DE102004012921A1 - New 7-butynyl-8-(3-amino-1-piperidinyl)xanthine derivatives useful as dipeptidyl peptidase IV inhibitors, e.g. for treating diabetes, arthritis, obesity and osteoporosis - Google Patents

Abstract

7-Butynyl-8-(3-amino-1-piperidinyl)xanthine derivatives (I) are new. 7-Butynyl-8-(3-amino-1-piperidinyl)xanthine derivatives of formula (I) and their tautomers, isomers and salts are new. R : benzyl, 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2,6-difluoro-benzyl, 3,4-difluoro-benzyl, 2-chlorobenzyl, 3-chlorobenzyl or 4-chlorobenzyl, 2-trifluoromethyl-benzyl, 3-trifluoromethyl-benzyl or 4-trifluoromethyl-benzyl, 3-trifluoromethoxy-benzyl or 4-trifluoromethoxy-benzyl, 2-cyanobenzyl, 3-cyanobenzyl or 4-cyanobenzyl, 2,6-dicyanobenzyl, 3,4-dicyanobenzyl, 3,5-dicyanobenzyl, 2-trifluoromethyl-4-cyano-benzyl, 3-nitro-4-cyano-benzyl, 2-cyano-3-methoxy-benzyl, 2-cyano-4-methoxy-benzyl, 2-cyano-5-methoxy-benzyl, 2-cyano-4-fluoro-benzyl, 2-cyano-5-fluoro-benzyl, 2-cyano-6-fluoro-benzyl, 3-cyano-4-fluoro-benzyl, 4-cyano-3-fluorobenzyl, 2-fluoro-4-cyano-benzyl, 2-cyano-3-chlorobenzyl, 2-chloro-4-cyano-benzyl or 2-cyano-4-bromobenzyl, 2-methoxy-benzyl, 3-methoxy-benzyl, 4-methoxy-benzyl, 2-fluoro-3-methoxybenzyl, 2-fluoro-4-methoxy-benzyl, 2-fluoro-5-methoxy-benzyl, 3-fluoro-4-methoxybenzyl, 3,4-dimethoxy-benzyl, 3,5-dimethoxybenzyl or 3,4-dimethoxy-6-fluorobenzyl, (benzo[1,3]dioxol-5-yl)methyl, [(4-cyano-benzo[1,3]dioxol-5-yl)methyl, 2-(3-cyclopropyloxy-phenyl)-2-oxo-ethyl, 2-(3-cyclopropylmethoxy-phenyl)-2oxo-ethyl or 2-(3-cyclobutyloxy-phenyl)-2-oxo-ethyl, 2-oxo-2-[2-(pyridin-3-yl)-phenyl]-ethyl or 2-oxo-2-[2-(pyridin-4-yl)-phenyl]ethyl, (3-cyano-1-naphthyl)methyl, (1,4-dicyano-2-naphthyl)methyl or (2,4-dimethoxy-1-naphthyl)methyl, (furan-2-yl)methyl, (furan-3-yl)methyl, (5-bromo-furan-2-yl)methyl, (5-methylfuran-2-yl)methyl, (5-cyano-furan-2-yl)methyl or (5-methoxycarbonyl-furan-2yl)methyl, (pyridin-2-yl)methyl, (6-fluoro-pyridin-2-yl)methyl or (5-methoxy-pyridin-2-yl)methyl, (3-cyanopyridin-2-yl)methyl, (6-cyanopyridin-2- yl)methyl, (5-cyano-pyridin-2-yl)methyl, (4-cyano-pyridin-2-yl)methyl, (4-cyano-pyridin-3-yl)methyl, (3-cyanopyridin-4-yl)methyl, (2-cyano-pyridin-3-yl)methyl, (2-cyano-pyridin-4-yl)methyl, (5cyano-pyridin-3-yl)methyl, (6-cyano-pyridin-3-yl)methyl or (5-cyano-6-methoxypyridin-2-yl)methyl, (6-phenyl-pyridin-2-yl)methyl or ([2,2']bipyridinyl-6-yl)methyl, (pyrimidin-2-yl)methyl, (4-methyl-pyrimidin-2-yl)methyl or (4,6-dimethylpyrimidin-2-yl)methyl, (2-phenyl-pyrimidin-4-yl)methyl or (4-phenyl-pyrimidin-2-yl)methyl, [(1-methyl-1H-benzotriazol-5-yl)methyl], (6-fluoro-quinolin-2-yl)methyl, (7-fluoro-quinolin-2-yl)methyl, (2-methyl-quinolin-4-yl)methyl, (3-cyano-quinolin-2-yl)methyl, (3-cyano-4-methyl-quinolin-2-yl)methyl, (4-cyano-quinolin-2-yl)methyl, (5-cyano-quinolin-2-yl)methyl, (6-cyano-quinolin-2-yl)methyl, (6-amino-quinolin-2-yl)methyl, (8-amino-quinolin-2-y1)methyl, (4-methoxy-quinolin-2-yl)methyl, (6-methoxy-quinolin-2-yl)methyl, (6,7-dimethoxyquinolin-2-yl)methyl or (8-cyano-quinolin-7-yl)methyl, (1-cyano-isoquinolin-3-yl)methyl, (4-cyano-isoquinolin-1-yl)methyl, (4-cyanoisoquinolin-3-yl)methyl or [(4-(pyridin-2-yl)-isoquinolin-1-yl)methyl, (quinazolin-6-yl)methyl, (quinazolin-7-yl)methyl, (2-methyl-quinazolin-4yl)methyl, (4,5-dimethyl-quinazolin-2-yl)methyl, (4-ethyl-quinazolin-2-yl)methyl, (4-cyclopropyl-quinazolin-2-yl)methyl, (2-phenyl-quinazolin-4-yl)methyl, (4-cyanoquinazolin-2-yl)methyl, (4-phenylamino-quinazolin-2-yl)methyl or (4-benzylaminoquinazolin-2-yl)methyl, (quinoxalin-5-yl)methyl, (quinoxalin-6-yl)methyl or (2,3-dimethyl-quinoxalin-6-yl)methyl, or ([1,5]naphthyridin-3-yl)methyl. An independent claim is also included for a process for preparing (I). [Image] ACTIVITY : Antidiabetic; Antiarthritic; Anorectic; Osteopathic; Tranquilizer; Hypotensive; Nephrotropic; Antiinflammatory; Antiulcer; Immunosuppressive; Virucide; Anti-HIV; Neuroprotective; Nootropic; Cytostatic; Cerebroprotective; Vasotropic; Antiparkinsonian; Antimigraine; Dermatological; Antipsoriatic; Antidepressant; Neuroleptic. MECHANISM OF ACTION : Dipeptidyl peptidase IV (DPP IV) inhibitor. 1-(4-Benzylamino-4-quinazolinylmethyl)-3-methyl-7-(2-butyn-1-yl)-8-(3-amino-1-piperidinyl)xanthine had an IC50 of 6 nM against DPP IV activity in Caco-2 cell extracts.

Description

deren Tautomere, Enantiomere, Diastereomere, deren Gemische und deren Salze, insbesonders deren physiologisch verträgliche Salze mit anorganischen oder organischen Säuren, welche wertvolle pharmakologische Eigenschaften aufweisen, insbesondere eine Hemmwirkung auf die Aktivität des Enzyms Dipeptidylpeptidase-IV (DPP-IV), deren Herstellung, deren Verwendung zur Prävention oder Behandlung von Krankheiten oder Zuständen, die in Zusammenhang mit einer erhöhten DPP-IV Aktivität stehen oder die durch Reduktion der DPP-IV Aktivität verhindert oder gemildert werden können, insbesondere von Diabetes mellitus Typ I oder Typ II, die eine Verbindung der allgemeinen Formel (I) oder ein physiologisch verträgliches Salz davon enthaltenden Arzneimittel sowie Verfahren zu deren Herstellung.The present invention relates to novel substituted xanthines of the general formula

their tautomers, enantiomers, diastereomers, their mixtures and their salts, in particular their physiologically tolerated salts with inorganic or organic acids, which have valuable pharmacological properties, in particular an inhibitory action on the activity of the enzyme dipeptidyl peptidase-IV (DPP-IV), their preparation, their use for the prevention or treatment of diseases or conditions associated with increased DPP-IV activity or which may be prevented or alleviated by reduction of DPP-IV activity, in particular diabetes mellitus type I or type II, which is a compound of the general formula (I) or a physiologically acceptable salt thereof containing medicaments and process for their preparation.

In the above formula I means
R is a benzyl, 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2,6-difluoro-benzyl, 2-chlorobenzyl, 3-chlorobenzyl or 4-chlorobenzyl group,
a 2-trifluoromethylbenzyl, 3-trifluoromethylbenzyl or 4-trifluoromethylbenzyl group,
a 3-trifluoromethoxybenzyl or 4-trifluoromethoxybenzyl group,
a 2-cyanobenzyl, 3-cyanobenzyl or 4-cyanobenzyl group,
2,6-dicyanobenzyl, 3,4-dicyanobenzyl, 3,5-dicyanobenzyl, 2-trifluoromethyl-4-cyano-benzyl, 3-nitro-4-cyano-benzyl, 2-cyano-4 methoxy-benzyl, 2-cyano-5-methoxy-benzyl, 2-cyano-4-fluoro-benzyl, 2-cyano-5-fluoro-benzyl, 2-cyano-6-fluoro-benzyl, 3 -Cyano-4-fluoro-benzyl, 2-fluoro-4-cyano-benzyl, 2-cyano-3-chlorobenzyl, 2-chloro-4-cyano-benzyl or 2-cyano-4-bromobenzyl group .
a 2-methoxybenzyl, 3-methoxybenzyl, 4-methoxybenzyl, 3,4-dimethoxybenzyl, 3,5-dimethoxybenzyl or 3,4-dimethoxy-6-fluorobenzyl group,
a (benzo [1,3] dioxol-5-yl) methyl group,
a 2- (3-cyclopropyloxy-phenyl) -2-oxo-ethyl, 2- (3-cyclopropylmethoxy-phenyl) -2-oxo-ethyl or 2- (3-cyclobutyloxyphenyl) -2-oxo-ethyl -Group,
a 2-oxo-2- [2- (pyridin-3-yl) -phenyl] -ethyl or 2-oxo-2- [2- (pyridin-4-yl) -phenyl] -ethyl group,
a (3-cyano-naphthalen-1-yl) methyl, (1,4-dicyano-naphthalen-2-yl) methyl or (2,4-dimethoxy-naphthalen-1-yl) methyl group,
a (5-methoxycarbonyl-furan-2-yl) methyl group,
a (pyridin-2-yl) methyl, (6-fluoropyridin-2-yl) methyl or (5-methoxypyridin-2-yl) methyl group,
a (3-cyanopyridin-2-yl) methyl, (6-cyanopyridin-2-yl) methyl, (5-cyano-pyridin-2-yl) methyl, (4-cyano-pyridin-2-yl) methyl, (4-cyanopyridin-3-yl) methyl, (3-cyanopyridin-4-yl) methyl, (2-cyano-pyridin-3-yl) methyl, (2-cyano) pyridin-4-yl) methyl, (5-cyano-pyridin-3-yl) methyl, (6-cyano-pyridin-3-yl) -methyl or (5-cyano-6-methoxy-pyridine-2-yl) yl) methyl group,
a (6-phenyl-pyridin-2-yl) methyl or a ([2,2 '] bipyridinyl-6-yl) methyl group,
a (2-phenyl-pyrimidin-4-yl) methyl or (4-phenyl-pyrimidin-2-yl) methyl group,
a (6-fluoro-quinolin-2-yl) methyl, (7-fluoro-quinolin-2-yl) methyl, (2-methyl-quinolin-4-yl) methyl, (3-cyanoquinoline) 2-yl) methyl, (3-cyano-4-methyl-quinolin-2-yl) methyl, (4-cyano-quinolin-2-yl) methyl, (5-cyano-quinolin-2-yl) methyl, (6-aminoquinolin-2-yl) methyl, (8-aminoquinolin-2-yl) methyl, (4-methoxyquinolin-2-yl) methyl, (6-methoxy) quinolin-2-yl) methyl or (6,7-dimethoxy-quinolin-2-yl) methyl group,
a (1-cyano-isoquinolin-3-yl) methyl, (4-cyano-isoquinolin-1-yl) methyl or [(4- (pyridin-2-yl) isoquinolin-1-yl] methyl group .
a (quinazolin-6-yl) methyl, (quinazolin-7-yl) methyl, (2-methylquinazolin-4-yl) methyl, (4,5-dimethyl-quinazolin-2-yl) methyl , (4-Ethylquinazolin-2-yl) methyl, (4-cyclopropyl-quinazolin-2-yl) methyl, (2-phenyl-quinazolin-4-yl) methyl, (4-cyanoquinazoline) 2-yl) methyl, (4-phenylamino-quinazolin-2-yl) methyl or (4-benzylamino-quinazolin-2-yl) methyl group,
a (quinoxalin-5-yl) methyl or (2,3-dimethyl-quinoxalin-6-yl) methyl group, or
a ([1,5] naphthyridin-3-yl) methyl group,
their tautomers, enantiomers, diastereomers, their mixtures and their salts.

• a) Umsetzung einer Verbindung der allgemeinen Formel
  
  in der R wie eingangs erwähnt definiert ist und Z¹ eine Austrittsgruppe wie ein Halogenatom, eine substituierte Hydroxy-, Mercapto-, Sulfinyl-, Sulfonyl- oder Sulfonyloxygruppe wie ein Chlor- oder Bromatom, eine Methansulfonyl- oder Methansulfonyloxygruppe darstellt, mit 3-Aminopiperidin, dessen Enantiomeren oder dessen Salzen. Die Umsetzung wird zweckmäßigerweise in einem Lösungsmittel wie Isopropanol, Butanol, Tetrahydrofuran, Dioxan, Dimethylformamid, Dimethylsulfoxid, Ethylenglycolmonomethylether, Ethylenglycoldiethylether oder Sulfolan gegebenenfalls in Gegenwart einer anorganischen oder tertiären organischen Base, z. B. Natriumcarbonat, Kaliumcarbonat oder Kaliumhydroxid, einer tertiären organischen Base, z. B. Triethylamin, oder in Gegenwart von N-Ethyl-diisopropylamin (Hünig-Base), wobei diese organischen Basen gleichzeitig auch als Lösungsmittel dienen können, und gegebenenfalls in Gegenwart eines Reaktionsbeschleunigers wie einem Alkalihalogenid oder einem Katalysator auf Palladiumbasis bei Temperaturen zwischen –20 und 180°C, vorzugsweise jedoch bei Temperaturen zwischen –10 und 120°C, durchgeführt. Die Umsetzung kann jedoch auch ohne Lösungsmittel oder in einem Überschuß des 3-Aminopiperidins durchgeführt werden.
• b) Entschützung einer Verbindung der allgemeinen Formel
  
  in der R wie eingangs definiert ist.

According to the invention, the compounds of general formula I are obtained by processes known per se, for example by the following processes:

• a) reaction of a compound of the general formula
  
  in which R is defined as mentioned above and Z ^{1 represents} a leaving group such as a halogen atom, a substituted hydroxy, mercapto, sulfinyl, sulfonyl or sulfonyloxy group such as a chlorine or bromine atom, a methanesulfonyl or methanesulfonyloxy group, with 3-aminopiperidine , its enantiomers or its salts. The reaction is conveniently carried out in a solvent such as isopropanol, butanol, tetrahydrofuran, dioxane, dimethylformamide, dimethyl sulfoxide, ethylene glycol monomethyl ether, ethylene glycol diethyl ether or sulfolane optionally in the presence of an inorganic or tertiary organic base, e.g. For example, sodium carbonate, potassium carbonate or potassium hydroxide, a tertiary organic base, z. As triethylamine, or in the presence of N-ethyl-diisopropylamine (Hünig base), said organic bases can also serve as a solvent, and optionally in the presence of a reaction accelerator such as an alkali metal halide or a palladium-based catalyst at temperatures between -20 and 180 ° C, but preferably at temperatures between -10 and 120 ° C performed. However, the reaction can also be carried out without a solvent or in an excess of 3-aminopiperidine.
• b) Deprotection of a compound of the general formula
  
  in the R is as defined above.

The Cleavage of the tert-Butyloxycarbonylrestes is preferably carried out by treatment with an acid such as trifluoroacetic acid or hydrochloric acid or by treatment with bromotrimethylsilane or iodotrimethylsilane optionally using a solvent such as methylene chloride, Essigester, dioxane, methanol, isopropanol or diethyl ether at Temperatures between 0 and 80 ° C.

at The reactions described above may optionally be present reactive groups such as amino, alkylamino or imino groups during the Implementation by usual Protected by protective groups will be split off after the implementation.

