intake is measured after 1, 2, 4 and 6 hours.

Said method of measuring food intake is also described in the literature publications of Kask et al., European Journal of Pharmacology 414 (2001), 215-224 and Turnbull et al., Diabetes, Vol. 51, August 2002. The respective parts of the descriptions are hereby incorporated by reference and form part of the disclosure.

The present invention is illustrated below with the aid of examples. These illustrations are given solely by way of example and do not limit the general spirit of the present invention.

Preparation of example compound 15: 6-(4-Methyl-naphthalene-1-sulfonylamino)-3,4-dihydro-1H-isoquinoline-2 -carboxylic acid tert-butyl ester

4-Methyl-naphthalene-1-sulfonyl chloride (310 mg, 1.288 mmol) was added to a solution of tert-butyl 6-amino-3,4-dihydroisoquinoline-2(1H)-carboxylate (318 mg, 1.28 mmol), pyridine (102 mg, 1.28 mmol) and dimethylaminopyridine (15 mg) in dichloromethane (50 mL). After stirring overnight at room temperature the mixture was washed with water, dried over sodium sulfate and filtered. The organic extracts were diluted with ethanol and partial evaporation afforded the title compound (435 mg, 74 %).

The example compounds 13, 14, 16, 17, 18 were prepared analogously to the process described for the preparation of example compound 15.

Preparation of example compound 6: 4-Methyl-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydroisoquinolin-6-yl)amide hydrochloride

A solution of hydrogen chloride [2.0 M in diethylether] was added to a suspension of 6-(4-methyl-naphthalene-1-sulfonylamino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (390 mg, 0.86mmol) in ethyl acetate (15 mL). Stirring was continued overnight at room temperature to precipitate the hydrochloride of 4-methyl-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)amide (320 mg, 95 %).

The example compounds 1, 4, 8, 10, 11 and 12 were prepared analogously to the process described for the preparation of example compound 6.

Preparation of example compound 7: 4-Methyl-naphthalene-1-sulfonic acid (2-methyl-1,2,3,4-tetrahydroiso quinolin-6-yl)amide hydrochloride

A solution of 4-methyl-naphthalene-1-sulfonic acid(1,2,3,4-tetrahydro-isoquinolin-6-yl)amide (254 mg, 0.72 mmol) in acetonitrile (15 mL) was treated with formaldehyde (37% aqueous solution, 1 mL) and stirred for 2 hours at room temperature. Sodium cyanoborohydride (210mg, 3.3 mmol) was added and the mixture was allowed to stir for 2 hours following addition of acetic acid (pH 7). After stirring overnight the mixture was evaporated and the residue partitioned between chloroform and water. The organic layer was separated and evaporated to give the crude free base which was purified by chromatography eluting with 2% methanol in chloroform. Treatment with a 2.0 M ethereal hydrogen chloride solution gave the title compound as the hydrochloride salt (104 mg, 41 %).

The example compounds 3, 4 and 9 were prepared analogously to the process described for the preparation of example compound 7.

Preparation of example compound 2: 2,2-Dimethyl-6-[methyl-(naphthalene-1-sulfonyl)-amino]-1,2,3,4-tetrahydro isoquinolinium iodide

Naphthalene-1-sulfonic acid (1,2,3,4-tetrahydrisoquinolin-6-yl)-amide hydrochloride (100 mg, 0.26 mmol) and potassium carbonate( 111 mg, 0.80 mmol) were dissolved in acetone (20 ml) and methyl iodide ( 150mg,1.04mmol) was added. The mixture was heated under reflux for 6 hours. The solution was evaporated and the crude quaternary ammonium salt was crystallised by addition of ethanol ( 5 ml ) to afforded the title compound (120 mg, 91 %).

Preparation of example compound 55: 4-Methyl-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7 -yl)amide hydrochloride

To a solution of 7-Amino-2-N-BOC-1,2,3,4-tetrahydroisoquinoline (318 mg, 1.28 mmol), pyridine (102 mg, 1.28 mmol) and dimethylaminopyridine (15 mg) in dichloromethane (50 mL) was added 4-methyl-naphthalene-1-sulfonyl chloride (310 mg, 1.288 mmol). After stirring overnight at room temperature the mixture was washed with water, dried over sodium sulfate and filtered. The organic extracts were diluted in ethyl acetate (15 mL) and a solution of hydrogen chloride 2,0 M in diethylether was added. Stirring was continued overnight at room temperature to precipitate the hydrochloride of 4-Methylnaphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)amide (292mg, 83 %) [MH]⁺= 353. ¹H NMR (400 MHz, DMSO-d ₆) δ ppm 2.67 (s, 3 H) 2.77 (t, J=6.06 Hz, 2 H) 3.21 (m, 2 H) 4.07 (br. s., 2 H) 6.89 (d, J=1.95 Hz, 1 H) 6.86 (s, 1 H) 6.94 - 7.00 (m, 1 H) 7.46 (d, J=7.42 Hz, 1 H) 7.65 - 7.76 (m, 2 H) 8.12 (t, J=7.23 Hz, 2 H) 8.72 (d, J=7.82 Hz, 1 H) 9.14 (br. s., 2 H) 10.72 (s, 1 H)

Preparation of example compound 91: 4-Methyl-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5 -yl)amide hydrochloride

To a solution of 5-Amino-2-N-BOC-1,2,3,4-tetrahydroisoquinoline (318 mg, 1.28 mmol), pyridine (102 mg, 1.28 mmol) and dimethylaminopyridine (15 mg) in dichloromethane (50 mL) was added 4-methyl-naphthalene-1-sulfonyl chloride (310 mg, 1.288 mmol). After stirring overnight at room temperature the mixture was washed with water, dried over sodium sulfate and filtered. The organic extracts were diluted in ethyl acetate (15 mL) and a solution of hydrogen chloride 2,0 M in diethylether was added. Stirring was continued overnight at room temperature to precipitate the hydrochloride of 4-Methylnaphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)amide (274mg, 78 %) [MH]⁺= 353. ¹H NMR (300 MHz, DMSO-d ₆) δ ppm 2.72 (s, 3 H) 2.85 (br. s., 2 H) 3.16 (br. s., 2 H) 4.15 (br. s., 2 H) 6.65 (d, J=7.03 Hz, 1 H) 6.93 - 7.13 (m, 2 H) 7.45 (d, J=7.62 Hz, 1 H) 7.73 (d, J=2.93 Hz, 1 H) 7.71 (br. s., 1 H) 7.93 (d, J=7.32 Hz, 1 H) 8.19 (br. s., 1 H) 8.72 (d, J=6.44 Hz, 1 H) 9.15 (br. s., 2 H) 10.00 (s, 1 H)

Preparation of example compound 140 4-Methyl-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-8 -yl)amide hydrochloride

To a solution of 8-Amino-2-N-BOC-1,2,3,4-tetrahydroisoquinoline (318 mg, 1.28 mmol), pyridine (102 mg, 1.28 mmol) and dimethylaminopyridine (15 mg) in dichloromethane (50 mL) was added 4-methyl-naphthalene-1-sulfonyl chloride (310 mg, 1.288 mmol). After stirring overnight at room temperature the mixture was washed with water, dried over sodium sulfate and filtered. The organic extracts were diluted in ethyl acetate (15 mL) and a solution of hydrogen chloride 2,0 M in diethylether was added. Stirring was continued overnight at room temperature to precipitate the hydrochloride of 4-Methylnaphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-8-yl)amide (182 mg, 51 %). [MH]⁺= 353.

Preparation of example compound 155 Naphthalene-2-sulfonic acid (2-cyclopropanecarbonyl-1,2,3,4-tetrahydro-isoquinolin-6-yl)amide

To a solution of naphthalene-2-sulfonic acid (1,2,3,4-tetrahydroisoquinoli-6-yl)amide (338 mg, 1 mmol) in dichloromethane (50 mL), N-ethyldiisopropylamine (194 mg, 1,50 mmol) and cyclopropanecarbonyl chloride (105 mg, 1 mmol) were added. After stirring overnight at room temperature the mixture was washed with water, dried over sodium sulfate and filtered, and recristallized in etanol to gave Naphthalene-2-sulfonic acid (2-cyclopropanecarbonyl-1,2,3,4-tetrahydro-isoquinolin-6-yl)amide (310 mg, 76%) [MH]⁺= 407 ¹H NMR (300 MHz, DMSO-d₆ ) δ ppm 0.68 (m, 4 H) 1.95 (br. s., 1 H) 2.60 (br. s., 1 H) 2.72 (br.s., 1 H) 3.54 (br. s., 1 H) 3.75 (br. s., 1 H) 4.41 (br. s., 1 H) 4.69 (br. s., 1 H) 6.86 - 7.02 (m, 3 H) 7.65 (td, J=7.76, 1.32 Hz, 2 H) 7.76 (dd, J=8.72, 1.39 Hz, 1 H) 7.98 (d, J=7.76 Hz, 1 H) 8.01 - 8.15 (m, 2 H) 8.43 (s, 1 H) 10.25 (br. s., 1 H)

Preparation of example compound 156 Naphthalene-2-sulfonic acid (2-cyclopropylmethyl-1,2,3,4-tetrahydroisoquinolin 6-yl) amide hydrochloride

To a solution of lithium aluminium hydride 1.0 M in tetrahydrofuran (5 mL,5 mmol) under nitrogen, naphthalene-2-sulfonic acid (2-cyclopropanecarbonyl -1,2,3,4-tetrahydro-isoquinolin-6-yl)amide (200 mg, 0.49 mmol) was added. The reaction mixture was heated to reflux for 3 hours, and then at room temperatura overnight. After cooling to 0 ºC, water was added and the mixture was filtered.The filtrate was extracted with dichloromethane and the organic layer was washed with saturated NaCl, dried and concentrated in vacuo. The resulting residue was chromatografed on silica gel with CHCl₃-MeOH (98:2). To a solution of Naphthalene-2-sulfonic acid (2-cyclopropylmethyl-1,2,3,4-tetrahydroisoquinolin 6-yl) amide in ethyl acetate ( 3 mL) a solution of hydrogen chloride 2,0 M in diethylether (2mL) was added. Stirring was continued overnight at room temperature to precipitate the hydrochloride of naphthalene-2-sulfonic acid (2-cyclopropylmethyl-1,2,3,4-tetrahydroisoquinolin-6-yl) amide (126 mg, 60 %) [MH]⁺= 394 ¹H NMR (300 MHz, DMSO-d ₆) δ ppm 0.38 (m, 2 H) 0.62 (m, 2 H) 1.06 - 1.19 (m, 1 H) 2.86 - 3.12 (m, 4 H) 3.19 (m, 1 H) 3.61 (m, 1 H) 4.15 (dd, J=15.09, 7.47 Hz, 1 H) 4.34 - 4.45 (m, 1 H) 6.99 - 7.08 (m, 3 H) 7.68 (td, J=7.47, 1.39 Hz, 2 H) 7.81 (dd, J=8.72, 1.83 Hz, 1 H) 8.01 (d, J=7.76 Hz, 1 H) 8.15 (d, J=7.47 Hz, 1 H) 8.10 (d, J=8.72 Hz, 1 H) 8.49 (d, J=1.32 Hz, 1 H) 10.49 (br.s., 1 H) 10.58 (s, 1 H)