For example come as protective remnants for an amino, alkylamino or imino group the formyl, acetyl, Trifluoroacetyl, ethoxycarbonyl, tert-butoxycarbonyl, benzyloxycarbonyl, Benzyl, methoxybenzyl or 2,4-dimethoxybenzyl group and for the amino group additionally the phthalyl group into consideration.

The optional subsequent cleavage of a protective moiety used is carried out, for example hydrolytically in an aqueous solvent, for. B. in water, isopropanol / water, acetic acid / water, tetrahydrofuran / water or dioxane / water, in the presence of an acid such as trifluoroacetic acid, hydrochloric acid or Sulfuric acid or in the presence of an alkali metal base such as sodium hydroxide or potassium hydroxide or aprotic, z. B. in the presence of iodotrimethylsilane, at temperatures between 0 and 120 ° C, preferably at temperatures between 10 and 100 ° C.

The Cleavage of a benzyl, methoxybenzyl or Benzyloxycarbonylrestes However, for example, hydrogenolytically, z. With hydrogen in the presence of a catalyst such as palladium / carbon in a suitable solvent such as methanol, ethanol, ethyl acetate or glacial acetic acid optionally with the addition of an acid such as hydrochloric acid at temperatures between 0 and 100 ° C, but preferably at room temperatures between 20 and 60 ° C, and at a hydrogen pressure of 1 to 7 bar, but preferably from 3 to 5 bar. The cleavage of a 2,4-dimethoxybenzyl radical takes place however, preferably in trifluoroacetic acid in the presence of anisole.

The Cleavage of a tert-Butyloxycarbonylrestes preferably takes place by treatment with an acid such as trifluoroacetic acid or hydrochloric acid or optionally by treatment with iodotrimethylsilane Use of a solvent such as methylene chloride, dioxane, methanol or diethyl ether.

The Cleavage of a Trifluoracetylrestes is preferably carried out by Treatment with an acid like hydrochloric acid optionally in the presence of a solvent such as acetic acid Temperatures between 50 and 120 ° C or by treatment with caustic soda optionally in the presence of a solvent such as tetrahydrofuran at temperatures between 0 and 50 ° C.

The Cleavage of a phthalyl radical is preferably carried out in the presence of hydrazine or a primary Amines such as methylamine, ethylamine or n-butylamine in a solvent such as methanol, ethanol, isopropanol, toluene / water or dioxane Temperatures between 20 and 50 ° C.

Further can the obtained compounds of general formula I, as already was mentioned in the beginning, be separated into their enantiomers and / or diastereomers. So can for example cis / trans mixtures into their cis and trans isomers, and compounds having at least one optically active carbon atom be separated into their enantiomers.

So For example, the resulting cis / trans mixtures can be allowed to pass through Chromatography into their cis and trans isomers, the obtained Compounds of general formula I, which occur in racemates after methods known per se (see Allinger N.L. and Eliel E.L. in "Topics in Stereochemistry", Vol. 6, Wiley Interscience, 1971) into their optical antipodes and compounds of the general Formula I with at least 2 asymmetric carbon atoms due their physicochemical differences according to known Methods, eg. B. by chromatography and / or fractional crystallization, into their diastereomers, which, if they are in racemic Form incurred, then as mentioned above can be separated into the enantiomers.

The Enantiomer separation is preferably carried out by column separation on chiral phases or by recrystallization from an optical active solvents or by reacting with one, with the racemic compound salts or derivatives such. As esters or amides forming optically active Substance, especially acids and their activated derivatives or alcohols, and separating the this diastereomeric salt mixture or derivative obtained, z. B. due to different solubilities, wherein from the pure diastereomeric salts or derivatives of the free antipodes can be released by the action of appropriate means. Especially common, optically active acids are z. B. the D and L forms of tartaric acid or dibenzoyltartaric acid, di-O-p-toluoyl-tartaric acid, malic acid, mandelic acid, camphorsulfonic acid, glutamic acid, aspartic acid or China acid. As an optically active alcohol, for example, (+) - or (-) - menthol and as an optically active acyl radical in amides, for example (+) - or (-) - menthyloxycarbonyl into consideration.

Furthermore can the compounds of the formula I obtained in their salts, in particular for the pharmaceutical Use in their physiologically acceptable salts with inorganic or organic acids. As acids come for this for example, hydrochloric acid, Hydrobromic acid, sulfuric acid, methanesulfonic acid, phosphoric acid, fumaric acid, succinic acid, lactic acid, citric acid, tartaric acid or maleic into consideration.

The used as starting materials compounds of the general formulas II and III are either known from the literature or you get this according to methods known from the literature (see Examples I to XX).

As already mentioned at the beginning, have the compounds of the invention the general formula I and their physiologically acceptable Salts have valuable pharmacological properties, in particular an inhibitory effect on the enzyme DPP-IV.

The biological properties of the new compounds were tested as follows:
The ability of the substances and their corresponding salts to inhibit DPP-IV activity can be demonstrated in an experimental set-up using an extract of the human colon carcinoma cell line Caco-2 as a DPP IV source. Differentiation of cells to induce DPP-IV expression was performed as described by Reiher et al. in an article entitled "Increased expression of intestinal cell line Caco-2", published in Proc. Natl. Acad. Sci. Vol. 90, pages 5757-5761 (1993). The cell extract was purified from cells solubilized in a buffer (10mM Tris HCl, 0.15M NaCl, 0.04% aprotinin, 0.5% Nonidet-P40, pH 8.0) by centrifugation at 35,000g for 30 minutes at 4 ° C (to remove cell debris). won.

The DPP-IV assay was performed as follows:
50 μl substrate solution (AFC, amido-4-trifluoromethylcoumarin AFC), final concentration 100 μM, were placed in black microtiter plates. 20 μl assay buffer (final concentrations 50 mM Tris HCl pH 7.8, 50 mM NaCl, 1% DMSO) was pipetted. The reaction was started by adding 30 μl solubilized Caco-2 protein (final concentration 0.14 μg protein per well). The test substances to be tested were typically added prediluted in 20 μl, with the assay buffer volume correspondingly reduced. The reaction was carried out at room temperature, the incubation time was 60 minutes. The fluorescence was then measured in a Victor 1420 Multilabel Counter with the excitation wavelength at 405 nm and the emission wavelength at 535 nm. Blank values (corresponding to 0% activity) were obtained in batches without Caco-2 protein (volume replaced by assay buffer), control values (corresponding to 100% activity) were obtained in batches without added substance. The potency of the respective test substances, expressed as IC ₅₀ values, were calculated from dose-response curves consisting of 11 measurement points each. The following results were obtained:

The produced according to the invention Compounds are well tolerated, for example, after oral administration of 10 mg / kg of the compound of Example 1 (30) to rats no changes in the behavior of the animals could be observed.

In view of the ability to inhibit DPP-IV activity, the compounds of general formula I according to the invention and their corresponding pharmaceutically acceptable salts are suitable for influencing all those conditions or diseases which are influenced by an inhibition of DPP-IV activity can be flown. It is therefore to be expected that the compounds according to the invention will be used for the prevention or treatment of diseases or conditions such as diabetes mellitus type 1 and type 2, diabetic complications (such as retinopathy, nephropathy or neuropathy), metabolic acidosis or ketosis, reactive hypoglycemia, Insulin resistance, metabolic syndrome, dyslipidaemias of various genesis, arthritis, atherosclerosis and related diseases, adiposity, allograft transplantation and calcitonin-induced osteoporosis are suitable. Moreover, these substances are suitable for B-cell degeneration such. B. to prevent apoptosis or necrosis of pancreatic B cells. The substances are further suited to improve or restore the functionality of pancreatic cells, in addition to increase the number and size of pancreatic B cells. In addition, and justified by the role of glucagon-like peptides, such as. For example, GLP-1 and GLP-2 and their linkage with DPP-IV inhibition, it is expected that the compounds of the invention are suitable, inter alia, to achieve a sedative or anxiolytic effect, moreover, to favorably influence catabolic states after surgery or hormonal stress responses or to reduce mortality and morbidity after myocardial infarction. Moreover, they are suitable for treating all conditions related to the above-mentioned effects mediated by GLP-1 or GLP-2. The compounds of the invention are also useful as diuretics or antihypertensives and are suitable for the prevention and treatment of acute renal failure. Furthermore, the compounds according to the invention can be used for the treatment of inflammatory diseases of the respiratory tract. Likewise, they are for the prevention and treatment of chronic inflammatory bowel disease such. As irritable bowel syndrome (IBS), Crohn's disease or ulcerative colitis as well as in pancreatitis suitable. Furthermore, it is expected that they can be used in any kind of injury or impairment in the gastrointestinal tract as well as e.g. B. in colitis and enterids. Moreover, it is expected that DPP-IV inhibitors, and thus also the compounds of the present invention, can be used to treat infertility or to improve fertility in humans or mammalian organisms, particularly if their infertility is associated with insulin resistance or polycystic ovarian syndrome stands. On the other hand, these substances are suitable for influencing sperm motility and thus can be used as contraceptives for use in men. Furthermore, the substances are suitable for influencing deficiency states of growth hormone associated with shortage growth, as well as being useful for all indications in which growth hormone can be used. The compounds of the invention are due to their inhibitory effect against DPP IV also suitable for the treatment of various autoimmune diseases such. As rheumatoid arthritis, multiple sclerosis, thyroiditis and Basedow's disease etc. Moreover, they can be used in viral diseases such as. As in HIV infections, to stimulate blood formation, in benign prostatic hyperplasia, in gingivitis, and for the treatment of neuronal defects and neurodegenerative diseases such. B. Alzheimer's disease. Described compounds are also to be used for the therapy of tumors, in particular for the modification of tumor invasion as well as metastatization, examples being the use in T-cell lymphomas, acute lymphoblastic leukemia, cell-based thyroid carcinomas, basal cell carcinomas or breast carcinomas. Other indications include stroke, ischemia of various origins, Parkinson's disease and migraine. In addition, other indications are follicular and epidermal hyperkeratosis, increased keratinocyte proliferation, psoriasis, encephalomyelitis, glomerulonephritides, lipodystrophies, as well as psychosomatic, depressive and neuropsychiatric disorders of various origins.

The compounds according to the invention can also be used in combination with other active substances. Among the suitable for such a combination therapeutics include, for. Antidiabetics such as metformin, sulfonylureas (eg glibenclamide, tolbutamide, glimepiride), nateglinides, repaglinide, thiazolidinediones (eg rosiglitazone, pioglitazone), PPAR-gamma agonists (eg GI 262570) and Antagonists, PPAR-gamma / alpha modulators (eg KRP 297), alpha-glucosidase inhibitors (eg acarbose, voglibose), other DPPIV inhibitors, alpha2-antagonists, insulin and insulin analogs, GLP-1 and GLP-1 Analogs (eg, exendin-4) or amylin. In addition, SGLT2 inhibitors such as T-1095 or KGT-1251 (869682), inhibitors of protein tyrosine phosphatase 1, substances that affect deregulated glucose production in the liver, such as. Inhibitors of glucose-6-phosphatase, or fructose-1,6-bisphosphatase, glycogen phosphorylase, glucagon receptor antagonists and inhibitors of phosphoenolpyruvate carboxykinase, glycogen synthase kinase or pyruvate dehydrokinase, lipid-lowering agents such as HMG-CoA reductase inhibitors (e.g. Simvastatin, atorvastatin), fibrates (eg bezafibrate, fenofibrate), nicotinic acid and its derivatives, PPAR-alpha agonists, PPAR-delta agonists, ACAT inhibitors (eg avasimibe) or cholesterol resorption inhibitors such as ezetimibe, bile acid binding agents such as for example colestyramine, inhibitors of ileal bile acid transport, HDL increasing compounds such as inhibitors of CETP or regulators of ABC1 or drugs for the treatment of obesity such as sibutramine or tetrahydrolipstatin, dexfenfluramine, axokines, antagonists of the cannabinoid 1 receptor, MCH-1 receptor antagonists, MC4 receptor agonists, NPY5 or NPY2 antagonists or β ₃ -A gonists like SB-418790 or AD-9677 as well as agonists of the 5HT2c receptor.

Besides is a combination with drugs to influence high blood pressure such as B. All antagonists or ACE inhibitors, diuretics, β-blockers, Ca antagonists and others or combinations thereof.

The To achieve a corresponding effect required dosage is expediently at intravenous Administration 1 to 100 mg, preferably 1 to 30 mg, and when given orally 1 to 1000 mg, preferably 1 to 100 mg, 1 to 4 times daily. For this can be prepared according to the invention Compounds of formula I, optionally in combination with others Active substances, together with one or more inert usual excipients and / or diluents, z. With corn starch, Lactose, cane sugar, microcrystalline cellulose, magnesium stearate, Polyvinylpyrrolidone, citric acid, Tartaric acid, water, Water / ethanol, water / glycerin, water / sorbitol, water / polyethylene glycol, Propylene glycol, cetylstearyl alcohol, carboxymethylcellulose or fatty substances such as hard fat or their suitable mixtures, in usual galenic preparations such as tablets, dragees, capsules, powders, Suspensions or suppositories incorporated.

The The following examples are intended to explain the invention in more detail:

Preparation of the starting compounds

Example I

1 - [(4-phenylamino-quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert.-butyloxycarbonylamino) -piperidin-1-yl ] xanthine

A mixture of 416 mg of 3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine and 456 mg of cesium carbonate in 4 ml of N, N-Dimethylformamide is stirred at 80 ° C for 10 minutes, then 324 mg of 2-chloromethyl-4-phenylamino-quinazoline are added and the reaction mixture is stirred at 80 ° C for two hours. Then again 50 mg of cesium carbonate and 50 mg of chloromethyl-4-phenylamino-quinazoline are added and the mixture is stirred for a further 1.5 hours at 80 ° C. Subsequently, the solvent is distilled off and the residue is partitioned between water and ethyl acetate. The organic phase is washed with dilute citric acid, water and saturated sodium chloride solution, dried over magnesium sulfate and concentrated. The crude product is purified by chromatography on a silica gel column with ethyl acetate / petroleum ether (8: 2 to 10: 0) as the eluent.
Yield: 425 mg (65% of theory)
R _f value: 0.33 (silica gel, ethyl acetate)
Mass spectrum (ESI ⁺ ): m / z = 650 [M + H] ⁺