1		Naphthalene-1-sulfonic acid (1,2,3,4-tetrahydroisoquinolin-6-yl)-amide hydrochloride	339
2		2,2-Dimethyl-6-[methyl-(naphthalene-1-sulfonyl)-amino]-1,2,3,4-tetrahydro isoquinolinium iodide	381
3		Naphthalene-1-sulfonic acid (2-methyl-1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride	353
4		5-Chloro-3-methyl-benzo[b]thiophene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride	393
5		5-Chloro-3-methyl-benzo[b]thiophene-2-sulfonic acid (2-methyl-1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride	407
6		4-Methyl-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)amide hydrochloride	353
7		4-Methyl-naphthalene-1-sulfonic acid (2-methyl-1,2,3,4 -tetrahydro-isoqui-nolin-6-yl)amide hydrochloride	367
8		Naphthalene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride	339
9		Naphthalene-2-sulfonic acid (2-methyl-1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride	353
10		6-Chloro-imidazo[2,1-b]thiazole-5-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride	369
11		2-Methoxy-5-methyl-N-(1,2,3,4-tetrahydro-isoquinolin-6-yl)-benzene sulfonamide hydrochloride	333
12		Pyridine-3-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide dihydrochloride	290
13		6-(Naphthalene-1-sulfonylamino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester	439
14		6-(5-Chloro-3-methyl-benzo[b]thiophene-2-sulfonylamino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester	493
15		6-(4-Methyl-naphthalene-1-sulfonylamino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester	453
16		6-(Naphthalene-2-sulfonylamino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester	439
17		6-(2-Methoxy-5-methyl-benzenesulfonylamino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester	433
18		6-(Pyridine-3-sulfonylamino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester	469
19		6-Chloro-imidazo[2,1-b]thiazole-5-sulfonic acid (2-methyl-1,2,3,4tetrahydro-isoquinolin-6-yl)-amide hydrochloride		383
20		6-(6-Chloro-imidazo[2,1-b]thiazole-5-sulfonylamino)-3,4-dihydro-1Hisoquinoline-2-carboxylic acid tert-butyl ester		469
21		4-Methyl-3,4-dihydro-2H-benzo[1,4]oxazine-7-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride		360
23	Benzo[1,2,5]thiadiazol e-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride	347
24	Benzo[b]thiophene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride	345
25	7-Chloro-benzo[1,2,5]oxadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride	365
26	Benzo[1,2,5]oxadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride	331
27	5-Methyl-benzo[1,2,5]thiadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride	361
28	7-Methyl-benzo[1,2,5]thiadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride	361
29	Benzo[b]thiophene-3-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride	345
30	4-Fluoro-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride	357
31	4-Chloro-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride	373
32	5-Dimethylaminonaphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride	382
33	2-Oxo-4a,8a-dihydro-2H-chromene-6-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride	359
34	2-Methyl-benzothiazole-6-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride	360
35	5-Ethyl-2-methoxy-N-(1,2,3,4-tetrahydro-isoquinolin-6-yl)-benzene sulfonamide hydrochloride	347
36	6-Methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-am ide hydrochloride	337
37	N-[4-Ethoxy-3-(1,2,3,4-tetrahydro-isoquinolin-6-ylsulfamoyl)-phenyl]-acetamide hydrochloride	390
38	4-Methoxy-3-(1,2,3,4-tetrahydro-isoquinolin-6-yl sulfamoyl)-benzoic acid methyl ester hydrochloride	377
39	2-(2,2,2-Trifluoro-acetyl)-1,2,3,4-tetrahydro-isoquinoline-7-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride	440
40	1,2,3,4-Tetrahydro-isoquinoline-7-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide dihydrochloride	344
41	5-Amino-2-ethoxy-N-(1,2,3,4-tetrahydro-isoquinolin-6-yl)-benzenesulfon amide dihydrochloride	348
42	5-Chloro-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride	373
43	1,2-Dimethyl-1H-imidazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride	307
44	N-[4-Methyl-5-(1,2,3,4-tetrahydro-isoquinolin-6-ylsulfamoyl)-thiazol-2-yl]-acetamide hydrochloride	367
45	1,3,5-Trimethyl-1H-pyrazole -4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride	321
46	N-[5-(1,2,3,4-Tetrahydro-isoquinolin-6-ylsulfamoyl)-naphthalen-1-yl]-acetamide hydrochloride	396
47	2-Naphthalen-1-yl-ethanesulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride	367
48	Dibenzofuran-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-ami de hydrochloride	379
49	2,5-Dimethoxy-N-(1,2,3,4-tetrahydro-isoquinolin-6-yl)-benzenesulfonamide hydrochloride	349
50	5-Chloro-2-methoxy-N-(1,2,3,4-tetrahydro-isoquinolin-6-yl)-benzene sulfonamide hydrochloride	353
51	2,5-Dimethyl-N-(1,2,3,4-tetrahydro-isoquinolin-6-yl)-benzenesulfonamide hydrochloride	317
52	2-Fluoro-5-methyl-N-(1,2,3,4-tetrahydro-isoquinolin-6-yl)-benzene sulfonamide hydrochloride	321
53	6-Chloro-imidazo[2,1-b]thiazole-5-sulfonic acid (2-methyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride	383
54	6-Chloro-imidazo[2,1-b]thiazole-5-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride	369
55	4-Methyl-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride	353
56	4-Methyl-naphthalene-1-sulfonic acid (2-methyl-1,2,3,4-tetrahydro-isoqui-nolin-7-yl)-amide hydrochloride	367
57	5-Chloro-naphthalene-2-sulfonic acid (2-methyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride	387
58	5-Chloro-naphthalene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride	373
59	4-Methyl-3,4-dihydro-2H-benzo[1,4]oxazine-7-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride	360
60	5-Chloro-3-methyl-benzo[b]thiophene -2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride	393
61	Naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride	339
63	2,3-Dihydro-benzo[1,4]dioxine-6-sulfonic acid (1,2,3,4-tetrahydro-iso-quinolin-7-yl)-amide hydrochloride	347
64	5-Fluoro-3-methyl-benzo[b] thiophene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride	377
65	3-Methyl-quinoline-8-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-y l)-amide hydrochloride	354
66	Naphthalene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride	339
67	Benzo[1,2,5]thiadiazol e-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl) -amide hydrochloride	347
68	1,4-Dimethyl-2,3-dioxo-1,2,3,4-tetrahydro-quino xaline-6-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride	401
69	Benzo[b]thiophene-2-sulfonic acid (1,2,3,4-tetrahydro -isoquinolin-7-yl)-amide hydrochloride	345
71	7-Chloro-benzo[1,2,5]oxadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride	365
72	Benzo[1,2,5]oxadiazol e-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride	331
73	2-Oxo-2,3-dihydro-benzo thiazole-6-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydro- chloride	362
74	2-Oxo-2,3-dihydro-benzo oxazole-6-sulfonic acid (1,2,3,4-tetrahydro-iso quinolin-7-yl)-amide hydrochloride	346
76	5-Methylbenzo[1,2,5] thiadiazole -4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride	361
77	7-Methyl-benzo[1,2,5]thiadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride	361
78	Benzo[b]thiophene-3-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride	345
79	Isoquinoline-5-sulfonic acid (1,2,3,4-tetrahydro -isoquinolin-7-yl)-ami de hydrochloride	340
80	4-Fluoro-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride	357
81	4-Chloro-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride	373
82	2,2-Dimethyl-chroman-6-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride	373
83	5-Dimethylamino-naphtha lene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride	382
84	2-Oxo-2H-chromene-6-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride	357
85	2-Methyl-benzothiazole-6-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride	360
86	5-Ethyl-2-methoxy-N-(1,2,3,4-tetrahydro-isoquinolin-7-yl)-benzenesulfonamide hydrochloride	347
87	6-Methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine- 5-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride	337
88	6-Chloro-imidazo[2,1-b]thiazole-5-sulfonic acid ethyl-(2-ethyl-1,2,3,4 -tetrahydro-isoquinolin-5-yl) -amide hydrochloride	425
89	6-Chloro-imidazo[2,1-b] thiazole-5-sulfonic acid (2-ethyl-1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride	397
90	6-Chloro-imidazo[2,1-b] thiazole-5-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride	369
91	5-Methyl-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride	353
92	Naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride	339
93	5-Chloro-naphthalene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride	373
94	4-Methyl-3,4-dihydro-2H-benzo[1,4]oxazine-7- sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride	360
95	5-Chloro-3-methyl-benzo[b]thiophene-2-sulfonic acid ethyl-(2-ethyl-1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride	449
96	5-Chloro-3-methyl-benzo[b]thiophene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride	393
98	2,3-Dihydro-benzo[1,4]dioxine-6-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride	347
99	5-Fluoro-3-methyl-benzo[b]thiophene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride	377
100	3-Methyl-quinoline-8-sulfonic acid ethyl-(2-ethyl -1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride	410
101	3-Methyl-quinoline-8-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride	354
102	Naphthalene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride	339
103	Benzo[1,2,5]thiadiazol e-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride	347
104	Benzo[b]thiophene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride	345
105	Benzo[1,2,5]oxadiazol e-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride	331
106	7-Chlorobenzo[1,2,5]oxa diazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride	365
107	2-Oxo-2,3-dihydro-benzooxazole-6-sulfonic acid (1,2,3,4-tetrahydro-isoquinofin-5-yl)-amide hydrochloride	346
108	5-Methyl-benzo[1,2,5]thiadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride	361
109	7-Methyl-benzo[1,2,5]thiadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride	361
110	Benzo[b]thiophene-3-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride	345
111	Isoquinoline-5-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide di hydrochloride	340
112	4-Fluoro-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride	357
113	4-Chloro-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride	373
114	2,2-Dimethyl-chroman-6-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride	373
115	5-Dimethylamino-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride	382
116	2,2,5,7,8-Pentamethyl-chroman-6-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride	415
117	2-Oxo-2H-chromene-6-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride	357
118	5-Ethyl-2-methoxy-N(1,2,3,4-tetrahydro-isoquinolin-5-yl)-benzenesulfonamide hydrochloride	347
119	N-[4-Ethoxy-3-(1,2,3,4-tetrahydro-isoquinolin-5-yl sulfamoyl)-phenyl]-aceta mide hydrochloride	390
120	2-Methoxy-5-methyl-N-(1,2,3,4-tetrahydro-isoquinolin-5-yl)-benze nesulfonamide hydrocloride	333
121	5-Chloro-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride	373
122	3-Methyl-2-oxo-2,3-dihydro-benzooxazole-6-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride	360
123	Quinoline-8-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride	340
124	Dibenzofuran-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride	379
125	6-Chloro-imidazo[2,1-b]thiazole-5-sulfonic acid (1,2,3,4-tetrahydro-is oquinolin-8-yl)-amide hydrochloride	369
126	6-chloro-N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-8-yl)imidazo[2,1-b]thiazole-5-sulfonamide hydrochloride	383
127	Benzo[b]thiophene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide hydrochloride	345
128	Benzo[b]thiophene-2-sulfonic acid (2-methyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide hydrochloride	359
129	Benzo[b]thiophene-3-sulfonic acid (2-methyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide hydrochloride	359
130	Benzo[b]thiophene-3-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide hydrochloride	345
131	5-Chloro-3-methyl-benzo[b]thiophene -2-sulfonic acid (2-methyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide hydrochloride	407
132	5-Chloro-3-methyl-benzo[b]thiophene -2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide hydrochloride	393
133	Naphthalene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide hydrochloride	339
134	Naphthalene-2-sulfonic acid (2-methyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide hydrochloride	353
137	Naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide hydrochloride	339
138	Naphthalene-1-sulfonic acid (2-methyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide Hydrochloride	353
139	4-Methyl-naphthalene-1-sulfonic acid (2-methyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide Hydrochloride	367
140	4-Methyl-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-8 -yl)-amide Hydrochloride	353
141	4-Chloro-naphthalene-1-sulfonic acid (1,2,3,4-tetra hydro-isoquinolin-8-yl)-amide Hydrochloride	373
142	4-Chloro-naphthalene-1-sulfonic acid (2-methyl -1,2,3,4-tetrahydro-isoquino lin-8-yl)-amide Hydrochloride	387
143	5-Chloro-naphthalene-1-sulfonic acid (2-methyl -1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide Hydrochloride	387
144	5-Chloro-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide Hydrochloride	373
145	5-Chloro-naphthalene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide Hydrochloride	373
146	5-Chloro-naphthalene-2-sulfonic acid (2-methyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide Hydrochloride	387
147	4-Methyl-3,4-dihydro-2H-benzo[1,4]oxazine-7-sulfonic acid (2-methyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide Hydrochloride	374
148	4-Methyl-3,4-dihydro-2H-benzo[1,4]oxazine-7-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide Hydrochloride	360
149	5-Ethyl-2-methoxy-N-(1,2,3,4-tetrahydro-isoquinolin-8-yl)-benzenesulfonamide Hydrochloride	347
150	5-Ethyl-2-methoxy-N-(2-methyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-benzene sulfonamide Hydrochloride	361
151	5-Methyl-benzo[1,2,5]thiadiazole-4-sulfonic acid (2-methyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide Hydrochloride	375
152	5-Methyl-benzo[1,2,5]thiadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide Hydrochloride	361
153	Naphthalene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide	339
154	5-Chloro-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl) -amide Hydrochloride	373
155	Naphthalene-2-sulfonic acid (2-cyclopropanecarbonyl-1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide	407
156	Naphthalene-2-sulfonic acid (2-cyclopropylmethyl-1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide Hydrochloride	393
157	6-Chloro-imidazo[2,1-b]thiazole-5-sulfonic acid (2-cyclopropanecarbonyl-1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide	437
158	6-Chloro-imidazo[2,1-b]thiazole-5-sulfonic acid (2-cyclopropylmethyl-1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride	423

Pharmacological data:

The binding of the substituted tetrahydroisoquinoline compounds to the 5-HT₆ receptor was determined as described above.

The binding results for some of these compounds are given in the following table :


1	13.8	74.8	53.3
2		19.6	17.0
3		18.2	3.9
4		71.1	27.3
5	79.8	76.3	25.9
6	14.5±3.8	88.8	60.1
7	13.3	92.2	80.3
8		74.6	37.4
9	9.2±1.2	86.5	60.1
10	1.3±0.12	94.6	85.8
13	1.3	28.8	30.7
14		-3,0	-7,3
15		8,2	-5,0
16		10,6	5,6
17		-2,0	-1,3
18		6,8	-0,8
19	2.3±0.2	90.0	74.2
24	12.6±1.1	86.8	53.6
29	5.3±0.4	89.6	88.0
30	7.8±0.1	85.2	63.2
31	5.7	85.5	72.3
35	14.2±1.5	81.6	48.8
42	9.3±2.2	88.9	78.2
53	3.8±1.0	82.8	55.4
54	10.7±4.8	91.9	81.0
55	3.8±1.2	84.9	82.3
56	10.3±0.0	92.8	86.8
60	49.4±8.2	65.1	44.8
61	3.2±0.4	85.5	78.6
64	55.8±24.1	66.9	41.9
72	54,6	64.7	45.5
76	19.2±2.4	83.2	73.1
78	2.1±0.0	85.8	77.5
80	6.5±0.5	83.6	70.0
81	9.4±3.7	84.1	70.3
86	6.1±0.7	88.4	78.9
153	8.7±0.4	88.2	52.9
154	39.7±7.4	85.1	65.7

Claims

A substituted tetrahydroisoquinoline compound of general formula Ih, wherein B represents a radical selected from the group consisting of
A^h represents a hydrogen atom or a radical selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 2-butyl and tert-butyl;

D^h represents an anion selected from the group consisting of chloride, bromide, iodide, fluoride, hydrogensulfate, nitrate, dihydrogenphosphate, thiocyanate, cyanate, acrylate, methanesulfonate, ethanesulfonate, toluenesulfonate and benzenesulfonate;

R^1h represents a radical selected from the group consisting of H, methyl, ethyl, -C(=O)-cyclopropyl, -C(=O)-O-tert-butyl and -CH₂-cyclopropyl;

R^2h, R^3h, R^4h and R^5h, independently of one another, each represents a hydrogen atom or a -N(R^11h)-S(=O)2-R^12h radical; with the proviso that at least one of the substituents R^2h, R^3h, R^4h and R^5h represents a -N(R^11h)-S(=O)₂-R^12h moiety;

R^11h represents a radical selected from the group consisting of H, methyl and ethyl;

R^12h represents a radical selected from the group consisting of
which is unsubstituted or substituted with 1, 2, 3, 4 or 5 substituents independently selected from the group consisting of H, F, Cl, methyl, ethyl, -NH₂, -N(CH₃)₂, oxo (=O), -O-CH₃, -O-CH₂-CH₃, -NH-(C=O)-CH₃, - C(=O)-O-CH₃, -C(=O)-CF₃; whereby the substitution can take place on any suitable position in the aforementioned radicals, including the heteroatom(s); or a substituted phenyl radical selected from the group consisting of: optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate, or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof, or a corresponding base thereof.
A compound according to claim 1, characterized in that B, A^h, D^h, R^1h, R^2h, R^3h, R^4h, R^5h and R^11h have the meaning as defined in claim 1; with the proviso that at least one of the substituents R^2h, R^3h, R^4h and R^5h represents a -N(R^11h)-S(=O)₂-R^12h moiety; and R^12h represents a radical selected from the group consisting of optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate, or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof, or a corresponding base thereof.
A compound according to claim 1 or 2, characterized in thatR^2h represents a -N(R^11h)-S(=O)₂-R^12h moiety; and B, A^h, D^h, R^1h, R^3h, R^4h, R^5h, R^11h and R^12h have the meaning as defined in claim 1; optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate, or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof, or a corresponding base thereof.
A compound according to claim 1 or 2, characterized in that R^3h represents a -N(R^11h)-S(=O)₂-R^12h moiety; and B, A^h, D^h, R^1h, R^2h, R^4h, R^5h, R^11h and R^12h have the meaning as defined in claim 1; optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate, or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof, or a corresponding base thereof.
A compound according to claim 1 or 2, characterized in that R^4h represents a -N(R^11h)-S(=O)₂-R^12h moiety; and B, A^h, D^h, R^1h, R^2h, R^3h, R^5h, R^11h and R^12h have the meaning as defined in claim 1; optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate, or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof, or a corresponding base thereof.
A compound according to claim 1 or 2, characterized in that R^5h represents a -N(R^11h)-S(=O)₂-R¹²ⁿ moiety; and B, A^h, D^h, R^1h, R^2h, R^3h, R^4h, R^11h and R^12h have the meaning as defined in claim 1; optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate, or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof, or a corresponding base thereof.
A compound according to one or more of claims 1 to 6 selected from the group consisting of
[1] N-(1,2,3,4-tetrahydroisoquinolin-6-yl)naphthalene-1-sulfonamide hydrochloride,