• (1) 1-[(4-Benzylamino-chinazolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.20 (Kieselgel, Essigester) Massenspektrum (ESI⁺): m/z = 664 [M + H]⁺
• (2) 1-[(2-Methyl-chinolin-4-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.80 (Kieselgel, Methylenchlorid/Methanol = 9:1) Massenspektrum (ESI⁺): m/z = 572 [M + H]⁺
• (3) 1-[(3-Cyano-naphthalin-1-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.67 (Kieselgel, Methylenchlorid/Methanol = 95:5) Massenspektrum (ESI⁺): m/z = 582 [M + H]⁺
• (4) 1-[(2-Phenyl-chinazolin-4-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.75 (Kieselgel, Methylenchlorid/Essigester = 1:1) Massenspektrum (ESI⁺): m/z = 635 [M + H]⁺
• (5) 1-[(4-Cyano-isochinolin-1-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.75 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:1) Massenspektrum (ESI⁺): m/z = 583 [M + H]⁺
• (6) 1-[(4-Cyano-chinolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin Massenspektrum (ESI⁺): m/z = 583 [M + H]⁺
• (7) 1-[2-(3-Cyclopropyloxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.75 (Kieselgel, Methylenchlorid/Essigester = 1:1) Massenspektrum (ESI⁺): m/z = 591 [M + H]⁺
• (8) 1-(2-(3-Cyclopropylmethoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.65 (Kieselgel, Methylenchlorid/Essigester = 1:1) Massenspektrum (ESI⁺): m/z = 605 [M + H]⁺
• (9) 1-[2-(3-Cyclobutyloxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.85 (Kieselgel, Methylenchlorid/Essigester = 1:1) Massenspektrum (ESI⁺): m/z = 605 [M + H]⁺
• (10) 1-[(1-Cyano-isochinolin-3-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin Massenspektrum (ESI⁺): m/z = 583 [M + H]⁺
• (11) 1-[(2,4-Methoxy-naphthalin-1-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.70 (Kieselgel, Essigester) Massenspektrum (ESI⁺): m/z = 617 [M + H]⁺
• (12) 1-[(2,3-Dimethyl-chinoxalin-6-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.50 (Kieselgel, Essigester) Massenspektrum (ESI⁺): m/z = 587 [M + H]⁺
• (13) 1-[(6-Nitro-chinolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.45 (Kieselgel, Essigester/Petrolether = 7:3) Massenspektrum (ESI⁺): m/z = 603 [M + H]⁺
• (14) 1-[(Chinoxalin-5-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin Massenspektrum (ESI⁺): m/z = 559 [M + H]⁺
• (15) 1-[(6-Methoxy-chinolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.65 (Kieselgel, Essigester) Massenspektrum (ESI⁺): m/z = 588 [M + H]⁺
• (16) 1-[(6-Phenyl-pyridin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.43 (Kieselgel, Methylenchlorid/Methanol = 96:4) Massenspektrum (ESI⁺): m/z = 584 [M + H]⁺
• (17) 1-{[(4-(Pyridin-2-yl)-isochinolin-1-yl]methyl}-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin
• (18) 1-[(7-Fluor-chinolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.24 (Kieselgel, Essigester/Petrolether = 1:1) Massenspektrum (ESI⁺): m/z = 576 [M + H]⁺
• (19) 1-[(8-Nitro-chinolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.63 (Kieselgel, Methylenchlorid/Methanol = 95:5) Massenspektrum (ESI⁺): m/z = 603 [M + H]⁺
• (20) 1-[(6-Fluor-chinolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.47 (Kieselgel, Methylenchlorid/Methanol = 95:5) Massenspektrum (ESI⁺): m/z = 576 [M + H]⁺
• (21) 1-[2-Oxo-2-(2-brom-phenyl)-ethyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.75 (Kieselgel, Methylenchlorid/Essigester = 1:1) Massenspektrum (ESI⁺): m/z = 613, 615 [M + H]⁺
• (22) 1-Cyanomethyl-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.80 (Kieselgel, Essigester) Massenspektrum (ESI⁺): m/z = 456 [M + H]⁺
• (23) 1-[(4-Methoxy-chinolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin Massenspektrum (ESI⁺): m/z = 588 [M + H]⁺
• (24) 1-[(2-Phenyl-pyrimidin-4-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.39 (Kieselgel, Methylenchlorid/Methanol = 96:4) Massenspektrum (ESI⁺): m/z = 585 [M + H]⁺
• (25) 1-[([1,5]Naphthyridin-3-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.28 (Kieselgel, Essigester) Massenspektrum (ESI⁺): m/z = 559 [M + H]⁺
• (26) 1-[(3-Cyano-4-methyl-chinolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.75 (Kieselgel, Methylenchlorid/Essigester = 1:1) Massenspektrum (ESI⁺): m/z = 597 [M + H]⁺
• (27) 1-[(4,5-Dimethyl-chinazolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin Massenspektrum (ESI⁺): m/z = 587 [M + H]⁺
• (28) 1-[(5-Cyano-chinolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.42 (Kieselgel, Petrolether/Essigester = 1:2) Massenspektrum (ESI⁺): m/z = 583 [M + H]⁺
• (29) 1-[(3-Cyano-chinolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.80 (Kieselgel, Methylenchlorid/Essigester = 1:1)
• (30) 1-[(4-Phenyl-pyrimidin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.46 (Kieselgel, Essigester)
• (31) 1-[2-(2-Nitro-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.75 (Kieselgel, Essigester) Massenspektrum (ESI⁺): m/z = 580 [M + H]⁺
• (32) 1-[(1,4-Dicyano-naphthalin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.54 (Kieselgel, Methylenchlorid/Methanol = 95:5) Massenspektrum (ESI⁺): m/z = 607 [M + H]⁺
• (33) 1-[(6,7-Dimethoxy-chinolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.36 (Kieselgel, Essigester) Massenspektrum (ESI⁺): m/z = 618 [M + H]⁺
• (34) 1-[(Chinazolin-6-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.20 (Kieselgel, Essigester) Massenspektrum (ESI⁺): m/z = 559 [M + H]⁺
• (35) 1-[(4-Cyano-chinazolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.40 (Kieselgel, Methylenchlorid/Essigester = 7:3) Massenspektrum (ESI⁺): m/z = 584 [M + H]⁺
• (36) 1-[(Chinazolin-7-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.20 (Kieselgel, Essigester) Massenspektrum (ESI⁺): m/z = 559 [M + H]⁺
• (37) 1-(2-Cyano-benzyl)-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.50 (Kieselgel, Methylenchlorid/Essigester = 7:3) Massenspektrum (ESI⁺): m/z = 532 [M + H]⁺
• (38) 1-(3-Cyano-benzyl)-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.58 (Kieselgel, Methylenchlorid/Essigester = 1:1) Massenspektrum (ESI⁺): m/z = 532 [M + H]⁺
• (39) 1-(4-Cyano-benzyl)-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.61 (Kieselgel, Methylenchlorid/Essigester = 1:1) Massenspektrum (ESI⁺): m/z = 532 [M + H]⁺
• (40) 1-[(Pyridin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin Massenspektrum (ESI⁺): m/z = 508 [M + H]⁺
• (41) 1-Benzyl-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.70 (Kieselgel, Methylenchlorid/Essigester = 1:1) Massenspektrum (ESI⁺): m/z = 507 [M + H]⁺
• (42) 1-(4-Methoxy-benzyl)-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.75 (Kieselgel, Essigester) Massenspektrum (ESI⁺): m/z = 537 [M + H]⁺
• (43) 1-(2-Chlor-benzyl)-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.80 (Kieselgel, Essigester) Massenspektrum (ESI⁺): m/z = 541, 543 [M + H]⁺
• (44) 1-(2,6-Dicyano-benzyl)-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin Massenspektrum (ESI⁺): m/z = 557 [M + H]⁺
• (45) 1-(2-Cyano-4-brom-benzyl)-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin Massenspektrum (ESI⁺): m/z = 610, 612 [M + H]⁺
• (46) 1-(3-Fluor-benzyl)-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.80 (Kieselgel, Essigester) Massenspektrum (ESI⁺): m/z = 525 [M + H]⁺
• (47) 1-(3,5-Dimethoxy-benzyl)-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.70 (Kieselgel, Essigester) Massenspektrum (ESI⁺): m/z = 567 [M + H]⁺
• (48) 1-(2-Fluor-benzyl)-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.85 (Kieselgel, Essigester) Massenspektrum (ESI⁺): m/z = 525 [M + H]⁺
• (49) 1-[(6-Cyano-pyridin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.60 (Kieselgel, Methylenchlorid/Essigester = 1:1) Massenspektrum (ESI⁺): m/z = 533 [M + H]⁺
• (50) 1-[(3-Cyano-pyridin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.60 (Kieselgel, Methylenchlorid/Essigester = 1:1) Massenspektrum (ESI⁺): m/z = 533 [M + H]⁺
• (51) 1-(2-Cyano-3-chlor-benzyl)-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin Massenspektrum (ESI⁺): m/z = 566, 568 [M + H]⁺
• (52) 1-(4-Fluor-benzyl)-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.80 (Kieselgel, Essigester) Massenspektrum (ESI⁺): m/z = 525 [M + H]⁺
• (53) 1-(4-Chlor-benzyl)-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.80 (Kieselgel, Essigester) Massenspektrum (ESI⁺): m/z = 541, 543 [M + H]⁺
• (54) 1-(2-Cyano-4-fluor-benzyl)-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin Massenspektrum (ESI⁺): m/z = 550 [M + H]⁺
• (55) 1-(3-Cyano-4-fluor-benzyl)-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin Massenspektrum (ESI⁺): m/z = 550 [M + H]⁺
• (56) 1-(2-Chlor-4-cyano-benzyl)-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin Massenspektrum (ESI⁺): m/z = 566, 568 [M + H]⁺
• (57) 1-[(5-Methoxycarbonyl-furan-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin Massenspektrum (ESI⁺): m/z = 555 [M + H]⁺
• (58) 1-(2-Trifluormethyl-4-cyano-benzyl)-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin Massenspektrum (ESI⁺): m/z = 600 [M + H]⁺
• (59) 1-(3,5-Dicyano-benzyl)-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin Massenspektrum (ESI⁺): m/z = 557 [M + H]⁺
• (60) 1-(3-Nitro-4-cyano-benzyl)-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin Massenspektrum (ESI⁺): m/z = 577 [M + H]⁺
• (61) 1-[(2-Cyano-pyridin-3-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.50 (Kieselgel, Methylenchlorid/Essigester = 1:1) Massenspektrum (ESI⁺): m/z = 533 [M + H]⁺
• (62) 1-(2-Cyano-4-methoxy-benzyl)-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.70 (Kieselgel, Methylenchlorid/Essigester = 1:1) Massenspektrum (ESI⁺): m/z = 562 [M + H]⁺
• (63) 1-(2-Cyano-5-methoxy-benzyl)-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.75 (Kieselgel, Methylenchlorid/Essigester = 1:1) Massenspektrum (ESI⁺): m/z = 562 [M + H]⁺
• (64) 1-(3-Methoxy-benzyl)-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.80 (Kieselgel, Essigester) Massenspektrum (ESI⁺): m/z = 537 [M + H]⁺
• (65) 1-(3-Trifluormethyl-benzyl)-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.80 (Kieselgel, Essigester) Massenspektrum (ESI⁺): m/z = 575 [M + H]⁺
• (66) 1-(3,4-Dimethoxy-benzyl)-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.65 (Kieselgel, Essigester) Massenspektrum (ESI⁺): m/z = 567 [M + H]⁺
• (67) 1-(3-Chlor-benzyl)-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.80 (Kieselgel, Essigester) Massenspektrum (ESI⁺): m/z = 541, 543 [M + H]⁺
• (68) 1-(4-Trifluormethyl-benzyl)-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.85 (Kieselgel, Essigester) Massenspektrum (ESI⁺): m/z = 575 [M + H]⁺
• (69) 1-[([2,2']Bipyridinyl-6-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.53 (Aluminiumoxid, Methylenchlorid/Methanol = 98:2) Massenspektrum (ESI⁺): m/z = 585 [M + H]⁺
• (70) 1-(3,4-Dimethoxy-6-fluor-benzyl)-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.65 (Kieselgel, Essigester) Massenspektrum (ESI⁺): m/z = 585 [M + H]⁺
• (71) 1-[(6-Fluor-pyridin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin Massenspektrum (ESI⁺): m/z = 526 [M + H]⁺
• (72) 1-[(5-Cyano-6-methoxy-pyridin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin Massenspektrum (ESI⁺): m/z = 563 [M + H]⁺
• (73) 1-(2,6-Difluor-benzyl)-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.62 (Kieselgel, Essigester) Massenspektrum (ESI⁺): m/z = 543 [M + H]⁺
• (74) 1-(3-Trifluormethoxy-benzyl)-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.67 (Kieselgel, Essigester) Massenspektrum (ESI⁺): m/z = 591 [M + H]⁺
• (75) 1-(4-Trifluormethoxy-benzyl)-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.62 (Kieselgel, Essigester) Massenspektrum (ESI⁺): m/z = 591 [M + H]⁺

Analogously to Example I, the following compounds are obtained:

• (1) 1 - [(4-Benzylamino-quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -piperidine 1-yl] -xanthine R _f value: 0.20 (silica gel, ethyl acetate) mass spectrum (ESI ⁺ ): m / z = 664 [M + H] ⁺
• (2) 1 - [(2-Methylquinolin-4-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert-butyloxycarbonylamino ) -piperidin-1-yl] -xanthine R _f value: 0.80 (silica gel, methylene chloride / methanol = 9: 1) Mass spectrum (ESI ⁺ ): m / z = 572 [M + H] ⁺
• (3) 1 - [(3-Cyano-naphthalen-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino ) -piperidin-1-yl] -xanthine R _f value: 0.67 (silica gel, methylene chloride / methanol = 95: 5) Mass spectrum (ESI ⁺ ): m / z = 582 [M + H] ⁺
• (4) 1 - [(2-phenyl-quinazolin-4-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino ) -piperidin-1-yl] -xanthine R _f value: 0.75 (silica gel, methylene chloride / ethyl acetate = 1: 1) Mass spectrum (ESI ⁺ ): m / z = 635 [M + H] ⁺
• (5) 1 - [(4-Cyanoisoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino ) piperidin-1-yl] -xanthine R _f value: 0.75 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 1) Mass spectrum (ESI ⁺ ): m / z = 583 [M + H] ⁺
• (6) 1 - [(4-Cyanoquinolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino ) -piperidin-1-yl] -xanthine mass spectrum (ESI ⁺ ): m / z = 583 [M + H] ⁺
• (7) 1- [2- (3-Cyclopropyloxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert .-butyloxycarbonylamino) -piperidin-1-yl] -xanthine R _f value: 0.75 (silica gel, methylene chloride / ethyl acetate = 1: 1) Mass spectrum (ESI ⁺ ): m / z = 591 [M + H] ⁺
• (8) 1- (2- (3-Cyclopropylmethoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert .-butyloxycarbonylamino) -piperidin-1-yl] -xanthine R _f value: 0.65 (silica gel, methylene chloride / ethyl acetate = 1: 1) Mass spectrum (ESI ⁺ ): m / z = 605 [M + H] ⁺
• (9) 1- [2- (3-Cyclobutyloxyphenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert .-butyloxycarbonylamino) -piperidin-1-yl] -xanthine R _f value: 0.85 (silica gel, methylene chloride / ethyl acetate = 1: 1) Mass spectrum (ESI ⁺ ): m / z = 605 [M + H] ⁺
• (10) 1 - [(1-Cyanoisoquinolin-3-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino ) -piperidin-1-yl] -xanthine mass spectrum (ESI ⁺ ): m / z = 583 [M + H] ⁺
• (11) 1 - [(2,4-Methoxynaphthalen-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert. -butyloxycarbonylamino) -piperidin-1-yl] -xanthine R _f value: 0.70 (silica gel, ethyl acetate) mass spectrum (ESI ⁺ ): m / z = 617 [M + H] ⁺
• (12) 1 - [(2,3-Dimethyl-quinoxalin-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert. -butyloxycarbonylamino) -piperidin-1-yl] -xanthin R _f value: 0.50 (silica gel, ethyl acetate) Mass spectrum (ESI ⁺ ): m / z = 587 [M + H] ⁺
• (13) 1 - [(6-nitroquinolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino ) -piperidin-1-yl] -xanthine R _f value: 0.45 (silica gel, ethyl acetate / petroleum ether = 7: 3) Mass spectrum (ESI ⁺ ): m / z = 603 [M + H] ⁺
• (14) 1 - [(Quinoxalin-5-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidine 1-yl] -xanthine mass spectrum (ESI ⁺ ): m / z = 559 [M + H] ⁺
• (15) 1 - [(6-Methoxy-quinolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino ) -piperidin-1-yl] -xanthine R _f value: 0.65 (silica gel, ethyl acetate) mass spectrum (ESI ⁺ ): m / z = 588 [M + H] ⁺
• (16) 1 - [(6-phenylpyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino ) -piperidin-1-yl] -xanthine R _f value: 0.43 (silica gel, methylene chloride / methanol = 96: 4) Mass spectrum (ESI ⁺ ): m / z = 584 [M + H] ⁺
• (17) 1 - {[(4- (pyridin-2-yl) isoquinolin-1-yl] methyl} -3-methyl-7- (2-butyn-1-yl) -8 - [(R) - 3- (tert.-butyloxycarbonylamino) -piperidin-1-yl] -xanthine
• (18) 1 - [(7-Fluoro-quinolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert-butyloxycarbonylamino ) -piperidin-1-yl] -xanthine R _f value: 0.24 (silica gel, ethyl acetate / petroleum ether = 1: 1) Mass spectrum (ESI ⁺ ): m / z = 576 [M + H] ⁺
• (19) 1 - [(8-nitroquinolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert-butyloxycarbonylamino ) -piperidin-1-yl] -xanthine R _f value: 0.63 (silica gel, methylene chloride / methanol = 95: 5) Mass spectrum (ESI ⁺ ): m / z = 603 [M + H] ⁺
• (20) 1 - [(6-Fluoro-quinolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert-butyloxycarbonylamino ) -pipe ridin-1-yl] -xanthine R _f value: 0.47 (silica gel, methylene chloride / methanol = 95: 5) Mass spectrum (ESI ⁺ ): m / z = 576 [M + H] ⁺
• (21) 1- [2-Oxo-2- (2-bromo-phenyl) -ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert .-butyloxycarbonylamino) -piperidin-1-yl] -xanthine R _f value: 0.75 (silica gel, methylene chloride / ethyl acetate = 1: 1) Mass spectrum (ESI ⁺ ): m / z = 613, 615 [M + H] ⁺
• (22) 1-Cyanomethyl-3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidin-1-yl] -xanthine R _f - Value: 0.80 (silica gel, ethyl acetate) Mass Spectrum (ESI ⁺ ): m / z = 456 [M + H] ⁺
• (23) 1 - [(4-Methoxyquinolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert-butyloxycarbonylamino ) -piperidin-1-yl] -xanthine mass spectrum (ESI ⁺ ): m / z = 588 [M + H] ⁺
• (24) 1 - [(2-phenylpyrimidin-4-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino ) -piperidin-1-yl] -xanthine R _f value: 0.39 (silica gel, methylene chloride / methanol = 96: 4) Mass spectrum (ESI ⁺ ): m / z = 585 [M + H] ⁺
• (25) 1 - [([1,5] -naphthyridin-3-yl) -methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert. butyloxycarbonylamino) -piperidin-1-yl] -xanthine R _f value: 0.28 (silica gel, ethyl acetate) mass spectrum (ESI ⁺ ): m / z = 559 [M + H] ⁺
• (26) 1 - [(3-Cyano-4-methyl-quinolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- ( tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine R _f value: 0.75 (silica gel, methylene chloride / ethyl acetate = 1: 1) Mass spectrum (ESI ⁺ ): m / z = 597 [M + H] ⁺
• (27) 1 - [(4,5-Dimethylquinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert. -butyloxycarbonylamino) -piperidin-1-yl] -xanthine mass spectrum (ESI ⁺ ): m / z = 587 [M + H] ⁺
• (28) 1 - [(5-Cyanoquinolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino ) -piperidin-1-yl] -xanthine R _f value: 0.42 (silica gel, petroleum ether / ethyl acetate = 1: 2) Mass spectrum (ESI ⁺ ): m / z = 583 [M + H] ⁺
• (29) 1 - [(3-Cyanoquinolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino ) -piperidin-1-yl] -xanthine R _f value: 0.80 (silica gel, methylene chloride / ethyl acetate = 1: 1)
• (30) 1 - [(4-phenylpyrimidin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino ) -piperidin-1-yl] -xanthine R _f value: 0.46 (silica gel, ethyl acetate)
• (31) 1- [2- (2-nitrophenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert .-butyloxycarbonylamino) -piperidin-1-yl] -xanthine R _f value: 0.75 (silica gel, ethyl acetate) mass spectrum (ESI ⁺ ): m / z = 580 [M + H] ⁺
• (32) 1 - [(1,4-Dicyano-naphthalen-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert. -butyloxycarbonylamino) -piperidin-1-yl] -xanthine R _f value: 0.54 (silica gel, methylene chloride / methanol = 95: 5) Mass spectrum (ESI ⁺ ): m / z = 607 [M + H] ⁺
• (33) 1 - [(6,7-Dimethoxyquinolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert. -butyloxycarbonylamino) -piperidin-1-yl] -xanthine R _f value: 0.36 (silica gel, ethyl acetate) Mass spectrum (ESI ⁺ ): m / z = 618 [M + H] ⁺
• (34) 1 - [(quinazolin-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert-butyloxycarbonylamino) -piperidine 1-yl] -xanthine R _f value: 0.20 (silica gel, ethyl acetate) mass spectrum (ESI ⁺ ): m / z = 559 [M + H] ⁺
• (35) 1 - [(4-Cyanoquinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert-butyloxycarbonylamino ) piperidin-1-yl] -xanthine R _f value: 0.40 (silica gel, methylene chloride / ethyl acetate = 7: 3) Mass spectrum (ESI ⁺ ): m / z = 584 [M + H] ⁺
• (36) 1 - [(Quinazolin-7-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidine 1-yl] -xanthine R _f value: 0.20 (silica gel, ethyl acetate) mass spectrum (ESI ⁺ ): m / z = 559 [M + H] ⁺
• (37) 1- (2-Cyanobenzyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidin-1-yl ] -xanthin R _f value: 0.50 (silica gel, methylene chloride / ethyl acetate = 7: 3) Mass spectrum (ESI ⁺ ): m / z = 532 [M + H] ⁺
• (38) 1- (3-Cyanobenzyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidin-1-yl ] -xanthine R _f value: 0.58 (silica gel, methylene chloride / ethyl acetate = 1: 1) Mass spectrum (ESI ⁺ ): m / z = 532 [M + H] ⁺
• (39) 1- (4-Cyanobenzyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidin-1-yl ] -xanthin R _f value: 0.61 (silica gel, methylene chloride / ethyl acetate = 1: 1) Mass spectrum (ESI ⁺ ): m / z = 532 [M + H] ⁺
• (40) 1 - [(pyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert-butyloxycarbonylamino) -piperidine 1-yl] -xanthine mass spectrum (ESI ⁺ ): m / z = 508 [M + H] ⁺
• (41) 1-Benzyl-3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidin-1-yl] -xanthine R _f - Value: 0.70 (silica gel, methylene chloride / ethyl acetate = 1: 1) Mass spectrum (ESI ⁺ ): m / z = 507 [M + H] ⁺
• (42) 1- (4-Methoxybenzyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidin-1-yl ] -xanthine R _f value: 0.75 (silica gel, ethyl acetate) mass spectrum (ESI ⁺ ): m / z = 537 [M + H] ⁺
• (43) 1- (2-Chloro-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidin-1-yl ] -xanthin R _f value: 0.80 (silica gel, ethyl acetate) Mass spectrum (ESI ⁺ ): m / z = 541, 543 [M + H] ⁺
• (44) 1- (2,6-Dicyano-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidine-1 -yl] -xanthin mass spectrum (ESI ⁺ ): m / z = 557 [M + H] ⁺
• (45) 1- (2-Cyano-4-bromo-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidine -1-yl] -xanthine mass spectrum (ESI ⁺ ): m / z = 610, 612 [M + H] ⁺
• (46) 1- (3-Fluoro-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidin-1-yl ] -xanthine R _f value: 0.80 (silica gel, ethyl acetate) mass spectrum (ESI ⁺ ): m / z = 525 [M + H] ⁺
• (47) 1- (3,5-Dimethoxybenzyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidine-1 -yl] -xanthine R _f value: 0.70 (silica gel, ethyl acetate) mass spectrum (ESI ⁺ ): m / z = 567 [M + H] ⁺
• (48) 1- (2-Fluoro-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidin-1-yl ] -xanthin R _f value: 0.85 (silica gel, ethyl acetate) Mass spectrum (ESI ⁺ ): m / z = 525 [M + H] ⁺
• (49) 1 - [(6-Cyano-pyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino ) -piperidin-1-yl] -xanthine R _f value: 0.60 (silica gel, methylene chloride / ethyl acetate = 1: 1) Mass spectrum (ESI ⁺ ): m / z = 533 [M + H] ⁺
• (50) 1 - [(3-Cyano-pyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino ) -piperidin-1-yl] -xanthine R _f value: 0.60 (silica gel, methylene chloride / ethyl acetate = 1: 1) Mass spectrum (ESI ⁺ ): m / z = 533 [M + H] ⁺
• (51) 1- (2-Cyano-3-chloro-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert-butyloxycarbonylamino) -piperidine -1-yl] -xanthine Mass Spectrum (ESI ⁺ ): m / z = 566, 568 [M + H] ⁺
• (52) 1- (4-Fluoro-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidin-1-yl ] -xanthine R _f value: 0.80 (silica gel, ethyl acetate) mass spectrum (ESI ⁺ ): m / z = 525 [M + H] ⁺
• (53) 1- (4-Chloro-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidin-1-yl ] -xanthin R _f value: 0.80 (silica gel, ethyl acetate) Mass spectrum (ESI ⁺ ): m / z = 541, 543 [M + H] ⁺
• (54) 1- (2-Cyano-4-fluoro-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidine -1-yl] -xanthine mass spectrum (ESI ⁺ ): m / z = 550 [M + H] ⁺
• (55) 1- (3-Cyano-4-fluoro-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidine -1-yl] -xanthine mass spectrum (ESI ⁺ ): m / z = 550 [M + H] ⁺
• (56) 1- (2-Chloro-4-cyano-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidine -1-yl] -xanthin mass spectrum (ESI ⁺ ): m / z = 566, 568 [M + H] ⁺
• (57) 1 - [(5-Methoxycarbonyl-furan-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert-butyloxycarbonylamino ) -piperidin-1-yl] -xanthine mass spectrum (ESI ⁺ ): m / z = 555 [M + H] ⁺
• (58) 1- (2-Trifluoromethyl-4-cyano-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidine -1-yl] -xanthine mass spectrum (ESI ⁺ ): m / z = 600 [M + H] ⁺
• (59) 1- (3,5-Dicyano-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidine-1 -yl] -xanthin mass spectrum (ESI ⁺ ): m / z = 557 [M + H] ⁺
• (60) 1- (3-nitro-4-cyano-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidine -1-yl] -xanthine mass spectrum (ESI ⁺ ): m / z = 577 [M + H] ⁺
• (61) 1 - [(2-Cyano-pyridin-3-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino ) -piperidin-1-yl] -xanthine R _f value: 0.50 (silica gel, methylene chloride / ethyl acetate = 1: 1) Mass spectrum (ESI ⁺ ): m / z = 533 [M + H] ⁺
• (62) 1- (2-Cyano-4-methoxybenzyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidine -1-yl] -xanthin R _f value: 0.70 (silica gel, methylene chloride / ethyl acetate = 1: 1) Mass spectrum (ESI ⁺ ): m / z = 562 [M + H] ⁺
• (63) 1- (2-Cyano-5-methoxybenzyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidine -1-yl] -xanthine R _f value: 0.75 (silica gel, methylene chloride / ethyl acetate = 1: 1) Mass spectrum (ESI ⁺ ): m / z = 562 [M + H] ⁺
• (64) 1- (3-Methoxybenzyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidin-1-yl ] -xanthin R _f value: 0.80 (silica gel, ethyl acetate) Mass spectrum (ESI ⁺ ): m / z = 537 [M + H] ⁺
• (65) 1- (3-trifluoromethyl-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidin-1-yl ] -xanthine R _f value: 0.80 (silica gel, ethyl acetate) mass spectrum (ESI ⁺ ): m / z = 575 [M + H] ⁺
• (66) 1- (3,4-Dimethoxybenzyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidine-1 -yl] -xanthine R _f value: 0.65 (silica gel, ethyl acetate) Mass spectrum (ESI ⁺ ): m / z = 567 [M + H] ⁺
• (67) 1- (3-Chloro-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidin-1-yl ] -xanthin R _f value: 0.80 (silica gel, ethyl acetate) Mass spectrum (ESI ⁺ ): m / z = 541, 543 [M + H] ⁺
• (68) 1- (4-Trifluoromethylbenzyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperi din-1-yl] -xanthine R _f value: 0.85 (silica gel, ethyl acetate) Mass spectrum (ESI ⁺ ): m / z = 575 [M + H] ⁺
• (69) 1 - [([2,2 '] bipyridinyl-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert. -butyloxycarbonylamino) -piperidin-1-yl] -xanthin R _f value: 0.53 (alumina, methylene chloride / methanol = 98: 2) Mass spectrum (ESI ⁺ ): m / z = 585 [M + H] ⁺
• (70) 1- (3,4-Dimethoxy-6-fluoro-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidin-1-yl] -xanthine R _f value: 0.65 (silica gel, ethyl acetate) mass spectrum (ESI ⁺ ): m / z = 585 [M + H] ⁺
• (71) 1 - [(6-Fluoro-pyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert-butyloxycarbonylamino ) -piperidin-1-yl] -xanthine mass spectrum (ESI ⁺ ): m / z = 526 [M + H] ⁺
• (72) 1 - [(5-Cyano-6-methoxypyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- ( tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine Mass spectrum (ESI ⁺ ): m / z = 563 [M + H] ⁺
• (73) 1- (2,6-Difluoro-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidine-1 -yl] -xanthin R _f value: 0.62 (silica gel, ethyl acetate) Mass spectrum (ESI ⁺ ): m / z = 543 [M + H] ⁺
• (74) 1- (3-trifluoromethoxybenzyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidin-1-yl ] -xanthin R _f value: 0.67 (silica gel, ethyl acetate) Mass spectrum (ESI ⁺ ): m / z = 591 [M + H] ⁺
• (75) 1- (4-trifluoromethoxybenzyl) -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidin-1-yl ] -xanthin R _f value: 0.62 (silica gel, ethyl acetate) Mass spectrum (ESI ⁺ ): m / z = 591 [M + H] ⁺

Example II

3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert.-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

To 15.00 g of 3-methyl-7- (2-butyn-1-yl) -8-bromo-xanthine and 16.00 g of potassium carbonate in 100 ml of dimethyl sulfoxide are added 11.00 g of (R) -3-tert-Butyloxycarbonylamino-piperidine and the thick light beige suspension is stirred for four hours with a mechanical stirrer at about 114 ° C. Then another 900 mg of (R) -3-tert-butyloxycarbonylamino-piperidine, dissolved in 10 ml of dimethyl sulfoxide, are added to the reaction mixture and this is stirred at 114 ° C. for a further two hours. After cooling to room temperature, the reaction mixture is diluted with plenty of water. The resulting precipitate is triturated thoroughly until no lumps are left, and vacuumed. The light solid is reslurried with water, filtered off, washed with water and diethyl ether and dried in a convection oven at 60 ° C.
Yield: 19.73 g (94% of theory)
R _f value: 0.64 (silica gel, ethyl acetate)
Mass spectrum (ESI ⁺ ): m / z = 417 [M + H] ⁺

• (1) 3-Methyl-7-(2-butin-1-yl)-8-[(3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin Schmelzpunkt: 235–237°C Massenspektrum (ESI⁺): m/z = 417 [M + H]⁺

Analogously to Example II, the following compound is obtained:

• (1) 3-Methyl-7- (2-butyn-1-yl) -8 - [(3- (tert -butyloxycarbonylamino) -piperidin-1-yl] -xanthine Melting point: 235-237 ° C Mass spectrum (ESI ⁺ ): m / z = 417 [M + H] ⁺

Example III

3-methyl-7- (2-butyn-1-yl) -8-bromo-xanthine

To 30.17 g of 3-methyl-8-bromo-xanthine and 27.00 ml of Hünig base in 370 ml of N, N-dimethylformamide are added 17.06 g of 1-bromo-2-butyne. The reaction mixture is stirred for two hours at room temperature, then another 1 ml of 1-bromo-2-buty added and stirred for a further hour at room temperature. For workup, the reaction mixture is diluted with about 300 ml of water. The resulting bright low Blow is sucked off and washed with water. The filter cake is washed with a little ethanol and diethyl ether and dried in a convection oven at 60 ° C.
Yield: 30.50 g (84% of theory)
R _f value: 0.24 (silica gel, methylene chloride / methanol = 95: 5)
Mass spectrum (ESI ⁺ ): m / z = 297, 299 [M + H] ⁺

Example IV

2-chloromethyl-4-phenylamino-quinazoline

Prepared by reaction of 500 mg of 4-chloro-2-chloromethyl-quinazoline with 438 mg of aniline in 12 ml of methylene chloride at room temperature.
Yield: 518 mg (82% of theory)
R _f value: 0.60 (silica gel, cyclohexane / ethyl acetate = 1: 1)
Mass spectrum (ESI ⁺ ): m / z = 270, 272 [M + H] ⁺

• (1) 2-Chlormethyl-4-benzylamino-chinazolin R_f-Wert: 0.60 (Kieselgel, Cyclohexan/Essigester = 1:1) Massenspektrum (ESI⁺): m/z = 284, 286 [M + H]⁺

Analogously to Example IV, the following compound is obtained:

• (1) 2-Chloromethyl-4-benzylamino-quinazoline R _f value: 0.60 (silica gel, cyclohexane / ethyl acetate = 1: 1) Mass spectrum (ESI ⁺ ): m / z = 284, 286 [M + H] ⁺

Example V

1-bromomethyl-4-cyano-isoquinoline

Prepared by bromination of 1-methyl-4-cyano-isoquinoline with N-bromosuccinimide in the presence of azobisisobutyronitrile in carbon tetrachloride at 80 ° C.
R _f value: 0.51 (silica gel, methylene chloride)
Mass spectrum (EI): m / z = 246, 248 [M] ⁺