[2] 2,2-dimethyl-6-(N-methylnaphthalene-1-sulfonamido)-1,2,3,4-tetrahydroisoquinolinium iodide,

[3] N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-6-yl)naphthalene-1-sulfonamide hydrochloride,

[4] 5-chloro-3-methyl-N-(1,2,3,4-tetrahydroisoquinolin-6-yl)benzo[b]thiophene-2-sulfonamide hydrochloride,

[5] 5-chloro-3-methyl-N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-6-yl)benzo[b]thiophene-2-sulfonamide hydrochloride,

[6] 4-methyl-N-(1,2,3,4-tetrahydroisoquinolin-6-yl)naphthalene-1-sulfonamide hydrochloride,

[7] 4-methyl-N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-6-yl)naphthalene-1-sulfonamide hydrochloride,

[8] N-(1,2,3,4-tetrahydroisoquinolin-6-yl)naphthalene-2-sulfonamide hydrochloride,

[9] N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-6-yl)naphthalene-2-sulfonamide hydrochloride,

[10] 6-chloro-N-(1,2,3,4-tetrahydroisoquinolin-6-yl)imidazo[2,1-b]thiazole-5-sulfonamide hydrochloride,

[11] 2-methoxy-5-methyl-N-(1,2,3,4-tetrahydroisoquinolin-6-yl)benzenesulfonamide hydrochloride,

[12] N-(1,2,3,4-tetrahydroisoquinolin-6-yl)pyridine-3-sulfonamide dihydrochloride,

[13] 6-(naphthalene-1-sulfonylamino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester,

[14] 6-(5-chloro-3-methyl-benzo[b]thiophene-2- sulfonylamino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester,

[15] 6-(4-methyl-naphthalene-1-sulfonylamino)-3,4 -dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester,

[16] 6-(naphthalene-2-sulfonylamino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester,

[17] 6-(2-methoxy-5-methyl-benzenesulfonylamino) -3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

[18] 6-(pyridine-3-sulfonylamino)-3,4-dihydro-1H-isoquinoline-2carboxylic acid tert-butyl ester;

[19] 6-Chloro-imidazo[2,1-b]thiazole-5-sulfonic acid (2-methyl-1,2,3,4tetrahydro-isoquinolin-6-yl)-amide hydrochloride

[20] 6-(6-Chloro-imidazo[2,1-b]thiazole-5-sulfonylamino)-3,4-dihydro-1-Hisoquinoline-2-carboxylic acid tert-butyl ester

[21] 4-Methyl-3,4-dihydro-2H-benzo[1,4]oxazine-7-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride

[23] Benzo[1,2,5]thiadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride

[24] Benzo[b]thiophene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride

[25] 7-Chloro-benzo[1,2,5] oxadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin -6-yl)-amide hydrochloride

[26] Benzo[1,2,5]oxadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride

[27] 5-Methyl-benzo[1,2,5] thiadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoqui- nolin-6-yl)-amide hydrochloride

[28] 7-Methyl-benzo[1,2,5] thiadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoqui- nolin-6-yl)-amide hydrochloride

[29] Benzo[b]thiophene-3-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-6-yl) -amide hydrochloride

[30] 4-Fluoro-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride

[31] 4-Chloro-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride

[32] 5-Dimethylaminonaphtha- lene-1-sulfonic acid (1,2,3,4 -tetrahydro-isoquinolin -6-yl)-amide hydrochloride

[33] 2-Oxo-4a,8a-dihydro-2H-chromene-6-sulfonic acid (1,2,3,4-tetrahydro-isoqui- nolin-6-yl)-amide hydrochloride

[34] 2-Methyl-benzothiazole-6-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-6-yl)-amide hydrochloride

[35] 5-Ethyl-2-methoxy-N-(1,2,3,4-tetrahydro- isoquinolin-6-yl)-benzene sulfonamide hydrochloride

[36] 6-Methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine-5-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride

[37] N-[4-Ethoxy-3-(1,2,3,4-tetrahydro-isoquinolin-6- ylsulfamoyl)-phenyl]-acetamide hydrochloride

[38] 4-Methoxy-3-(1,2,3,4-tetrahydro-isoquinolin-6-yl sulfamoyl)-benzoic acid methyl ester hydrochloride

[39] 2-(2,2,2-Trifluoro-acetyl)-1,2,3,4-tetrahydro-isoquinoline-7-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide hydrochloride

[40] 1,2,3,4-Tetrahydro-isoquino line-7-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6- yl)-amide dihydrochloride

[41] 5-Amino-2-ethoxy-N-(1,2,3,4-tetrahydro-isoquinolin-6-yl)-benzenesulfonamide dihydrochloride

[42] 5-Chloro-naphthalene-1-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-6-yl)-amide hydrochloride

[43] 1,2-Dimethyl-1H-imidazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin- 6-yl)-amide hydrochloride

[44] N-[4-Methyl-5-(1,2,3,4-tetrahydro-isoquinolin-6- ylsulfamoyl)-thiazol-2-yl] -acetamide hydrochloride

[45] 1,3,5-Trimethyl-1H-pyrazole -4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl) -amide hydrochloride

[46] N-[5-(1,2,3,4-Tetrahydro-isoquinolin-6-ylsulfamoyl) -naphthalen-1-yl]-acetamide hydrochloride

[47] 2-Naphthalen-1-yl-ethanesulfonic acid (1,2,3,4 -tetrahydro-isoquinolin-6-yl) -amide hydrochloride

[48] Dibenzofuran-2-sulfonic acid (1,2,3,4-tetrahydro- isoquinolin-6-yl)-amide hydrochloride

[49] 2,5-Dimethoxy-N-(1,2,3,4-tetrahydro-isoquinolin -6-yl)-benzenesulfonamide hydrochloride

[50] 5-Chloro-2-methoxy-N-(1,2,3,4-tetrahydro-iso quinolin-6-yl)-benzene sulfonamide hydrochloride

[51] 2,5-Dimethyl-N-(1,2,3,4-tetrahydro-isoquinolin -6-yl)-benzenesulfonamide hydrochloride

[52] 2-Fluoro-5-methyl-N-(1,2,3,4-tetrahydro- isoquinolin-6-yl)-benzene sulfonamide hydrochloride

[53] 6-Chloro-imidazo[2,1-b]thiazole-5-sulfonic acid (2-methyl-1,2,3,4-tetrahydro -isoquinolin-7-yl)-amide hydrochloride

[54] 6-Chloro-imidazo[2,1-b]thiazole-5-sulfonic acid (1,2,3,4-tetrahydro-iso- quinolin-7-yl)-amide hydrochloride

[55] 4-Methyl-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride

[56] 4-Methyl-naphthalene-1-sulfonic acid (2-methyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride

[57] 5-Chloro-naphthalene-2-sulfonic acid (2-methyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride

[58] 5-Chloro-naphthalene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl) -amide hydrochloride

[59] 4-Methyl-3,4-dihydro-2H-benzo[1,4]oxazine-7-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride

[60] 5-Chloro-3-methyl-benzo[b]thiophene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin -7-yl)-amide hydrochloride

[61] Naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro- isoquinolin-7-yl)-amide hydrochloride

[63] 2,3-Dihydro-benzo[1,4] dioxine-6-sulfonic acid (1,2,3,4-tetrahydro-iso- quinolin-7-yl)-amide hydrochloride

[64] 5-Fluoro-3-methyl-benzo[b] thiophene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin -7-yl)-amide hydrochloride

[65] 3-Methyl-quinoline-8-sulfonic acid (1,2,3,4-tetra hydro-isoquinolin-7-yl)-amide hydrochloride

[66] Naphthalene-2-sulfonic acid (1,2,3,4-tetrahydro -isoquinolin-7-yl)-amide hydrochloride

[67] Benzo[1,2,5]thiadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl) -amide hydrochloride

[68] 1,4-Dimethyl-2,3-dioxo-1,2,3,4-tetrahydro-quino xaline-6-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride

[69] Benzo[b]thiophene-2-sulfonic acid (1,2,3,4-tetrahydro -isoquinolin-7-yl)-amide hydrochloride

[71] 7-Chloro-benzo[1,2,5] oxadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride

[72] Benzo[1,2,5]oxadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride

[73] 2-Oxo-2,3-dihydro-benzo thiazole-6-sulfonic acid (1,2,3,4-tetrahydro-isoqui- nolin-7-yl)-amide hydro- chloride

[74] 2-Oxo-2,3-dihydro-benzo oxazole-6-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride

[76] 5-Methylbenzo[1,2,5] thiadiazole -4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride

[77] 7-Methyl-benzo[1,2,5] thiadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride

[78] Benzo[b]thiophene-3-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-7-yl) -amide hydrochloride

[79] Isoquinoline-5-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride

[80] 4-Fluoro-naphthalene-1-sulfonic acid (1,2,3,4 -tetrahydro-isoquinolin-7-yl) -amide hydrochloride

[81] 4-Chloro-naphthalene-1-sulfonic acid (1,2,3,4 -tetrahydro-isoquinolin-7-yl) -amide hydrochloride

[82] 2,2-Dimethyl-chroman-6-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-7-yl) -amide hydrochloride

[83] 5-Dimethylamino-naphtha lene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl) -amide hydrochloride

[84] 2-Oxo-2H-chromene-6-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)- amide hydrochloride

[85] 2-Methyl-benzothiazole-6-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-7-yl) -amide hydrochloride

[86] 5-Ethyl-2-methoxy-N-(1,2,3,4-tetrahydro-isoquinolin-7-yl)-benzenesulfonamide hydrochloride

[87] 6-Methyl-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidine- 5-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-7-yl)-amide hydrochloride

[88] 6-Chloro-imidazo[2,1-b] thiazole-5-sulfonic acid ethyl-(2-ethyl-1,2,3,4-tetrahydro-isoquinolin-5-yl) -amide hydrochloride

[89] 6-Chloro-imidazo[2,1-b] thiazole-5-sulfonic acid (2-ethyl-1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride

[90] 6-Chloro-imidazo[2,1-b] thiazole-5-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride

[91] 5-Methyl-naphthalene-l-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-5-yl) -amide hydrochloride

[92] Naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro- isoquinolin-5-yl)-amide hydrochloride

[93] 5-Chloro-naphthalene-2-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-5-yl) -amide hydrochloride

[94] 4-Methyl-3,4-dihydro-2H-benzo[1,4]oxazine-7- sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride

[95] 5-Chloro-3-methyl-benzo[b] thiophene-2-sulfonic acid ethyl-(2-ethyl-1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride

[96] 5-Chloro-3-methyl-benzo[b] thiophene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride

[98] 2,3-Dihydro-benzo[1,4] dioxine-6-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride

[99] 5-Fluoro-3-methyl-benzo[b] thiophene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride

[100] 3-Methyl-quinoline-8-sulfonic acid ethyl-(2-ethyl -1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride

[101] 3-Methyl-quinoline-8-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-5-yl) -amide hydrochloride

[102] Naphthalene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquino lin-5-yl)-amide hydrochloride

[103] Benzo[1,2,5]thiadiazole-4.-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-5-yl) -amide hydrochloride

[104] Benzo[b]thiophene-2-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-5-yl) -amide hydrochloride

[105] Benzo[1,2,5]oxadiazole-4-sulfonic acid (1,2,3,4-tetra hydro-isoquinolin-5-yl)- amide hydrochloride

[106] 7-Chlorobenzo[1,2,5]oxa diazole -4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride

[107] 2-Oxo-2,3-dihydro-benzooxazole-6-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl) -amide hydrochloride

[108] 5-Methyl-benzo[1,2,5] thiadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride

[109] 7-Methyl-benzo[1,2,5] thiadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride

[110] Benzo[b]thiophene-3-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-5-yl) -amide hydrochloride

[111] Isoquinoline-5-sulfonic acid (1,2,3,4-tetrahydro-isoqui nolin-5-yl)-amide dihydrochloride

[112] 4-Fluoro-naphthalene-1-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-5-yl) -amide hydrochloride

[113] 4-Chloro-naphthalene-1-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-5-yl) -amide hydrochloride

[114] 2,2-Dimethyl-chroman-6-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-5-yl) -amide hydrochloride

[115] 5-Dimethylamino-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl)-amide hydrochloride

[116] 2,2,5,7,8-Pentamethyl-chroman-6-sulfonic acid (1,2,3,4-tetrahydro-isoquino lin-5-yl)-amide hydrochloride

[117] 2-Oxo-2H-chromene-6-sulfonic acid (1,2,3,4-tetrahy dro-isoquinolin-5-yl) -amide hydrochloride

[118] 5-Ethyl-2-methoxy-N(1,2, 3,4-tetrahydro-isoquinolin-5-yl)-benzenesulfonamide hydrochloride

[119] N-[4-Ethoxy-3-(1,2,3,4-tetrahydro-isoquinolin-5-yl sulfamoyl)-phenyl]-acetamide hydrochloride

[120] 2-Methoxy-5-methyl-N-(1,2,3,4-tetrahydro-isoquinolin-5-yl)-benze nesulfonamide hydrocloride

[121] 5-Chloro-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-5-yl) -amide hydrochloride

[122] 2-Methoxy-5-methyl-N-(1,2,3,4-tetrahydro-isoquinolin-5-yl)-benzenesulfonamide hydrocloride

[123] Quinoline-8-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin -5-yl)-amide hydrochloride

[124] Dibenzofuran-2-sulfonic acid (1,2,3,4-tetrahydro- isoquinolin-5-yl)-amide hydrochloride

[125] 6-Chloro-imidazo[2,1-b] thiazole-5-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide hydrochloride

[126] 6-chloro-N-(2-methyl-1,2,3,4-tetrahydroisoquinolin-8-yl)imidazo[2,1-b]thiazote-5-sulfonamide hydrochloride

[127] Benzo[b]thiophene-2-sulfonic acid (1,2,3,4-tetra hydro-isoquinolin-8-yl) -amide hydrochloride

[128] Benzo[b]thiophene-2-sulfonic acid (2-methyl- 1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide hydrochloride

[129] Benzo[b]thiophene-3-sulfonic acid (2-methyl- 1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide hydrochloride

[130] Benzo[b]thiophene-3-sulfonic acid (1,2,3,4-tetra hydro-isoquinolin-8-yl) -amide hydrochloride

[131] 5-Chloro-3-methyl-benzo[b]thiophene-2-sulfonic acid (2-methyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide hydrochloride

[132] 5-Chloro-3-methyl-benzo[b]thiophene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin -8-yl) -amide hydrochloride

[133] Naphthalene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide hydrochloride

[134] Naphthalene-2-sulfonic acid (2-methyl-1,2,3,4-tetrahydro-isoquinolin-8-yl) -amide hydrochloride

[137] Naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide hydrochloride

[138] Naphthalene-1-sulfonic acid (2-methyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide Hydrochloride

[139] 4-Methyl-naphthalene-1-sulfonic acid (2-methyl- 1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide Hydrochloride

[140] 4-Methyl-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide Hydrochloride