• (1) 2-Brommethyl-4-cyano-chinolin Massenspektrum (ESI⁺): m/z = 247, 249 [M + H]⁺
• (2) 3-Brommethyl-1-cyano-isochinolin Massenspektrum (ESI⁺): m/z = 247, 249 [M + H]⁺
• (3) 1-Brommethyl-4-(pyridin-2-yl)-isochinolin R_f-Wert: 0.47 (Kieselgel, Methylenchlorid/Methanol = 9:1)
• (4) 2-Brommethyl-4-methoxy-chinolin Massenspektrum (ESI⁺): m/z = 252, 254 [M + H]⁺
• (5) 3-Brommethyl-[1,5]naphthyridin Massenspektrum (ESI⁺): m/z = 223, 225 [M + H]⁺
• (6) 2-Brommethyl-5-cyano-chinolin R_f-Wert: 0.28 (Kieselgel, Petrolether/Essigester = 5:1) Massenspektrum (ESI⁺): m/z = 247, 249 [M + H]⁺
• (7) 2-Brommethyl-3-cyano-chinolin R_f-Wert: 0.65 (Kieselgel, Cyclohexan/Essigester = 3:1)
• (8) 2-Brommethyl-4-phenyl-pyrimidin R_f-Wert: 0.88 (Kieselgel, Essigester) Massenspektrum (ESI⁺): m/z = 249, 251 [M + H]⁺
• (9) 2-Brommethyl-1,4-dicyano-naphthalin R_f-Wert: 0.48 (Kieselgel, Petrolether/Essigester = 9:1) Massenspektrum (EI⁺): m/z = 270, 272 [M]⁺
• (10) 2-Brommethyl-6,7-dimethoxy-chinolin R_f-Wert: 0.70 (Kieselgel, Methylenchlorid/Methanol = 95:5) Massenspektrum (ESI⁺): m/z = 282, 284 [M + H]⁺
• (11) 2-Brommethyl-4-cyano-chinazolin R_f-Wert: 0.85 (Kieselgel, Methylenchlorid/Methanol = 99:1) Massenspektrum (EI⁺): m/z = 247, 249 [M]⁺
• (12) 7-Brommethyl-chinazolin R_f-Wert: 0.15 (Kieselgel, Methylenchlorid/Methanol = 99:1) Massenspektrum (ESI⁺): m/z = 223, 225 [M + H]⁺
• (13) 2-Trifluormethyl-4-cyano-benzylbromid
• (14) 2-Brommethyl-5-cyano-6-methoxy-pyridin Massenspektrum (ESI⁺): m/z = 227, 229 [M + H]⁺

Analogously to Example V, the following compounds are obtained:

• (1) 2-Bromomethyl-4-cyano-quinoline mass spectrum (ESI ⁺ ): m / z = 247, 249 [M + H] ⁺
• (2) 3-Bromomethyl-1-cyano-isoquinoline mass spectrum (ESI ⁺ ): m / z = 247, 249 [M + H] ⁺
• (3) 1-Bromomethyl-4- (pyridin-2-yl) -isoquinoline R _f value: 0.47 (silica gel, methylene chloride / methanol = 9: 1)
• (4) 2-Bromomethyl-4-methoxy-quinoline mass spectrum (ESI ⁺ ): m / z = 252, 254 [M + H] ⁺
• (5) 3-Bromomethyl- [1,5] naphthyridine mass spectrum (ESI ⁺ ): m / z = 223, 225 [M + H] ⁺
• (6) 2-Bromomethyl-5-cyano-quinoline R _f value: 0.28 (silica gel, petroleum ether / ethyl acetate = 5: 1) Mass spectrum (ESI ⁺ ): m / z = 247, 249 [M + H] ⁺
• (7) 2-bromomethyl-3-cyano-quinoline R _f value: 0.65 (silica gel, cyclohexane / ethyl acetate = 3: 1)
• (8) 2-Bromomethyl-4-phenyl-pyrimidine R _f value: 0.88 (silica gel, ethyl acetate) Mass spectrum (ESI ⁺ ): m / z = 249, 251 [M + H] ⁺
• (9) 2-Bromomethyl-1,4-dicyano-naphthalene R _f value: 0.48 (silica gel, petroleum ether / ethyl acetate = 9: 1) Mass spectrum (EI ⁺ ): m / z = 270, 272 [M] ⁺
• (10) 2-Bromomethyl-6,7-dimethoxy-quinoline R _f value: 0.70 (silica gel, methylene chloride / methanol = 95: 5) Mass spectrum (ESI ⁺ ): m / z = 282, 284 [M + H] ⁺
• (11) 2-Bromomethyl-4-cyano-quinazoline R _f value: 0.85 (silica gel, methylene chloride / methanol = 99: 1) Mass spectrum (EI ⁺ ): m / z = 247, 249 [M] ⁺
• (12) 7-bromomethyl-quinazoline R _f value: 0.15 (silica gel, methylene chloride / methanol = 99: 1) Mass spectrum (ESI ⁺ ): m / z = 223, 225 [M + H] ⁺
• (13) 2-trifluoromethyl-4-cyano-benzylbromide
• (14) 2-Bromomethyl-5-cyano-6-methoxy-pyridine Mass Spectrum (ESI ⁺ ): m / z = 227, 229 [M + H] ⁺

Example VI

2-bromo-1- (3-cyclopropyloxy-phenyl) -ethanone

Prepared by bromination of 1- (3-cyclopropyloxy-phenyl) -ethanone with phenyltrimethylammonium tribromide in methylene chloride under reflux.
R _f value: 0.75 (silica gel, cyclohexane / ethyl acetate = 3: 1)
Mass spectrum (ESI ⁺ ): m / z = 255, 257 [M + H] ⁺

• (1) 2-Brom-1-(3-cyclopropylmethoxy-phenyl)-ethanon R_f-Wert: 0.70 (Kieselgel, Cyclohexan/Essigester = 3:1)
• (2) 2-Brom-1-(3-cyclobutyloxy-phenyl)-ethanon R_f-Wert: 0.70 (Kieselgel, Cyclohexan/Essigester = 3:1)

The following compounds are obtained analogously to Example VI:

• (1) 2-bromo-1- (3-cyclopropylmethoxy-phenyl) -ethanone R _f value: 0.70 (silica gel, cyclohexane / ethyl acetate = 3: 1)
• (2) 2-bromo-1- (3-cyclobutyloxyphenyl) -ethanone R _f value: 0.70 (silica gel, cyclohexane / ethyl acetate = 3: 1)

Example VII

1- (3-cyclopropyloxy-phenyl) -ethanone

Prepared by reaction of 3-hydroxyacetophenone with bromocyclopropane in the presence of potassium iodide and potassium tert-butoxide in N, N-dimethylformamide in the microwave at 220 ° C.
R _f value: 0.65 (silica gel, cyclohexane / ethyl acetate = 3: 1)
Mass spectrum (ESI ⁺ ): m / z = 177 [M + H] ⁺

• (1) 1-(3-Cyclopropylmethoxy-phenyl)-ethanon R_f-Wert: 0.70 (Kieselgel, Cyclohexan/Essigester = 3:1) Massenspektrum (ESI⁺): m/z = 191 [M + H]⁺
• (2) 1-(3-Cyclobutyloxy-phenyl)-ethanon R_f-Wert: 0.65 (Kieselgel, Cyclohexan/Essigester = 3:1) Massenspektrum (ESI⁺): m/z = 191 [M + H]⁺

The following compounds are obtained analogously to Example VII:

• (1) 1- (3-Cyclopropylmethoxy-phenyl) -ethanone R _f value: 0.70 (silica gel, cyclohexane / ethyl acetate = 3: 1) Mass spectrum (ESI ⁺ ): m / z = 191 [M + H] ⁺
• (2) 1- (3-Cyclobutyloxyphenyl) -ethanone R _f value: 0.65 (silica gel, cyclohexane / ethyl acetate = 3: 1) Mass spectrum (ESI ⁺ ): m / z = 191 [M + H] ⁺

Example VIII

1-chloromethyl-2,4-dimethoxy-naphthalene

Prepared by chlorinating 1-hydroxymethyl-2,4-dimethoxy-naphthalene with thionyl chloride in methylene chloride at room temperature.
R _f value: 0.78 (silica gel, cyclohexane / ethyl acetate = 1: 1)
Mass spectrum (EI): m / z = 236, 238 [M] ⁺

Example IX

1-hydroxymethyl-2,4-dimethoxy-naphthalene

Prepared by reduction of 2,4-dimethoxy-naphthalene-1-carboxaldehyde with sodium borohydride in a mixture of dioxane and water (3: 1) at room temperature.
R _f value: 0.48 (silica gel, cyclohexane / ethyl acetate = 1: 1)

Example X

1 - [(6-amino-quinolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert.-butyloxycarbonylamino) -piperidin -1-yl] -xanthine

Prepared by treatment of 1 - [(6-nitro-quinolin-2-yl) methyl] -3-methyl-7- (2-bu tin-1-yl) -8 - [(R) -3- (tert -butyloxycarbonylamino) -piperidin-1-yl] -xanthine with sodium dithionite in a mixture of ethanol / water (5: 2) at 55-60 ° C.
R _f value: 0.40 (silica gel, methylene chloride / methanol = 95: 5)
Mass spectrum (ESI ⁺ ): m / z = 573 (M + H] ⁺

Example XI

1-Methyl-4- (pyridin-2-yl) -isoquinoline

Prepared by reacting 4-bromo-1-methylisoquinoline with lithium triisopropoxy-2-pyridinyl boronate in the presence of tetrakis (triphenylphosphine) palladium, triphenylphosphine, sodium carbonate and copper (I) iodide in 1,4-dioxane at reflux.
R _f value: 0.22 (silica gel, methylene chloride / methanol = 95: 5)
Mass spectrum (ESI ⁺ ): m / z = 221 [M + H] ⁺

Example XII

1 - [(8-amino-quinolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert.-butyloxycarbonylamino) -piperidin -1-yl] -xanthine

Prepared by treatment of 1 - [(8-nitro-quinolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert. butyloxycarbonylamino) -piperidin-1-yl] -xanthine with iron powder in a mixture of glacial acetic acid, ethanol and water (2: 20: 5) under reflux.
R _f value: 0.50 (silica gel, methylene chloride / methanol = 95: 5)
Mass spectrum (ESI ⁺ ): m / z = 573 [M + H] ⁺

Example XIII

1- {2-Oxo-2- [2- (pyridin-3-yl) -phenyl] -ethyl} -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3 - (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine

Prepared by reaction of 1- [2-oxo-2- (2-bromophenyl) ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- ( tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine with pyridine-3-boronic acid in the presence of tetrakis (triphenylphosphine) palladium, tetra-n-butylammonium bromide and sodium carbonate in a mixture of toluene / ethanol (1: 1) at 105 ° C.
R _f value: 0.55 (silica gel, ethyl acetate)
Mass spectrum (ESI ⁺ ): m / z = 612 [M + H] ⁺

• (1) 1-{2-Oxo-2-[2-(pyridin-4-yl)-phenyl]-ethyl}-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin (Die Umsetzung erfolgt mit 4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin.) R_f-Wert: 0.40 (Kieselgel, Essigester) Massenspektrum (ESI⁺): m/z = 612 [M + H]⁺

The following compound is obtained analogously to Example XII:

• (1) 1- {2-Oxo-2- [2- (pyridin-4-yl) -phenyl] -ethyl} -3-methyl-7- (2-butyn-1-yl) -8 - [(R ) -3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine (The reaction is carried out with 4- (4,4,5,5-tetramethyl- [1,3,2] dioxaborolan-2-yl) -pyridine.) R _f value: 0.40 (silica gel, ethyl acetate) Mass spectrum (ESI ⁺ ): m / z = 612 [M + H] ⁺

Example XIV

1 - [(4-ethyl-quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert.-butyloxycarbonylamino) -piperidin -1-yl] -xanthine

Prepared by treating 1-cyanomethyl-3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine with potassium tert-butoxide in methanol and subsequent reaction of the resulting iminoester with 2-aminopropiophenone in the presence of glacial acetic acid.
R _f value: 0.60 (silica gel, ethyl acetate)
Mass spectrum (ESI ⁺ ): m / z = 587 [M + H] ⁺

• (1) 1-[(4-Cyclopropyl-chinazolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-[(R)-3-(tert.-butyloxycarbonylamino)-piperidin-1-yl]-xanthin R_f-Wert: 0.70 (Kieselgel, Essigester) Massenspektrum (ESI⁺): m/z = 599 [M + H]⁺

The following compound is obtained analogously to Example XIV:

• (1) 1 - [(4-Cyclopropyl-quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert-butyloxycarbonylamino ) - piperidin-1-yl] -xanthine R _f value: 0.70 (silica gel, ethyl acetate) Mass spectrum (ESI ⁺ ): m / z = 599 [M + H] ⁺

Example XV

2-chloromethyl-3-cyano-4-methyl-quinoline

Prepared by reaction of 3-cyano-2,4-dimethyl-1-oxy-quinoline with benzosulfonyl chloride in toluene at 80 ° C.
R _f value: 0.55 (silica gel, cyclohexane / ethyl acetate = 2: 1)
Mass spectrum (ESI ⁺ ): m / z = 217, 219 [M + H] ⁺

Example XVI

3-Cyano-2,4-dimethyl-1-oxy-quinolin

Prepared by treating 3-cyano-2,4-dimethyl-quinoline with aqueous hydrogen peroxide solution (35%) in glacial acetic acid at 60 ° C.
R _f value: 0.35 (silica gel, ethyl acetate)
Mass spectrum (ESI ⁺ ): m / z = 199 [M + H] ⁺

Example XVII

2-chloromethyl-4,5-dimethyl-quinazoline

Prepared by reacting 1- (2-amino-6-methyl-phenyl) -ethanone with chloroacetonitrile in dioxane with hydrogen chloride at 30-38 ° C.
Mass spectrum (ESI ⁺ ): m / z = 207, 209 [M + H] ⁺

Example XVIII

1 - [(2-methyl-quinazolin-4-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert.-butyloxycarbonylamino) -piperidin -1-yl] -xanthine

Prepared by reaction of 1- [2- (2-acetylamino-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- ( tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine with ethanolic ammonia (6 M) and ammonium chloride in an autoclave at 150 ° C.
R _f value: 0.35 (silica gel, ethyl acetate)
Mass spectrum (ESI ⁺ ): m / z = 573 [M + H] ⁺

Example XIX

1- [2- (2-acetylamino-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert-butyloxycarbonylamino ) piperidin-1-yl] -xanthine

Prepared by reaction of 1- [2- (2-amino-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- ( tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine with acetyl chloride in the presence of pyridine in methylene chloride at room temperature.
R _f value: 0.79 (silica gel, ethyl acetate)
Mass spectrum (ESI ⁺ ): m / z = 592 [M + H] ⁺

Example XX

1- [2- (2-Amino-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- (tert-butyloxycarbonylamino ) piperidin-1-yl] -xanthine

Prepared by reduction of 1- [2- (2-nitrophenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - [(R) -3- ( tert-butyloxycarbonylamino) -piperidin-1-yl] -xanthine with tin (II) chloride dihydrate in tetrahydrofuran at room temperature.
R _f value: 0.85 (silica gel, ethyl acetate)
Mass spectrum (ESI ⁺ ): m / z = 550 [M + H] ⁺

Preparation of the end compounds

example 1

1 - [(4-phenylamino-quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) -xanthine

A mixture of 400 mg of 1 - [(4-phenylamino-quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- [3- (tert-butyloxycarbonylamino) -] piperidin-1-yl] -xanthine in 10 ml of methylene chloride, we added 2 ml of isopropanolic hydrochloric acid (5-6 M) and stirred for three hours at room temperature. Subsequently, the reaction mixture is diluted with methylene chloride, treated with ice-water and made alkaline with 3 M potassium carbonate solution. The aqueous phase is extracted with methylene chloride. The combined extracts are washed with water, dried over magnesium sulfate and concentrated. The flask residue is stirred with diethyl ether, filtered off, washed with diethyl ether and dried in vacuo.
Yield: 274 mg (81% of theory)
R _f value: 0.50 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 0.1)
Mass spectrum (ESI ⁺ ): m / z = 550 [M + H] ⁺

• (1) 1-[(4-Benzylamino-chinazolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-(3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.43 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:0.1) Massenspektrum (ESI⁺): m/z = 564 [M + H]⁺
• (2) 1-[(2-Methyl-chinolin-4-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin Massenspektrum (ESI⁺): m/z = 472 [M + H]⁺
• (3) 1-[(3-Cyano-naphthalin-1-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.55 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:1) Massenspektrum (ESI⁺): m/z = 482 [M + H]⁺
• (4) 1-[(2-Phenyl-chinazolin-4-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.45 (Reversed Phase DC-Fertigplatte (E. Merck), Acetonitril/Wasser/Trifluoressigsäure = 50:50:1) Massenspektrum (ESI⁺): m/z = 535 [M + H]⁺
• (5) 1-[(4-Cyano-isochinolin-1-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.15 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:1) Massenspektrum (ESI⁺): m/z = 483 [M + H]⁺
• (6) 1-[(4-Cyano-chinolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin Massenspektrum (ESI⁺): m/z = 483 [M + H]⁺
• (7) 1-[2-(3-Cyclopropyloxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.45 (Reversed Phase DC-Fertigplatte (E. Merck), Acetonitril/Wasser/Trifluoressigsäure = 50:50:1) Massenspektrum (ESI⁺): m/z = 491 [M + H]⁺
• (8) 1-[2-(3-Cyclopropylmethoxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.35 (Reversed Phase DC-Fertigplatte (E. Merck), Acetonitril/Wasser/Trifluoressigsäure = 50:50:1) Massenspektrum (ESI⁺): m/z = 505 [M + H]⁺
• (9) 1-[2-(3-Cyclobutyloxy-phenyl)-2-oxo-ethyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.40 (Reversed Phase DC-Fertigplatte (E. Merck), Acetonitril/Wasser/Trifluoressigsäure = 50:50:1) Massenspektrum (ESI⁺): m/z = 505 [M + H]⁺
• (10) 1-[(1-Cyano-isochinolin-3-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin Massenspektrum (ESI⁺): m/z = 483 [M + H]⁺
• (11) 1-[(2,4-Methoxy-naphthalin-1-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.55 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:0.1) Massenspektrum (ESI⁺): m/z = 517 [M + H]⁺
• (12) 1-[(2,3-Dimethyl-chinoxalin-6-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.48 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:0.1) Massenspektrum (ESI⁺): m/z = 487 [M + H]⁺
• (13) 1-[(6-Amino-chinolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.40 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:0.1) Massenspektrum (ESI⁺): m/z = 473 [M + H]⁺
• (14) 1-[(Chinoxalin-5-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin-hydrochlorid Massenspektrum (ESI⁺): m/z = 459 [M + H]⁺
• (15) 1-[(6-Methoxy-chinolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.50 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:0.1) Massenspektrum (ESI⁺): m/z = 488 [M + H]⁺
• (16) 1-[(6-Phenyl-pyridin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.37 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:1) Massenspektrum (ESI⁺): m/z = 484 [M + H]⁺
• (17) 1-{[(4-(Pyridin-2-yl)-isochinolin-1-yl]methyl}-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.37 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 80:20:1) Massenspektrum (ESI⁺): m/z = 535 [M + H]⁺
• (18) 1-[(7-Fluor-chinolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.58 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:1) Massenspektrum (ESI⁺): m/z = 476 [M + H]⁺
• (19) 1-[(8-Amino-chinolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.50 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:1) Massenspektrum (ESI⁺): m/z = 473 [M + H]⁺
• (20) 1-[(6-Fluor-chinolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.50 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:1) Massenspektrum (ESI⁺): m/z = 476 [M + H]⁺
• (21) 1-{2-Oxo-2-[2-(pyridin-3-yl)-phenyl]-ethyl}-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.55 (Reversed Phase DC-Fertigplatte (E. Merck), Acetonitril/Wasser/Trifluoressigsäure = 50:50:1) Massenspektrum (ESI⁺): m/z = 512 [M + H]⁺
• (22) 1-[(4-Ethyl-chinazolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.45 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:0.1) Massenspektrum (ESI⁺): m/z = 487 [M + H]⁺
• (23) 1-[(4-Cyclopropyl-chinazolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin (BOC-Spaltung erfolgt mit Trifluoressigsäure) R_f-Wert: 0.45 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:0.1) Massenspektrum (ESI⁺): m/z = 499 [M + H]⁺
• (24) 1-[(4-Methoxy-chinolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin Massenspektrum (ESI⁺): m/z = 488 [M + H]⁺
• (25) 1-[(2-Phenyl-pyrimidin-4-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.50 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:1) Massenspektrum (ESI⁺): m/z = 485 [M + H]⁺
• (26) 1-[([1,5]Naphthyridin-3-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.52 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:1) Massenspektrum (ESI⁺): m/z = 459 [M + H]⁺
• (27) 1-[(3-Cyano-4-methyl-chinolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin (BOC-Spaltung erfolgt mit Trifluoressigsäure) R_f-Wert: 0.50 (Reversed Phase DC-Fertigplatte (E. Merck), Acetonitril/Wasser/Trifluoressigsäure = 50:50:1) Massenspektrum (ESI⁺): m/z = 497 [M + H]⁺
• (28) 1-[(4,5-Dimethyl-chinazolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin (BOC-Spaltung erfolgt mit Trifluoressigsäure) Massenspektrum (ESI⁺): m/z = 487 [M + H]⁺
• (29) 1-[(5-Cyano-chinolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.50 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:1) Massenspektrum (ESI⁺): m/z = 483 [M + H]⁺
• (30) 1-[(3-Cyano-chinolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin (BOC-Spaltung erfolgt mit Trifluoressigsäure) R_f-Wert: 0.50 (Reversed Phase DC-Fertigplatte (E. Merck), Acetonitril/Wasser/Trifluoressigsäure = 50:50:1) Massenspektrum (ESI⁺): m/z = 483 [M + H]⁺
• (31) 1-[(4-Phenyl-pyrimidin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.50 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:1) Massenspektrum (ESI⁺): m/z = 485 [M + H]⁺
• (32) 1-[(2-Methyl-chinazolin-4-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin (BOC-Spaltung erfolgt mit Trifluoressigsäure) R_f-Wert: 0.38 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:1) Massenspektrum (ESI⁺): m/z = 473 [M + H]⁺
• (33) 1-[(1,4-Dicyano-naphthalin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin-hydrochlorid R_f-Wert: 0.86 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:1) Massenspektrum (ESI⁺): m/z = 507 [M + H]⁺
• (34) 1-{2-Oxo-2-[2-(pyridin-4-yl)-phenyl]-ethyl}-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin (BOC-Spaltung erfolgt mit Trifluoressigsäure) R_f-Wert: 0.55 (Reversed Phase DC-Fertigplatte (E. Merck), Acetonitril/Wasser/Trifluoressigsäure = 50:50:1) Massenspektrum (ESI⁺): m/z = 512 [M + H]⁺
• (35) 1-[(6,7-Dimethoxy-chinolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.45 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:1) Massenspektrum (ESI⁺): m/z = 518 [M + H]⁺
• (36) 1-((Chinazolin-6-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin-hydrochlorid R_f-Wert: 0.50 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:0.1) Massenspektrum (ESI⁺): m/z = 459 [M + H]⁺
• (37) 1-[(4-Cyano-chinazolin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin (BOC-Spaltung erfolgt mit Trifluoressigsäure) R_f-Wert: 0.50 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:1) Massenspektrum (ESI⁺): m/z = 484 [M + H]⁺
• (38) 1-[(Chinazolin-7-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.43 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:0.1) Massenspektrum (ESI⁺): m/z = 459 [M + H]⁺
• (39) 1-(2-Cyano-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin (BOC-Spaltung erfolgt mit Trifluoressigsäure) R_f-Wert: 0.35 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:1) Massenspektrum (ESI⁺): m/z = 432 [M + H]⁺
• (40) 1-(3-Cyano-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin (BOC-Spaltung erfolgt mit Trifluoressigsäure) R_f-Wert: 0.40 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:1) Massenspektrum (ESI⁺): m/z = 432 [M + H]⁺
• (41) 1-(4-Cyano-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin (BOC-Spaltung erfolgt mit Trifluoressigsäure) R_f-Wert: 0.31 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:1) Massenspektrum (ESI⁺): m/z = 432 [M + H]⁺
• (42) 1-[(Pyridin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.52 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:1) Massenspektrum (ESI⁺): m/z = 408 [M + H]⁺
• (43) 1-Benzyl-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin (BOC-Spaltung erfolgt mit Trifluoressigsäure) Schmelzpunkt: 207–209°C Massenspektrum (ESI⁺): m/z = 407 [M + H]⁺
• (44) 1-(4-Methoxy-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin-hydrochlorid R_f-Wert: 0.50 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:0.1) Massenspektrum (ESI⁺): m/z = 437 [M + H]⁺
• (45) 1-(2-Chlor-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.50 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:0.1) Massenspektrum (ESI⁺): m/z = 441, 443 [M + H]⁺
• (46) 1-(2,6-Dicyano-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin x Trifluoressigsäure (BOC-Spaltung erfolgt mit Trifluoressigsäure) Massenspektrum (ESI⁺): m/z = 457 [M + H]⁺
• (47) 1-(2-Cyano-4-brom-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin x Trifluoressigsäure (BOC-Spaltung erfolgt mit Trifluoressigsäure) Massenspektrum (ESI⁺): m/z = 510, 512 [M + H]⁺
• (48) 1-(3-Fluor-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin (BOC-Spaltung erfolgt mit Trifluoressigsäure) R_f-Wert: 0.45 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:0.1) Massenspektrum (ESI⁺): m/z = 425 [M + H]⁺
• (49) 1-(3,5-Dimethoxy-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin (BOC-Spaltung erfolgt mit Trifluoressigsäure) R_f-Wert: 0.45 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:0.1) Massenspektrum (ESI⁺): m/z = 467 [M + H]⁺
• (50) 1-(2-Fluor-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin (BOC-Spaltung erfolgt mit Trifluoressigsäure) R_f-Wert: 0.45 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:0.1) Massenspektrum (ESI⁺): m/z = 425 [M + H]⁺
• (51) 1-[(6-Cyano-pyridin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin (BOC-Spaltung erfolgt mit Trifluoressigsäure) Massenspektrum (ESI⁺): m/z = 433 [M + H]⁺
• (52) 1-[(3-Cyano-pyridin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin (BOC-Spaltung erfolgt mit Trifluoressigsäure) Massenspektrum (ESI⁺): m/z = 433 [M + H]⁺
• (53) 1-(2-Cyano-3-chlor-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin x Trifluoressigsäure (BOC-Spaltung erfolgt mit Trifluoressigsäure) Massenspektrum (ESI⁺): m/z = 466, 468 [M + H]⁺
• (54) 1-(4-Fluor-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin (BOC-Spaltung erfolgt mit Trifluoressigsäure) Massenspektrum (ESI⁺): m/z = 425 [M + H]⁺
• (55) 1-(4-Chlor-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin (BOC-Spaltung erfolgt mit Trifluoressigsäure) Massenspektrum (ESI⁺): m/z = 441, 443 [M + H]⁺
• (56) 1-(2-Cyano-4-fluor-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin x Trifluoressigsäure (BOC-Spaltung erfolgt mit Trifluoressigsäure) Massenspektrum (ESI⁺): m/z = 450 [M + H]⁺
• (57) 1-(3-Cyano-4-fluor-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin x Trifluoressigsäure (BOC-Spaltung erfolgt mit Trifluoressigsäure) Massenspektrum (ESI⁺): m/z = 450 [M + H]⁺
• (58) 1-(2-Chlor-4-cyano-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin x Trifluoressigsäure (BOC-Spaltung erfolgt mit Trifluoressigsäure) Massenspektrum (ESI⁺): m/z = 466, 468 [M + H]⁺
• (59) 1-[(5-Methoxycarbonyl-furan-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin x Trifluoressigsäure (BOC-Spaltung erfolgt mit Trifluoressigsäure) Massenspektrum (ESI⁺): m/z = 455 [M + H]⁺
• (60) 1-(2-Trifluormethyl-4-cyano-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthinx x Trifluoressigsäure (BOC-Spaltung erfolgt mit Trifluoressigsäure) Massenspektrum (ESI⁺): m/z = 500 [M + H]⁺
• (61) 1-(3,5-Dicyano-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin (BOC-Spaltung erfolgt mit Trifluoressigsäure) Massenspektrum (ESI⁺): m/z = 457 [M + H]⁺
• (62) 1-(3-Nitro-4-cyano-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin x Trifluoressigsäure (BOC-Spaltung erfolgt mit Trifluoressigsäure) Massenspektrum (ESI⁺): m/z = 477 [M + H]⁺
• (63) 1-[(2-Cyano-pyridin-3-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin (BOC-Spaltung erfolgt mit Trifluoressigsäure) R_f-Wert: 0.50 (Reversed Phase DC-Fertigplatte (E. Merck), Acetonitril/Wasser/Trifluoressigsäure = 50:50:1) Massenspektrum (ESI⁺): m/z = 433 [M + H]⁺
• (64) 1-(2-Cyano-4-methoxy-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin (BOC-Spaltung erfolgt mit Trifluoressigsäure) R_f-Wert: 0.50 (Reversed Phase DC-Fertigplatte (E. Merck), Acetonitril/Wasser/Trifluoressigsäure = 50:50:1) Massenspektrum (ESI⁺): m/z = 462 [M + H]⁺
• (65) 1-(2-Cyano-5-methoxy-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin (BOC-Spaltung erfolgt mit Trifluoressigsäure) R_f-Wert: 0.45 (Reversed Phase DC-Fertigplatte (E. Merck), Acetonitril/Wasser/Trifluoressigsäure = 50:50:1) Massenspektrum (ESI⁺): m/z = 462 [M + H]⁺
• (66) 1-(3-Methoxy-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin (BOC-Spaltung erfolgt mit Trifluoressigsäure) R_f-Wert: 0.45 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:0.1) Massenspektrum (ESI⁺): m/z = 437 [M + H]⁺
• (67) 1-(3-Trifluormethyl-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin (BOC-Spaltung erfolgt mit Trifluoressigsäure) R_f-Wert: 0.60 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:0.1) Massenspektrum (ESI⁺): m/z = 475 [M + H]⁺
• (68) 1-(3,4-Dimethoxy-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin (BOC-Spaltung erfolgt mit Trifluoressigsäure) R_f-Wert: 0.50 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:0.1) Massenspektrum (ESI⁺): m/z = 467 [M + H]⁺
• (69) 1-(3-Chlor-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin (BOC-Spaltung erfolgt mit Trifluoressigsäure) R_f-Wert: 0.45 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:0.1) Massenspektrum (ESI⁺): m/z = 441,443 [M + H]⁺
• (70) 1-(4-Trifluormethyl-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin (BOC-Spaltung erfolgt mit Trifluoressigsäure) R_f-Wert: 0.45 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:0.1) Massenspektrum (ESI⁺): m/z = 475 [M + H]⁺
• (71) 1-[([2,2']Bipyridinyl-6-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.50 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:1) Massenspektrum (ESI⁺): m/z = 485 [M + H]⁺
• (72) 1-(3,4-Dimethoxy-6-fluor-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.50 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:0.1) Massenspektrum (ESI⁺): m/z = 485 [M + H]⁺
• (73) 1-[(6-Fluor-pyridin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.41 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:1) Massenspektrum (ESI⁺): m/z = 426 [M + H]⁺
• (74) 1-[(5-Cyano-6-methoxy-pyridin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.40 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:1) Massenspektrum (ESI⁺): m/z = 463 [M + H]⁺
• (75) 1-(2,6-Difluor-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.41 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:1) Massenspektrum (ESI⁺): m/z = 443 [M + H]⁺
• (76) 1-(3-Trifluormethoxy-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.36 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:1) Massenspektrum (ESI⁺): m/z = 491 [M + H]⁺
• (77) 1-(4-Trifluormethoxy-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin R_f-Wert: 0.38 (Kieselgel, Methylenchlorid/Methanol/konz. wässriges Ammoniak = 90:10:1) Massenspektrum (ESI⁺): m/z = 491 [M + H]⁺

Analogously to Example 1, the following compounds are obtained:

• (1) 1 - [(4-Benzylamino-quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- (3-amino-piperidin-1-yl) - xanthin R _f value: 0.43 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 0.1) Mass spectrum (ESI ⁺ ): m / z = 564 [M + H] ⁺
• (2) 1 - [(2-Methyl-quinolin-4-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 -yl) -xanthine mass spectrum (ESI ⁺ ): m / z = 472 [M + H] ⁺
• (3) 1 - [(3-Cyano-naphthalen-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 -yl) -xanthin R _f value: 0.55 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 1) Mass spectrum (ESI ⁺ ): m / z = 482 [M + H] ⁺
• (4) 1 - [(2-phenyl-quinazolin-4-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 -yl) -xanthine R _f value: 0.45 (Reversed Phase DC precast plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1) Mass spectrum (ESI ⁺ ): m / z = 535 [M + H ] ⁺
• (5) 1 - [(4-Cyano-isoquinolin-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 -yl) -xanthine R _f value: 0.15 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 1) Mass spectrum (ESI ⁺ ): m / z = 483 [M + H] ⁺
• (6) 1 - [(4-Cyanoquinolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 -yl) -xanthine mass spectrum (ESI ⁺ ): m / z = 483 [M + H] ⁺
• (7) 1- [2- (3-Cyclopropyloxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino) piperidin-1-yl) -xanthine R _f value: 0.45 (reversed phase DC precast plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1) Mass spectrum (ESI ⁺ ): m / z = 491 [ M + H] ⁺
• (8) 1- [2- (3-Cyclopropylmethoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino) piperidin-1-yl) -xanthine R _f value: 0.35 (Reversed Phase DC precast plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1) Mass spectrum (ESI ⁺ ): m / z = 505 [ M + H] ⁺
• (9) 1- [2- (3-Cyclobutyloxyphenyl) -2-oxo-ethyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino) piperidin-1-yl) -xanthine R _f value: 0.40 (Reversed phase DC precast plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1) Mass spectrum (ESI ⁺ ): m / z = 505 [ M + H] ⁺
• (10) 1 - [(1-Cyanoisoquinolin-3-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 -yl) -xanthine mass spectrum (ESI ⁺ ): m / z = 483 [M + H] ⁺
• (11) 1 - [(2,4-Methoxynaphthalen-1-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine -1-yl) -xanthine R _f value: 0.55 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 0.1) Mass spectrum (ESI ⁺ ): m / z = 517 [M + H] ⁺
• (12) 1 - [(2,3-Dimethyl-quinoxalin-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine -1-yl) -xanthin R _f value: 0.48 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 0.1) Mass spectrum (ESI ⁺ ): m / z = 487 [M + H] ⁺
• (13) 1 - [(6-Aminoquinolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 yl) xanthine R _f value: 0.40 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 0.1) Mass spectrum (ESI ⁺ ): m / z = 473 [M + H] ⁺
• (14) 1 - [(quinoxalin-5-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) - xanthine hydrochloride mass spectrum (ESI ⁺ ): m / z = 459 [M + H] ⁺
• (15) 1 - [(6-Methoxy-quinolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 -yl) -xanthin R _f value: 0.50 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 0.1) Mass spectrum (ESI ⁺ ): m / z = 488 [M + H] ⁺
• (16) 1 - [(6-phenylpyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 -yl) -xanthin R _f value: 0.37 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 1) Mass spectrum (ESI ⁺ ): m / z = 484 [M + H] ⁺
• (17) 1 - {[(4- (pyridin-2-yl) isoquinolin-1-yl] methyl} -3-methyl-7- (2-butyn-1-yl) -8 - ((R) - 3-amino-piperidin-1-yl) -xanthine R _f value: 0.37 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 80: 20: 1) Mass spectrum (ESI ⁺ ): m / z = 535 [M + H] ⁺
• (18) 1 - [(7-Fluoro-quinolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 -yl) -xanthin R _f value: 0.58 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 1) Mass spectrum (ESI ⁺ ): m / z = 476 [M + H] ⁺
• (19) 1 - [(8-Aminoquinolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 -yl) -xanthin R _f value: 0.50 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 1) Mass spectrum (ESI ⁺ ): m / z = 473 [M + H] ⁺
• (20) 1 - [(6-Fluoro-quinolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 -yl) -xanthin R _f value: 0.50 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 1) Mass spectrum (ESI ⁺ ): m / z = 476 [M + H] ⁺
• (21) 1- {2-Oxo-2- [2- (pyridin-3-yl) -phenyl] -ethyl} -3-methyl-7- (2-butyn-1-yl) -8 - ((R. ) -3-amino-piperidin-1-yl) -xanthine R _f value: 0.55 (reversed phase DC precast plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1) Mass Spectrum (ESI ⁺ ): m / z = 512 [M + H] ⁺
• (22) 1 - [(4-Ethylquinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 -yl) -xanthine R _f value: 0.45 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 0.1) Mass spectrum (ESI ⁺ ): m / z = 487 [M + H] ⁺
• (23) 1 - [(4-Cyclopropyl-quinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 -yl) -xanthine (BOC cleavage with trifluoroacetic acid) R _f value: 0.45 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 0.1) Mass spectrum (ESI ⁺ ): m / z = 499 [M. + H] ⁺
• (24) 1 - [(4-Methoxy-quinolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 -yl) -xanthine mass spectrum (ESI ⁺ ): m / z = 488 [M + H] ⁺
• (25) 1 - [(2-Phenyl-pyrimidin-4-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 -yl) -xanthin R _f value: 0.50 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 1) Mass spectrum (ESI ⁺ ): m / z = 485 [M + H] ⁺
• (26) 1 - [([1,5] naphthyridin-3-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidine 1-yl) -xanthine R _f value: 0.52 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 1) Mass spectrum (ESI ⁺ ): m / z = 459 [M + H] ⁺
• (27) 1 - [(3-Cyano-4-methyl-quinolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino -piperidin-1-yl) -xanthine (BOC cleavage with trifluoroacetic acid) R _f value: 0.50 (Reversed Phase DC precast plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1) Mass Spectrum (ESI ⁺ ): m / z = 497 [M + H] ⁺
• (28) 1 - [(4,5-Dimethylquinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine -1-yl) -xanthine (BOC cleavage with trifluoroacetic acid) Mass spectrum (ESI ⁺ ): m / z = 487 [M + H] ⁺
• (29) 1 - [(5-Cyanoquinolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 -yl) -xanthin R _f value: 0.50 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 1) Mass spectrum (ESI ⁺ ): m / z = 483 [M + H] ⁺
• (30) 1 - [(3-Cyanoquinolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 -yl) -xanthine (BOC cleavage with trifluoroacetic acid) R _f value: 0.50 (reversed phase DC precast plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1) Mass spectrum (ESI ⁺ ): m / z = 483 [M + H] ⁺
• (31) 1 - [(4-phenylpyrimidin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 -yl) -xanthin R _f value: 0.50 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 1) Mass spectrum (ESI ⁺ ): m / z = 485 [M + H] ⁺
• (32) 1 - [(2-Methylquinazolin-4-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 -yl) -xanthine (BOC cleavage with trifluoroacetic acid) R _f value: 0.38 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 1) Mass spectrum (ESI ⁺ ): m / z = 473 [M. + H] ⁺
• (33) 1 - [(1,4-Dicyano-naphthalen-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine -1-yl) -xanthine hydrochloride R _f value: 0.86 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 1) Mass spectrum (ESI ⁺ ): m / z = 507 [M + H] ⁺
• (34) 1- {2-Oxo-2- [2- (pyridin-4-yl) -phenyl] -ethyl} -3-methyl-7- (2-butyn-1-yl) -8 - ((R. ) -3-amino-piperidin-1-yl) -xanthine (BOC cleavage with trifluoroacetic acid) R _f value: 0.55 (reversed phase DC precast plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1) Mass spectrum (ESI ⁺ ): m / z = 512 [M + H] ⁺
• (35) 1 - [(6,7-Dimethoxy-quinolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine -1-yl) -xanthine R _f value: 0.45 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 1) Mass spectrum (ESI ⁺ ): m / z = 518 [M + H] ⁺
• (36) 1 - ((quinazolin-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) - xanthine hydrochloride R _f value: 0.50 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 0.1) Mass spectrum (ESI ⁺ ): m / z = 459 [M + H] ⁺
• (37) 1 - [(4-Cyanoquinazolin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 -yl) -xanthine (BOC cleavage with trifluoroacetic acid) R _f value: 0.50 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 1) Mass spectrum (ESI ⁺ ): m / z = 484 [M. + H] ⁺
• (38) 1 - [(Quinazolin-7-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) - xanthin R _f value: 0.43 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 0.1) Mass spectrum (ESI ⁺ ): m / z = 459 [M + H] ⁺
• (39) 1- (2-Cyanobenzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) -xanthine (BOC Cleavage takes place with trifluoroacetic acid) R _f value: 0.35 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 1) Mass spectrum (ESI ⁺ ): m / z = 432 [M + H] ⁺
• (40) 1- (3-Cyanobenzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) -xanthine (BOC Cleavage takes place with trifluoroacetic acid) R _f value: 0.40 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 1) Mass spectrum (ESI ⁺ ): m / z = 432 [M + H] ⁺
• (41) 1- (4-Cyanobenzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) -xanthine (BOC Cleavage with trifluoroacetic acid) R _f value: 0.31 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 1) Mass spectrum (ESI ⁺ ): m / z = 432 [M + H] ⁺
• (42) 1 - [(pyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) - xanthine R _f value: 0.52 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 1) Mass spectrum (ESI ⁺ ): m / z = 408 [M + H] ⁺
• (43) 1-Benzyl-3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) -xanthine (BOC cleavage with trifluoroacetic acid) Melting point: 207-209 ° C Mass spectrum (ESI ⁺ ): m / z = 407 [M + H] ⁺
• (44) 1- (4-Methoxybenzyl) -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine hydrochloride R _f value: 0.50 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 0.1) Mass spectrum (ESI ⁺ ): m / z = 437 [M + H] ⁺
• (45) 1- (2-Chloro-benzyl) -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine R _f Value: 0.50 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 0.1) Mass spectrum (ESI ⁺ ): m / z = 441, 443 [M + H] ⁺
• (46) 1- (2,6-Dicyano-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) -xanthine x Trifluoroacetic acid (BOC cleavage with trifluoroacetic acid) Mass spectrum (ESI ⁺ ): m / z = 457 [M + H] ⁺
• (47) 1- (2-Cyano-4-bromo-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) xanthine x trifluoroacetic acid (BOC cleavage with trifluoroacetic acid) Mass spectrum (ESI ⁺ ): m / z = 510, 512 [M + H] ⁺
• (48) 1- (3-Fluoro-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) -xanthine (BOC Cleavage with trifluoroacetic acid) R _f value: 0.45 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 0.1) Mass spectrum (ESI ⁺ ): m / z = 425 [M + H] ⁺
• (49) 1- (3,5-Dimethoxybenzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) -xanthine (BOC cleavage with trifluoroacetic acid) R _f value: 0.45 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 0.1) Mass spectrum (ESI ⁺ ): m / z = 467 [M + H] ⁺
• (50) 1- (2-Fluoro-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) -xanthine (BOC Cleavage with trifluoroacetic acid) R _f value: 0.45 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 0.1) Mass spectrum (ESI ⁺ ): m / z = 425 [M + H] ⁺
• (51) 1 - [(6-Cyano-pyridin-2-yl) -methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 -yl) -xanthine (BOC cleavage with trifluoroacetic acid) Mass spectrum (ESI ⁺ ): m / z = 433 [M + H] ⁺
• (52) 1 - [(3-Cyano-pyridin-2-yl) -methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 -yl) -xanthine (BOC cleavage with trifluoroacetic acid) Mass spectrum (ESI ⁺ ): m / z = 433 [M + H] ⁺
• (53) 1- (2-Cyano-3-chloro-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) xanthine x trifluoroacetic acid (BOC cleavage with trifluoroacetic acid) Mass spectrum (ESI ⁺ ): m / z = 466, 468 [M + H] ⁺
• (54) 1- (4-Fluoro-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) -xanthine (BOC Cleavage with trifluoroacetic acid) mass spectrum (ESI ⁺ ): m / z = 425 [M + H] ⁺
• (55) 1- (4-Chloro-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) -xanthine (BOC Cleavage takes place with trifluoroacetic acid) mass spectrum (ESI ⁺ ): m / z = 441, 443 [M + H] ⁺
• (56) 1- (2-Cyano-4-fluoro-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) xanthine x trifluoroacetic acid (BOC cleavage with trifluoroacetic acid) Mass spectrum (ESI ⁺ ): m / z = 450 [M + H] ⁺
• (57) 1- (3-Cyano-4-fluoro-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) xanthine x trifluoroacetic acid (BOC cleavage with trifluoroacetic acid) Mass spectrum (ESI ⁺ ): m / z = 450 [M + H] ⁺
• (58) 1- (2-chloro-4-cyanobenzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) xanthine x trifluoroacetic acid (BOC cleavage with trifluoroacetic acid) Mass spectrum (ESI ⁺ ): m / z = 466, 468 [M + H] ⁺
• (59) 1 - [(5-Methoxycarbonyl-furan-2-yl) -methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 -yl) -xanthine x trifluoroacetic acid (BOC cleavage with trifluoroacetic acid) Mass spectrum (ESI ⁺ ): m / z = 455 [M + H] ⁺
• (60) 1- (2-trifluoromethyl-4-cyano-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) xanthinex x trifluoroacetic acid (BOC cleavage with trifluoroacetic acid) Mass spectrum (ESI ⁺ ): m / z = 500 [M + H] ⁺
• (61) 1- (3,5-Dicyano-benzyl) -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine (BOC cleavage with trifluoroacetic acid) Mass spectrum (ESI ⁺ ): m / z = 457 [M + H] ⁺
• (62) 1- (3-nitro-4-cyano-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) xanthine x trifluoroacetic acid (BOC cleavage with trifluoroacetic acid) Mass spectrum (ESI ⁺ ): m / z = 477 [M + H] ⁺
• (63) 1 - [(2-Cyano-pyridin-3-yl) -methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 yl) xanthine (BOC cleavage with trifluoroacetic acid) R _f value: 0.50 (reversed phase DC precast plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1) Mass spectrum (ESI ⁺ ): m / z = 433 [ M + H] ⁺
• (64) 1- (2-Cyano-4-methoxybenzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) -xanthine (BOC cleavage with trifluoroacetic acid) R _f value: 0.50 (reversed phase DC precast plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1) Mass spectrum (ESI ⁺ ): m / z = 462 [M + H] ⁺
• (65) 1- (2-Cyano-5-methoxybenzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) -xanthine (BOC cleavage with trifluoroacetic acid) R _f value: 0.45 (reversed phase DC precast plate (E. Merck), acetonitrile / water / trifluoroacetic acid = 50: 50: 1) Mass spectrum (ESI ⁺ ): m / z = 462 [M + H] ⁺
• (66) 1- (3-Methoxybenzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) -xanthine (BOC Cleavage with trifluoroacetic acid) R _f value: 0.45 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 0.1) Mass spectrum (ESI ⁺ ): m / z = 437 [M + H] ⁺
• (67) 1- (3-Trifluoromethyl-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) -xanthine (BOC Cleavage with trifluoroacetic acid) R _f value: 0.60 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 0.1) Mass spectrum (ESI ⁺ ): m / z = 475 [M + H] ⁺
• (68) 1- (3,4-Dimethoxybenzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) -xanthine (BOC cleavage with trifluoroacetic acid) R _f value: 0.50 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 0.1) Mass spectrum (ESI ⁺ ): m / z = 467 [M + H] ⁺
• (69) 1- (3-Chloro-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) -xanthine (BOC Cleavage with trifluoroacetic acid) R _f value: 0.45 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 0.1) Mass spectrum (ESI ⁺ ): m / z = 441.443 [M + H] ⁺
• (70) 1- (4-trifluoromethyl-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) -xanthine (BOC Cleavage with trifluoroacetic acid) R _f value: 0.45 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 0.1) Mass spectrum (ESI ⁺ ): m / z = 475 [M + H] ⁺
• (71) 1 - [([2,2 '] bipyridinyl-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine -1-yl) -xanthine R _f value: 0.50 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 1) Mass spectrum (ESI ⁺ ): m / z = 485 [M + H] ⁺
• (72) 1- (3,4-Dimethoxy-6-fluoro-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 yl) -xanthine R _f value: 0.50 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 0.1) Mass spectrum (ESI ⁺ ): m / z = 485 [M + H] ⁺
• (73) 1 - [(6-Fluoro-pyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 -yl) -xanthin R _f value: 0.41 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 1) Mass spectrum (ESI ⁺ ): m / z = 426 [M + H] ⁺
• (74) 1 - [(5-Cyano-6-methoxypyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino -piperidin-1-yl) -xanthine R _f value: 0.40 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 1) Mass spectrum (ESI ⁺ ): m / z = 463 [M + H] ⁺
• (75) 1- (2,6-Difluoro-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) -xanthine R _f value: 0.41 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 1) Mass spectrum (ESI ⁺ ): m / z = 443 [M + H] ⁺
• (76) 1- (3-trifluoromethoxybenzyl) -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine R _f Value: 0.36 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 1) Mass spectrum (ESI ⁺ ): m / z = 491 [M + H] ⁺
• (77) 1- (4-trifluoromethoxybenzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) -xanthine R _f Value: 0.38 (silica gel, methylene chloride / methanol / concentrated aqueous ammonia = 90: 10: 1) Mass spectrum (ESI ⁺ ): m / z = 491 [M + H] ⁺

• (1) 1-(2-Cyano-4-fluor-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (2) 1-(2-Cyano-5-fluor-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (3) 1-(2-Cyano-6-fluor-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (4) 1-(3-Cyano-4-fluor-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (5) 1-(3,5-Dicyano-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (6) 1-(3,4-Dicyano-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (7) 1-(3-Nitro-4-cyano-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (8) 1-(2-Chlor-4-cyano-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (9) 1-(2-Fluor-4-cyano-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (10) 1-(2-Trifluormethyl-4-cyano-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (11) 1-[(5-Cyano-pyridin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (12) 1-[(4-Cyano-pyridin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (13) 1-[(4-Cyano-pyridin-3-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (14) 1-[(3-Cyano-pyridin-4-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (15) 1-[(2-Cyano-pyridin-3-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (16) 1-[(2-Cyano-pyridin-4-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (17) 1-[(5-Cyano-pyridin-3-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (18) 1-[(6-Cyano-pyridin-3-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (19) 1-(2-Cyano-4-methoxy-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (20) 1-(2-Cyano-5-methoxy-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (21) 1-[([2,2']Bipyridinyl-6-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (22) 1-[(5-Methoxy-pyridin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (23) 1-[(6-Fluor-pyridin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (24) 1-[(5-Cyano-6-methoxy-pyridin-2-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (25) 1-(2-Methoxy-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (26) 1-(3-Methoxy-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (27) 1-(3-Chlor-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (28) 1-(4-Trifluormethyl-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (29) 1-(3-Trifluormethyl-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (30) 1-(2-Trifluormethyl-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (31) 1-(3,4-Dimethoxy-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (32) 1-(3,4-Dimethoxy-6-fluor-benzyl)-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin
• (33) 1-[(Benzo[1,3]dioxol-5-yl)methyl]-3-methyl-7-(2-butin-1-yl)-8-((R)-3-amino-piperidin-1-yl)-xanthin

Analogously to the above examples and other methods known from the literature, the following compounds can also be obtained:

• (1) 1- (2-Cyano-4-fluoro-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) xanthine
• (2) 1- (2-Cyano-5-fluoro-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) xanthine
• (3) 1- (2-Cyano-6-fluoro-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) xanthine
• (4) 1- (3-Cyano-4-fluoro-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) xanthine
• (5) 1- (3,5-Dicyano-benzyl) -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine
• (6) 1- (3,4-Dicyano-benzyl) -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine
• (7) 1- (3-nitro-4-cyano-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) xanthine
• (8) 1- (2-chloro-4-cyano-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) xanthine
• (9) 1- (2-Fluoro-4-cyano-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) xanthine
• (10) 1- (2-trifluoromethyl-4-cyano-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) xanthine
• (11) 1 - [(5-Cyano-pyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 yl) xanthine
• (12) 1 - [(4-Cyano-pyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 yl) xanthine
• (13) 1 - [(4-Cyano-pyridin-3-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 yl) xanthine
• (14) 1 - [(3-Cyano-pyridin-4-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 yl) xanthine
• (15) 1 - [(2-Cyano-pyridin-3-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 yl) xanthine
• (16) 1 - [(2-Cyano-pyridin-4-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 yl) xanthine
• (17) 1 - [(5-Cyano-pyridin-3-yl) -methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 yl) xanthine
• (18) 1 - [(6-Cyano-pyridin-3-yl) -methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 yl) xanthine
• (19) 1- (2-Cyano-4-methoxybenzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) xanthine
• (20) 1- (2-Cyano-5-methoxybenzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) xanthine
• (21) 1 - [([2,2 '] bipyridinyl-6-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine -1-yl) -xanthine
• (22) 1 - [(5-Methoxypyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 yl) xanthine
• (23) 1 - [(6-Fluoro-pyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 yl) xanthine
• (24) 1 - [(5-Cyano-6-methoxypyridin-2-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino piperidin-1-yl) -xanthine
• (25) 1- (2-Methoxybenzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) -xanthine
• (26) 1- (3-Methoxybenzyl) -3-methyl-7- (2-butyn-1-yl) -8- ((R) -3-amino-piperidin-1-yl) -xanthine
• (27) 1- (3-Chloro-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) -xanthine
• (28) 1- (4-trifluoromethylbenzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) -xanthine
• (29) 1- (3-Trifluoromethyl-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) -xanthine
• (30) 1- (2-Trifluoromethylbenzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) -xanthine
• (31) 1- (3,4-Dimethoxybenzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidin-1-yl) -xanthine
• (32) 1- (3,4-Dimethoxy-6-fluoro-benzyl) -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine-1 yl) -xanthine
• (33) 1 - [(Benzo [1,3] dioxol-5-yl) methyl] -3-methyl-7- (2-butyn-1-yl) -8 - ((R) -3-amino-piperidine -1-yl) -xanthine

Example 2

Dragées with 75 mg active substance 1 Dragéekern contains: active substance 75.0 mg calcium phosphate 93.0 mg corn starch 35.5 mg polyvinylpyrrolidone 10.0 mg hydroxypropyl methylcellulose 15.0 mg magnesium stearate 1.5 mg 230.0 mg

production:

The active substance is mixed with calcium phosphate, corn starch, polyvinylpyrrolidone, hydroxypropylmethylcellulose and half of the stated amount of magnesium stearate. On a tabletting machine compacts are produced with a diameter of about 13 mm, these are ground on a suitable machine through a sieve with a mesh size of 1.5 mm and mixed with the remaining amount of magnesium stearate. This granulate is pressed on a tabletting machine into tablets of the desired shape. Weight of core: 230 mg Stamp: 9 mm, arched

The thus prepared dragee cores are coated with a film consisting essentially of hydroxypropylmethylcellulose. The finished Filmdragées are shined with beeswax. Weight of coated tablet: 245 mg.

Example 3

Tablets containing 100 mg of active substance Composition: 1 tablet contains: active substance 100.0 mg lactose 80.0 mg corn starch 34.0 mg polyvinylpyrrolidone 4.0 mg magnesium stearate 2.0 mg 220.0 mg

Production process:

Active ingredient, lactose and starch are mixed and uniformly moistened with an aqueous solution of polyvinylpyrrolidone. After screening of the moist mass (2.0 mm mesh size) and drying in a rack oven at 50 ° C is again sieved (1.5 mm mesh) and the lubricant mixed. The ready-to-use mixture is processed into tablets. Tablet weight: 220 mg Diameter: 10 mm, biplan with facet on both sides and one-sided part notch.

Example 4

Tablets with 150 mg active substance Composition: 1 tablet contains: active substance 150.0 mg Milk sugar powder. 89.0 mg corn starch 40.0 mg Colloidal silicic acid 10.0 mg polyvinylpyrrolidone 10.0 mg magnesium stearate 1.0 mg 300.0 mg

production:

The with milk sugar, corn starch and silica mixed active substance is moistened with a 20% aqueous solution of polyvinylpyrrolidone and beaten through a sieve of 1.5 mm mesh size.

The granules dried at 45 ° C are again rubbed through the same sieve and mixed with the stated amount of magnesium stearate. From the mixture tablets are pressed. Tablet weight: 300 mg Stamp: 10 mm, flat

Example 5

Hard gelatine capsules with 150 mg active substance 1 capsule contains: active substance 150.0 mg Corn starch drink. about 180.0 mg Milk sugar powder. about 87.0 mg magnesium stearate 3.0 mg about 420.0 mg

production:

The active ingredient is mixed with the excipients, passed through a sieve of 0.75 mm mesh size and mixed homogeneously in a suitable device. The final mixture is filled into size 1 hard gelatin capsules. Capsule filling: about 320 mg Capsule shell: Hard gelatin capsule size 1.

Example 6

Suppositories with 150 mg active substance 1 suppository contains: active substance 150.0 mg Polyethylene glycol 1500 550.0 mg Polyethylene glycol 6000 460.0 mg polyoxyethylene 840.0 mg 2000.0 mg

production:

To the melting of the suppository mass becomes the active ingredient therein distributed homogeneously and the melt poured into pre-cooled molds.

Example 7

Suspension with 50 mg active substance 100 ml suspension contain: active substance 1.00 g Carboxymethylcellulose-Na-salt 0.10 g p-hydroxybenzoate 0.05 g p-hydroxybenzoate 0.01 g cane sugar 10.00 g glycerin 5.00 g Sorbitol solution 70% 20.00 g Aroma 0.30 g Water dist. ad 100 ml

production:

Least. Water gets to 70 ° C heated. Herein is stirring p-hydroxybenzoate and -propylester and glycerol and carboxymethylcellulose sodium salt. It will cooled to room temperature and stirring the active ingredient added and dispersed homogeneously. After adding and Solve the Sugar, the sorbitol solution and the aroma, the suspension is evacuated to vent with stirring.

5 ml of suspension contain 50 mg of active ingredient.

Example 8

Ampoules with 10 mg active substance Composition: active substance 10.0 mg 0.01 n hydrochloric acid sq Aqua bidest ad 2.0 ml

production:

The Active substance is dissolved in the required amount of 0.01 N HCl, with Saline is isotonic, sterilized by filtration and in 2 ml ampoules bottled.

Example 9

Ampoules with 50 mg active substance Composition: active substance 50.0 mg 0.01 n hydrochloric acid sq Aqua bidest ad 10.0 ml

production:

The Active substance is dissolved in the required amount of 0.01 N HCl, with Saline is isotonic, sterile filtered and in 10 ml ampoules bottled.

Claims (6)

Compounds of the general formula

in the R is a benzyl, 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2,6-difluoro-benzyl, 2-chlorobenzyl, 3-chlorobenzyl or 4-chlorobenzyl group, a 2- Trifluoromethyl-benzyl, 3-trifluoromethyl-benzyl or 4-trifluoromethyl-benzyl group, a 3-trifluoromethoxy-benzyl or 4-trifluoromethoxy-benzyl group, a 2-cyanobenzyl, 3-cyanobenzyl or 4-cyanobenzyl Group, a 2,6-dicyanobenzyl, 3,4-dicyanobenzyl, 3,5-dicyanobenzyl, 2-trifluoromethyl-4-cyano-benzyl, 3-nitro-4-cyano-benzyl, 2-cyano 4-methoxy-benzyl, 2-cyano-5-methoxy-benzyl, 2-cyano-4-fluoro-benzyl, 2-cyano-5-fluoro-benzyl, 2-cyano-6-fluoro-benzyl , 3-Cyano-4-fluoro-benzyl, 2-fluoro-4-cyano-benzyl, 2-cyano-3-chlorobenzyl, 2-chloro-4-cyano-benzyl or 2-cyano-4- bromobenzyl group, a 2-methoxy-benzyl, 3-methoxy-benzyl, 4-methoxy-benzyl, 3,4-dimethoxybenzyl, 3,5-dimethoxybenzyl or 3,4-dimethoxy-6-fluoro benzyl group, a (benzo [1,3] dioxol-5-yl) methyl group, a 2- (3-cyclopropyloxy-phenyl) -2-oxo-ethyl, 2- (3-cyclopropyloxy-phenyl) 3-Cyclopropylmethoxy-phenyl) -2-oxo-ethyl or 2- (3-cyclobutyloxyphenyl) -2-oxo-ethyl group, a 2-oxo-2- [2- (pyridin-3-yl) - phenyl] -ethyl or 2-oxo-2- [2- (pyridin-4-yl) -phenyl] -ethyl group, a (3-cyano-naphthalen-1-yl) methyl, (1,4-dicyano-naphthalen-2-yl) methyl or (2,4-dimethoxy-naphthalen-1-yl) methyl group, a ( 5-methoxycarbonyl-furan-2-yl) methyl group, a (pyridin-2-yl) methyl, (6-fluoro-pyridin-2-yl) methyl or (5-methoxy-pyridin-2-yl) methyl group, a (3-cyanopyridin-2-yl) methyl, (6-cyanopyridin-2-yl) methyl, (5-cyano-pyridin-2-yl) methyl, (4-cyano-pyridine) 2-yl) methyl, (4-cyano-pyridin-3-yl) methyl, (3-cyano-pyridin-4-yl) methyl, (2-cyano-pyridin-3-yl) -methyl, ( 2-Cyano-pyridin-4-yl) methyl, (5-cyano-pyridin-3-yl) methyl, (6-cyano-pyridin-3-yl) -methyl or (5-cyano-6-methoxy) pyridin-2-yl) methyl group, a (6-phenyl-pyridin-2-yl) methyl or a ([2,2 '] bipyridinyl-6-yl) methyl group, a (2-phenyl-pyrimidine 4-yl) methyl or (4-phenyl-pyrimidin-2-yl) methyl group, a (6-fluoro-quinolin-2-yl) methyl, (7-fluoro-quinolin-2-yl) methyl -, (2-methyl-quinolin-4-yl) methyl, (3-cyano-quinolin-2-yl) methyl, (3-cyano-4-methyl-quinolin-2-yl) -methyl, (4 cyano-chino lin-2-yl) methyl, (5-cyano-quinolin-2-yl) methyl, (6-amino-quinolin-2-yl) methyl, (8-amino-quinolin-2-yl) methyl , (4-methoxy-quinolin-2-yl) methyl, (6-methoxy-quinolin-2-yl) methyl or (6,7-dimethoxy-quinolin-2-yl) methyl group, a (1- Cyano-isoquinolin-3-yl) methyl, (4-cyano-isoquinolin-1-yl) methyl or [(4- (pyridin-2-yl) -isoquinolin-1-yl] methyl, one (quinazoline -6-yl) methyl, (quinazolin-7-yl) methyl, (2-methyl-quinazolin-4-yl) methyl, (4,5-dimethyl-quinazolin-2-yl) methyl, (4 Ethyl-quinazolin-2-yl) methyl, (4-cyclopropyl-quinazolin-2-yl) methyl, (2-phenyl-quinazolin-4-yl) methyl, (4-cyanoquinazolin-2-yl ) methyl, (4-phenylamino-quinazolin-2-yl) methyl or (4-benzylamino-quinolin-2-yl) methyl group, a (quinoxalin-5-yl) methyl or (2,3-dimethyl -quinoxaline-6-yl) methyl group, or a ([1,5] naphthyridin-3-yl) methyl group, their tautomers, enantiomers, diastereomers, their mixtures and their salts. Physiologically acceptable salts of the compounds according to claim 1 with inorganic or organic acids. A pharmaceutical composition containing a compound according to claim 1 or a physiologically acceptable Salt according to claim 2 next to optionally one or more inert carriers and / or diluents. Use of a compound after at least one the claims 1 to 2 for the manufacture of a medicament for the treatment diabetes mellitus type I and type II, arthritis, obesity, allograft Transplantation and calcitonin-induced osteoporosis is. Process for the preparation of a medicament according to claim 3, characterized in that non-chemical Way a compound according to any one of claims 1 to 2 in one or more inert carriers and / or diluents is incorporated. A process for the preparation of the compounds of general formula I according to claims 1 to 2, characterized in that a) a compound of general formula

in which R is defined as defined in claim 1 and Z ^{1 represents} a leaving group such as a halogen atom, a substituted hydroxy, mercapto, sulfinyl, sulfonyl or sulfonyloxy group, is reacted with 3-aminopiperidine, its enantiomers or its salts, or b) a compound of the general formula

in which R is as defined in claim 1 is deprotected, and / or subsequently optionally used during the reaction used protecting groups are split off and / or the compounds of general formula I thus obtained are separated into their enantiomers and / or diastereomers and / or the obtained compounds of formula I are converted into their salts, in particular for the pharmaceutical application in their physiologically acceptable salts with inorganic or organic acids.