[141] 4-Chloro-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-8-yl)- amide Hydrochloride

[142] 4-Chloro-naphthalene-1-sulfonic acid (2-methyl -1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide Hydrochloride

[143] 5-Chloro-naphthalene-1-sulfonic acid (2-methyl -1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide Hydrochloride

[144] 5-Chloro-naphthalene-1-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-8-yl)- amide Hydrochloride

[145] 5-Chloro-naphthalene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-8-yl)- amide Hydrochloride

[146] 5-Chloro-naphthalene-2-sulfonic acid (2-methyl -1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide Hydrochloride

[147] 4-Methyl-3,4-dihydro-2H-benzo[1,4]oxazine-7-sulfonic acid (2-methyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide Hydrochloride

[148] 4-Methyl-3,4-dihydro-2H-benzo[1,4]oxazine-7-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide Hydrochloride

[149] 5-Ethyl-2-methoxy-N-(1,2,3,4-tetrahydro-isoquinolin-8-yl)-benzenesulfonamide Hydrochloride

[150] 5-Ethyl-2-methoxy-N-(2-methyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-benzene sulfonamide Hydrochloride

[151] 5-Methyl-benzo[1,2,5] thiadiazole-4-sulfonic acid (2-methyl-1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide Hydrochloride

[152] 5-Methyl-benzo[1,2,5] thiadiazole-4-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-8-yl)-amide Hydrochloride

[153] Naphthalene-2-sulfonic acid (1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide and

[154] 5-Chloro-naphthalene-1-sulfonic acid (1,2,3,4- tetrahydro-isoquinolin-7-yl)-amide Hydrochloride

[155] Naphthalene-2-sulfonic acid (2-cyclopropanecarbonyl-1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide

[156] Naphthalene-2-sulfonic acid (2-cyclopropylmethyl-1,2,3,4-tetrahydro-isoqui nolin-6-yl)-amide Hydrochloride

[157] 6-Chloro-imidazo[2, 1-b] thiazole-5-sulfonic acid (2-cyclopropanecarbonyl- 1,2,3,4-tetrahydro-isoquinolin-6-yl)-amide and

[158] 6-Chloro-imidazo[2,1-b] thiazole-5-sulfonic acid (2-cyclopropylmethyl-1,2,3,4- tetrahydro-isoquinolin-6-yl)-amide hydrochloride
optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate, or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof, or a corresponding base thereof.
Process for the preparation of a compound according to one or more of claims 1 to 7, characterised in that at least one compound of general formula IVh, wherein R^12h has the meaning according to one or more of claims 1 to 7 and X represents a leaving group, preferably a halogen atom, particularly preferably a chlorine atom, is reacted with at least one compound of general formula VhA, wherein R^1h to R^5h have the meaning according to one or more of claims 1 to 7, with the proviso that at least one substituent of the group consisting of R^2h, R^3h, R^4h and R^5h represents a -N(H)(R^11h) moiety, wherein R^11h has the meaning according to one or more of claims 1 to 7, or a protected derivative thereof, in a reaction medium, preferably in the presence of at least one base.
A medicament comprising at least one substituted tetrahydroisoquinoline compound of general formula Ih according to one or more of claims 1 to 7, optionally in form of one of its stereoisomers, preferably enantiomers or diasteromers, a racemate or in form of a mixture of at least two of its stereoisomers, preferably enantiomers and/or diastereomers, in any mixing ratio, or a salt thereof, or a corresponding solvate thereof and optionally at least one physiologically acceptable auxiliary agent.
A medicament according to claim 9 for the prophylaxis and/or treatment of a disorder or disease related to food intake, preferably for the regulation of appetite, for the maintenance, increase or reduction of body weight, for the prophylaxis and/or treatment of obesity, bulimia, anorexia, cachexia, type II diabetes (non insulin dependent diabetes mellitus), preferably type II diabetes that is caused by obesity; for the prophylaxis and/or treatment of stroke; migraine; head trauma; epilepsy; irritable colon syndrome; irritable bowl syndrome; emesis; vertigo; disorders of the central nervous system; anxiety; panic attacks; depression; bipolar disorders; obsessive compulsory disorder; cognitive disorders; cognitive dysfunction associated with psychiatric diseases; memory disorders; senile dementia; mood disorders; sleep disorders; psychosis; neurodegenerative disorders, preferably selected from the group consisting of Morbus Alzheimer, Morbus Parkinson, Morbus Huntington and Multiple Sclerosis; schizophrenia; amnesia; autism; sexual dysfunction; gastric motility disorders; circadian rhythm disorders; chronic intermittent hypoxia; convulsions; or hyperactivity disorder (ADHD, attention deficit/hyperactivity disorder); for improvement of cognition (cognitive enhancement) or cognitive memory (cognitive memory enhancement); for the prophylaxis and/or treatment of drug addiction and/or withdrawal; for the prophylaxis and/or treatment of alcohol addiction and/or withdrawal, for the prophylaxis and/or treatment of nicotine addiction and/or withdrawal.
Use of at least one substituted tetrahydroisoquinoline compound of general formula Ih according to one or more of claims 1 to 7 for the manufacture of a medicament for the prophylaxis and/or treatment of a disorder or disease related to food intake, preferably for the regulation of appetite, for the maintenance, increase or reduction of body weight, for the prophylaxis and/or treatment of obesity, bulimia, anorexia, cachexia, type II diabetes (non insulin dependent diabetes mellitus), preferably type II diabetes that is caused by obesity; for the prophylaxis and/or treatment of stroke; migraine; head trauma; epilepsy; irritable colon syndrome; irritable bowl syndrome; emesis; vertigo; disorders of the central nervous system; anxiety; panic attacks; depression; bipolar disorders; obsessive compulsory disorder; cognitive disorders; cognitive dysfunction associated with psychiatric diseases; memory disorders; senile dementia; mood disorders; sleep disorders; psychosis; neurodegenerative disorders, preferably selected from the group consisting of Morbus Alzheimer, Morbus Parkinson, Morbus Huntington and Multiple Sclerosis; schizophrenia; amnesia; autism; sexual dysfunction; gastric motility disorders; circadian rhythm disorders; chronic intermittent hypoxia; convulsions; or hyperactivity disorder (ADHD, attention deficit/hyperactivity disorder); for improvement of cognition (cognitive enhancement) or cognitive memory (cognitive memory enhancement); for the prophylaxis and/or treatment of drug addiction and/or withdrawal; for the prophylaxis and/or treatment of alcohol addiction and/or withdrawal, for the prophylaxis and/or treatment of nicotine addiction and/or withdrawal.
A substituted tetrahydroisoquinoline compound of general formula Ig, wherein R^1g represents a hydrogen atom; a radical selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, -CH₂-NH₂, -CH₂-NH-CH₃, -CH₂-N(CH₃)₂, -CH₂-N(C₂H₅)₂, -CH₂-NH-C₂H₅, -CH₂-CH₂-NH₂, -CH₂-CH₂-NH-CH₃, -CH₂-CH₂-N(CH₃)₂, -CH₂-CH₂-N(C₂H₅)₂, -CH₂-CH₂-NH-C₂H₅, -CH₂-CH₂-CH₂-NH-CH₃, -CH₂-CH₂-CH₂-N(CH₃)₂, -CH₂-CH₂-CH₂-N(C₂H₅)₂ and -CH₂-CH₂-CH₂-NH-C₂H₅; or a (hetero)cycloaliphatic radical selected from the group consisting of imidazolidinyl, aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, pyrazolidinyl and azepanyl, which may be bonded via a -(CH₂)₁, _{2 or 3}- group and which may be unsubstituted or optionally substituted with 1, 2, 3, 4 or 5 substituent(s) independently selected from the group consisting of oxo (=O), thioxo (=S), methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, sec-butyl, isobutyl, -C(=O)-CH₃, -C(=O)-C₂H₅, -C(=O)-CH₂-CH₂-CH₃, - C(=O)-CH(CH₃)₂, -C(=O)-C(CH₃)₃, -C(=O)-NH₂, -C(=O)-NH-CH₃, -C(=O)-NH-C₂H₅, -C(=O)-N(CH₃)₂, -C(=O)-N(C₂H₅)₂ and -S(=O)₂-CH₃; R^2g, R^3g, R^4g and R^5g, independently of one another, each represent a hydrogen atom; F, Cl, Br, I, -NO₂; -NH₂; -SH; -OH; -CN; -C(=O)-OH; - C(=O)-H; -S(=O)₂-OH; -C(=O)-NH₂; -S(=O)₂-NH₂; -OR^8g; -SR^9g; -N(R^11g)-S(=O)₂-R^12g; a radical selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, vinyl, allyl, ethinyl, -CF₃, -CFH₂, -CF₂H, -CH₂-CF₃ and -CF₂-CF₃; or a radical selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; with the proviso that at least one of the substituents R^2g, R^3g, R^4g and R^5g represents a -N(R^11g)-S(=O)₂-R^12g moiety; R^8g and R^9g, independently of one another, each represent a radical selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, -CF₃, -CFH₂, -CF₂H, -CH₂-CF₃ and - CF₂-CF₃; a (hetero)cycloaliphatic radical selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; or an aryl or heteroaryl radical selected from the group consisting of phenyl, naphthyl, furyl (furanyl), thienyl (thiophenyl), pyrrolyl, and pyridinyl, which may be bonded via a -(CH₂)₁, _{2 or 3}-group and which may be unsubstituted or optionally substituted with 1, 2 or 3 substituent(s) independently selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, sec-butyl, isobutyl, -O-CH₃, -O-C₂H₅, -O-CH₂-CH₂-CH₃, - O-CH(CH₃)₂, -O-C(CH₃)₃, -S-CH₃, -S-C₂H₅, -S-CH₂-CH₂-CH₃, F, Cl, Br, I, -CN, -CF₃, -OCF₃, -SCF₃, -OH, -SH, -NH₂, -NO₂, -CHO, -CF₂H and - CFH₂; R^11g represents a hydrogen atom, -S(=O)₂-R^12g or an alkyl radical selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl and tert-butyl; R^12g represents a phenyl radical of general formula (Ag), wherein R^19g, R^20g, R^21g and R^22g, independently of one another, each represent a hydrogen atom; F, Cl, Br, I, -NO₂; -NH₂; - SH; -OH; -CN; -C(=O)-OH; -C(=O)-H; -S(=O)₂-OH; -C(=O)-NH₂; -S(=O)₂-NH₂; -C(=O)-R^23g; -S(=O)-R^24g; -S(=O)_2-R^24g; - OR^25g; -SR^26g; -C(=O)-OR^27g; methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, -CF₃, - CF₂H, -CFH₂, -CH₂-CF₃, -CF₂-CF₃, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; with the proviso that at least one of the substituents R^19g, R^20g, R^21g and R^22g is unlike hydrogen; or a naphthyl radical, which may be unsubstituted or optionally substituted with 1, 2, 3, 4 or 5 substituent(s) independently selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, sec-butyl, isobutyl, n-pentyl, -O-CH₃, - O-C₂H₅, -O-CH₂-CH₂-CH₃, -O-CH(CH₃)₂, -O-C(CH₃)₃, -S-CH₃, -S-C₂H₅, -S-CH₂-CH₂-CH₃, -S-CH(CH₃)₂, -S-C(CH₃)₃, F, Cl, Br, I, -CN, -CF₃, -OCF₃, -SCF₃, -OH, -SH, -NH₂, -NO₂, -CHO, -CF₂H and - CFH₂; R^23g and R^27g, independently of one another, each represent a radical selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, -CF₃, -CFH₂, -CF₂H, -CH₂-CF₃ and -CF₂-CF₃; or an aryl or heteroaryl radical selected from the group consisting of phenyl, naphthyl, furyl (furanyl), thienyl (thiophenyl), pyrrolyl, and pyridinyl, which may be bonded via a -(CH₂)_{1, 2 or 3}-group and which may be unsubstituted or optionally substituted with 1, 2 or 3 substituent(s) independently selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, sec-butyl, isobutyl, n-pentyl, -O-CH₃, -O-C₂H₅, -O-CH₂-CH₂-CH₃, F, Cl, Br, I, -CN, -CF₃, -OCF₃, -SCF₃, -OH, -SH, -NH₂-NO₂, -CHO, -CF₂H and -CFH₂; R^24g and R^26g, independently of one another, each represent a radical selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, vinyl, allyl, ethinyl, - CF₃, -CFH₂, -CF₂H, -CH₂-CF₃ and -CF₂-CF₃; or an aryl or heteroaryl radical selected from the group consisting of phenyl, naphthyl, furyl (furanyl), thienyl (thiophenyl), pyrrolyl, and pyridinyl, which may be unsubstituted or optionally substituted with 1, 2 or 3 substituent(s) independently selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, sec-butyl, isobutyl, n-pentyl, -O-CH₃, -O-C₂H₅, -O-CH₂-CH₂-CH₃, -O-CH(CH₃)₂, -O-C(CH₃)₃, F, Cl, Br, I, -CN, - CF₃, -OCF₃, -SCF₃, -OH, -SH, -NH₂, -NO₂, -CHO, -CF₂H and -CFH₂; R^25g represents a radical selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, -CF₃, - CFH₂, -CF₂H, -CH₂-CF₃ and -CF₂-CF₃ and R^37g represents a radical selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, fluorenyl, fluorenylmethyl, phenyl, benzyl and naphthyl;
A compound according to claim 12, characterized in that
R¹⁹ represents a hydrogen atom; or a radical selected from the group consisting of methyl, ethyl, n-propyl, n-butyl, n-pentyl and n-hexyl;

R^2g, R^3g, R^4g and R^5g, independently of one another, each represent a hydrogen atom or -N(R^11g)-S(=O)₂-R^12g; with the proviso that at least one of the substituents R^2g, R^3g, R^4g and R^5g represents a -N(R^11g)-S(=O)₂-R^12g moiety;

R^11g represents a hydrogen atom, -S(=O)₂-R^12g or an alkyl radical selected from the group consisting of methyl, ethyl and n-propyl;

R^12g represents a phenyl radical of general formula (Ag), wherein R^19g, R^20g, R^21g and R^22g, independently of one another, each represent a hydrogen atom; F, Cl, Br, I, -O-CH₃; -O-C₂H₅; -O-CF₃; -O-CFH₂ -O=CF₂H; -O-CH₂-CF₃; -O-CF₂-CF₃; methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl; with the proviso that at least one of the substituents R^19g, R^20g, R^21g and R^22g is unlike hydrogen;
or a naphthyl radical, which may be unsubstituted or optionally substituted with 1, 2, 3, 4 or 5 substituent(s) independently selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, F, Cl and Br; and R^37g represents a radical selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, n-hexyl, fluorenyl, fluorenylmethyl, phenyl, benzyl and naphthyl.
A compound according to claim 12 or 13 selected from the group consisting of
[13] 6-(naphthalene-1-sulfonylamino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester,

[15] 6-(4-methyl-naphthalene-1-sulfonylamino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester,

[16] 6-(naphthalene-2-sulfonylamino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester and

[17] 6-(2-methoxy-5-methyl-benzenesulfonylamino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester.