SK114498A3 - Imidazo triazolo pyrimidinone derivatives, method of preparing them and their use - Google Patents

Abstract

1,2,4-TriazoloÄ1,5-aÜpurin-9-one derivatives of formula (I), and their racemates, enantiomers, diastereomers and/or acid addition salts are new. R1 or R3 and R4 or R5 = H, Z, COOZ, SO2Z, SO2A, COZ, aralkyl, aralkenyl, aralkynyl, A, COOA, SO2A, COA, CONHR or (all optionally substituted) benzyloxycarbonyl, benzylsulphonyl, 4-8C cycloalkenyl, 6-8C cycloalkynyl, benzyl, or benzylcarbonyl; Z = 1-10C alkyl, 3-8C cycloalkyl, 6-10C aryl, heteroaryl (all optionally substituted), 2-10C alkenyl or 2-10C alkynyl; A = optionally substituted 5-7 membered heterocycle (containing one or more of N, S and O as heteroatom(s) and bonded via C); R = H, or phenyl, benzyl or 3-6C cycloalkyl (all optionally substituted), or alkyl, alkenyl or alkynyl (all of up to 10C and optionally substituted by OH, optionally substituted phenyl or optionally substituted amino); R2 = H, OH, NH2, halo, NO2, CF3, COOH, SH, 1-6C alkylthio, SO2Z, benzylsulphonyl, OSO2Z, NHSO2Z, CONHZ, di-(1-10C alkyl or 2-10C alkenyl)-aminocarbonyl, N-(1-10C alkyl)-N-(2-10C alkenyl or alkynyl)-aminocarbonyl, NHCOOZ, OCONHZ, C(=NH)NHZ, OZ, COOZ, OCOZ, SZ, optionally substituted amino, preferably NR8R9, or (all optionally substituted) 1-10C alkyl, 2-10C alkenyl, 2-10C alkynyl, 3-8C cycloalkyl, 5-8C cycloalkanone, 4-8C cycloalkenyl, 6-8C cycloalkynyl, 6-10C aryl, aryl-(1-6C)alkyl, aryl-(2-6C)alkenyl, aryl-(2-6C)alkynyl, cycloalkyl-(1-6C)alkyl, cycloalkyl-(2-6C)alkenyl, cycloalkyl-(2-6C)alkynyl, 5-7 membered heterocycle (containing one or more of O, S and optionally substituted N as heteroatom(s) and linked via C- or N- or via a 1-6C alkyl, 2-6C alkenyl or 2-6C alkynyl bridge), or (all optionally substituted) 1-10C alkyl, 2-10C alkenyl, 2-10C alkynyl, 3-8C cycloalkyl, 5-8C cycloalkanone, 4-8C cycloalkenyl, 6-8C cycloalkynyl, 6-10C aryl, aryl-(1-6C)alkyl, aryl-(2-6C)alkenyl, aryl-(2-6C)alkynyl, cycloalkyl-(1-6C)alkyl, cycloalkyl-(2-6C)alkenyl, cycloalkyl-(2-6C)alkynyl, 5-7 membered heterocycle (containing one or more of O, S and optionally substituted N as heteroatom(s) and linked via C- or N- or via a 1-6C alkyl, 2-6C alkenyl or 2-6C alkynyl bridge), methylenedioxyphenyl, ethylenedioxyphenyl, fluorenyl or optionally substituted group of formula (a)-(e); R6 = as for R2 or CHO; x = 1 or 2; y = 0-2; dotted lines in (a) = optional bonds; Q = H or 1-6C alkyl, but cannot be alkyl if the ring system in (a) contains two double bonds; Y = bond, 1-6C alkylene, 2-6C alkenylene or 2-6C alkynylene; R8, R9 = 1-10C alkyl, 2-10C alkenyl or 2-10C alkynyl (optionally substituted by OH, optionally substituted phenyl, optionally substituted benzyl, optionally substituted amino or 1-6C alkoxy), H, optionally substituted 3-6C cycloalkyl, (CH2)mNHCOOR4; or NR8R9 = saturated or unsaturated 5- or 6- membered ring (optionally containing another O, S or N heteroatom and optionally substituted by 1-4C alkyl, (CH2)nPh, (CH2)nNH2, oxo, ketal (preferably OCH2CH2O), (CH2)nNH-(1-4C alkyl), (CH2)nN(1-8C alkyl)2, (CH2)nNHCOOR10, halo, OR10, CN, NO2, NH2, CH2NR8R9 (sic), OH, COOH, SO3H, COOR10, CONR8R9 (sic) or SO2R10); m = 1-4; n = 2-4; R10 = H, 1-4C alkyl, 2-4C alkenyl, 2-4C alkynyl, or benzyl or phenyl (both optionally substituted by one or more OMe).

Description

Imidazotriazolopyrimidone derivatives, process for their preparation, pharmaceutical composition containing them and their use

Technical field

The invention relates to imidazotriazolopyrimidinone derivatives as well as their basic structure, processes for their preparation and their use as medicaments.

BACKGROUND OF THE INVENTION

Adenosine is an endogenous neuromodulator, particularly with a depressant (inhibitory) effect in the CNS, heart, kidney and other organs. The effects of adenosine are mediated by at least three receptor subtypes: adenosine A, A ₂ and A ₃ receptors.

In the CNS, adenosine exerts an inhibitory effect predominantly by activating A _r receptors presynaptically by inhibiting synaptic transmission (inhibiting the release of neurotransmitters such as acetylcholine, dopamine, noradrenaline, serotonin, glutamate and others), postsynaptically by attenuating neuronal activities.

A 2 antagonists abolish the inhibitory effects of adenosine and promote neuronal transmission and neuronal activity.

Antagonists A! are therefore of great interest in the treatment of degenerative diseases of the central nervous system, such as senile dementia from Alzheimer's type of disease and age-related memory and learning disabilities.

These diseases include, in addition to mild forgetfulness to utter helplessness and the absolute necessity of providing helplessness in the most severe form, a host of other concomitant symptoms, such as sleep disorders, movement coordination disorders to Parkinson's disease, increased intellectual lability, and depressive symptoms. The disease is progressive and can lead to death. The current therapy is not satisfactory. Specific therapeutics have so far failed completely. Therapeutic experiments with acetylcholine-2 -

esterase inhibitors only had a positive outcome in a limited number of patients, but this was associated with a high rate of side effects.

The pathophysiology of Alzheimer's disease and SDAT is characterized by severe damage to the choline system, while other transmitter systems are also affected. The loss of presynoptic choline and other neurons and the resulting lack of neurotransmitter preparation causes the neuronal transmission and neuronal activity for learning and memory of the necessary brain areas to be greatly reduced.

Selective adenosine α 1 -receptor antagonists promote neuronal transmission by multiplying (increased) neurotransmitter preparation, increased irritability of postsynaptic neurons, and may thus counteract the disease.

Another indication for centrally acting adenosine A 4 antagonists is depression. Antidepressant therapy appears to be linked to the regulation of α-receptors. Ατ-antagonists can lead to the regulation of adenosine βR receptors and thus offer a new therapeutic option for the management of depressed patients.

A further field of use for particularly A ₂ -selective adenosine antagonists is neurodegenerative diseases such as Parkinson's disease and migraine in connection therewith. Adenosine inhibits the release of dopamine from the central synaptic terminals by interaction with dopamine D ₂ -receptors. And _2- antagonists increase dopamine release and readiness and therefore offer a new therapeutic principle for the treatment of Parkinson's disease.

For accompaniment of migraine it is considered to be over A ₂ -receptor mediated vasodilation of cerebral blood vessels. Selective A ₂ antagonists inhibit vasodilation and may thus be useful in the treatment of migraine.

Adenosine antagonists may also find use in the treatment of peripheral indications.

Activation of α-receptors in the lung, for example, can lead to bronchoconstriction. Selective alpha-antagonists relax the tracheal look muscle, cause bronchodilation and are therefore useful as antiasthmatics.

By activating the A ₂ -receptors, adenosine can cause respiratory depression and respiratory arrest, among other things, A ₂ -agonists cause respiratory stimulation. For example, adenosine antagonists (theophylline) are used for the treatment of shortness of breath and for the prophylaxis of “sudden infant deaths” at premature birth.

Important areas of therapy using adenosine antagonists are also cardiovascular diseases and kidney diseases.

Adenosine acts on the heart through activation of β1 -receptors by inhibiting electrical and contraction activities. Adenosine-mediated vasodilatation mediated by A ₂ -receptors causes a negative chromotrope, -inotrope, -dromotrope, -bathmotrope, bradycardium and decreases cardiac minute volume (Herzminutenvolumen).

Adenosine Α, -receptor antagonists make it possible to reduce ischemia and subsequent reperfusion caused by heart and lung damage. Therefore, adenosine antagonists can be used for the prevention or early treatment of ischemia -reperfusion-induced cardiac damage following, for example, coronary by-pass surgery, heart transplantation, angiplasty or thrombolytic therapy of the heart and other procedures. The same applies to the lungs.

Activation of β1 -receptors causes vasoconstriction of the arteries in the kidneys, thereby causing a decrease in renal blood flow and glomerular filtration.

Antagonists A, act on the kidneys as a potent potassium-sparing diuretic and can thus be used for renal protection as well as for the treatment of edema, renal insufficiency and acute renal failure.

Based on adenosine antagonism and diuretic effects, antagonists can be used therapeutically effectively in various cardiovascular diseases such as cardiac insufficiency, arrhythmia (Bradyarrhythmia) associated with hypoxia or ischemia, hypertonia, ascites in liver failure (hepato-analgetic syndrome) and as blood flow disorders.

SUMMARY OF THE INVENTION

The present invention provides imidazotriazolopyrimidinone derivatives of formula (I):

in which

R ¹ and R ³

denotes hydrogen, an optionally substituted C ₁ -C ₁₀ alkyl ,. C ₂ -C ₁₀ -alkenyl or C ₂ -C _w -alkynyl, optionally substituted C ₃ -C ₈ -cycloalkyl, optionally substituted C ₄ -C ₈ cycloalkenyl or an optionally substituted C ₆ -C ₈ -cykloalkinyl; R ¹ or R ³ can be substituted C ₆ -C ₁₀ -aryl-C ₆ -C 8 -alkyl, C ₆ -C ₁₀ -aryl-C ₂ -C ₆ -alkenyl, C ₆ -C ₁₀ -aryl-C ₂ -C _6- alkynyl, optionally substituted C ₆ -C ₁₀ -aryl- or optionally substituted heteroaryl, 5, 6 or 7-membered hetero ring, optionally substituted, containing one or more nitrogen, oxygen or sulfur atoms, wherein said heterocycle is bound via a carbon ring atom;

R ¹ or R ³ may be substituted C ₁ -C ₁₀ -alkyloxycarbonyl, optionally substituted C ₂ -C ₁₀ -alkenyloxycarbonyl, optionally substituted C ₂ -C ₁₀ alkynyloxycarbonyl, optionally substituted C ₃ -C ₈ -cycloalkyloxycarbonyl, optionally substituted C ₆ -C ₁₀ -aryloxycarbonyl radical, optionally substituted C ₆ -C ₁₀ -aryl-C 1 -C 6 -alkyloxycarbonyl, AO-CO-, where A can be a 5, 6 or 7-membered heterocycle, optionally substituted, containing one or more nitrogen, oxygen or sulfur atoms, wherein A is attached via a ring carbon atom;

R ¹ or R ³ may be substituted C ₃ -C ₈ -alkylsulfonyl, C ₂ -C ₁₀ -alkenylsulfonyl, C ₂ -C ₁₀ alkynylsulfonyl, an optionally substituted C ₃ -C ₈ -cycloalkylsulfonyl radical, optionally

-5-substituted C ₆ -C ₁₀ -arylsulfonyl, optionally substituted C ₆ -C ₁₀ aryl-alkylsulfonyl, A-SO ₂ - in which A is as defined above and is bonded via a carbon ring atom;

R ¹ or R ³ can be substituted C ₁ -C ₁₀ -alkylcarbonyl, optionally substituted C ₂ -C ₁₀ -alkenylcarbonyl, optionally substituted C ₂ -C ₁₀ -alkynylcarbonyl, optionally substituted C ₃ -C ₈ -cycloalkylcarbonyl, optionally substituted substituted C ₆ -C ₁₀ -arylcarbonyl, optionally substituted C ₆ -C ₁₀ -aryl-C ₁ -C ₆ alkylcarbonyl, A-CO-, wherein A is as defined above;

R ^{@ 1} or R ^{@ 3} may be a radical of the formula ## STR6 ## in which it may be hydrogen, phenyl, substituted phenyl, optionally substituted benzyl, optionally substituted C3 -C6 cycloalkyl, branched or unbranched C1 -C4 -alkyl-, preferably C 1 -C 4 alkyl-, C ₂ -C ₁₀ -alkenyla or C ₂ -C ₁₀ -alkynyl, which may be optionally substituted by hydroxy, phenyl, substituted by phenyl, amino, substituted by amino;

can be hydrogen, hydroxy, amino, halogen, nitro, CF ₃ , COOH, mercapto, C 1 -C 6 -alkyl mercapto, optionally substituted C 1 -C 4 -alkyl, optionally substituted C ₂ -C ₁₀ -alkenyl, optionally substituted C ₂ -C ₁₀ -alkynyl, optionally substituted C ₃ -C ₈ -cycloalkyl, optionally substituted C ₅ -C ₈ -cycloalkanone, optionally substituted C ₄ -C ₈ cycloalkenyl, optionally substituted C ₆ -C ₈ -cycloalkynyl optionally substituted C ₆ -C ₁₀ -aryl, optionally substituted C ₈ -C ₁₀ -aryl-C ₁ -C ₆

-6alkyl, C ₆ -C ₁₀ -aryl-C ₂ -C ₆ -alkenyl, C ₆ -C ₁₀ -aryl-C ₂ -C ₆ -alkynyl, C 6 -C 8 -cycloalkyl-C 6 -C 6 alkyl, C ₃ -C ₈ -cycloalkyl-C ₂ -C ₆ -alkenyl, or C ₃ -C ₈ -cycloalkyl-C ₂ -C ₆ -alkynyl;

R ² denotes an optionally substituted 5, 6 or 7 membered heterocycle containing one or more atoms from the group N, O or S, wherein the nitrogen may be optionally substituted and the heterocyclic group may be linked via a carbon or nitrogen, or via A C 1 -C 6 -alkyl, a C ₂ -C ₆ alkenyl or a C ₂ -C ₆ -alkynyl bridge;

R ²

denotes an optionally substituted C ₁ -C ₁₀ alkylsulfonyl, C ₂ -C ₁₀ alkenylsulfonyl, C ₂ or C ₁₀ -alkynylsulfonyl, an optionally substituted C ₃ -C ₈ cycloalkylsulfonyl, optionally substituted C ₆ -C ₁₀ -arylsulfonyl, or substituted C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkylsulfonyl or optionally substituted heteroarylsulfonyl;

R ² denotes an optionally substituted C _r C ₁₀ -alkylsulfonyloxy, C ₂ -C ₁₀ alkenylsulfonyloxy, or C ₂ -C ₁₀ -alkinylsulfonyloxy, an optionally substituted C ₃ -C ₈ -cykloalkylsulfonyloxy, an optionally substituted C ₆ -C ₁₀ - arylsulfonyloxy, optionally substituted C 8 -C 6 -aryl-C 6 -C 6 -alkylsulfonyloxy or optionally substituted heteroarylsulfonyloxy;

R ² denotes an optionally substituted C ₁ -C ₁₀ alkylsulfonylamino, C ₂ -C ₁₀ alkanesulfonylamino, or C ₂ -C ₁₀ -alkinylsulfonylamino, an optionally substituted C ₃ -C ₈ -cykloalkylsulfonylamino, an optionally substituted C ₆ -C ₁₀ -arylsulfonylamino, optionally substituted C 8 -C 8 -aryl-C 8 -C 8 -alkylsulfonylamino or optionally substituted heteroarylsulfonylamino;

R ² may be an optionally substituted C 1 -C 4 -alkylaminocarbonyl, C ₁ -C ₁₀ dialkylaminocarbonyl, C ₁ -C ₁₀ -alkyl-C ₂ -C ₁₀ -alkenylaminocarbonyl, C ₂ -C ₁₀ -alkenylaminocarbonyl, C ₂ -C ₁₀ -dialkenylaminocarbonyl, C ₂ -C ₁₀ -alkylaminocarbonyl or

-7C ₁ -C ₁₀ -alkyl-C ₂ -C ₁₀ -alkylaminocarbonyl, optionally substituted C ₃ -C ₈ cycloalkylaminocarbonyl, optionally substituted C ₆ -C ₁₀ -arylaminocarbonyl, optionally substituted C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkylaminocarbonyl or an optionally substituted heteroarylaminocarbonyl radical;

R ²

denotes an optionally substituted C ₁ -C ₁₀ -alkyloxykarbonylamino, C ₂ -C ₁₀ -alkenyloxykarbonylamino or C ₂ -C ₁₀ -alkinyloxykarbonylamino, an optionally substituted C ₃ -C ₈ -cykloalkyloxykarbonylamino, an optionally substituted C ₆ -C ₁₀ -aryloxykarbonylamino , optionally substituted C ₆ -C ₁₀ -arylC 1 -C 8 -alkyloxycarbonylamino or optionally substituted heteroaryloxycarbonylamino;

R ² denotes an optionally substituted C ^ C ^ alkylaminocarbonyloxy, C ₂ -C ₁₀ -alkenylaminokarbonyloxy or C ₂ -C -alkinylaminokarbonyloxy _W, an optionally substituted C ₃ -C ₈ -cykloalkylaminokarbonyloxy, an optionally substituted C ₆ -C ₁₀ - arylaminocarbonyloxy, optionally substituted C ₈ -C ₁₀ -arylC 1 -C 6 -alkylaminocarbonyloxy or optionally substituted heteroarylaminocarbonyloxy;

R ² denotes an optionally substituted C ₁ -C ₁₀ alkyl-N-amidino, C ₂ -C ₁₀ alkenyl-N-amidino, or C ₂ -C ₁₀ alkynyl-N-amidino, an optionally substituted C ₃ -C ₈ -cycloalkyl-N-amidino, optionally substituted C ₆ -C ₁₀ -aryl-N-amidino, optionally substituted C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl-N-amidino, or optionally substituted heteroaryl- N-amidino;

R ² denotes an optionally substituted C ₁ -C ₁₀ alkyloxy, C ₂ -C ₁₀ alkenyloxy, or C ₂ -C ₁₀ alkynyloxy, an optionally substituted C ₃ -C ₈ -cycloalkyloxy, an optionally substituted C ₆ -C ₁₀ -aryloxy, optionally substituted C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyloxy or optionally substituted heteroaryloxy;

-8R ² denotes an optionally substituted C ₁ -C ₁₀ alkyloxycarbonyl, C ₂ -C ₁₀ alkenyloxycarbonyl or C ₂ -C ₁₀ -alkinyloxykarbonyl, an optionally substituted C ₃ -C ₈ -cykloalkyloxykarbonyl, an optionally substituted C ₆ -C ₁₀ -aryloxycarbonyl, optionally substituted C ₆ -C ₁₀ -aryloxycarbonyl, optionally substituted C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyloxycarbonyl, or optionally substituted heteroaryloxycarbonyl;

R ² may be an optionally substituted C ₁ -C ₁₀ -alkylcarbonyloxy, C ₂ -C ₁₀ alkenylcarbonyloxy or C ₂ -C ₁₀ -alkynylcarbonyloxy radical, optionally substituted C ₃ -C ₈ -cycloalkylcarbonyloxy radical, optionally substituted C ₆ -C _10- arylcarbonyloxy, optionally substituted C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkylcarbonyloxy or optionally substituted heteroarylcarbonyloxy;

R ² denotes an optionally substituted C ₁ -C ₁₀ alkylthio, C ₂ -C ₁₀ -alkenyltio or C ₂ -C ₁₀ -alkinyltio, an optionally substituted C ₃ -C -cykloalkyltio _B, an optionally substituted C ₆ -C ₁₀ -arylthio, optionally substituted C ₆ -C ₁₀ -arylC 1 -C 6 -alkylthio or optionally substituted heteroarylthio;

R ² may be an optionally substituted amine, preferably NR ⁸ R ⁹ ;

R ² denotes a group, optionally substituted, having the formula

R ² denotes a group, optionally substituted, having the formula

wherein Y is a single bond, or an alkyl, alkylene or alkynyl group having up to 6, preferably up to 4, carbon atoms in the chain;

R ² denotes a group, optionally substituted, having the formula

C _{f -C 6} -Alkyl C ^ -C-alkyl wherein Y is a single bond or an alkyl, alkylene or alkynyl group having up to 6, preferably up to 4 carbon atoms in the chain;

R ² denotes a group, optionally substituted, having the formula

Y is a single bond, or an alkyl, alkylene or alkynyl group having up to 6, preferably up to 4, carbon atoms in the chain;

R ⁴ or R ⁵ may be hydrogen, optionally substituted C ₁ -C ₁₀ -alkyl, C ₂ -C ₁₀ -alkenyl or C ₂ -C ₁₀ -alkynyl, optionally substituted C ₃ -C ₈ -cycloalkyl, optionally substituted with C ₄ -C ₈ -cycloalkenyl or optionally substituted C ₆ -C ₈ -cycloalkynyl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl-C ₂ -C ₆ -alkenyl, C ₆ -C ₁₀ -aryl-C ₂ -C ₆ -alkynyl, optionally substituted C ₆ -C ₁₀ -aryl or optionally substituted heteroaryl; R ⁴ or R ⁵

it may be a 5, 6 or 7 membered hetero ring, optionally substituted, containing as heteroatoms one or more of nitrogen, oxygen or sulfur atoms, the hetero ring being bonded through a ring carbon atom;

R ⁴ or R ⁵ may be optionally substituted C ₁ -C ₁₀ -alkyloxycarbonyl, optionally substituted C ₂ -C ₁₀ -alkenyloxycarbonyl, optionally substituted C ₂ -C ₁₀ -alkyloxycarbonyl, optionally substituted C ₃ -C ₈ cycloalkyloxycarbonyl, optionally substituted C ₆ -C ₁₀ -aryl-C 6 -C 6 alkyloxycarbonyl, optionally substituted C ₆ -C ₁₀ -aryloxycarbonyl;

R ⁴ or R ⁵ may be A - O - CO -, wherein A may be a 5, 6 or 7 membered hetero ring, optionally substituted, containing one or more nitrogen, oxygen or sulfur atoms as heteroatoms;

R ⁴ or R ⁵ may be substituted C 1 -C ₈ -alkylsulfonyl, C ₂ -C ₁₀ -alkenylsulfonyl, C ₂ -C ₁₀ alkynylsulfonyl, optionally substituted C ₃ -C ₈ -cycloalkylsulfonyl, optionally substituted C ₆ -C ₁₀ -arylsulfonyl the residue a-SO ₂ -, wherein a is as defined above and is linked via a ring carbon atom;

R ⁴ or R ⁵ may be substituted C ₁ -C ₁₀ -alkylcarbonyl, optionally substituted C ₂ -C ₁₀ -alkenylcarbonyl, optionally substituted C ₂ -C ₁₀ -alkynylcarbonyl,

- 11 optionally substituted C ₃ -C ₈ -cycloalkylcarbonyl, optionally substituted C ₆ -C ₁₀ -arylcarbonyl, optionally substituted C ₆ -C ₁₀ -aryl-C ₁ -C ₆ alkylcarbonyl, A-CO- in which: A is as defined above;

R ⁴ or R ⁵ may be a radical having the general formula

R 0

in which it may be hydrogen, phenyl, substituted phenyl, optionally substituted benzyl, optionally substituted C 3 -C 6 cycloalkyl, branched or unbranched C 1 -C 4 -alkyl-, preferably C ₁ -C 4 -alkyl-, C ₂ -C -alkyl- _w -alkenylalebo _C2-10 -alkynyl group which may be substituted by hydroxy, phenyl, substituted phenyl, amino or substituted amino;

R ⁶ can be hydrogen, hydroxy, -CHO, amino, halogen, nitro, CF ₃ , COOH, mercapto, C ₁ -C ₈ -alkyl mercapto, optionally substituted C ₁ -C ₁₀ -alkyl, optionally substituted C ₂ -C ₁₀ -alkenyl, optionally substituted C ₂ -C ₁₀ -alkynyl, optionally substituted C ₃ -C ₈ -cycloalkyl, optionally substituted C ₅ -C ₈ -cycloalkanone, optionally substituted C ₄ -C ₈ cycloalkenyl, optionally substituted C C ₆ -C ₈ -cycloalkynyl, optionally substituted C ₆ -C ₁₀ -aryl, optionally substituted C ₆ -C ₁₀ -aryl-C ₁ -C ₆ alkyl, C ₆ -C ₁₀ -aryl-C ₂ -C ₆ - alkenyl, C ₆ -C ₁₀ -aryl-C ₂ -C ₆ -alkynyl, C 6 -C 8 -cyclalkyl-C 6 -C 8 -alkyl, C ₃ -C ₈ -cycloalkyl-C ₂ -C ₆ -alkenyl, or C ₃ - C ₈ -cycloalkyl-C ₂ -C ₆ alkynyl;

R ⁶ may be a 5, 6 or 7 membered heterocycle, optionally substituted, containing one or more nitrogen, oxygen or sulfur atoms, wherein the nitrogen

- 12 may be optionally substituted by a heterocycle is linked via a carbon or nitrogen atom or via a C _r C ₆ -alkyl, C ₂ -C ₆ -alkenyl or C ₂ -C ₆ -alkynyl bridge;

R ⁶

denotes an optionally substituted C ₁ -C ₁₀ alkylsulfonyl, C ₂ -C ₁₀ alkenylsulfonyl, C ₂ or C ₁₀ -alkynylsulfonyl, an optionally substituted C ₃ -C ₈ cycloalkylsulfonyl, optionally substituted C ₆ -C ₁₀ -arylsulfonyl, or substituted C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkylsulfonyl or optionally substituted heteroarylsulfonyl;

^R6 denotes an optionally substituted C ₁ -C ₁₀ -alkylsulfonyloxy, C ₂ -C ₁₀ alkenylsulfonyloxy, or C ₂ -C ₁₀ -alkinylsulfonyloxy, an optionally substituted C ₃ -C ₈ -cykloalkylsulfonyloxy, an optionally substituted C ₆ -C ₁₀ -arylsulfonyloxy, optionally substituted C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkylsulfonyloxy or optionally substituted heteroarylsulfonyloxy;

R ⁶

may be optionally substituted C 1 -C 6 -alkylsulfonylamino, C ₂ -C ₁₀ alkenylsulfonylamino, or C ₂ -C ₁₀ -alkylsulfonylamino, optionally substituted C ₃ -C ₈ -cycloalkylsulfonylamino, optionally substituted C ₆ -C ₁₀ arylsulfonylamino, optionally substituted C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkylsulfonylamino or optionally substituted heteroarylsulfonylamino;

R ⁶ can be an optionally substituted C ₆ -C ₁₀ -alkylaminocarbonyl, C ₁ -C ₁₀ dialkylaminocarbonyl, C ₁ -C ₁₀ -alkyl-C ₂ -C ₁₀ -alkenylaminocarbonyl, C ₂ -C ₁₀ -alkenylaminocarbonyl, C ₂ -C ₁₀ -dialkenylaminocarbonyl, C ₂ -C ₁₀ -alkylaminocarbonyl or C ₁ -C ₁₀ -alkyl-C ₂ -C ₁₀ -alkylaminocarbonyl, optionally substituted C ₃ -C ₈ cycloalkylaminocarbonyl, optionally substituted C ₆ -C ₁₀ -arylaminocarbonyl, optionally substituted C _6- C ₁₀ -aryl-C ₁ -C ₆ -alkylaminocarbonyl or an optionally substituted heteroarylaminocarbonyl radical;

- 13 R ⁶ denotes an optionally substituted 0-C ^ alkylaminocarbonylamino, C ₂ -C ₁₀ -alkenylaminokarbonylamino or C ₂ -C ₁₀ -alkinylaminokarbonylamino, an optionally substituted C ₃ -C ₈ -cykloalkylaminokarbonylamino, an optionally substituted C ₆ -C ₁₀ -arylaminocarbonylamino, optionally substituted C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkylaminocarbonylamino or optionally substituted heteroarylaminocarbonylamino;

R ⁶

denotes an optionally substituted C ₁ -C ₁₀ -alkyloxykarbonylamino, C ₂ --C ₁₀ -alkenyloxykarbonylamino or C ₂ -C ₁₀ -alkinyloxykarbonylamino, an optionally substituted C ₃ -C ₈ -cykloalkyloxykarbonylamino, an optionally substituted C ₆ -C ₁₀ - aryloxycarbonylamino, optionally substituted C ₆ -C ₁₀ -aryl (N-C 6 -alkyloxycarbonylamino) or optionally substituted heteroaryloxycarbonylamino;

R ⁶ may be an optionally substituted C ₃ -C ₈ -alkylaminocarbonyloxy, C ₂ -C ₁₀ -alkenylaminocarbonyloxy or C ₂ -C ₁₀ -alkylaminocarbonyloxy radical, an optionally substituted C ₃ -C ₈ -cycloalkylaminocarbonyloxy radical, optionally substituted C ₆ -C ₁₀ - arylaminocarbonyloxy, optionally substituted C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkylaminocarbonyloxy or optionally substituted heteroarylaminocarbonyloxy;

R ⁶ may be optionally substituted C ₁ -C ₁₀ -alkyl-N-amidino, C ₂ -C ₁₀ alkenyl-N-amidino or C ₂ -C ₁₀ -alkynyl-N-amidino, optionally substituted C ₃ -C ₃ -cycloalkyl-N-amidino, optionally substituted C ₆ -C ₁₀ -aryl-N-amidino, optionally substituted C ₆ -C 6 -aryl-C 1 -C 8 -alkyl-N-arnidino, or optionally substituted heteroaryl-N- amidino;

^R6 denotes an optionally substituted C ₁ -C ₁₀ alkyloxy, C ₂ -C ₁₀ alkenyloxy, or C ₂ -C ₁₀ alkynyloxy, an optionally substituted C ₃ -C ₈ -cycloalkyloxy,

14 optionally substituted C ₆ -C ₁₀ -aryloxy, optionally substituted C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyloxy or optionally substituted heteroaryloxy;

^R6 denotes an optionally substituted C _l -C ₁₀ -alkylcarbonyl, C ₂ -C ₁₀ alkenylcarbonyl and C ₂ -C -alkinylkarbonyl _W, an optionally substituted C ₃ -C ₈ cycloalkylcarbonyl, an optionally substituted C ₆ -C ₁₀ -arylkarbonyl optionally substituted C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkylcarbonyl;

R ⁶

may be A - CO in which A is as defined above;

R ⁶ may be optionally substituted C 1 -C 6 -alkyloxycarbonyl, C ₂ -C ₁₀ alkenyloxycarbonyl or C ₂ -C ₁₀ -alkyloxycarbonyl, optionally substituted C ₃ -C ₈ -cycloalkyloxycarbonyl, optionally substituted C ₆ -C ₁₀ -aryloxycarbonyl , an optionally substituted C ₆ -C ₁₀ -aryloxykarbonyl, an optionally substituted C ₆ -C ₁₀ -aryl-C _r C ₆ alkyloxycarbonyl or an optionally substituted heteroaryloxycarbonyl;

R ⁶ may be optionally substituted C ₁ -C ₁₀ -alkylcarbonyloxy, C ₂ -C ₁₀ alkenylcarbonyloxy or C ₂ -C ₁₀ -alkynylcarbonyloxy, optionally substituted C ₃ -C ₈ -cycloalkylcarbonyloxy, optionally substituted C ₆ -C _10- arylcarbonyloxy, optionally substituted C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkylcarbonyloxy or optionally substituted heteroarylcarbonyloxy;

R ⁶ may be an optionally substituted C ₁ -C ₁₀ -alkylthio, C ₂ -C ₁₀ -alkenylthio or C ₂ -C ₁₀ -alkynyl radical, an optionally substituted C ₃ -C ₈ -cycloalkylthio radical, an optionally substituted C ₆ -C ₁₀ radical -aryltio, an optionally substituted C ₆ -C ₁₀ -arylC _r C ₆ alkylthio, or an optionally substituted heteroarylthio;

R ⁶ may be an optionally substituted C ₁ -C ₆ -alkylcarbonyloxy-C ₁ -C ₆ -alkyl radical, C ₂ -C ₁₀ -alkenylcarbonyloxy-C ₁ -C ₆ -alkyl or C ₂ -C ₁₀ -alkynylcarbonyloxy-C ₁ -C ₆ -alkyl,

15 optionally substituted C ₃ -C ₈ -cycloalkylcarbonyloxy-C ₁ -C ₆ -alkyl, optionally substituted C ₅ -C ₆ -arylcarbonyloxy-C ₁ -C ₆ -alkyl, C ₆ -C ₆ -aryl-C 1 -C 6 -alkylcarbonyloxy- C _r C ₆ alkyl, or an optionally substituted heteroarylcarbonyloxy-C ₁ -C ₆ alkyl;

R ⁶ may be an optionally substituted radical having the formula

R ¹⁰ - O - B - (CH ₂ ) _n -

wherein n = 1, 2, 3, or 4, wherein B may be C ₆ -C ₁₀ -aryl, or a single bond;

R ⁶ may be an optionally substituted amino moiety, preferably NR ⁸ R ⁹ ;

R ⁶ may be an optionally substituted radical having the formula

R ⁶ may be an optionally substituted radical having the formula

C ^ Cg-alkyl

C 1 -C 8 -alkyl wherein Y may be a single bond, or an alkyl, alkenyl or alkynyl group of up to 6, preferably up to 4, carbon atoms in the chain;

R ⁶ may be an optionally substituted radical having the formula

wherein Y may be a single bond, or an alkyl, alkenyl or alkynyl group of up to 6, preferably up to 4, carbon atoms in the chain;

R ⁸ may be hydrogen, optionally substituted cycloalkyl of 3 to 6 carbon atoms, branched or unbranched alkyl, alkenyl or alkynyl of up to 10 carbon atoms, preferably alkyl of 1 to 4 carbon atoms, which may optionally be substituted with hydroxy, phenyl, substituted phenyl, benzyl, substituted benzyl, amino, substituted amino, C 1 -C ₈ -alkoxy, preferably C 1 -C ₄ alkoxy, - (CH ₂ ) _m NHCOOR ¹⁰ m = 1.2 , 3, or 4;

- 17 R ⁸ may be a direct or via an alkyl chain of 1 to 4 carbon atoms via a carbon atom linked 5, 6, or 7 membered heterocycle containing one or more heteroatoms from the group nitrogen, oxygen or sulfur and optionally one or more times, preferably once, substituted with benzyl, optionally substituted benzyl, C 1 -C 4 alkyl, halogen, -OR ¹⁰ , -CN, - NO ₂ , - NH ₂ , - OH, = O, - COOH, - SO ₃ H, - COOR ¹⁰ ;

R ⁸

may be bicyclic, directly or via a C1-C4 alkyl chain, through a carbon-bonded heterocycle containing one or more nitrogen, oxygen or sulfur heteroatoms, optionally one or more times, preferably once, substituted with benzyl or optionally substituted benzyl , C 1 -C 4 alkyl, halogen, - OR ¹⁰ , - CN, - NO ₂ , - NH ₂ , - OH, = O, - COOH, SO ₃ H, - COOR ¹⁰ ;

R ⁹

may be hydrogen, optionally substituted cycloalkyl of 3 to 6 carbon atoms, branched or unbranched alkyl, alkenyl or alkynyl of up to 10, preferably alkyl of 1 to 4 carbon atoms, which may be optionally substituted with hydroxy, phenyl, substituted phenyl , benzyl, substituted benzyl, amino, substituted amino, C, - to C ₈ -, preferably C _r to C ₄ - alkoxy, - (CH _{2) m} -NHCOOR ¹⁰ m = 1, 2, 3, or 4 ;

R ⁹ may be, directly or through an alkyl chain of 1 to 4 carbon atoms, bonded via a carbon atom through a 5, 6, or 7 membered heterocycle containing one or more heteroatoms selected from nitrogen, oxygen or sulfur and optionally one or more times, preferably monosubstituted, by benzyl, optionally substituted benzyl, C _r C ₄ -alkyl, halogen, - oR ^10, - CN, - NO _2, - NH _2> - OH, = 0, - COOH, - SO ₃ H, - COOR ¹⁰ ;

-18R ⁹ denotes a bicyclic, directly or through an alkyl chain of 1 to 4 carbon atoms, a C-linked heterocycle which contains one or more heteroatoms from the group N, O or S, optionally mono- or polysubstituted, preferably monosubstituted, by benzyl, optionally substituted benzyl, C _r C ₄ alkyl, halogen, - oR ^10, - CN, - NO ₂₁ - NH _2, - OH, = 0, - COOH,

- SO ₃ H, - COOR ¹⁰ ;

or

R ⁸ and R ⁹

together with nitrogen may form a saturated or unsaturated 5 or 6 membered ring which may contain as further heteroatoms nitrogen, oxygen, or sulfur, said hetero ring may be substituted by a branched or unbranched alkyl group having 1 to 4 carbon atoms, preferably a methyl group, or may bind the following groups

- (CH ₂ ) _n -phenyl,

- (CH ₂ ) _n -NH ₂ , = O, ketal, preferably - O-CH ₂ -CH ₂ - O

- (CH ₂ ) _n -NH-C 1 -C 4 alkyl,

- (CH ₂ ) _n - N - (C 1 -C 6 -alkyl) ,,

- (CH ₂ ) _n -NH COOR ¹⁰ , (n = 1, 2, 3, 4), halogen,

- OR ¹⁰ , - CN, - NO ₂ , - NH ₂ , - CH ₂ NR ⁸ R ⁹ ,

- OH, - COOH, - SO ₃ H, - COOR ¹⁰ , - CONR ⁸ R ⁹ , - SO ₂ - R ¹⁰ ;

R ¹⁰ can be hydrogen, C 1 -C 4 alkyl, C ₂ -C ₄ -alkenyl, C ₂ -C ₄ -alkynyl, benzyl or phenyl, optionally substituted one or more times with -OCH ₃ , optionally in the form of their racemates, enantiomers, diastereomers and mixtures thereof, and optionally their pharmacologically acceptable acid addition salts.

The dotted lines between the nitrogen atoms in the above formula (I) show the existing double bond at one of its two possible positions, so that both R ¹ and R ³ and R ⁴ and R ⁵ respectively are not possible at the same time.

The compounds having the general formula (I) form the following isomers:

preferred isomers having formulas (Ia) and (1b), especially those isomers in which R ¹ or R ³ is hydrogen or C 1 -C 4 alkyl. Even more preferred are compounds having formulas (Ia) and (1b) wherein R ¹ or R ³ is hydrogen - in which case the isomers (Ia) and (1b) are tautomers.

Preferred are compounds having the formulas (Ia) to (Id) in which:

R ¹ or R ³ can be hydrogen, C 1 -C 4 alkyl, benzyl, especially hydrogen;

R ² can be hydrogen, C 1 -C ₈ -alkyl, C ₂ -C ₈ -alkenyl or C ₂ -C ₈ -alkynyl which is substituted with-CN, -CH ₂ NR ⁸ R ⁹ , OH (possibly multiple) - OR ¹⁰ , - NR ⁸ R ⁹ , - NHCOR ¹⁰ , - NHCONR ⁸ R ⁹ , - NHCOOR ¹⁰ , halogen, - OCOR ¹⁰ , - OCO-pyridyl, - OCH ² COOH, - OCH ² COR ¹⁰ , - SO ² R ⁷ , - SR ⁷ ,

- NHCONHPh, - OCH ₂ - CONR ⁸ R ^9, - OCH ₂ .CH ₂ · OH, - SO ₂ - CH ₂ - CH ₂ - O - R ^10,

- OCH ₂ -CH ₂ -NR ⁸ R ^9, - SO2-CH2CH2OH, -CONHSO 2 R ¹ °, - CH2CONHSO ₂ R ^10,

- OCH ₂ CH ₂ OR ¹⁰ - COOH - COOR ¹⁰ - CONR ⁸ R ⁹ CHO SR ¹⁰ SOR ¹⁰ SO ₂ R ¹⁰

--so ₃ h, --so ₂ nr ⁸ r ⁹ , - OCH ₂ -CH ₂ OCOR ¹⁰ , - CH = NOH, - CH = NOR ¹⁰ , = O,

- COR ¹¹ , - CH (OH) R ¹¹ , - CH (OR ¹⁰ ) ₂ , - CH = CH-R ¹² , OCONR ⁸ R ⁹ ,

1,3-dioxolane or 1,3-dioxane optionally substituted one or more times, preferably once, with methyl;

R ² can be phenyl-C 1 -C 6 -alkyl-, preferably phenyl-C ₁ -C ₆ -alkyl-, phenyl-C ₂ -C ₆ -alkenyl or phenylC ₂ -C ₆ -alkynyl, wherein the phenyl ring is optionally substituted directly or through an alkylene bridge having 1 to 4 carbon atoms by one or more, preferably one, of -C ₁ -C ₃ -alkyl, -CN, -NR ⁸ R ⁹ , -NO 2, -OH, -OR ¹⁰ , -CH ₂ NHHSO ₂ R ¹⁰ , - NHCOR ¹⁰ , -NHCONR ⁸ R ⁹ , halogen, - OCOR ¹⁰ , - OCO-pyridyl, Φ - OCH ² COOH, - OCH ² COOR ¹⁰ , -CH ² OCOR ¹⁰ , - SO ² R ⁷ , -OCH 2 -CON ⁸ R ⁹ , -och 2 ch 2 OH, -och 2 - CH 2 NR ⁸ R ^9, -CONHSO 2 R ^10, -och2ch2or ^10, - COOH, -COOR ^10, -CF 3, cyclopropyl, -CONR ⁸ R ^9, -CH 2 OH, -CH 2 OR ^10, CHO, -SR ^10, -SOR ^10, - SO ² R ¹⁰ , -SO 3 H, -SO 2 NR ⁸ R ⁹ , -OCH ₂ -CH ₂ OCOR ¹⁰ , -CH = NOH, -CH = NOR ¹⁰ , -COR ¹¹ , -CH (OH) R ¹¹ , -CH (OR ¹⁰ ) 2 , -NHCOOR ¹⁰ , -CH ₂ CONHSO ₂ R ¹⁰ , -CH = CH-R ¹² ,

-OCONR ⁸ R ⁹ , -CH 2 -O-CONR ⁸ R ⁹ , -CH 2 -CH ₂ -O-CONR ⁸ R ⁹ , optionally one or more, preferably one, methyl-substituted 1,3-dioxolano or 1,3- dioxane;

R ² can be C ₃ -C ₇ -cycloalkyl-C ₁ -C ₆ -alkyl-, C ₃ -C ₇ -cycloalkyl-C ₂ -C ₆ -alkenyl-, C ₃ -C ₇ cycloalkyl-C ₂ -C ₆ -alkynyl, wherein the cycloalkyl radical may be substituted, directly or through a C 1 -C 4 alkylene bridge, by one or more, preferably one,-CN, NR ⁹ R ⁸ , = O, -OH, -OR ¹⁰ , - NR ⁸ R ⁹ , -NHCOR ¹⁰ , -NHCONR ⁸ R ⁹ , halogen, - OCOR ¹⁰ , - OCO-pyridyl, - OCH ² COOH, -OCH 2 COOR ¹⁰ , -CH ² OCOR ¹⁰ , -SO ² R ⁷ , -OCH 2 -CON ⁸ R ⁹ , - OCH ₂ CH ₂ OH, -och ₂ CH ₂ -NR ⁸ R ⁹ , -OCH ₂ -CH ₂ -OR ¹⁰ , -COOH, -COOR ¹⁰ , -CONR ⁸ R ⁹ , -CH 2 OH, -CH 2 OR ¹⁰ , -CHO, -SR ¹⁰ , -SOR ¹⁰ , -SO ² R ¹⁰ , -SO 3 H, -SO 2 NR ⁸ R ⁹ , -OCH ₂ -CH ₂ OCOR ¹⁰ , -CH = NOH, -CH = NOR ¹⁰ , -COR ¹¹ , -CH (OH) R ¹¹ , -CONHSO ² R ¹⁰ , -CH (OR ¹⁰ ) 2,

-NHCOOR ¹⁰ , -CH = CH-R ¹² , -OCONR ⁸ R ⁹ , -CH 2 -O-CONR ⁸ R ⁹ , -CH 2 -CH ₂ -O-CONR ⁸ R ⁹ , optionally substituted 1,3-dioxolane by methyl or 1,3-dioxane;

-21 R ² denotes a residue of the formula

AC ₁ -C ₆ -alkyl-, Α-CONHCT-C 6 -alkyl-, A-CONH-C ₂ -C ₆ -alkenyl-, A-CONH-C ₂ -C ₆ alkynyl, Α-ΝΗ-CO-CrCo -alkyl-, A-NH-CO-C ₂ -C ₆ -alkenyl, A-NH-COC ₂ -C ₆ -alkynyl, AC ₂ -C ₆ -alkenylene, AC ₂ -C ₆ -alkynylene or A-, wherein: a is a 5, 6 or 7 membered heterocyclic, be carbon or nitrogen, containing one or more atoms selected from nitrogen, oxygen or sulfur and may optionally be mono- or polysubstituted, preferably mono-substituted benzyl, optionally substituted benzyl, C ₁ -C ₄ -alkyl, halogen, -OR ¹⁰ , -CN, -NO 2, -NH 2, -CH ² NR ⁸ R ⁹ , -OH, = O, ketal, ethylene ketal, -COOH, -SO 3 H, -COOR ¹⁰ , 9 -CONR ⁸ R ⁹ , -COR ¹¹ , -SO ₂ R ¹⁰ , or -CONR ⁸ R ⁹ ;

R ² may be C ₃ -C ₇ -cycloalkyl, preferably cyclopentyl or cyclohexyl, which is optionally substituted with = O, -OH, -OR ¹⁰ , OCOR ¹⁰ , or -OCO-pyridyl;

R ² denotes phenyl, optionally substituted by -OH, halogen, ^-OR10, Ml ^ alkyl, preferably methyl, -NH 2, -COOH, -SO 3 H, -COOR ^10, --OCH2 ^10, -CN, or -OCH ₂ CONR ⁸ R ⁹ group;

R ² may be a norbornene, norbornene, C ₃ -C ₆ -dicycloalkylmethyl, preferably a dicyclopropylmethyl, adamantane, or noradamantane radical, optionally substituted with a C 1 -C 6 alkyl group, preferably a methyl group;

R ² may be -CH = CH-phenyl, wherein the phenyl ring is substituted one or more times with methoxy, hydroxy, or halogen;

R ² may be a [3.3.0] -bicyclooctane, preferably a [3.3.0] -bicyclooctan-2-yl;

R ² denotes a piperidine or furan, be carbon;

-22R ² denotes an amine of general formula NR ⁸ R ^9;

R ⁴ or R ⁵ may be hydrogen, optionally branched C ₁ -C ₈ -alkyl, C ₂ -C ₈ -alkenyl or C ₂ -C ₈ -alkynyl, which is substituted by -CN, -CH ₂ NR ⁸ R ⁹ , OH (s) multiple substitution), - OR ¹⁰ , - NR ⁸ R ⁹ , - NHCOR ¹⁰ , - NHCONR ⁸ R ⁹ , halogen, - OCOR ¹⁰ , - OCO-pyridyl, - OCH ² COOH, - OCH ² COOR ¹⁰ , - SO ² R ⁷ ,

- SR ⁷ , - NHCONH-phenyl, - OCH 2 - CONR ⁸ R ⁹ , - O-CH ₂ CH ₂ OH, - SO ₂ -CH ₂ - CH ₂ O-COR ¹⁰ , - OCH ₂ -CH ₂ -NR ⁸ R ⁹ , - SO2, -CH ₂ CH ₂ OH, -conhso ₂ r ¹⁰ , -ch ₂ CONONHSO ₂ R ^w , - OCH ₂ CH ₂ OR ¹⁰ , - COOH, - COOR ¹⁰ , - CONR ⁸ R ⁹ , - CHO, - SR ¹⁰ ,

- SOR ¹⁰ , - SO ₂ R ¹⁰ , - SO 3 H, - SO ₂ NR ⁸ R ⁹ , - OCH ₂ -CH ₂ OCOR ¹⁰ , - CH = NOH,

- CH = NOR ¹⁰ , - COR ¹¹ , - CH (OH) R ¹¹ , - CH (OR ¹⁰ ) ₂ , - CH = CH-R ¹² , OCONR ⁸ R ⁹ ,

1,3-dioxolane or 1,3-dioxane optionally substituted one or more times, preferably once, with methyl;

R ⁴ or R ⁵ may be phenyl-C 1 -C 6 -alkyl-, preferably phenyl-C ₁ -C ₄ -alkyl-, phenyl-C ₂ -C ₆ -alkenyl or phenyl-C ₂ -C ₆ -alkynyl, wherein the phenyl the ring is optionally substituted directly or through an alkylene bridge of 1 to 4 carbon atoms by one or more, preferably one, of -C ₁ -C ₃ -alkyl, -CN, -NR ⁸ R ⁹ , -NO 2, -OH, -OR ^10, -CH2NHSO ₂ R ^10, -NHCOR ^10, -NHCONR ⁸ R ^9, halogen, -OCOR ^10, -OCO-pyridyl, -OCH 2 COOH, --OCH2 ^w, -CH2OCOR ^10, -SO 2 R ^7, -OCH 2 CONR ⁸ R ⁹ , -och2ch2oh, -och2-ch2-nr ⁸ r ⁹ , -conhso2r ¹⁰ , -och2ch2or ¹⁰ , - COOH, -COOR ¹⁰ , -CF 3, cyclopropyl, -CONR ⁸ R ⁹ , -CH 2 OH, -CH 2 OR ¹⁰ , -CHO , -SR ¹⁰ , -SOR ¹⁰ , -SO ² R ¹⁰ , -SO 3 H, -SO 2 NR ⁸ R ⁹ , -OCH ₂ -CH ₂ OCOR ¹⁰ , -CH = NOH, -CH = NOR ¹⁰ , -COR ¹¹ , -CH (OH) R ¹¹ , -CH (OR ¹⁰ ) 2, -NHCOOR ¹⁰ , -CH 2 CONHSO ₂ R ¹⁰ , -CH = CH-R ¹² , -OCONR ⁸ R ⁹ , -CH 2 -O-CONR ⁸ R ⁹ , -CH 2 -CH ₂ -O-CONR ^with R ⁹ , optionally once or more, preferably once, with methyl-substituted 1,3-dioxolane or o 1,3-dioxane;

R ⁴ or R ⁵ may be an optionally substituted C ₃ -C ₇ -cycloalkyl radical;

-23R ⁴ or R ⁵ denotes C Cg-cycloalkyl-C ^ Cg-alkyl, C ₃ -C ₇ -cycloalkyl-C ₂ -C ₆ -alkenyl, C ₃ -C ₇ cycloalkyl-C ₂ -C ₆ -alkynyl-, wherein the cycloalkyl moiety may be directly or via an alkylene bridge having 1 to 4 carbon atoms substituted with a -CN, NR ⁹ R ^8, = 0, -OH, -OR ^10, -NR ⁸ R ^9, -NHCOR ^10, -NHCONR ⁹ R ^8, halogen, - OCOR ^10, - OCOpyridyl, - OCH2COOH, - OCH2COOR ^1D, -CH2OCOR ^10, - SO 2 R ^7, -OCH 2 CONR ⁸ R ^9, -OCH2CH2OH, -OCH 2 CH 2 NR ⁸ R ⁹ , -OCH ₂ -CH ₂ -OR ¹⁰ , -COOH, -COOR ¹⁰ , -CONR ⁸ R ⁹ , -CH 2 OH, -CH 2 OR ¹⁰ , -OHO, -SR ¹⁰ , -SOR ¹⁰ , -SO ² R ¹⁰ , -SO 3 H, -SO 2 NR ⁸ R ⁹ , -OCH ₂ CH ₂ OCOR ¹⁰ , -CH = NOH, -CH = NOR ¹⁰ , -COR ¹¹ , -CH (OH) R ¹¹ , -conhso ₂ r ¹⁰ ,

-CH (OR ¹⁰ ) 2, -nhcoor ¹⁰ , -ch = ch-r ¹² , -OCONR ⁸ R ⁹ , -ch 2 -o-conr ⁸ r ⁹ , -ch ₂ -ch ₂ O-CONR ⁸ R ⁹ , methyl optionally substituted 1,3-dioxolane or 1,3-dioxane;

R ⁴ or R ⁵ may be a radical having the formula

AC ₁ -C ₆ alkyl, and _{R CONHC-C6} alkyl, C0NH-A-C ₂ -C ₆ -alkenyl, A-CONHC ₂ -C ₆ -alkynyl, A-NH-CO-C ^ -C -alkyl-, A-NH-CO-C ₂ -C ₆ -alkenyl, A-NH-COC ₂ -C ₆ -alkynyl, AC ₂ -C ₆ alkenyl, AC ₂ -C ₆ -alkynyl, wherein A is a heterocycle, bonded via carbon or nitrogen, which contains one or more nitrogen, oxygen or sulfur atoms, and optionally can be mono- or poly-substituted, preferably once, substituted by C 1 -C 4 alkyl, halogen, -OR ¹⁰ , -CN, -NO 2 , -NH 2, -CH ² NR ⁸ R ⁹ , -OH, = 0, ketal, ethylene ketal, -COOH, -SO 3 H,

-COOR ¹⁰ , -CONR ⁸ R ⁹ , -COR ¹¹ , -SO ₂ R ¹⁰ , or -CONR ⁸ R ⁹ ;

R ⁶ may be hydrogen, optionally branched C 1 -C 8 -alkyl, C ₂ -C ₈ -alkenyl or C ₂ -C ₈ -alkynyl, which is substituted with - CN, - CH ₂ NR ⁸ R ⁹ , OH (possibly - OR ¹⁰ , - NR ⁸ R ⁹ , - NHCOR ¹⁰ , - NHCONR ⁸ R ⁹ , halogen, - OCOR ¹⁰ , - OCO-pyridyl, - OCH ² COOH, - OCH ² COOR ¹⁰ , - SO ² R ⁷ , - SR ⁷ , - NHCONH-phenyl, - OCH 2 - CONR ⁸ R ⁹ , - O-CH ₂ CH ₂ OH, - SO ₂ -CH ₂ - CH ₂ O-COR ¹⁰ , - OCH ₂ -CH ₂ -NR ⁸ R ⁹ , -SO ₂ --CH ₂ -CH ₂ OH, -CONHSO ₂ R ^10, -ch2CONHSO2R ^10, - OCH 2 CH ₂ OR ^10, -COOH, -COOR ^10, - CONR ⁸ R ^9, - CHO, -SR ^10,

- SOR ¹⁰ , - SO ₂ R ¹⁰ , - SO 3 H, - SO ₂ NR ⁸ R ⁹ , - OCH ₂ -CH ₂ OCOR ¹⁰ , - CH = NOH,

- CH = NOR ¹⁰ , - COR ¹¹ , - CH (OH) R ¹¹ , - CH (OR ¹⁰ ) ₂ , - CH = CH-R ¹² , OCONR ⁸ R ⁹ ,

1,3-dioxolane or 1,3-dioxane, optionally one or more times, preferably once, substituted with a methyl group;

R ⁶ can be phenyl-C 1 -C 6 -alkyl-, preferably phenyl-C ₁ -C ₄ -alkyl-, phenyl-C ₂ -C ₆ -alkenyl or phenyl-C ₂ -C ₆ -alkynyl, the phenyl ring being optionally substituted directly or through an alkylene bridge of 1 to 4 carbon atoms by one or more of -C 1 -C 4 alkyl, -CN, NR ⁸ R ⁹ , -NO 2, -OH, -OR ¹⁰ , -CH ₂ NH-SO ₂ R ¹⁰ , -NHCOR ¹⁰ ,

-NHCONR ⁹ R ^8, halogen, - OCOR ^10, - OCO-pyridyl, - -OCH2COOH, - OCH2COOR ^10, -CH2OCOR ^10, -SO 2 R ^7, -OCH 2 CONR ⁸ R ^9, -OCH2CH2OH, -OCH 2 CH 2 NR ⁸ R ⁹ , -CONHSO 2 R ^10, -OCH2CH2OR ^10, -CONR ⁸ R ^9, -CH 2 OH, -CH ₂ OR ^10, CHO, -SR ^10, -OCH ₂ -CH ₂ OCOR ^10, -CH = NOH, -CH = NOR ¹⁰ .

- COOH, -COOR ¹⁰ , -CF 3) cyclopropyl, -SOR ¹⁰ , -SO ² R ¹⁰ , -so 3h, -SO ² NR ⁸ R ⁹ , -COR ¹¹ , -CH (OH) R ¹¹ , -CH (OR ¹⁰ ) 2,

-NHCOOR ¹⁰ , -CH 2 CONONHSO ² R ¹⁰ , -CH = CH-R ¹² , -OCONR ⁸ R ⁹ , -CH 2 -O-CONR ⁸ R ⁹ ,

-CH ₂ -CH ₂ -O-CONR ⁸ R ⁹ , -CO-R 10, -CO-C ₁ -C ₄ -alkyl-NR ⁸ R ⁹ , optionally one or more times, preferably one, by methyl-substituted 1,3- dioxolane or 1,3-dioxane;

R ⁶ can be C ₃ -C ₇ -cycloalkyl-C ₁ -C ₆ -alkyl-, C ₃ -C ₇ -cycloalkyl-C ₂ -C ₆ -alkenyl-, C ₃ -C ₇ cycloalkyl-C ₂ -C ₆ -alkynyl, wherein the cycloalkyl radical may be substituted, directly or through a C1-C4 alkylene bridge, by one or more, preferably one,-CN, NR ⁹ R ⁸ , = O, -OH, -OR ¹⁰ , -NR ⁸ R ⁹ , -NHCOR ¹⁰ , -NHCONR ⁸ R ⁹ , halogen, - OCOR ¹⁰ , - OCO-pyridyl, - OCH ² COOH, -OCH 2 COOR ¹⁰ , -CH ² OCOR ¹⁰ , -SO ² R ⁷ , -OCH 2 -CON ⁸ R ⁹ , -OCH 2 CH 2 OH, -och ₂ CH ₂ -NR ⁸ R ⁹ , -OCH ₂ -CH ₂ -OR ¹⁰ , -COOH, -COOR ¹⁰ , -CONR ⁸ R ⁹ , -CH 2 OH, -CH 2 OR ¹⁰ , -CHO, -SR ¹⁰ , -SOR ¹⁰ , -SO 2 R ¹⁰ , -SO 3 H, -SO 2 NR ⁸ R ⁹ , -OCH ₂ -CH ₂ OCOR ¹⁰ , -CH = NOH, -CH = NOR ¹⁰ , -COR ¹¹ , -CH (OH) R ¹¹ , -CONHSO ² R ¹⁰ , -CH (OR ¹⁰ ) 2, -NHCOOR ¹⁰ ,

-CH = CH-R ¹² , -OCONR ⁸ R ⁹ , -CH 2 -O-CONR ⁸ R ⁹ , -CH 2 -CH ₂ -O-CONR ⁸ R ⁹ , optionally substituted with 1,3-dioxolane or 1,3-dioxolane or methyl dioxane;

-25R ⁶ denotes a residue of the formula

AC _r C ₆ -alkyl, A-CONHC ^ Cg-alkyl, A-CONHC ₂ -C ₆ -alkenyl, A-CONHC ₂ -C ₆ -alkynyl, Α-ΝΗ-CO-C-Cg-alkyl, -, A-NH-CO-C ₂ -C ₆ -alkenyl, A-NH-COC ₂ -C ₆ -alkynyl, AC ₂ -C ₆ alkenyl, AC ₂ -C ₆ -alkynyl, wherein A is 5, 6 or A 7 membered heterocycle bonded via carbon or nitrogen containing one or more nitrogen, oxygen or sulfur atoms and optionally one or more times, preferably once, substituted with benzyl, optionally substituted with benzyl, C 1 -C 4 alkyl, halogen , -OR ¹⁰ , -CN, -NO 2, -NH 2, -CH ² NR ⁸ R ⁹ , -OH, = O, ketal, ethylene ketal, -COOH, -SO 3 H, -COOR ¹⁰ , -CONR ⁸ R ⁹ , Φ -COR ¹¹ , -SO ₂ R ¹⁰ , or -CONR ⁸ R ⁹ ;

R ⁶ can be -CHO, -COOR ¹⁰ , -CONR ⁸ R ⁹ ;

R ⁶ may be C ₃ -C ₇ -cycloalkyl, preferably cyclopentyl or cyclohexyl, which is optionally substituted with = O, -OH, -OR ¹⁰ , OCOR ¹⁰ , or -OCO-pyridyl;

R ⁶ can be phenyl, which is optionally substituted with -OH, halogen, -OR ¹⁰ , C 1 -C 4 alkyl, preferably methyl, -NH 2, -COOH, -SO 3 H, -COOR ¹⁰ , -OCH ² COOR ¹⁰ , -CN, or -OCH ₂ CONR ⁸ R ⁹ group;

denotes norbornane, norbornene, C ₃ -C ₆ -dicykloalkyl-methyl, preferably dicyclopropylmethyl, adamantane or noradamantane group optionally substituted by C ₁ -C ₄ -alkyl, preferably methyl;

R ⁶ may be -CH = CH-phenyl, wherein the phenyl ring may be substituted one or more times with methoxy, hydroxy, or halogen;

R ⁶ can be [3,3,0] -bicyclooctane-, preferably [3,3,0] -bicycloctan-2-yl;

-26R ⁶ denotes a C-linked piperidine or furan;

R ⁷ may be C 1 -C 4 alkyl, optionally substituted with OH, OCOR ¹⁰ , -OCOpyridyl, -NH 2, NR ⁸ R ⁹ or NHCOR ¹⁰ , preferably -CH 2 -CH ₂ -OH, -CH ₂ -CH ₂ -OCOR ¹⁰ , -CH ₂ -CH ₂ -CH ₂ -OH, or CH ₂ -CH ₂ -CH ₂ -OCOR ¹⁰ ;

R ⁸

may be hydrogen, optionally substituted cycloalkyl of 3 to 6 carbon atoms, branched or unbranched alkyl, alkenyl or alkynyl of up to 10, preferably alkyl of 1 to 4 carbon atoms, which may optionally be substituted with hydroxy, phenyl, substituted phenyl, benzyl, substituted benzyl, amino, substituted amino, C 1 -C ₈ -alkoxy, preferably C 1 -C ₄ alkoxy, - (CH ₂ ) _m -NHCOOR ¹⁰ m = 1, 2, 3 , or 4;

R ⁸ may be, directly or through an alkyl chain of 1 to 4 carbon atoms, bonded via a carbon atom through a 5, 6, or 7 membered heterocycle containing one or more heteroatoms from the group nitrogen, oxygen or sulfur and optionally one or more times, preferably once, substituted with benzyl, optionally substituted benzyl, C 1 -C 4 alkyl, halogen, - OR ¹⁰ , - CN, - NO ₂ , - NH ₂ , - OH, = O, - COOH, - SO ₃ H, - COOR ¹⁰ ;

R ⁸ may be bicyclic, directly or through a C 1 -C 4 alkyl chain, a carbon-linked heterocycle containing one or more heteroatoms selected from nitrogen, oxygen or sulfur, optionally one or more times, preferably once, substituted with benzyl, optionally substituted benzyl, C _r C ₄ alkyl, halogen, - oR ^10, - CN, - NO _2, - NH _2, - OH, = 0, - COOH, - SO ₃ H, or - COOR ^10;

-27R ⁹ denotes hydrogen, an optionally substituted cycloalkyl of 3 to 6 carbon atoms, branched or unbranched alkyl, alkenyl or alkynyl having up to 10, preferably C 1 -C 4 alkyl which may optionally be substituted by hydroxy, phenyl , substituted phenyl, benzyl, substituted benzyl, amino, substituted amino, C 1 -C ₈ -alkoxy, preferably C 1 -C ₄ alkoxy, - (CH ₂ ) _m -NHCOOR ¹⁰ m = 1.2 , 3, or 4, preferably hydrogen;

R ⁹

can be directly, or via an alkyl chain of 1 to 4 carbon atoms, through a 5, 6, or 7 membered hetero ring attached via a carbon atom containing one or more heteroatoms from the group nitrogen, oxygen or sulfur and is optionally one or more times, preferably once, substituted with benzyl, optionally substituted benzyl, C 1 -C 4 alkyl, halogen, - OR ¹⁰ , - CN, - NO ₂ , - NH ₂ , - OH, = O, - COOH, - SO ₃ H, or - COOR ¹⁰ ;

R ⁹ may be bicyclic, directly or via a C 1 -C 4 alkyl chain, a carbon-linked heterocycle containing one or more nitrogen, oxygen or sulfur heteroatoms and optionally one or more times, preferably one, substituted with benzyl, optionally substituted benzyl, C 1 -C ₄ alkyl, halogen, - OR ¹⁰ , - CN, - NO ₂ , - NH ₂ , - OH, = O, - COOH, - SO ₃ H, or - COOR ¹⁰ , or

R ⁸ and R ⁹ together with the nitrogen may form a saturated or unsaturated 5 or 6 membered ring which may contain as further heteroatoms nitrogen, oxygen or sulfur, said hetero ring may be substituted by a branched or unbranched alkyl group having 1 to 4 carbon atoms, preferably a methyl group, or may bind the following groups

- (CH ₂ ) _n -phenyl,

- (CH ₂ ) _n -NH ₂ = O, ketal, preferably -O-CH ₂ -CH ₂ -O-,

- (CH ₂ ) _n -NH-C 1-6 -alkyl,

- (CH ₂ ) _n - N - (C 1 -C 6 -alkyl) ,,

- (CH ₂ ) _n -NH COOR ¹⁰ , (n = 1, 2, 3, 4), halogen,

- OR ¹⁰ , - CN, - NO ₂ , - NH ₂ , - CH ₂ NR ⁸ R ⁹ ,

- OH, - COOH, - SO ₃ H, - COOR ¹⁰ , - CONR ⁸ R ⁹ , - SO ₂ - R ¹⁰ ;

R ¹⁰

denotes hydrogen, C ₁ -C ₄ -alkyl, C ₂ -C ₄ -alkenyl, C ₂ -C ₄ alkynyl, benzyl or phenyl radical, optionally mono- or polysubstituted by -OCH _3;

R ¹¹ can be C 1 -C 4 alkyl, C ₂ -C ₄ -alkenyl, C ₂ -C ₄ -alkynyl, optionally substituted phenyl, optionally substituted benzyl, C ₃ -C ₆ -cycloalkyl;

R ¹² may be -COOR ¹⁰ , -CH ² OR ¹⁰ , -CONR ⁸ R ⁹ , hydrogen, C 1-6 -alkyl, optionally substituted phenyl, -CH ² NR ⁸ R ⁹ , optionally in the form of their racemates, their enantiomers, diastereomers, and mixtures thereof, such as as well as their pharmacologically acceptable acid addition salts.

Further preferred are compounds having formulas (Ia) to (Id).

-29 in which

R ¹ or R ³ can be hydrogen, C ₁ -C ₄ -alkyl, benzyl;

R ² denotes hydrogen, by lower alkyl, preferably C ^ -alkyl;

R ² denotes phenyl which is optionally substituted by halogen, preferably fluorine or chlorine, C ₁ -C ₄ alkyl, C _r C ₄ -alkyloxy, hydroxy or NR ⁸ R ^9;

R ²

can be phenyl-C 1 -C 6 -alkyl-, preferably benzyl, phenyl-C ₂ -C ₆ -alkenyl- or phenyl C ₂ -C ₆ -alkynyl, the phenyl ring being optionally substituted by halogen, preferably fluorine or chlorine, C 1 -C ₆ -alkenyl- C 1-4 alkyl, C ₁ -C ₄ -alkyloxy, hydroxy or NR ⁸ R ⁹ ;

R ² denotes an amino radical, optionally substituted, preferably NR ⁸ R ^9;

R ² may optionally be either directly or through a C 1 -C 4 alkylene bridge of a 5 or 6 membered heterocycle bonded via a carbon or nitrogen atom containing one or more nitrogen or oxygen heteroatoms and optionally substituted by benzyl or C ₁ -C ₄ -alkyl;

R ² may be a C ₃ -C ₆ -cycloalkyl group which may be optionally substituted with = O, hydroxy, C 1 -C 6 alkyl, or C 1 -C 6 alkyloxy;

R ² can be norborane, norborene, adamantane or noradamantane, optionally substituted with a C 1 -C 4 alkyl group, preferably a methyl group;

R ⁴ or R ⁵ may be hydrogen, C 1 -C 6 -alkyl, phenyl-C 1 -C 6 -alkyl, preferably benzyl, phenyl-C ₂ -C ₆ -alkenyl or phenyl-C ₂ -C ₆ -alkynyl, wherein the phenyl ring may be possibly

-30substituovaný halogen, preferably chlorine or fluorine, hydroxy, C, -C ₄ alkyl, C ₁ -C ₄ alkyloxy group, or NR ⁸ R ^9;

R ⁶

may be hydrogen, C 1 -C ₈ -alkyl, wherein the alkyl chain may be optionally substituted by halogen, hydroxy, = O, C 1 -C ₄ -alkyloxy, NR ⁸ R ⁹ , phenyloxy, -O-phenyl-C, - C4-alkyloxy, benzyloxy, -O-benzyl-O-C1-C4-alkyloxy, -OCO-C1-C4-alkyl, -OCO-phenyl, -OCO-benzyl, -OCO-pyridyl, -O-C2-C4 -alkylene, -CO-C 1 -C 4 -alkyl, -CHO, = NOH, -COOH, -COO-C 1 -C 4 -alkyl, -COO-phenyl, -COO-benzyl, -CONR ⁸ R ⁹ , -NHCOC , -C 4 -alkyl, -NHCO-phenyl, -CO-C 1 -C ₄ -alkyl-NR ⁸ R ⁹ , -SO ₂ OH, -SO ₂ -C, -C ₄ -alkyl, or -SO ₂ -phenyl group;

R ⁶ may be phenyl, which may optionally be substituted by halogen, preferably chlorine or fluorine, hydroxy, C 1 -C ₄ -alkyl, C 1 -C ₄ -alkyloxy, benzyloxy, phenyloxy, NR ⁸ R ⁹ , -OCO- C1-C4-alkyl, -OCO-phenyl, -OCO-benzyl, -OCO-pyridyl, -O-C2-C4-alkylene, -CO-C1-C4-alkyl, -C1-C4-alkyl-NH2, -C C4-alkyl-OH, C, -C 4 alkyl = NOH, -COOH, -COO-C, -C4-alkyl, -COO-phenyl, -COO-benzyl, -CONR ⁸ R ^9, -COC C4 -alkyl-NH ₂ , -SO ₂ OH, -SO ₂ -C, -C ₄ -alkyl, or -SO ₂ -phenyl;

R ⁶ may be phenyl-C 1 -C ₄ -alkyl-, preferably benzyl, phenyl-C ₂ -C ₆ -alkenyl, or phenylC ₂ -C ₆ -alkynyl, wherein the phenyl ring may be substituted with halogen, preferably chlorine or fluorine, hydroxy, C 1 -C ₄ -alkyl, C 1 -C ₄ -alkoxy, benzyloxy, phenyloxy, NR ⁸ R ⁹ , -OCO-C 1 -C 4 -alkyl, -OCO-phenyl, -OCO-benzyl, -OCO -pyridyl, -O-C 2 -C 4 -alkylene, -CO-C 1 -C 4 -alkyl, -C 1 -C 4 -alkyl-NR ⁸ R ⁹ , C 1 -C ₄ -alkyl-OH, -C 1 -C ₄ -alkyl = NOH, -COOH, -COO-C 1 -C ₄ -alkyl, -COO-phenyl, -COO-benzyl, -CONR ⁸ R ⁹ , -CO-C 1 -C ₄ -alkylNH ₂ , -SO ₂ OH, -SO ₂ -C, -C ₄ -alkyl, or -SO ₂ -phenyl;

R ⁶ may optionally be either a 5 or 6-membered heterocycle bound via a carbon or nitrogen atom containing one, two or three heteroatoms from the group, either directly or through a C 1 -C 4 alkylene bridge

-31 nitrogen or oxygen and may optionally be mono- or poly-substituted with benzyl or C 1 -C 4 alkyl;

R ⁶ may be a C ₃ -C ₆ -cycloalkyl or a C ₃ -C ₆ -cycloalkyl-C ₁ -C ₄ -alkyl radical, which may optionally be substituted by = O, hydroxy, C 1 -C 4 alkyl or C 1 -C 6 alkyl; -alkyloxy;

R ⁶

may be norbornyl, norbornenyl, adamntyl or noradamantyl, optionally substituted with C 1 -C 4 alkyl, preferably methyl;

R ⁶ can be -CHO, -COOH, -COO-C ₁ -C ₄ -alkyl, -COO-phenyl, -COO-benzyl, or -CONR ⁸ R ⁹ ;

R ⁶ can be an amine having the formula NR ⁸ R ⁹ ;

R ⁸ can be hydrogen, a branched or unbranched alkyl group having 1 to 4 carbon atoms;

R ⁸ denotes a 5 or 6 membered heterocycle, linked through a carbon atom, containing one, two, or three heteroatoms selected from nitrogen, oxygen or sulfur and optionally substituted benzyl, C ₁ -C ₄ -alkyl, C _r C ₄ -alkyloxy, halogen, -CN, -NO ₂ , -NH ₂ , -OH, or = O;

R ⁹ can be hydrogen, a branched or unbranched alkyl group having 1 to 4 carbon atoms;

R ⁹ denotes a 5 or 6 membered heterocycle, linked through a carbon atom, containing one, two, or three heteroatoms selected from nitrogen, oxygen or sulfur and optionally substituted benzyl, C _r C ₄ -alkyl, C ₁ - C ₄ -alkyloxy, halogen, -CN, -NO ₂ , -NH ₂ , -OH, or = O;

-32alebo

R ⁸ and R ⁹

form, together with the nitrogen atom, a saturated or unsaturated 5 or 6 membered ring which, as further heteroatoms, may contain nitrogen or oxygen, said hetero ring may be substituted by a branched or unbranched alkyl group having 1 to 4 carbon atoms, preferably a methyl group, or CH 2 -phenyl, preferably benzyl, optionally in the form of their racemates, enantiomers, in the form of diastereomers and mixtures thereof, and optionally in the form of their pharmacologically acceptable acid addition salts.

Further preferred are compounds having the general formula (Ia) and (Ib)

In which

R ¹ or R ³ can be hydrogen, C 1 -C 6 alkyl, preferably C 1 -C 6 alkyl, benzyl;

R ² denotes hydrogen, C ^ Cg alkyl, preferably C ₁ -C ₄ alkyl;

R ² denotes cyclopentyl, cyclohexyl, cyclopentanone, cyclohexanone, hydroxycyclopentane or hydroxycyclohexane;

^R2 denotes a morpholine radical which is optionally substituted by C _r C ₄ alkyl, preferably methyl, piperidino, piperazinyl radical which is optionally substituted by C ₁ -C ₄ -alkyl, preferably methyl, pyridyl, tetrahydrofuranyl, tetrahydropyranyl or furyl;

R ² denotes phenyl, optionally substituted by C _r C ₄ -alkyl, halogen or hydroxy;

R ² may be phenyl-C 1 -C 4 alkyl, preferably benzyl, wherein the phenyl ring may be optionally substituted by halogen, preferably fluorine or chlorine, C 1 -C 4 alkyl, C 1 -C 4 alkyloxy, hydroxy or NR ⁸ R ⁹ ;

R ² may be an amine having the formula NR ⁸ R ⁹ ;

R ² may be norbornenyl, norbornyl, adamantyl or noradamantyl, optionally substituted with a C ₁ -C ₄ -alkyl group, preferably a methyl group;

R ⁴ may be hydrogen, C 1 -C 6 -alkyl, preferably C 1 -C 6 -alkyl, phenyl-C 1 -C 6 -alkyl, preferably benzyl, wherein the phenyl ring may be substituted by halogen, preferably chlorine or fluorine, hydroxy, C ₁ -C 6 _4- alkyloxy or NR ⁸ R ⁹ ;

R ⁶ denotes hydrogen, C ^ -alkyl, preferably C ^ C ^ alkyl, wherein the alkyl chain is optionally substituted by halogen, hydroxy, = O, C _r C ₄ alkoxy, NR ⁸ R ^9, phenoxy, -O- phenyl-C1-C4-alkyloxy, benzyloxy, -O-benzyl-O-C1-C4alkyloxy, -OCO-C1-C4 alkyl, -OCO-phenyl, -OCO-benzyl, -OCO-pyridyl, -O-C2-C4alkylene , -CO-C 1 -C 6 -alkyl, -CHO, = NOH, -COOH, -COO-C 1 -C 6 -alkyl, -COO-phenyl, -COO-benzyl, -CONR ⁸ R ⁹ , -NHCO- C 1 -C 4 -alkyl, -NHCO-phenyl, -CO-C 1 -C ₄ -alkyl-NR ⁸ R ⁹ , -SO ₂ OH, -SO ₂ -C ₁ -C ₄ -alkyl, or -SO ₂ -phenyl group;

R ⁶ may be phenyl, wherein the phenyl ring may be substituted with halogen, preferably fluorine or chlorine, hydroxy, C 1 -C 4 alkyl, C ₁ -C ₄ -alkyloxy or NR ⁸ R ⁹ ;

R ⁶ may be phenyl-C ₁ -C ₃ -alkyl-, preferably benzyl, wherein the phenyl ring may be substituted by halogen, preferably chlorine or fluorine, hydroxy, C ₁ -C ₄ alkyl, C ₁ -C ₄ -alkyloxy, benzyloxy, phenyloxy, NR ⁸ R ⁹ , -OCO-C 1 -C 4 alkyl, -OCO-phenyl, -OCO-benzyl, -OCO-pyridyl, -OC ₂ -C ₄ -alkylene, -CO-C 1 -C 4 alkyl, -C ₁ -C ₄ alkyl NR ⁸ R ⁹ , C 1 -C 6 -alkyl-OH,

-C 1 -C 6 -alkylkOH, -COOH, -COO-C 1 -C 4 alkyl, -COO-phenyl, -COO-benzyl, -CONR ⁸ R ⁹ , -CO-C 1 -C 4 -alkyl-NR ⁸ R ⁹ , - SO ₂ OH, -SO ₂ -C ₁ -C ₄ -alkyl, or -SO ₂ -phenyl;

R ⁶ may be a single bond, or a cyclopentyl, cyclohexyl, cyclohexyl-C 1 -C 4 alkyl, preferably cyclohexylmethyl, cyclopentanone, cyclohexanone, hydroxycyclopentane or hydroxycyclohexane bonded via a C 1 -C 4 alkylene bridge;

R ⁶ may be a single bond, or via a C 1 -C 4 alkylene bridge bound furan, tetrahydrofuran, α-pyran, γ-pyran, dioxolane, tetrahydropyran, dioxane, thiophene, thiolane, dithiolane, pyrrole, pyroline, pyrrolidine, pyrazole pyrazoline, imidazole, imidazoline, imidazolidine, triazole, pyridine, piperidine, pyridazine, pyrimidine, pyrazine, piperazine, triazine, morpholine, thiomorpholine, oxazole, isoxazole, oxazine, thiazole, isothiazole, thiadiazole, oxadiazole or pyrazolidine;

^R6 denotes -CHO, -COOH, -COOC ^ C ^ alkyl, -COO-phenyl, -COO-benzyl, -CONH-C ^ C ^ alkyl, -CO-N (C ₁ -C ₄ alkyl) ₂ , or -CO-NH-phenyl;

R ⁶ can be an amine having the formula NR ⁸ R ⁹ ;

-35R ⁸ denotes hydrogen, branched or unbranched alkyl having 1 to 4 carbon atoms;

R ⁸

can be a carbon-bonded pyrrole, pyroline, pyrrolidine, pyrazole, pyrazoline, imidazole, imidazoline, imidazolidine, triazole, pyridine, piperidine, pyridazine, pyrimidine, pyrazine, piperazine, morpholine, oxazole, isoxazole, thiazole, isothiazole, or thiadiazole, or thiadiazole chloro, bromo, C 1 -C 4 alkyl, C 1 -C 4 alkyloxy, NO ₂ , NH ₂ , or OH;

R ⁹ can be hydrogen, a branched or unbranched alkyl group having 1 to 4 carbon atoms;

R ⁹

can be a carbon-bonded pyrrole, pyroline, pyrrolidine, pyrazole, pyrazoline, imidazole, imidazoline, imidazolidine, triazole, pyridine, piperidine, pyridazine, pyrimidine, pyrazine, piperazine, morpholine, oxazole, isoxazole, thiazole, isothiazole, or thiadiazole, or thiadiazole chlorine, bromine, C 1 -C 4 alkyl, C 1 -C 4 alkyloxy, NO ₂ , NH ₂ , or OH, or

R ⁸ and R ⁹ together with the nitrogen atom form a saturated or unsaturated 5 or 6 membered ring which, as further heteroatoms, may contain nitrogen or oxygen, said hetero ring may be substituted by a branched or unbranched alkyl group having 1 to 4 carbon atoms, preferably methyl , or a radical - (CH _{2) first 4-} phenyl, preferably benzyl, optionally in the form of their racemates, their enantiomers, in the form of diastereomers and mixtures thereof, optionally in the form of their pharmacologically acceptable acid addition salts.

Further preferred are compounds having the general formula (Ib)

in which

R ² denotes hydrogen, CJC-alkyl, phenyl, benzyl, where the phenyl ring is optionally substituted by fluorine, pyridyl, piperidinyl, morpholinyl, piperazinyl, 4-benzylpiperazinyl, furyl, tetrahydrofuranyl, tetrahydropyranyl, NR ⁸ R ^9, cyclopentyl, cyclohexyl, adamantyl, noradamantyl, norbornyl or norbornenyl;

R ³ can be hydrogen, C 1 -C 4 -alkyl or benzyl;

R ⁴ can be hydrogen, C 1 -C 4 -alkyl or benzyl;

R ⁶ may be hydrogen, C 1 -C 4 alkyl, preferably methyl, and may be optionally substituted by chlorine, fluorine, hydroxy, C 1 -C 6 alkoxy, NR ⁸ R ⁹ , furthermore denote -CHO, -COOH, -COO- C ₁ -C ₄ -alkyl, preferably -COOCH _3, phenyl or phenyl-C _r C ₃ alkyl substituted by fluorine or benzyloxy, preferably benzyl, phenyloxy-C ₁ -C ₃ alkyl optionally substituted by methoxy, preferably phenyloxymethyl, benzyloxy-C ₁ -C ₃ -alkyl optionally substituted by methoxy, preferably benzyloxymethyl, benzyloxybenzyl, benzoyloxymethyl, pyridylcarbonyloxymethyl, cyclopentyl, furyl, cyclohexylmethyl, pyridylmethyl, N-pyrrolylmethyl or N-morpholinomethyl;

R ⁸ can be hydrogen, C 1 -C 4 alkyl or pyridyl;

-37R ⁹ denotes hydrogen, C ^ C ^ alkyl or pyridyl, optionally in the form of the racemates, the enantiomers, the diastereomers and mixtures thereof, and optionally the pharmacologically acceptable acid addition salts thereof.

Further preferred are compounds having the formula (Ia)

in which

R ¹ can be hydrogen, C ₁ -C ₃ -alkyl or benzyl;

R ² may be hydrogen, C 1 -C 4 alkyl, phenyl, benzyl, wherein the phenyl ring may be optionally substituted by fluorine, pyridyl, piperidinyl, morpholinyl, piperazinyl, 4-benzylpiperazinyl, furyl, tetrahydrofuranyl, tetrahydropyranyl, NR ⁸ R ⁹ , cyclopentyl, cyclohexyl, adamantyl, noradamantyl, norbornyl or norbornenyl;

R ⁴ can be hydrogen, C 1 -C 6 -alkyl or benzyl;

R ⁶ denotes H, O ^ C ^ alkyl, preferably methyl, which is optionally substituted with chloro, fluoro, hydroxy, CLC alkyloxy, NR ⁸ R ^9; denotes -CHO, -COOH, -COO-ClC ^ alkyl, preferably -COOCH ₃ , phenyl, optionally phenyl-C 1 -C 6 -alkyl, substituted with fluorine, or benzyloxy, preferably benzyl, phenyloxy-C 1 -C 6 -alkyl optionally substituted with methoxy,

preferably phenyloxymethyl, benzyloxy-C1-C4-alkyl optionally substituted by methoxy, preferably benzyloxymethyl, benzyloxybenzyl, benzoyloxymethyl, pyridylcarbonyloxymethyl, cyclopentyl, furyl, cyclohexylmethyl, pyridylmethyl, N-pyrrolylmethyl or N-morpholinomethyl;

R ⁸ can be hydrogen, C 1 -C 4 alkyl or pyridyl;

R ⁹ can be hydrogen, C 1-6 alkyl or pyridyl, optionally in the form of their racemates, their enantiomers, in the form of their diastereomers and mixtures thereof, optionally as their pharmacologically acceptable acid addition salts.

Of note are other compounds having the general formula (Ic)

R ¹ denotes hydrogen or C ^ alkyl;

R ² can be hydrogen, C 1 -C 4 alkyl, cyclopentyl, cyclopentanone, hydroxycyclopentane, furan or benzyl;

R ⁵ can be C 1 -C 6 -alkyl, preferably C 1 -C 6 -alkyl, more preferably methyl, ethyl or tertiary butyl;

- 39R ⁶ denotes hydrogen, benzyl or cyclopentyl, optionally in the form of the racemates, the enantiomers, the diastereomers and mixtures thereof, and optionally the pharmacologically acceptable acid addition salts thereof.

Of note are other compounds having the general formula (Id)

ABOUT

in which

R ¹ can be hydrogen or C 1 -C 6 -alkyl;

R ² can be hydrogen, C 1 -C 4 alkyl, cyclopentyl, cyclopentanone, hydroxycyclopentane, furan or benzyl;

may be C 1 -C 6 -alkyl, preferably C 1 -C 6 -alkyl, more preferably methyl, ethyl or tertiary butyl;

R ⁶ may be hydrogen, benzyl or cyclopentyl, optionally in the form of their racemates, their enantiomers, in the form of their diastereomers and mixtures thereof, optionally as their pharmacologically acceptable acid addition salts.

Further preferred are compounds having the general formula (Ib)

in which

R ² denotes hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, t-butyl, phenyl, benzyl, 4-fluorobenzyl, pyridyl, N-piperidinyl, N-morpholinyl, N-piperazinyl, 4benzylpiperazinyl, 2-furyl, 3-tetrahydrofuranyl, 4-tetrahydropyranyl, -NMe ₂ , cyclopentyl, cyclohexyl, adamantan-1-yl, noradamantan-3-yl, norboran-2-yl or 5-norbornen-2-yl;

R ³ can be hydrogen, methyl, ethyl, n-propyl or benzyl;

R ⁴ denotes hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, t-butyl, n-pentyl

or benzyl;

R ⁶ denotes hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, t-butyl, phenyl, benzyl, cyclopentyl, 2-furyl, 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, cyclohexylmethyl, phenylethyl, N-morpholinomethyl, N-pyrrolylmethyl, (3-pyridyl) -NH-CH _{2, phenyl-CO-O-CH2} -, pyridyl-CO-O-CH _2, phenyl-O-CH ₂ -, (4 -MeO-phenyl) -O-CH ₂ -, (4-MeOphenyl) -CH ₂ -O-CH ₂ -, (4-phenyl-CH ₂ -O-phenyl) -CH ₂ -, 4-F-phenyl- CH ₂ -, 3,4-F-phenyl-CH ₂ -, -COOH, -COOMe, -CH ₂ -OH, -CH ₂ -OMe, -CH ₂ -O-Et, or -CH ₂ -NMe ₂ , optionally in the form of their racemates, their enantiomers, in the form of their diastereomers and mixtures thereof, optionally also as their pharmacologically acceptable acid addition salts.

Of particular note are also compounds having the general formula (Ia)

in which

R ¹ can be hydrogen, methyl, ethyl, n-propyl, or benzyl;

R ² denotes hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, t-butyl, phenyl, benzyl, 4-fluorobenzyl, pyridyl, N-piperidinyl, N-morpholinyl, N-piperazinyl, 4- benzylpiperazinyl, 2-furyl, 3-tetrahydrofuranyl, 4-tetrahydropyranyl, -NMe ₂ , cyclopentyl, cyclohexyl, adamantan-1-yl, noradamantan-3-yl, norboran-2-yl or 5-norbornene-

2-yl;

R ⁴

it may be hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, tert-butyl, n-pentyl or benzyl;

R ⁶ denotes hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, t-butyl, phenyl, benzyl, cyclopentyl, 2-furyl, 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, cyclohexylmethyl, phenylethyl, N-morpholinomethyl, N-pyrrolylmethyl, (3-pyridyl) -NH-CH _{2, phenyl-CO-O-CH2} -, _{pyridyl-CO-O-CH2} -, _phenyl-CH2-O -, ( 4-MeO-phenyl) -O-CH ₂ -, (4-MeOphenyl) -CH ₂ -O-CH ₂ , (4-phenyl-CH ₂ -O-phenyl) -CH ₂ -, 4-fural-phenyl- CH ₂ -, 3,4-F-phenyl-CH ₂ , -COOH, -COOMe, -CH ₂ -OH, -CH ₂ -OMe, -CH ₂ -O-Et, or -CH ₂ -NMe ₂ , optionally in the form of their racemates, their enantiomers, their diastereomers and mixtures thereof, optionally also as their pharmacologically acceptable acid addition salts.

Preference is further given to compounds having the general formula (1b)

in which

R ² denotes hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, t-butyl, phenyl, benzyl, 4-fluorobenzyl, pyridyl, N-piperidinyl, N-morpholinyl, N-piperazinyl, 4benzylpiperazinyl, 2-furyl, 3-tetrahydrofuranyl, 4-tetrahydropyranyl, -NMe ₂ , cyclopentyl, cyclohexyl, adamantan-1-yl, noradamantan-3-yl, norboran-2-yl or 5-norbornen-2-yl;

R ³ can be hydrogen;

R ⁴ denotes hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, t-butyl, n-pentyl or benzyl;

R ⁶ denotes hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, t-butyl, phenyl, benzyl, cyclopentyl, 2-furyl, 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, cyclohexylmethyl, 2-phenylethyl, N-morpholinomethyl, N-pyrrolylmethyl, (3-pyridyl) -NH-CH ₂ -, phenyl-CO-O-CH ₂ -, _{3-pyridyl-CO-O-CH2} -, phenyl-O- CH ₂ -, (4-MeO-phenyl) -O-CH ₂ -, (4MeO-phenyl) -CH ₂ -O-CH ₂ , 4-F-phenyl-CH ₂ -, 3,4-F-phenyl- CH ₂ -, -CH ₂ -OH, -CH ₂ -OMe, -CH ₂ -O-Et, -CH ₂ -NMe ₂ , -COOMe, or -COOH, optionally in the form of their racemates, their enantiomers, in the form of their diastereomers and mixtures thereof, optionally as pharmacologically acceptable acid addition salts thereof.

Of particular note are particularly compounds having the general formula (Ia)

in which

R ¹ can be hydrogen;

R ² denotes hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, t-butyl, phenyl, benzyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, N-piperidinyl, N-morpholinyl, N-piperazinyl, 4-benzylpiperazinyl, 3-tetrahydrofuranyl, 4-tetrahydropyranyl, -NMe ₂ , cyclopentyl, cyclohexyl, adamantan-1-yl, noradamantan-3-yl, norboran-2-yl or 5-norbornene-

2-yl;

R ⁴ denotes hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, t-butyl, n-pentyl or benzyl;

R ⁶ denotes hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, t-butyl, phenyl, benzyl, cyclopentyl, 2-furyl, 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, cyclohexylmethyl, phenylethyl, N-morpholinomethyl, N-pyrrolylmethyl, (3-pyridyl) -NH-CH _2, phenyl-CO-O-CH ₂ -, _{3-pyridyl-CO-O-CH2} -, phenyl-O-CH ₂ - , (4-MeO-phenyl) -O-CH ₂ -, (4-MeO-phenyl) -CH ₂ -O-CH _2, 4-F-phenyl-CH ₂ -, 3,4-F-phenyl-CH _2, -COOH, -COOMe, -CH ₂ OH, -CH ₂ -OMe, -CH ₂ -O-Et, or -CH ₂ -NMe ₂ , optionally in the form of their racemates, their enantiomers, in the form of their diastereomers and mixtures thereof, optionally as pharmacologically acceptable acid addition salts thereof.

The invention of the group of novel compounds also relates to the basis of formulas (Ia) to (Id).

ABOUT

(Id)

Preferred are derivatives of the general formula

ABOUT

having substituents at the 2, 4 and 6 positions.

The compounds of formulas (Ia) to (Id) may optionally be converted into their salts, in particular for pharmaceutical use, into their physiologically acceptable salts with an inorganic or organic acid. Suitable acids can be, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, acetic acid, fumaric acid, acid

succinic acid, lactic acid, citric acid, tartaric acid, or maleic acid. However, mixtures of these acids may also be used.

Suitable alkyl groups (also as part of other radicals) are branched and unbranched alkyl groups having 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms, for example methyl, ethyl, n-propyl, i-propyl, butyl, ibutyl , sec-butyl, tert-butyl, pentyl, i-pentyl, hexyl, heptyl and octyl.

Substituted alkyl groups, unless otherwise specified, may (as part of other moieties) carry, for example, one or more of the following substituents: halogen, hydroxy, mercapto, Ο, -C 8 -alkyloxy, amino, alkylamino, dialkylamino, cyano, nitro , = O, -CHO, -COOH, -COO-C 1 -C 6 -alkyl, -SC 1 -C 6 -alkyl.

Suitable alkenyl groups (also as part of other radicals) are branched or unbranched alkenyl groups having 2 to 10 carbon atoms, preferably 2 to 3 carbon atoms, and containing at least one double bond, for example also the above alkyl groups if they have at least one a double bond such as vinyl (unless it forms an unstable enamine or enol ether), propenyl, i-propenyl, butenyl, pentenyl, hexenyl.

Substituted alkenyl groups, unless otherwise indicated, may (as part of other moieties) carry, for example, one or more of the following substituents: halogen, hydroxy, mercapto, C1-C6-alkyloxy, amino, alkylamino, dialkylamino, cyano, nitro, = O, -CHO, -COOH, -COO-C _r C ₆ -alkyl, -S0, -C alkyl.

Suitable alkynyl groups (also as part of other radicals) are branched or unbranched alkynyl groups having 2 to 10 carbon atoms and containing at least one triple bond, for example ethynyl, propargyl, butynyl, pentynyl, hexynyl.

Substituted alkynyl groups, unless otherwise indicated, may (as part of other moieties) carry, for example, one or more of the following substituents: halogen, hydroxy, mercapto, C ₁ -C ₆ -alkyloxy, amino, alkylamino, dialkylamino, cyano, nitro, = O, -CHO, -COOH, -COO-C 1 -C 8 -alkyl, -SC 1 -C 8 -alkyl.

A cycloalkyl radical having 3 to 6 carbon atoms is, for example, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, which may also be substituted by a branched or unbranched alkyl group having 1 to 4 carbon atoms, a hydroxy group and / or halogen, or a substitution as defined above. Halogen is generally understood to mean fluorine, chlorine, bromine or iodine.

The term aryl refers to an aromatic ring system of 6 to 10 carbon atoms and, unless otherwise indicated, may bear one or more of the following substituents: C 1 -C 6 -alkyl, C 1 -C 6 -alkyloxy, halogen, hydroxy, mercapto,

amino, alkylamino, dialkylamino, CF ₃ , cyano, nitro, -CHO, -COOH, -COOC 1 -C 6 -alkyl, -S-C 1 -C 6 -alkyl. Preferred aryl is phenyl.

Examples of the nitrogen-bonded cyclic radical of the formula NR ⁸ R ⁹ include: pyrrole, pyrroline, pyrrolidine, 2-methylpyrrolidine, 3-methylpyrrolidine, piperidine, piperazine, N-methylpiperazine, N-ethylpiperazine, N- (n-propyl) piperazine, N-benzylpiperazine, morpholine, thiomorpholine, imidazole, imidazoline, imidazolidine, parazole, pyrazoline, pyrazolidine, preferably are morpholine, N-benzylpiperazine, piperazine and piperidine, wherein said heterocyclic radicals may also be substituted with C 1 -C 4 alkyl, preferably methyl, or may be substituted as previously defined.

Examples of the carbon-bonded 5-6 membered heterocyclic ring which may contain nitrogen, oxygen or sulfur as heteroatoms are: furan, tetrahydrofuran, 2-methyltetrahydrofuran, 2-hydroxymethylfuran, tetrahydrofuranone, γbutyrolactone, α-pyran, γ-pyran, dioxalan , tetrahydropyran, dioxane, thiophene, dihydrothiophene, thiol, dithiolane, pyrrole, pyrrole, pyrrolidine, pyrazole, pyrazoline, imidazole, imidazoline, imidazolidine, triazole, tetrazole, pyridine, piperidine, pyridazine, pyrimidine, pyrazine, piperazine, triazine, triazine, triazine, triazine , thiomorpholine, oxazole, isoxazole, thiazole, isothiazole, thiadiazole, oxadiazole, pyrazolidine, wherein the heterocycle may be substituted as described above.

The term ^1-O "is an oxygen atom, a double bond.

The compounds of the present invention are characterized by an affinity for adenosine receptors and thus represent a novel class of adenosine antagonists.

In general, adenosine antagonists can provide the desired therapeutic effect in diseases or pathologies that are associated with the activation of adenosine receptors.

The high receptor affinity and receptor selectivity of the individual claimed compounds allow lower drug doses to be administered in Alzheimer's disease and SDAT, thereby almost avoiding side effects, thereby avoiding back blockade of α, -receptors.

Unexpectedly, the compounds of the invention demonstrated affinity for the adenosine _{β 3} -receptor. Β ₃ -receptor antagonists inhibit _{β 3} -receptor activation, caused by mast cell degranulation, and are therefore therapeutically useful in all diseases and pathologies associated with mast cell degranulation; as anti-inflammatory agents, in hypersensitivity reactions such as asthma, allergic rhinitis, urticaria, reperfusion heart damage, scleroderma, arthritis, autoimmune diseases, inflammatory bowel diseases, and others.

Cystic fibrosis - also known as mucovisidosis - is an inherited metabolic disorder caused by genetic damage to a particular chromosome. Increased production and increased viscosity of mucosal secretions in this disease can cause severe airway complications in the bronchi. Initial experiments have shown that α-antagonists increase the efflux of chloride ions in, for example, CF PAC cells. Based on this finding, it can be expected that in patients suffering from said cystic fibrosis, the compounds of the invention can regulate the electrolyte management of the cells and thus alleviate the symptoms of the disease.

The Α1 -receptor binding values found were determined analogously to Ensinger et al. In Cloning and Functional Characterization of Human A, Adenosine Receptor - Biochemical and Biophysicyl Communications, Vol. 187, No. 2, 919-926 (1992) ”and are summarized in Table 20.

Table 21 summarizes the results of the A ₃ receptor binding values obtained in a similar manner to that described by Salvatore et al., "Molecular Cloning and Characterization of the Human A ₃ -Adenosine Receptor" (Proc. Natl. Acad. Sci USA). 90, 10365-10369 (1993)).

New compounds having the formulas (Ia) to (Id) may be administered orally, transdermally, by inhalation or parenterally. The compounds of the invention serve as the active ingredient in conventional dosage forms, for example in compositions consisting essentially of an inert pharmaceutical carrier and an effective dose of the active compound; suitable dosage forms are, for example, tablets, dragees, capsules, cachets, powders, solutions, suspensions, emulsions, syrups, suppositories, transdermal systems and the like. Effective dosages of the compounds of this invention when administered orally are between 1 and 100 mag / dose, preferably between 1 and 50, more preferably between 5 and 30 mg / dose, for intravenous or intramuscular

administered between 0.001 and 50 mg / dose, preferably between 0.1 and 10 mg / dose. For inhalation, solutions of the compounds of the present invention, when they contain from 0.01 to 0.1, are suitable

1.0, preferably 0.1 to 0.5% of active ingredient. For inhalation applications, the use of powders is preferred. At the same time, the compounds of the invention may be used as infusion solutions, preferably in physiological saline solution or in nutrient salt solution.

The compounds of the invention may be prepared as follows. For the synthesis of both isomers

which have the formulas (Ia) and (Ib), wherein the substituents are as defined above, are as follows.

In the first reaction step, the aminoguanidine (1) is reacted with a carbonic acid derivative of general formula (2) to give a triazole of general formula (3)

-49 (Scheme 1). This reaction can be carried out according to published instructions in J. Chem. Soc. 816 (1929); J. Org. Chem. 1729 (1926) or Org. Synthesis 26, 11.

Scheme 1

R = COOH or

R - CN (1) (2) step 1

----------- p.

(3)

Then, in a second reaction step, the triazole of formula (3) is reacted with an alkyl cyanoacetate by a cyclization reaction in an alkaline medium to give the triazolopyrimidine of formula (4) (Scheme 1).

2) ·

Scheme 2

Alkali metal or alkaline earth metal alcoholates can be used as the alkali reactants, for example, methoxides, ethanolates, isipropanolates, n-, sec-, tert-butyl alcoholates. Suitable alkali and alkaline earth metals are, for example, lithium, sodium, potassium, magnesium, calcium. Preference is given to the use of sodium methoxide, sodium ethoxide, sodium isopropanolate and potassium tert-butanolate. Further, hydrides can be used as bases according to the invention

-50 alkali and corrosive earth metals. Sodium, lithium, potassium as well as magnesium and calcium hydrides are preferred. Suitable inert solvents are dimethylformamide, dimethylacetamide, methylene chloride, tetrahydrofuran. Further, alkali metal and alkaline earth metal hydroxides such as lithium, sodium, potassium, as well as magnesium, calcium, preferably sodium hydroxide, potassium hydroxide, lithium hydroxide and calcium hydroxide, in an alcoholic or aqueous solution can be used as bases.

In addition to the cyanoacetic acid alkyl esters, cyanoacetic acid can also be used. The mixture thus obtained is stirred at room temperature for 0.5 to 4 hours, preferably 1 to 2 hours. Then, a compound of the general formula is added

(3) and the reaction mixture is stirred for 2 to 12 hours, preferably 4 to 6 hours, preferably at reflux temperature. At room temperature, the reaction mixture is then diluted with water and acidified, then the solid is filtered off, washed and dried. Suitable acids are, for example, formic acid, acetic acid, or mineral acids such as hydrochloric acid or sulfuric acid.

In a third reaction step, the residues R ⁴ and R ⁵ are introduced into the triazopyrimidine of formula (4) to give compounds of formulas (5) and (12) (Scheme 3).

Scheme 3

To this end, the compound having the general formula (4) is dissolved in 5 to 40 times, preferably in 10 to 20 times the amount of a polar solvent such as dimethylformamide, dimethylacetamide, methylene chloride, tetrahydrofuran, preferably

Anhydrous or absolute dimethylformamide is particularly preferred. The solution obtained is mixed with a base and an appropriate amount of an alkylating agent. As a base, alkali metal and alkaline earth metal carbonates of lithium, sodium, potassium, calcium such as sodium carbonate, lithium carbonate, potassium carbonate, calcium carbonate, preferably potassium carbonate can be used. Further, lithium, sodium and potassium bicarbonates can also be used. Alkali and alkaline earth metal hydroxides of lithium, sodium, potassium, magnesium, calcium, preferably sodium hydroxide, potassium hydroxide, lithium hydroxide and calcium hydroxide, in an alcohol or water environment are also useful. Further alkali and alkaline earth metal alcoholates can be considered in the second reaction step. In addition, the aforementioned alkali and alkaline earth hydrides may be used, preferably in inert solvents such as dimethylformamide, dimethylacetamide, methylene chloride, ethers, tetrahydrofuran and toluene.

As alkylating agents, alkyl halides such as alkyl chloride, alkyl bromide, especially alkyl iodide, as well as alkylsylate, -methylate, -triflate, -dialkyl sulfate may be used. The alkyl radical of the alkylating agent corresponds to the above definitions of R ⁴ and R ⁵ . The reaction mixture is stirred for 0.5 to 4 days, preferably 1 to 2 days at room temperature, and then concentrated to dryness. Further, the mixture can be worked up by stirring the residue with water and a solvent, for example a halogenated solvent such as carbon tetrachloride, methylene chloride, preferably methylene chloride, by filtration to isolate the compound of formula (5) as a solid. From the filtrate the solvent of formula (12) is then removed by removal of the solvent. In the event that no solid is precipitated, further to isolate the compound of formula (12) from the filtrate, the aqueous solution is mixed with a halogenated solvent, preferably methylene chloride, and extracted; the combined organic extracts are dried and further processed by purification. After chromatographic purification of the residues, compounds of general formula (5) and (12) are obtained (Scheme 3).

Nitrosating the compound having the general formula (5) yields the compound having the general formula (6) in the fourth reaction step (Scheme 4).

-52Scheme 4

Two variants of the preparation method are suitable for this purpose according to the invention.

Reaction step 4, process for preparation of variant A

The compound of formula (5) is dissolved or suspended in a polar solvent, the above solvents and dimethylacetamide or alcohol being used as the polar solvent, for example methanol, ethanol, propanol, isopropanol or butanol are preferred. Dimethylformamide is particularly preferred. The use of selected solvents in anhydrous form or as absolute solvents is recommended. The resulting mixture is cooled below 0 ° C, preferably below -5 ° C. To this mixture is added a nitrosating agent, for example an alkyl nitrite such as methyl-, ethyl-, η-propyl-, isopropyl-, η-butyl-, sec-butyl-, tert-butyl- and pentylnitrite, preferably isoamylnitrite, with the temperature being preferred not rise above 0 ° C. The mixture is then stirred at this temperature for 2 to 48 hours, preferably 4 to 24 hours, more preferably 8 to 12 hours. The reaction mixture may then optionally be stirred at room temperature to complete the reaction. The solvent is then removed in vacuo, the residue is stirred in a solvent such as diethyl ether, filtered, washed with water and the residue thus obtained is dried under vacuum.

Reaction step 4, process for preparation of variant B

The compound of formula (5) is stirred into an aqueous acid solution, wherein the acid may be organic acids, formic acid,

Acetic acid, preferably acetic acid, and inorganic acids such as hydrochloric acid or dilute sulfuric acid, preferably hydrochloric acid, as well as mixtures thereof. The reaction mixture is heated to 30 to 100 ° C, preferably to 50 to 80, more preferably to 70 ° C and mixed with a nitrosating agent, preferably sodium nitrite, more preferably sodium nitrite in water, and maintained at said temperature of 0.5 to 2 ° C. hours, then preferably one hour at 0 to 20 ° C, preferably at 5 to 15 ° C, more preferably at 10 ° C. The product is then filtered off, the filter residue is washed and dried under vacuum.

The fifth reaction step is followed by reduction of the nitroso compound (6) to a diamine derivative having the general formula (7) (Scheme 5).

Scheme 5:

The following variants of the preparation method are applicable, among others

Reaction step 5, process for preparation of variant A

The nitro compound (6) is suspended in water with stirring and reacted with a suitable reducing agent. Suitable reducing agents are dithionite in acidic or basic solution. Ammonium sulfite, lithium sulfite, sodium sulfite, potassium bisulfite, triethylphosphite, triphenylphosphine or lithium aluminum hydride may also be used. The nitroso group can also be hydrogenated with hydrogen using transition metal catalysts such as palladium, platinum, nickel, rhodium, or by hydrogen transfer, for example with cyclohexene or ammonium formate.

I

- 54i as sources of hydrogen. Sodium dithionite is preferred. Alkali metal and alkaline earth metal hydroxide solutions, for example lithium, sodium, potassium or magnesium hydroxide, calcium and barium hydroxide solutions may also be used as bases in addition to the aqueous ammonia solutions which are preferably used, preferably dilute solutions. Furthermore, methyl, ethyl, isopropyl, η-propyl, iso-butyl, tert-butyl, n-butyl alcoholates of the above-mentioned alkali metals and alkaline earth metals can be used. Said suspensions are heated to 20 to 100 ° C, preferably to 50 to 90, more preferably to 60 to 80 ° C, and admixed with the acid, preferably initially, more preferably in the first 30 minutes. Useful acids include inorganic acids such as hydrochloric acid and sulfuric acid as well as organic acids such as formic acid and acetic acid as well as mixtures thereof, with sulfuric acid being preferred, more preferably 50% sulfuric acid. The resulting mixture was heated to reflux temperature to complete the reaction. Upon cooling, the product precipitates as semisulfate. Further, the product can be precipitated by neutralization with an aqueous base solution, for example lithium hydroxide, sodium hydroxide, potassium hydroxide, preferably sodium hydroxide, more preferably a 30% (w / w) aqueous sodium hydroxide solution, and filtered as the free base.

Reaction step 5, process for preparation of variant B

To the mixture of the aqueous solution of the base and the alcohol is added with stirring the nitroso compound (6). After the nitroso compound is dissolved or suspended in said medium, a reducing agent is added, preferably in solution. As the reducing agent, the reagents of variant A may be used, with aqueous sodium dithionite solution being particularly preferred. Thereafter, the reaction mixture is stirred at room temperature for 0.5 to 6 hours, preferably 1 to 4, more preferably 1.5 to 3 hours. The precipitated product is isolated by filtration.

In a sixth reaction step isomeric compounds (8) are prepared from a diamine of formula (7) (Scheme 6).

-55Scheme 6

NH ₂

NHCOR ²

To carry out said reaction step, the amino compound of formula (7) is suspended in an organic solvent and reacted with an organic base. Thereafter, the mixture is kept at room temperature for 40 to 60 minutes, preferably 20 to 50 minutes, more preferably 25 to 45 minutes; then the mixture is cooled to 0 to 15 ° C, preferably to 5 to 15 ° C and reacted with a carboxylic acid derivative, the residue R ² being as defined above. Suitable organic solvents are dimethylformamide, dimethylacetamide, methylene chloride, toluene and tetrahydrofuran, with the use of dimethylformamide being preferred, even more preferably the use of absolute dimethylformamide. Suitable organic bases are dimethylaminopyridine, pyridine, a tertiary amine, for example trimethylamine, triethylamine, diisopropylethylamine, DBU (diazabicycloundecene), or any of the aforementioned inorganic bases, in particular alkali metal and alkaline earth metal carbonates or bicarbonates thereof. Dimethylaminopyridine is particularly suitable as a base.

The carbonic acid derivatives according to the invention are carboxylic acid halides, preferably carboxylic acid chlorides, but also carboxylic acids, if activated appropriately. Activation can be achieved by reaction with chloroformic esters, carbonyldiimidazole, carbodiimides, for example dicyclohexylcarbodiimide, EDAC, or benztriazoles, for example HOBt (1-hydroxy-

1-H-benzotriazole) and TBTU. The corresponding aldehyde can also be used in place of the carboxylic acid derivative and the intermediate can be oxidized with ferric chloride, azodicarboxylic acid esters and other oxidizing agents. The reaction mixture is then stirred for 0.5 to 4 hours, preferably 1 to 3 hours, more preferably 2 hours at 5 to 20 ° C, preferably at 7 to 15 ° C, more preferably at 10 ° C, and allowed to stir at room temperature over night. The solvent is then removed in vacuo. The residue after removal of the solvent is stirred with water, the solid is filtered off, washed and optionally purified by recrystallization or chromatography, preferably by column chromatography.

In the seventh reaction step, a cyclization reaction (ring-closing reaction) of a compound having the general formula (6), (7), or (8) to a compound of the general formula (9) is carried out using methods A to C (Scheme 7). .

Scheme 7

Method C

Reaction Step 7, Preparation A

The compound of formula (8) is suspended in an alcohol and heated for 24 hours with a base at reflux temperature. After cooling, the reaction mixture is acidified, the solid is filtered off and dried. The product is optionally purified by recrystallization or chromatography, preferably by column chromatography. Suitable bases include alkali and alkaline earth metal hydroxides, for example lithium, sodium, potassium, calcium and barium hydroxides, as well as mixtures thereof, in the form of aqueous solutions or optionally in admixture with an alcohol and / or water miscible ether. Suitable alcohols are methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol. Suitable ethers include, in particular, a cyclic ether, for example tetrahydrofuran, dioxane.

The cyclization reaction can be carried out in a similar manner using inorganic acid chlorides such as thionyl chloride, phosphorus oxychloride and phosphorus pentachloride, as well as polyphosphoric acid.

Another similar method is based on the reaction of the carboxylic acid amide in an acidic medium with a mineral acid / methanol, preferably hydrochloric acid / methanol, or in an alkaline metal / methanol, preferably sodium / methanol, environment and subsequent thermal cyclization.

Reaction Step 7, Preparation B

Starting from the diamine (7), a compound (9) with R ² equal to hydrogen can be prepared by another method. In an embodiment, compound (7) is mixed with an equimolar amount, preferably with an excess of formamide, for 0.5 to 3 hours, preferably 1 to 2 hours, more preferably 1.5 hours at 50 to 250 ° C, preferably 100 to 225 ° C, more preferably between 180 and 200 ° C. Excess formamide is distilled off in vacuo and the evaporation residue is stirred in water. The solid is filtered off, washed with water and the resulting solid product is optionally purified by recrystallization or chromatography, preferably column chromatography.

Reaction Step 7, Preparation C

Furthermore, a compound of formula (9) is directly accessible from a nitroso compound having the formula (6) when R ² is NR ⁸ R ⁹ , wherein R ⁸ and R ⁹ are as defined above.

Phosphorus oxychloride is added to a solution of the desired N-formylamine in Diglyme at minus 10 to plus 20 ° C, preferably at minus 5 to plus 5, more preferably at 0 ° C. The reaction mixture is then stirred with cooling in an ice bath and nitroso compound (6) is added. The mixture is stirred for 15 to 120 minutes, preferably 30 to 80 minutes, more preferably 40 to 60 minutes, at 30 to 120 ° C, preferably at 50 to 100 ° C, more preferably at 70 to 80 ° C; then the mixture is diluted with ice water. The solid product is filtered off, washed and dried; the product is optionally purified by recrystallization or chromatography, preferably by column chromatography.

Compounds of formula (Ia) and (Ib) are available by the eighth reaction step from a compound of formula (9) (Scheme 8).

Scheme 8

For the above preparation, the starting compound is dissolved in an organic solvent and reacted with a suitable alkylating agent using a base. The reaction mixture was allowed to stir at room temperature. Alternatively, it can also be operated at elevated temperature. The reaction time will depend on the conditions and may be up to one week. After complete reaction, the batch is concentrated to dryness. The residue is stirred into an aqueous basic solution, using as a base lithium hydroxide, sodium hydroxide, potassium hydroxide, preferably sodium hydroxide, and more preferably 2M sodium hydroxide solution. The solution is then washed with a non-polar organic solvent such as benzene, toluene, xylene, preferably toluene, and the pH is adjusted to 6. The precipitated solid is filtered off and optionally purified by chromatography, preferably by column chromatography. In this way, a dialkylated product as well as a monoalkylated product of a compound of formula (Ia) and (Ib) can be prepared and isolated.

As the organic solvent in the alkylation reaction, an inert solvent such as dimethylformamide, dimethylacetamide, methylene chloride, alkyl ether, preferably diethyl ether, tetrahydrofuran, benzene, toluene, xylene and most preferably dimethylformamide can be used. Suitable bases are, for example, carbonates such as lithium carbonate, sodium carbonate, potassium carbonate, calcium carbonate, as well as the bicarbonates of the aforementioned alkali and alkaline earth metals, as well as their hydroxides and alcoholates. Preferred are the alkali and alkaline earth metal alcoholates with methanol, isopropanol, tert-butanol, sodium methoxide being particularly preferred. In the case of carbonate, bicarbonate, alcoholate and hydroxide, it may be preferable to use alcohol or water as solvent. Other bases useful in the alkylation include sodium hydride, potassium hydride, lithium hydride, calcium hydride in the above-mentioned inert solvents. Furthermore, hydrocarbon halides such as alkyl chlorides, alkyl bromides, alkyl iodides as well as hydrocarbon (s) may be used as alkylating agent. alkyl tosylate, -methylate, -triflate, and alkyl sulphate; alkyl iodide is preferred.

The invention further relates to a process for the preparation of compounds having the general formulas (Id) and (Ic).

Starting from a compound having the general formula (12), a compound of the general formula (13) can be prepared analogously to the above-described process for the preparation of (6) from (5) (cf. Scheme 4, reaction step 4); (Scheme 9).

Scheme 9

The prepared compound (13) can be converted to the compound having the general formula (14) (Scheme 10) by the method of Preparation 5 (cf. Scheme 5).

Scheme 10

(14)

-61 -

Compounds having the general formula (14) can be converted to compounds of the general formula (15) in analogy to the above mentioned variants of the methods of preparation by reaction of compounds (7) to (8) (cf. scheme in reaction step 6).

Scheme 11

step 6 —— r ^s - _N 'r \ = N

O clay

RS, NHCOR ² _N N NH ₂ ⁺ H \ N (15) R ⁶

NH ₂

NHCOR ²

Compounds of formula (16) can then be obtained from the latter compounds in a manner similar to the cyclization reaction described in the reaction step (cf. Scheme 7) (Scheme 12).

step 7 method A

step 7 method C step 7 method B

(13)

Compounds of formulas (Ic) and (Id) may be obtained from the latter compound by the method of reaction steps 3 and 8 by alkylation reactions, which may optionally be isolated by a suitable partial and separation procedure, for example, recrystallization or column chromatography. (Scheme 13).

Scheme 13

By inserting appropriately substituted R ¹ , R ² , R ³ , R ⁴ , R ⁵ or R ⁶ , the imidazo triazolopyrimidinones (Ia), (Ib), (Ic) and (Id) obtainable by the methods described above can be further functionalized by known methods. Suitable protecting groups may be employed for this purpose. Scheme 14 below illustrates by way of example

The possibility of modifying compound (Ib) of the invention to a residue R ⁶ .

In Scheme 14, the exemplary reactions outlined result in reactive imidazo triazolopyrimidinones, which can serve as starting compounds for other structural variations (transesterification, alkylation, substitution, and the like). Included within the scope of the invention are feasible functionalizations of all residues R ¹ , R ² , R ³ , R ⁴ , R ⁵ or R ⁶ . These treatments are not limited to compounds of formula (Ib) but also include treatments of imidazo triazolopyrimidinones with i.

of the general formulas (Ia), (Ic) and J (Id). Scheme 14 serves to clarify the possible

Structural changes of imidazo triazolopyrimidinones (Ia), (Ib), (Ic), and (Id) by form i

without limiting the invention to the reactions shown in the scheme.

-63Scheme 14

ι

C-O-H ₂ CHjAlkyt-

X — R 'oxidation oxidation

R ': -CH 2 Alkyl-, X: halogen oxidation halogenation

· -CHjAlkyl.

In order to further illustrate the synthesis process of the present invention, examples are given below. These examples are intended to illustrate the invention in greater detail without limiting its scope. .

DETAILED DESCRIPTION OF THE INVENTION

Step 1: Synthesis of 5-substituted 3-amino-1,2,4-triazolene (3)

(3)

Unsubstituted 3-amino-1,2,4-triazole is commercially available, and the required 5-substituted 3-amino-1,2,4-triazole can be prepared by methods described and published in the literature, such as J. Chem. Soc. 816 (1929); J. Org. Chem. 1729 (1926) or Org. Synthesis 26, 11. The carboxylic acids ^R6-COOH, where R ⁶ CN nitriles are commercially available or can be prepared by methods known in the literature.

Table 1

Number R ⁶ yield % Melting point ° C 1.1 - H sales product - 1.2 - methyl 76 145-148 1.3 - ethyl 75 152 1.4 - n - propyl 62 140-143 1.5 - i - propyl 67 103-104 1.6 - n-butyl 62 118 1.7 -1-butyl 39 130 -131 1.8 benzyl 70 167-169 1.9 cyclopentyl- 64 168-172 1.10 2 - furyl (semisulfate) 76 207 - 208 1.11 phenyl - 68 185-186 1.12 cyclohexylmethyl - 51 186-188 1.13 2 - phenylethyl - 53 139-14 1.14 (4 - MeO - phenyl) - 0 - CH ₂ - 41 - 1.15 (4-MeO-phenyl) -CH ₂ -O-CH ₂ - ⁵⁴ 153 1.16 (4-phenyl-CH ₂ O-phenyl) - CH ₂ - 57 196-200 1.17 4-fluorobenzyl - 100 163 -164 1.18 3,4-difluorobenzyl - 81 135-137 1.19 3-pyridylmethyl - 58 192-196

Reaction Step 2: Synthesis of 2-substituted 4 H- 5-amino-1,2,4-triazolo [1,5- a] pyrimidin-7-one derivatives; derivatives (4)

(4)

General working regulation:

2.3 g (0.1 mol) of sodium are dissolved in 10 ml of absolute alcohol, then 14.7 g (0.14 mol) of cyanacetic acid ester are added. The mixture is stirred at room temperature for 1-2 hours, then treated with 0.1 mole of the appropriate 5-substituted 3-aminotriazole and heated at reflux for 4-6 hours. The cooled reaction mixture is mixed with water, acidified with stirring, then the solid is filtered off, washed and dried.

The following compounds were prepared as follows:

Table 2

Number R ⁶ Yield% Melting point, ° C 2.1 - H 73 > 370 2.2 - methyl 76 > 300 2.2 - ethyl 81 > 300 2.4 - n - propyl 80 290 (dec) 2.5 - i - propyl 61 294 (decomposition) 2.6 - n-butyl 77 256 2.7 -1-butyl 78 > 300 2.8 benzyl 82 300 (dec) 2.9 cyclopentyl- 83 310 (decomposition)

Number R ⁶ Yield% Melting point, ° C 2.10 2-furyl 61 - 2.11 phenyl - 75 - 2.12 cyclohexylmethyl - 81 > 300 2.13 2 - phenylethyl - 83 295-296 2.14 (4 - MeO - phenyl) - 0 - CH ₂ - 68 302 2.15 (4-MeO-phenyl) -CH ₂ -O-CH ₂ - 89 245 2.16 (4-phenyl-CH ₂ O-phenyl) - CH ₂ - 96 296-298 2.17 4-fluorobenzyl - 79 300-302 2.18 3,4-difluorobenzyl - 62 290-292 2.19 3-pyridylmethyl - 82 > 300

Step 3: Synthesis of alkylated triazolopyrimidine derivatives (5) and (12)

General working regulation:

mmol of said 5-amino-1,2,4-triazolo [1,5-a] pyrimidin-7-one (4) is dissolved in a 10-20 fold amount of anhydrous dimethylformamide and 76 mmol of potassium carbonate and 76 mmol of the corresponding alkyl iodide are added. . The reaction mixture was stirred for 1-2 days at room temperature and then concentrated to dryness. The residue was stirred with water and methylene chloride. In many cases, the solid product (5) precipitates during this treatment, which is filtered off and thus isolated. From the filtrate, the isomer (12) can be obtained as described below.

If, after dilution, no solids have precipitated, or if deivate (12) needs to be isolated by treating the filtrate, the aqueous phase is shaken with methylene chloride, the combined organics are dried over magnesium sulphate and evaporated to dryness. Chromatographic purification of the residue isolated (5) and (12), respectively. The required alkyl halide R 1 -X (where R 1 = R ⁴ , R ⁵ ) is commercially available or can be prepared by methods known in the literature.

The following substances were prepared as follows:

Table 3

Number R ⁶ R ⁴ R ⁵ yield % Melting point ° C 3.1 -H methyl - 80 310 (decomposition) 3.2 -H n-propyl - 58 184-186 3.3 -H - n-propyl 18 183 3.4 methyl n-propyl - 61 228 3.5 ethyl n-propyl - 65 194 3.6 n-propyl n-propyl - 69 170 3.7 -i-propyl n-propyl - 50 138 3.8 butyl n-propyl - 62 167 3.9 t-butyl n-propyl - 64 164-165 3.10 2-furyl n-propyl - 45 260-262 3.11 cyclopentyl- n-propyl - 64 148-150 3.12 cyclopentyl- - n-propyl 22 173 3.13 benzyl n-propyl - 60 208 3.14 benzyl methyl - 52 296 3.15 benzyl ethyl - 58 213 3.16 benzyl -i-propyl - 29 232

Number R ⁶ R ⁴ R ⁵ yield % Melting point ° C 3.17 benzyl -n-butyl - 55 175 3.18 benzyl pentyl - 63 188 3.19 benzyl benzyl - 51 180-181 3.20 phenyl -n-.propyl - 30 270-271 3.21 Cyclolhexylmethyl ethyl - 67 210-212 3.22 2-phenylethyl ethyl - 29 173-174 3.23 (4-MeO-Ph) -O-CH ₂ - ethyl - 58 177-180 3.24 (4-MeO-phenyl) -CH ₂ -O- CH ₂ - ethyl 100 3.25 (4-phenyl-CH ₂ O-phenyl) - CH ₂ - ethyl 63 240-242 3.26 4-fluorobenzyl - ethyl - 53 - 3.27 3,4-difluorobenzyl - ethyl - 61 228 3.28 3-pyridylmethyl - ethyl - 94 186-188

Note: they were used to separate the isomers in the next step

Step 4: Synthesis of nitroso compounds (6) or (13)

General Working Instructions (Variant A) mmol of 5-amino-1,2,4-triazolo [1,5-a] pyrimidin-7-one (4), (5) or (12) was dissolved or suspended in 10 to 30 ml of anhydrous dimethylformamide and the mixture was cooled to -5 ° C. Then 20 mmol of isoamyl nitrite was added so that the temperature did not rise above 0 ° C and the mixture was stirred at this temperature for 4 to 24 hours. If the reaction was incomplete, the reaction mixture was stirred at room temperature until the reaction was complete. The solvent was removed in vacuo, the residue was stirred in ether, filtered off, washed with water and dried in vacuo.

The following compounds were prepared as follows:

Table 4a

Number R ⁶ R ⁴ R ⁵ yield % Melting point ° C 4.1 -H -H - 85 > 350 4.2 -H methyl - 79 248 4.3 -H n-propyl - 81 211 (decomposition) 4.4 methyl n-propyl - 88 226 (dec) 4.5 ethyl n-propyl - 94 190 4.6 n-propyl n-propyl - 96 206 (dec) 4.7 -i-propyl n-propyl - 72 210 (dec) 4.8 -n-butyl n-propyl - 95 196 (decomposition) 4.9 t-butyl n-propyl - 93 200 (decomposition) 4.10 2-furyl n-propyl - 85 261 4.11 cyclopentyl- n-propyl - 97 224 (decomposition) 4.12 cyclopentyl- -H 89 225 (dec) 4.13 benzyl -H - 97 238 (decomposition) 4.14 benzyl n-propyl - 95 208 (decomposition) 4.15 benzyl methyl - 96 233 (dec) 4.16 benzyl ethyl - 97 226 (dec) 4.17 benzyl -i-propyl - 88 190 (dec) 4.18 benzyl -n-butyl - 93 196 4.19 benzyl n-pentyl - 74 190 (dec) 4.20 benzyl benzyl - 96 236 4.21 phenyl -n-.propyl - 92 4.22 -H -n- propyl 63 206 (dec)

Number R ⁶ R ⁴ R ⁵ yield % Melting point ° C 4.23 cyclopentyl- -n-propyl 74 146 4.24 Cyclolhexylmethyl ethyl - 83 208 - 209 4.25 2-phenylethyl ethyl - 90 200 - 201 4.26 (4-MeO-Ph) -O-CH ₂ - ethyl - 93 214-216 4.27 (4-MeO-phenyl) -CH ₂ -O- ch ₂ - ethyl 56 156-158 4.28 (4-phenyl-CH ₂ O-phenyl) - CH ₂ - ethyl 97 201 (decomposition) 4.29 4-fluorobenzyl - ethyl - 89 241-242 4.30 3,4-difluorobenzyl - ethyl - 97 234-236 4.31 3-pyridylmethyl - ethyl - 44 229

General working instructions (variant B) of 5-amino-1,2,4-triazolo [1,5-a] pyrimidin-7-one (4), (5) or (12) mmol are suspended in 80 to 100 ml of acid acid. The mixture is heated to 70 ° C, a solution of 20 mmol of sodium nitrite in 2-4 ml of water is added, the reaction mixture is stirred at 70 ° C for 0.5 to 2 hours, then stirred at 10 ° C for another 0 , 5 to 2 hours. The product was filtered off, washed and dried in vacuo.

The following compound was prepared, among others, by this method.

Table 4b

Number R ⁶ R ⁴ R ⁵ yield % Melting point ° C 4:32 benzyl -H - 65 236 (dec)

-71 Reaction Step 5: Synthesis of diamine (7) and (14)

General working instructions (variant A)

12.7 mMol of nitroso compound (6) or (13) was suspended with stirring in 86 ml of water and mixed with 4.9 g (2.9 mmol) of Na ₂ S ₂ O _4th The suspension is heated to 80 ° C and 15 ml of 50% sulfuric acid are gradually added over 15 minutes. The reaction mixture is then heated to reflux until complete conversion. Upon cooling, in most cases a solid product precipitates as a semisulfate. If no solid forms, the mixture is neutralized with 30% sodium hydroxide solution and the precipitated free base is filtered off.

General law of right (variant B)

To a mixture of 175 ml of a 25% aqueous ammonia solution and 36 ml of ethanol are added

of stirring, 11.5 mmol of nitroso compound (6) or (13) are added. The mixture was then stirred at 30 ° C until the nitroso compound was largely dissolved, a solution of 6.1 g (34.7 mmol) of Na ₂ S ₂ O ₄ in 57 mL of water was added dropwise. The reaction mixture was stirred for an additional 1.5 to 3 hours at room temperature. If a starting compound is still present, 10% or another amount of Na ₂ S ₂ O ₄ is added with stirring until the conversion is complete.

The product is isolated by filtration.

One of the listed variants (A or B, see Table 5) was prepared among others in Table 5 of the listed compounds.

-72Table 5

Number R ⁶ R ⁴ R ⁵ Yield% (variant) salt form Melting point ° C 5.1 -H -H 73 / A semisulfát > 300 5.2 -H methyl - 65 / A / - 267 (decomposition) 5.3 -H n-propyl - 65 / A / - 185-188 5.4 methyl n-propyl - 70 / A / - 174 5.5 ethyl n-propyl - 78 / A / - 170-172 5.6 n-propyl n-propyl - 82 / A / - 148-150 5.7 -i-propyl n-propyl - 52 / A / - 193 5.8 -n-butyl n-propyl - 71 / A / - 140-142 5.9 t-butyl n-propyl - 90 / B / - 168 5.10 cyclopentyl- -H 74 / A / semisulfát 224 5.11 cyclopentyl- n-propyl 48 (A) semisulfate 195-197 5.12 2-furyl n-propyl - 75 / B / - 204-205 5.13 benzyl -i-propyl 8 (A) semisulfate 223 5.14 benzyl n-propyl 62 / A / semisulfát 217 5.15 benzyl methyl - 91 / B / - 248 5.16 benzyl ethyl - 95 / B / - 175 5.17 benzyl -n-butyl 48 (A) semisulfate 203 - 205 5.18 benzyl n-pentyl - 92 / B / - 146

Number R ⁶ R ⁴ R ⁵ % T variant yield salt form Melting point ° C 5.19 benzyl -H 47 (A) semisulfate 218-220 5.20 benzyl benzyl - 80 / B / - 273 5.21 phenyl -n-.propyl 79 / A / semisulfát 260 5.22 -H -n-propyl 81 / A / - 222-224 5.23 cyclopentyl- -n-propyl 86 / A / - 175 5.24 Cyclolhexylmethyl ethyl - 94 / B / - 158-160 5.25 2-phenylethyl ethyl - 94 / B / - 204-205 5.26 (4-MeO-phenyl) -Och _2- ethyl 86 / B / - 154-156 5.27 (4-MeO-Ph) -CH ₂ -O-CH ₂ - ethyl 88 / B / - 133-139 5.28 (4-phenyl-CH ₂ O-phenyl) CH ₂ - ethyl 84 / B / - 155 5.29 4-fluorobenzyl - ethyl - 88 / B / - 202 - 205 5.30 3,4-difluorobenzyl - ethyl - 95 / B / - 209-212 5.31 3-pyridylmethyl - ethyl - 82 / B / - 179-180

-74 Reaction Step 6: Synthesis of amide (8) or (15)

NHCOR ²

NH ₂

The general working procedure (variant A) of the mmol of the diamino compound (7) or (14) is suspended in anhydrous dimethylformamide (165 ml) and treated with 45 mmol (in the case of semisulfates with 78 mmol) of 4-dimethylaminopyridine. The mixture was stirred at room temperature for 30 minutes, then the mixture was cooled to 5-10 ° C and a solution of 39 mmol of the appropriate carboxylic acid chloride in 16 mL of anhydrous dimethylformamide was added. Then the reaction mixture was stirred at 10 ° C and ambient temperature overnight. The solvent was then removed in vacuo. The residue is stirred with water, the solid is filtered off, washed and optionally recrystallized or purified by chromatography.

The carboxylic acid chloride used is commercially available or can be prepared by methods known in the literature.

In this manner, compounds having the general formulas (8) and (15) and prepared in Table 6a were prepared.

Table 6a

Melting point ° C 284 (dec) 306 178 192 208 209 1 210 205 200 148 173 100 205 243 l 160 l yield % 86 35 65 95 h- 72 77 06 89 84 r- 99 09 ¼ 70 76 74 CM X cyclopentyl- benzyl benzyl cyclopentyl- cyclopentyl- cyclopentyl- (D 1 cyclopentyl- | phenyl 4-fluorobenzyl cyclopentyl- cyclopentyl- cyclopentyl- ω 1 methyl benzyl cyclopentyl- m CL ' 1 1 1 1 1 1 1 I 1 I I 1 1 1 and 1 X X methyl n-propyl n-propyl n-propyl n-propyl n-propyl n-propyl n-propyl n-propyl n-propyl n-propyl n-propyl -n-propyl ' -n-propyl j n-propyl n-propyl <D Article X 1 T T x 1 x 1 methyl ethyl ethyl -n-propyl | n-propyl n-propyl -i-propyl -n-butyl t-butyl cyclopentyl- cyclopentyl- cyclopentyl- 2-furyl number what 6.2 6.3 6.4 6.5 6.6 6.7 6.8 ' 6.9 ABOUT WHAT 6.11 6.12 6.13 6.14! L_________I 6.15 6.16 6.17 I

Melting point ° C T 254-257 1 227 237 223 T 183 166 205 - 208 188-189 170 163 162 165-166 > 300 yield % 73 m 06 09 65 63 55 IN" CD 62 00 00 06 77 09 67 47 68 69 CN qí -4- » Q) 1 cyclopentyl- cyclopentyl- 3-tetrahydrofuranyl- 4-tetrahydrofuranyl- 2-pyridyl 4-pyridyl 4— »(D I n-propyl -cyclopentyl- | cyclopentyl- cyclopentyl cyclopentyl and cyclopentyl >> Φ 1 cyclopentyl- cyclopentyl- UO Article 1 1 1 1 1 1 1 1 I 1 I 1 1 T 1 n-propyl 't Article n-propyl T 1 benzyl and > 4— »Φ 1 >> 4— »Φ >> 4— · Φ 1 ethyl n-propyl n-propyl methyl W * φ 1 n-propyl -n-butyl! n-pentyl -n-.propyl n-propyl 1 ₉ y 2-furyl benzyl benzyl benzyl L benzyl benzyl benzyl benzyl benzyl benzyl benzyl benzyl benzyl benzyl phenyl phenyl T 1 number 6.18 6.19 6.20 6.21 6.22 6.23 6.24 6.25 6.26 r C \ l WHAT 6.28 6.29 6.30 6.31 6:32 6:33 6:34

I

Melting point ° C 223 1 206 l · - 00 CD CO 231 -232 276-279 305-307 163-165 186-187 228 204-207 196-198 182-183 155 -156 179-180 306-308 160 -164 176-178 yield % 40 55 CO CO 98 84 CM h- 69 73 V r- WHAT T " 00 70 95 ναό 65 M 93 76 CM Article 2-pyridyl 4-pyridyl 3-pyridyl cyclohexyl- I phenyl 2-furyl cyclopentyl- ethyl 2-furyl > < 4 (D 1 cyclopentyl- ethyl cyclopentyl- 3-tetrahydrofuryl cyclopentyl- ethyl cyclopentyl- m DĹ 1 1 1 1 1 1 1 and I 1 1 1 1 1 1 1 1 1 1 xt Article ethyl 4— »Φ 1 ethyl 4- * d) 1 -n-butyl T T 1 4 — t Φ 1 >> 4— · Φ 1 1 and l 1 1 n-propyl >. 4- * Φ 1 4- * Φ 1 ethyl > x 4— »Φ 1 n-propyl n-propyl >. 4 » Φ 1 4- * Φ 1 CD Article benzyl benzyl benzyl benzyl benzyl benzyl benzyl 3-pyridylmethyl- 1 T >> · + - * I Pi i— CL 1 CO I 2-furyl Cyclolhexylmethyl Cyclolhexylmethyl 2-phenylethyl 2-phenylethyl cyclopentyl- cyclopentyl- 1 CN T Q O C Ä 4 Φ S 4 1 CM T o o>. c £ 1 o Φ s 1 number 6:35 6:36 6:37 6:38 6:39 6:40 6:41 6:42 6:43 6:44 6:45 6:46 6:47 6:48 6:49 6:50 6:51 6:52

Melting point ° C 133 -136 190 T 206-208 1 1 222-224 1 1 134-137 yield % IN" ABOUT 86 86 62 53 75 τ- Ο 100 100 87 79 CM CC cyclopentyl- cyclopentyl- cyclopentyl tert-butyl cyclopentyl- ή 4 it CC 1 1 I I 1 1 and 1 1 1 1 CC > - 4—, Φ t >> 4— »(D 1 4 - ^{1 1} - + -, (D 1 >> 4— »Φ 1 4— <Φ 1 > - 4— »Φ 4> Φ >> Φ 1 4—4 Φ 1 4 — J Φ 1 CD (L 1 CM T about ω o Oh, oh φ WITH 1 > - c Φ ABOUT tN CN T T o o> c Ä 1 Cyclolhexylmethyl 4-fluorobenzyl - 4-fluorobenzyl 4-fluorobenzyl 4-fluorobenzyl 3,4-difluorobenzyl - 4-fluorobenzyl benzyl 3-pyridylmethyl - number 6:53 6:54 6:55 6:56 6:57 6:58 CD tO CD 1 6.60 6.61 6.62 • 6.63

^J 79 General working instructions (option B)

6.6 mmol of the diamine (7) or (14) and 7.3 mmol of the corresponding carboxylic acid are suspended in 15 to 25 ml of acetonitrile. N-methylmorpholine (7.3 mmol) was added slowly with stirring. A solution of 7.3 mmol of isobutyl chloroformate in 6-7 ml of acetonitrile is added dropwise at 20-25 ° C over 10-20 minutes. The suspension is stirred for 6-8 hours at room temperature. Then, the suspension is filtered and the filter residue is washed with acetonitrile. The filtrate was concentrated and chromatographed on silica gel.

In this way, the compounds of the general formulas (8) and (15) described in Table 6b were prepared.

Table 6b

Number R ⁶ R ⁴ R ⁵ R ² yield in % 6.64 4-fluorobenzyl ethyl - R ^B ' 26

Step 7: Cyclization reaction to triazlopurines (9) or (16)

General working instructions (method A, variant A)

14.4 mmol of compound (8) or (15) are suspended in 75.5 ml of water and 37.8 ml of ethanol, 17.4 ml of 50% NaOH solution and 4.82 g (65 mmol) of calcium hydroxide are added. ; the reaction mixture was refluxed for 24 hours. It is then allowed to cool, acidified, the solid is filtered and dried. The product is optionally purified by recrystallization or chromatography.

The compounds of formulas (9) and (16) described in Table 7a were prepared in this manner.

Table 7a

temperature mp ° C 1 > 360 306 222-223 250 262-264 253 229 256 300 (dec) 221 260-261 246 310 245-248 248-250 yield % 1 08 35 89 59 62 58 89 75 49 65 62 72 64 85 56 OJ Article cyclopentyl- benzyl and benzyl cyclopentyl- cyclopentyl- cyclopentyl- Φ cyclopentyl- phenyl 4-fluorobenzyl cyclopentyl- cyclopentyl- cyclopentyl- (D 1 methyl m Article 1 J 1 1 1 1 T 1 1 1 T 1 1 1 oL X methyl n-propyl n-propyl n-propyl n-propyl n-propyl n-propyl n-propyl n-propyl n-propyl n-propyl n-propyl n-propyl n-propyl WHAT Article X x 1 x 1 x 1 methyl ethyl >> • w Q) 1 n-propyl n-propyl n-propyl -i-propyl -n-butyl t-butyl cyclopentyl- cyclopentyl- Number T " r- ' 7.2 7.3 l < 7.5 7.6 zz 7.8 7.9 7.10 7.12 7.13 7.14 7.15

Melting point ° C | 233 I_______________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ N O Ι- CO o CO A N O O o CO A 270 (dec) 270 227 237 287 346 223 202 265-267 242 234-235 yield % 70 τ- Ο 44 ⁴⁰ CO t— 09 64 T C \ J what 57 53 _____________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________1 WHAT 56 67 CM Article benzyl cyclopentyl- ethyl cyclopentyl- cyclopentyl- 3-tetrahydrofuranyl- 4-tetrahydrofuranyl- 2-pyridyl 4-pyridyl and > * + »(D 1 n-propyl ______________________________________________________________________________________________________________________________________________________________________________________________________________________________1 cyclopentyl- cyclopentyl- cyclopentyl- R ⁵ 1 1 1 1 1 1 l 1 1 1 1 1 1 ai n-propyl n-propyl n-propyl T s j benzyl- > ♦ - »(d) 1 Φ 1 'T *' 4- »Φ 1 ethyl n-propyl n-propyl methyl ethyl n-propyl CD ai cyclopentyl- 2-furyl 2-furyl benzyl benzyl benzyl benzyl benzyl benzyl benzyl-. benzyl benzyl benzyl benzyl Number 7.16 7.17 7.18 7.19 7.20 7.21 CM <N r < 7.23 7.24 1 7.25 7.26 7.27 7.28 7.29

Melting point ° C 238-240 231 -236 > 300 (dec.) > 300 217-220 260 331-322 260-262 261 -263 225-227 385-387 352–354 230-232 273-274 282-283 292-294 yield % 53 and 56 97 78 36 2.4 - 74 09 62 CD Ν ' 73 62 WHAT 53 CN Article cyclopentyl- cyclopentyl- • 4— »Φ 1 cyclopentyl- cyclopentyl- cyclopentyl- 3-pyridyl cyclohexyl- cyclopentyl- 4— «Φ 1 -2-furanyl 2-furyl 4— · Φ 1 cyclopentyl- 4— · Φ 1 cyclopentyl- m Article 1 1 1 I n-propyl * - » φ 1 1 1 1 1 • 1 1 1 Article -n-butyl n-pentyl -n-.propyl n-propyl I 1 4— · Φ 1 4— »Φ t 4— · Φ 1 4- »φ 1 n-propyl T 1 ethyl ethyl 4-J Φ 1 >> 4— * Φ 1 <D Article benzyl benzyl phenyl phenyl T T benzyl benzyl 3-pyridylmethyl- 3-pyridylmethyl- 2-furyl benzyl Cyclolhexylmethyl Cyclolhexylmethyl 2-phenylethyl 2-phenylethyl Number 7.30 7.31 WHAT 7:33 7:34 7:35 7:36 7:37 7:38 7:39 7:40 7:41 7:42 7:43 7:44 7:45

Melting point ° C 289-290 306-308 1 225 234-236 182 251 252-254 262-264 337–339 325-327 yield % 56 M 47 20 70 70 N- CO h- 53 45 CM Article 3-tetrahydro- furanyl cyclopentyl- >. . ♦ - »φ cyclopentyl- cyclopentyl- cyclopentyl- cyclopentyl tert-butyl ID Article T T I 1 1 1 T 1 1 ’T CĹ n-propyl n-propyl ethyl • w (D 1 ethyl >> 4— »Φ 1 >> (D 1 CD 1 + (D 1 > ^ (D 1 <0 Article cyclopentyl- cyclopentyl- t o 1 c * i £ Ó o Φ Z 1 WITH- 1 o 1 >> C 1 φ CM T ¾ o o Φ and 1 CM T o f f * š ó Φ p 1 >. c Ä CM CM CM IT oo 1 >> ¹ c £ 4-fluorobenzyl - 4-fluorobenzyl 4-fluorobenzyl 4-fluorobenzyl Number 7:46 7:47 7:48 7:49 7:50 7:51 and 7:52 7:53 7:54 7:55

-S4-

Melting point ° C 264-266 315-317 320–322 330-332 yield % 09 58 67 57 CM CL ' cyclopentyl- 10 oL l • 1 rf oL >. Φ 1 - · - »Φ 1 > 1 Φ 1 • 4— »Φ t (0 or 3,4-difluorobenzyl - 3,4-difluorobenzyl - benzyl-! 3-pyridylmethyl - 1 1 Number 7:56 7:57 7.58 ¹ 7:59

- General Working Instructions (Method A, Variant B) The mmoles of amide (8) or (15) are mixed in 10 to 15 ml of tetrahydrofuran and up to 35 ml of water with 46 mmol of lithium hydroxide monohydrate for 14 days at i.

45 ° to 65 ° C. The reaction mixture was then acidified with 6M hydrochloric acid solution and filtered off with suction. The crude product was recrystallized from methanol. The product obtained is then further chromatographed on a column of acid gel i

silica. j

In this way, the compounds of the general formula (9) described in Table 7b were prepared.

Table 7b

Number R ⁶ R ⁴ R ² yield in % Melting point ° C 7.62 Cyclolhexylmethyl ethyl 10 246-248 7.63 cyclohexylmethyl ethyl 3 258-260 (dec)

General working rules (method B)

10.1 mmol of compound (7) or (14) is stirred in 34 ml of formamide at 200 ° C for 1.5 hours. Excess formamide is distilled off under vacuum, and the residue is stirred in water. The solid is then filtered off, washed with water and the product purified by recrystallization or chromatography.

The compounds of formulas (9) and (16) included among others in Table 7c were prepared as described above.

-86 Table 7c

Number R ⁶ R ⁵ R ⁴ R ² yield in % Melting point ° C 7.64 ethyl - n-propyl -H 84 > 300 7.65 cyclopentyl- - -H -H 53 215 7.66 cyclopentyl- - methyl -H 7 > 300 7.67 3-pyridylmethyl- - ethyl -H 58 328-330 7.68 cyclopentyl- - n-propyl -H 58 287 (dec) 7.69 2-furyl - n-propyl -H 74 > 300 7.70 benzyl - methyl -H 9 > 300 7.71 benzyl - n-propyl -H 75 > 300 7.72 benzyl - -i-propyl -H 90 > 300 7.73 benzyl - -n-butyl -H 75 > 300 7.74 benzyl - -H -H 63 > 300 7.75 phenyl n-propyl -H 75 295-296 (Decomposition) 7.76 cyclopentyl- -n-propyl -H 35 202-203 7.77 3-pyridylmethyl- - ethyl -H 58 328-330 7.78 Cyclolhexylmethyl - ethyl -H 87 328-330 7.79 2-phenylethyl - ethyl -H 84 273

General working instructions (method C)

To a solution of 6.8 mmol of the appropriate N-formylamine in 6 mL of Diglym was added at 0 ° C 0.66 mL (7.2 mmol) of phosphorus oxychloride. Then, the reaction mixture is stirred for 30 minutes while cooling in an ice bath, and 4.8 mmol of nitroso compound (6) or (13) are added. The mixture is then stirred at 80 ° C for 30 to 60 minutes. The mixture is poured

In ice-water, the solid is filtered, washed and dried. It is purified by recrystallization or can be purified by chromatography.

The compounds (9) included among others in Table 7d were prepared as described above.

Table 7d

Number R ⁶ R ⁴ R ² yield in % Melting point ° C 7.80 benzyl n-propyl N-morpholinyl 21 298 7.81 benzyl n-propyl 4-benzyl-1-piperazinyl 21 266-268 7.82 benzyl n-propyl dimethylamino- 9 272-274 7.83 benzyl n-propyl N-piperidinyl 22 294-297

The necessary formylamine can be prepared by converting the amine with 88% formic acid and acetic anhydride by methods known in the literature.

Step 8: alkylation reactions mmol of 1,2,4-triazolo [11,5-a] purin-9-one, which is substituted in the 4 and 5, [compound (9) with ^R4 = H; (16) with R ⁵ = H] was mixed with 26 ml of anhydrous dimethylformamide, then the first with a solution of 0.1 g (4.2 mmol) of sodium in 4 ml of anhydrous ethanol, followed by 4.2 mmol of the alkyl iodide. The reaction mixture was stirred overnight at room temperature and concentrated to dryness. The residue was dissolved in 2M NaOH solution, washed with toluene and then adjusted to pH 6. The precipitated solid was filtered off and purified by chromatography. If desired, the dialkylated products (Ia) and (Ib) can also be isolated.

The compounds (9) mentioned in U.S. Pat

Table 8a.

Table 8a

Number R ⁶ R ⁴ R ⁵ R ² yield in % Melting point ° C 8.1 benzyl methyl - -H 9 > 300 8.2 cyclopentyl- methyl - -H 7 > 300 8.3 -H methyl - cyclopentyl- 44 285 8.4 -H ethyl - cyclopentyl- 57 249-253 8.5 -H -n-propyl cyclopentyl- 52 255 8.6 -H -n- butyl - cyclopentyl- 45 243 8.7 -H t-butyl - cyclopentyl- 10 190-191 8.8 benzyl ethyl - t-butyl 24 243-244 8.9 benzyl ethyl - phenyl 24 343–345 8.10 -H -n-butyl - cyclopentyl- 45 243 8.11 -H - t-butyl cyclopentyl- 4 149-150

In addition, the following compounds (Ia) and (Ib) can be prepared by this procedure:

-89Table 8b

Number R ⁶ R ⁴ R ¹ and R ³ R ² yield in % Melting point ° C 8.12 benzyl ethyl ethyl -H 4 > 300 8.13 -H methyl methyl cyclopentyl- 4 206 8.14 cyclopentyl- -n-propyl -n-propyl -H 10 146 8.15 cyclopentyl- -n-propyl -n- propyl -H 5 151 8.16 benzyl ethyl ethyl 2-furyl 16 187-189

General working rules (variant B)

20.4 mmol of 1,2,4-triazolo [11,5-a] purin-9-one, which is not substituted at positions 4 and 5, [compound (9) with R ⁴ = H; (16) with R ⁵ = H], together with 40.8 mmol of potassium carbonate and 40.8 mmol of tert-butyl bromide in 100 mL of anhydrous dimethylformamide was stirred at 70 ° C for 7 days. Then the reaction mixture is evaporated to dryness, the residue is treated with 100 ml of a 2M NaOH solution, the aqueous phase is washed with toluene and neutralized. The precipitate was filtered off, extracted with CH ₂ Cl ₂ / CH ₃ OH 9: 1 and the extract was evaporated. Isomeric alkylated products (9) and (16) can be obtained by chromatography on silica gel with CH ₂ Cl ₂ / CH ₃ OH 95: 5 as eluent (Table 8c).

The following compounds were prepared, among others, in this manner.

Table 8c

Number R ⁶ R ⁴ R ⁵ R ² yield in % Melting point ° C 8.17 -H t-butyl - cyclopentyl- 10 190-191 8.18 -H - t-butyl cyclopentyl- 5 149-150

General working rules (variant C)

0.05 mol of the starting compound (9) is dissolved in 500 ml of absolute dimethylformamide and stirred with 0.055 mol of potassium carbonate and 0.055 mol of benzyl bromide overnight at room temperature. The reaction mixture is further worked up by distilling off the solvent in vacuo and the residue is stirred in a mixture of methylene chloride and water. The organic phase is separated, washed once with water, dried over magnesium sulphate and evaporated. The residue was recrystallized from ether. Said and other prepared compounds (Ia / Ib) are shown in Table 8d.

Table 8d

Number R ⁶ R ⁴ R ¹ and R ³ R ² yield in % Melting point ° C 8.19 (4-MeO-phenyl) -CH ₂ -O-CH ₂ - ethyl benzyl cyclopentyl- 85 127 -128 8.20 (4-phenyl-CH ₂ O-phenyl) CH ₂ - ethyl benzyl cyclopentyl- 66 138 -140

-91 Reaction step 9a: Deblocking of imidazofriazolopyrimidinones (1a) / (1b) with protected hydroxyl functional groups

General synthetic scheme for an example of a compound having the general formula (1b):

DDQ = 2,3-dichloro-5,6-dicyno-benzoquinone

The above reaction is carried out according to the literature procedure (Tetrahedron 42, 3021 (1986)). In this way, the compound shown in Table 9 was prepared, among others.

Table 9

Number R ⁶ R ⁴ R ¹ and R ³ R ² yield in % Melting point ° C 9.1 HO - CH ₂ - ethyl benzyl cyclopentyl- 97 204-207

92 Reaction Step 9b. Deblocking of imidazo triazolopyrimidinones (Ia) / (Ib) with protected amine functional groups on the side chain

General synthetic scheme for an example of a compound having the general formula (Ib):

0.83 mmol of 2- (4-N-benzyl-1-piperazinyl) -1,2,4-triazolo [1,5-a] purin-9-one is mixed with 30 ml of acetic acid and hydrogenated at 60 ° C in the presence of 0.1 g of 10% palladium on carbon under a pressure of 5 bar and for 6 hours. Then the catalyst is filtered off, the residue is concentrated to dryness and stirred in CH ₃ OH. The solid was filtered, washed and dried.

In this way, the compound shown in Table 10 was prepared, among others.

Table 10

Number R ⁶ R ⁴ R ¹ and R ³ R ² yield in % / form salt Melting point ° C 10.1 benzyl -n- propyl -H 1- piperazinyl 53 / ethyl 260

93 Reaction Step 9c. Cleavage of protecting groups from amino groups of the imidazo triazolopyrimidinone structural core

General synthetic scheme for an example of a compound having the general formula (1b):

The 3-N-benzylated triazolopurine of formula (I) is dissolved in methanol or absolute glacial acetic acid and hydrogenated under a hydrogen atmosphere (1-5 bar) at 25-80 ° C using a palladium catalyst (e.g. Pd / C) after 2.5 to 40 hours. The catalyst is then removed by suction, the solution is evaporated and the residue is purified by chromatography on silica gel. The purified product is crystallized from the eluate, preferably from ether, and then preferably crystallized in the form of a salt.

The compounds listed in Table 11 were prepared, among others.

Table 11

Number R ⁶ R ⁴ R ² salt form % Yield Melting point ° C 11.1 methoxymethyl- ethyl cyclopentyl- - 27 246-248 11.2 ethoxymethyl- ethyl cyclopentyl- - 45 224-225 11.3 hydroxymethyl ethyl cyclopentyl- - 37 305-307

Number R ^{3 * * 6} R ⁴ R ² salt form % Yield Melting point ° C 11.4 benzoyloxymety I- ethyl cyclopentyl- 54 238-239 11.5 dimetylaminometyl- ethyl cyclopentyl- mesylate 29 224-225 11.6 N-morfolinylmetyl- ethyl cyclopentyl- mesylate 40 229 11.7 phenoxymethyl ethyl cyclopentyl- - 40 229

Step 9d: Alkylation of the hydroxy substituted imidazo triazolopyrimidinone

General synthetic scheme for an example of a compound having the general formula (Ib):

mmol of hydroxyalkyl- or hydroxyaryl-substituted imidazo triazolopyrimidinone of formula (Ia), (Ib), (Ic), or (Id) are dissolved in 30 ml of dimethylformamide and reacted with 3.6 mmol of sodium hydride (60%). suspension in mineral oil) with stirring for 1 hour at room temperature, then 3.6 mmol of alkyl iodide are added and the reaction mixture is stirred for 1 to 2 days at 25 to 60 ° C. 50% sodium hydride and an alkyl halide are added for complete conversion. The reaction mixture is then evaporated to dryness, the residue is treated with methylene chloride and water, acidified with 2M HCl solution, the aqueous phase is extracted once more with methylene chloride, and the combined organic phases are washed with a solution.

And dried over magnesium sulphate. Evaporation gave a residue which was purified on silica gel and the eluate was crystallized from ether.

The compounds listed in Table 12 were prepared in this manner.

Table 12

Number R ⁶ R ⁴ R ¹ and R ³ R ² % Yield Melting point ° C 12.1 methoxymethyl- ethyl benzyl cyclopentyl- 37 1 16 -118 12.2 ethoxymethyl- ethyl benzyl cyclopentyl- 36 120-123

Step 9e: Acylation of the hydroxy substituted imidazo triazolopyrimidinone

General synthetic scheme for an example of a compound having the general formula (1b):

N γ-R ²

N ^: <

ABOUT

... ^k N W pyridine - ·· - yL chloride of a carboxylic No ³

The hydroxyl compound was stirred in pyridine and treated with a stoichiometric amount of acid chloride under ice-cooling. After complete conversion, the batch was poured into ice water and acidified with 2M hydrochloric acid solution. The aqueous phase is extracted several times with methylene chloride. The combined organic phases are washed with brine, dried over magnesium sulphate and evaporated.

The residue is purified by chromatography on silica gel and the eluate is crystallized from ether.

The compounds listed in Table 13 were prepared in this manner.

Table 13

Number R ⁶ R ⁴ R ¹ and R ³ R ² yield in % 13.1 phenyl-C (O) -O-CH ₂ - ethyl benzyl cyclopentyl- 73 13.2 3-pyridyl-C (O) -O- CH ₂ - ethyl benzyl cyclopentyl- 36

Reaction step 9f: Halogenation of hydroxy substituted imidazo triazolopyrimidinone

General synthetic scheme for an example of a compound having the general formula (1b):

Hydroxylated imidazo-trizazolopyrmidinones are converted to the corresponding halides in a conventional manner using halogenating agents such as SOCl ₂ , SOBr ₂ , POCl ₃ and the like, in the presence of bases (e.g. NEt ₃ ).

In this way, the compound mentioned in U.S. Pat

Table 14.

Table 14

Number R ⁶ R ⁴ R ¹ and R ³ R ² % Yield Melting point ° C 14.1 Br-CH ₂ - ethyl benzyl cyclopentyl- 66 188-189

Reaction step 9g: Nucleophilic substitution of halogen-substituted imidazotriazolopyrimidinones

General synthetic scheme for an example of a compound having the general formula (Ib):

an alcohol or an amine base

X = chlorine, bromine, iodine

Using commonly known conventional procedures, halogen-substituted imidazotriazolopyrimidinone derivatives can be converted by reaction with nucleophiles (e.g., alcohol, amine) in the presence of a base to the corresponding amines and alkyloxy / aryloxy compounds. To obtain the amines, reference is made to the synthesis procedure already described in Reaction Step 8. Alkyloxy / aryloxy compounds can be prepared according to the corresponding general operating procedure given under IX d. Thus, among others, the compounds listed in Table 15 were prepared.

-98Table 15

Number R ⁶ R ⁴ R ¹ and R ³ R ² % Yield Melting point ° C 15.1 (CH ₃ ) ₂ N- ch ₂ - ethyl benzyl cyclopentyl- 100 15.2 N-morfolínometyl- ethyl benzyl cyclopentyl- 96 15.3 fenyloxymetyl- ethyl benzyl cyclopentyl- 86 155

Reaction Step 9h: Oxidation of the hydroxy substituted imidazole triazolopyrimidinone

General synthetic scheme for an example of a compound having the general formula (Ib):

Using commonly known conventional procedures (e.g. Tetrahedron Letters 5, 399-402 (1979)), hydroxy-substituted imidazotriazolopyrimidinone derivatives can be converted to imidazotriazolopyrimidinones with higher oxidation degree functionalities (e.g., aldehydes, carboxylic acids).

Thus, among others, the compounds listed in Table 16 were prepared.

Table 16

Number R ⁶ R ⁴ R ¹ and R ³ R ² yield in % Melting point ° C 16.1 CHO ethyl benzyl cyclopentyl- 48 153-154 16.2 COOH ethyl benzyl cyclopentyl- 38 157-158

Reaction step 9i: Derivatization of imidazole-triazolopyrimidinone carboxylic acids

General synthetic scheme for an example of a compound having the general formula (Ib):

ABOUT

Using procedures known in the literature, imidazole-triazolopyrimidinone carboxylic acids can be converted to a large number of different carboxylic acid derivatives (e.g., halide, anhydride, amide, ester and the like). In order to obtain the corresponding imidazole-triazolopyrimidinonic carboxylic acid methyl ester, the following working instructions can be used:

0.003 mol of imidazole-triazolopyrinidinonic carboxylic acid is suspended in a 1 M solution of SOCl ₂ (1.5 equivalents) in MeOH. The clear solution obtained is

-100 stirred at room temperature. After the reaction is complete, the solvent is distilled off in vacuo and the residue is purified by chromatography on silica gel.

In this way, the compound shown in Table 17 was obtained, among others.

Table 17

Number R ⁶ R ⁴ R ¹ and R ³ R ² yield in % Melting point ° C 17.1 COOCH ₃ ethyl benzyl cyclopentyl- 71 155-157

Reaction step 9k: Reductive amination of trazolopurine aldehydes

General synthetic scheme for an example of a compound having the general formula (Ib):

1) amine

------>

2) reduction or H ₂

Using procedures known in the literature, imidazolriazolopyrimidinone aldehydes can be converted to the corresponding amine by conversion with primary or secondary amines and subsequent reduction or hydrogenation of the transiently formed Schiff base.

In this way, the compound mentioned in U.S. Pat

Table 18.

Table 18

Number R ⁶ R ⁴ R ¹ and R ³ R ² yield in % Melting point ° C 18.1 3-Pyridyl- ₂ -ch ₂ - ethyl- benzyl cyclopentyl-

Table 19 summarizes compounds prepared in a similar manner to those described above having the general formula (I):

(D

- 102-

Table 19

Chemical name 6-benzyl-1,2,4-triazolo [1,5-a] purin-9-one 6-benzyl-4-methyl-1,2,4-triazolo [1,5- a] purin-9-one 6-benzyl-4-n-propyl-1,2,4-triazolo [1,5- a] purin-9-one 6-benzyl-4-n-butyl-1,2,4-triazolo [1,5- a] purin-9-one 6-benzyl-4-i-propyl-1,2,4-triazolo [1,5- a] purin-9-one 6-benzyl-2-ethyl-4-n-propyl-1,2,4- triazolo [1,5-a] purin-9-one 6-benzyl-2,4-di-n-propyl-1,2,4-triazolo [1,5-a] purin-9-one 6-benzyl-2-cyclopentyl-4-methyl-1,2,4 triazolo [1,5-a] purin-9-one Melting point ° C > 300 > 300 > 300 o o CO A > 300 223 202 265-267 CO or 1 9 9 9 9 9 9 9 9 and: 1 O -T- jd rä m Hon * 1 1 1 1 1 1 1 M CĽ 1 II m a: O -r -Q Φ ¹ CO XT Di methyl n-propyl n-butyl i-propyl n-propyl n-propyl methyl CM Article 1 X 1 x F x l x T x 1 >> 4 * 0) 1 n-propyl 9 R ¹ and R ³ T 1 x 1 T. 1 T 1 T 1 I 1 T i T T Example No .: T " CM WHAT M m CD b- CD

103-

Chemical name 6-benzyl-2-cyclopentyl-4-ethyl-1,2,4- triazolo [1,5-a] purin-9-one 6-benzyl-2-cyclopentyl-4-n-propyl 1,2,4-triazolo [1,5-a] purin-9-one I 6-benzyl-4-n-butyl-2-cyclopentyl- 1,2,4-triazolo [1,5-a] purin-9-one 4,6-dibenzyl-2-cyclopentyl - 1,2,4- triazolo [1,5-a] purin-9-one 6-benzyl-4-n-propyl-2- (N-morpholino) - 1,2,4-triazolo [1,5-a] purin-9-one 6-benzyl-4- (4-benzyl) -4-n-propyl-1,2,4-triazolo [1,5-a] purin-9-one 6-benzyl-4-n-propyl-2- (1-piperaunyl) - 1,2,4-triazolo [1,5-a] purin-9-one 6-benzyl-4-ethyl-2- (3-tetrahydrofuryl) - 1,2,4-triazolo [1,5-a] purin-9-one Melting point ° C 242 234-235 238-240 270 298 266-268 260 237 (D or 1 9 9 9 9 9 9 9 ABOUT\ m CC 1 1 1 • 1 1 xr CC t > * 4— »(D 1 n-propyl n-butyl 9 n-propyl n-propyl n-propyl 4— »G) 1 <N CC '9 9 PART 9 ABOUT z I R® C) FROM J ABOUT 1 9 -On CC CD CC ro T T T 1 T 1 T 1 r 1 T 1 T T 1 Example No .: CD about - CXI WHAT IN" g · and WHAT

- 104-

- 105-

Chemical name 6-cyclopentyl-1,2,4-triazolo [1,5-a] purin 9-one 1 WHAT about* ABOUT N ro V c M; - About CM CD V. = (D CL E ro 1 1 N C Q -Q 1 CN 1 ID 'about O N ro • 4 » 1 M; c c \ '9 -U CL □ 2 CL 9- ro c 1 m · 1 > »N C Φ _Q 1 CM 2-cyclopentyl-1,2,4-triazolo [1,5- a] purin-9-one 2-cyclopentyl-4-methyl-1,2,4-triazolo [1,5-a] purin-9-one 2-cyclopentyl-4-ethyl-1,2,4-triazolo [1,5- a] purin-9-one 2-cyclopentyl-4-n-propyl-1,2,4-triazolo [1,5-a] purin-9-one 6-carboxymethyl-2-cyclopentyl-4-ethyl 1,2,4-triazolo [1,5-a] purin-9-one Melting point ° C 231 -236 CD O CO 222-223 o CD CO A m co CM 249-253 o m CM 270-271 (0 ai l 9 LC 1 T 1 T T 1 T 1 T 1 CO T o o o 1 lO Article 1 1 1 OT - °. Ra ¹ ra ¹¹ tf) k * 1 1 1 1 CL ' 1 n-pentyl >, Φ E 1 n-propyl II IC CC O t -Q, Φ ¹ 05 'T CC 'E 1 ">> 4— * Φ n-propyl Φ t CM OĹ l 9 9 9 9 9 9 9 9 about t- ^ 7 CĹ Φ ÓĹ ro T T X 1 T X T and X 1 T l T 1 Example No .: ID CM CD CM r ^ CM co CM CD CM o CO WHAT CM CO

- 106-

> Pollen-1,2,4-1 one 1 tfj o ¹⁰ O M * of IN" 1 0 one yi-1,2,4-I one i-propyl- | 9-one -propyl- H c> o 1 CT> 1 -propyl 9-one , 2,4-I what > ο IN Q. 1 ABOUT) 1 C IN co O u. CL 1 o 1 c CL O L- 1 ABOUT) 1 c [_ 1 M 1 C ΙΟ C 1 N- C \ _ D c .Ξ • 4 □ 1 1 o 1 c N 05 C 1 'C □ l c Ό 1 C 1 'CZ Σ3 Q. 1 C 'C D CL Q. 05 >> 4 · CL 05 d. £ x-> CQ C D C D C 1 CL CM about TR Cl 1 dL ABOUT CZ C> (CN CL O l_ CL >, -X. o E 5-methyl WHAT 1 LO T * " 1 Q. o r C '1 - D Q. 1 4 * Φ I CO cp ιό x ^- TJ 1 CD xf Φ 1 in l_U u. CL _i_ 1 CO 1 LD "O O O CL O >. U0 θ 'O (D LO CL t-3 ä 5k O CO 1 LO x ^- ABOUT o o t 05 >> ABOUT > x ABOUT >> N ABOUT N O N CL about -C Q 1 *> » Q. ABOUT C about 4 · C 05 CM 05 CN -S 1 C about 4 » N C C N Φ N a> 1 F * J. 4 = 1 N c Φ OJ 1 Φ CL WHAT CL o WHAT CL o 1 xf 1 M ^- u. t- xt X) 1 WHAT 'ZZ CL O J * s >> O JZ >. 4 ' 4 · CN JD CN cm ' CD 4— * Φ >% o about T C x- IN N ^- >, O CN 1 WHAT About CM I CM 1 CM 'i CD CD > g · _{_} __ _{_} 05 ro WHAT WHAT] TJ about ABOUT CN about WHAT WHAT CN CD ABOUT ABOUT 05 c. 1 about ΙΩ m 1 xT •in ABOUT JTI Q_ Φ Φ Q. ABOUT CM WHAT A CM CM about CN what WHAT N O H ABOUT 4 · CD CM CO CM L_ Y > » pollen CL Y CL <£> X about about D ABOUT Article ABOUT φ Φ 1 Q. 1 C 1 u. CL 1 1 C 1 Y n-cl m QL T 1 1 1 >. > >. >. Y > x Q. Cl CL CL CL CL ql CL · $ ABOUT ABOUT ABOUT ABOUT ABOUT ABOUT 2 about ° r and Q. Q. Q. CL CL CL CL C 1 C 1 C C 1 C 1 C C 1 C 1 ----- / - ' L / - y b CM oL 9 x 1 9 9 s ) with ) ? with ABOUT Article XJ Φ WHAT oL T T 1 T T from τ T. I it TJ (0 pi WHAT M m CD > - 00 σ> about > About what WHAT WHAT WHAT what what what xt t CL

- 107-

Chemical name 1 oí 1 N -O -e = 'O ä é? In m CM <>> * o e s 1 \ - C * _l_ 1 CD M · ' 2,6-diethyl-4-n-propyl-1,2,4-triazolo [1,5- a] purin-9-one 6-phenyl-4-n-propyl-1,2,4-triazolo [1,5- a] purin-9-one 2-ethyl-6-phenyl-4-n-propyl-1,2,4-triazolo [1,5-a] purin-9-one 2-cyclopentyl-6-phenyl-4-n-propyl-1,2,4- triazolo [1,5-a] purin-9-one 6- (2-furyl) -4-n-propyl-1,2,4-triazolo [1,5- a] purin-9-one 2-ethyl-6- (2-furyl) -4-n-propyl-1,2,4- triazolo [1,5-a] purin-9-one 2-cyclopentyl-6- (2-furyl) -4-n-propyl 1,2,4-triazolo [1,5-a] purin-9-one Melting point in ° C 221 229 295 - 296 (decomposition) > 300 (Decomposition) > 300 (Decomposition) -------------------------------------------------- -------------------------------------------------- --------------------------------- 1 > 300 (Decomposition) > 300 (Decomposition) > 300 (Decomposition) what to do 1 n-propyl ethyl 9 9 9 ° F ° F ° F m CĹ ( 1 1 1 - 1 1 1 1 • tf · CĹ 1 n-propyl n-propyl n-propyl n-propyl n-propyl n-propyl n-propyl n-propyl CN CC 1 U. r φ t T 1 >> 4— · Φ 1 9 T 1 φ 9 about r-O CO CC Φ CC WHAT I 1 T 1 T T T T T 1 T 1 T J T I Example No .: t • m- 42 43 44 45 46 47 CO xr

- 108-

> 1 M * CN 1 >. 9-one rin-9-one 1 LO ί, j about about N CO 1 l- yl-1,2,4- 9-one ty 1-1,2,4- 9-one 1 ID θ ' O N 05 · L - yl-1,2,4- 9-one □ pollen-1,2,4 C-o ct> ο N '05 Q. ABOUT Q. C 1_ D = 5 Q. Ή 1 1 xt cn what Q. o Q. c \ _ D φ E c u. D 1 CXI C Ό Q. O u. Q. C 3 = L. CL 1 C c '1— Σ3 1 Q. CT> 1 CL Ό CL a> and CL 1 CL in* C 1 05 ΙΌ 1 C C 1 (0 4 Γ ·· | WHAT 1 1 c C WHAT ABOUT 05 about E φ 7 t U0 ΤΟ O 4 » Φ 2 m 1 L. O Q. u? 1 in WHAT 1 2? 1 in > x 4- »φ ABOUT □ Q. lo 1> » 4-4 LO x ^- 1 1 LO x- about N 05 CZ about C about 05 C about >. about -What φ Q. o N .WITH * u > c O CL o o N Φ Q. o N Μ · _ co Φ CL O 2 *. >, about 1 CD o IN t-1 C 0) o N O J * O <d .WITH 4-* 1 tf 04 IN Φ Q. O-X. >> O S>, O 1 CM .5 4 · ABOUT >, o 1 CN .52 L4- ^ 1>. N C Φ X} 1 .52 'k_ 4 ^ CL O >. o 1 CD cu 'ĹZ 4-4 CN CD 05 > what ABOUT WHAT ra c φ Q CN ABOUT 4- »O CL Φ U ABOUT CM 1 o o CO A About CD CN CXI 1 r ^. CD O CN O O CO Λ CN 1 CN CD ' H ABOUT 4 ' CN · l CN ABOUT 04 (0 oL 1 9 T 1 T T and T 1 9 9 9 o x> T o x> T >> Q. >. Q. m Φ Φ 05 ¹ ABOUT ABOUT CC WHAT II and II m 4 * Φ 1 U. Q. ¹ 1 LCL 1 m- CC CC CC DC C C 1 II II - CC CC (0 ">> 4Φ >. Q. ’T CĹ o X) Φ 05 T l o x> Φ T 1 1 1 T o ABOUT Q. 05 C 1 M ^- M · CC CC CN Article 1 T 1 LC 1 9 '9 9 T 1 T 1 T about WHAT >. or XJ Φ ω CL ' C Q. O T T T T o 4 · Φ T C CL O 05 Q. CL U σ> about IN- CXI WHAT M m CD > About M ^- LO m LO LO LO and LO · L. Q_

-109-

Chemical name 2-Cyclopentyl-4-n-butyl-1,2,4-triazolof 1,5-a] purin-9-one 2-cyclopentyl-4-n-butyl-1,2,4-triazolo [1,5-a] purin-9-one 6-benzyl-4-ethyl-2- (2-pyridyl) -1,2,4 triazolo [1,5-a] purin-9-one 1 XT <N £ £ 4 f = 4 Ä V ra Sl 4. 4 'Φ o 4 o _L N >> r and N' C C Φ .Q 1 CD 2-cyclopentyl-5-t-butyl-1,2,4- triazolo [1,5-a] purin-9-ori 2-cyclopentyl-4-tert-butyl-1,2,4 triazolo [1,5-a] purin-9-one 6-benzyl-4-ethyl-2- (3-pyridyl) -1,2,4 triazolo [1,5-a] purin-9-one 1 T cT - c ¾ '9> a CD Q. A O L- Ι- Ο. ZJ A * - i i _L l If uo ZL D O * 7 CXI N .2 1 CD cxf Melting point ° C r " LO t WHAT CN Ν- 00 CXI CD WHAT 149 -150 190-191 331-322 385-387 (ABOUT qí 1 9 T I 9 9 T 1 x J 9 ° F uo CC 1 T 1 à 1 1 1 OC 1 n-propyl -n-butyl Φ 1 "> X (d) 1 1 Ý w (D 1 n-propyl (XI CC 1 x T 9 9 9 9 9 9 ° F o r- .Q CO CC Φ CC ra -n-propyl T 1 X 1 T 1 T 1 X 1 X 1 x 1 Example No .: RIO 00 IO CD U0 o CD with CXI CD co CD M CD

110-

Chemical name 6-benzyl-2-dimethylamino-4-n-propyl 1,2,4-triazolo [1,5-a] purin-9-one 6-benzyl-2-cyclohexyl-4-ethyl-1,2,4- triazolo [1,5-a] purin-9-one 6-benzyl-2- (N-piperidinyl) -4-n-propyl 1,2,4-triazolo [1,5-a] purin-9-one 6-benzyl-2-tert-butyl-4-ethyl-1,2,4- triazolo [1,5-a] purin-9-one 6-benzyl-4-ethyl-2-phenyl-1,2,4-triazolo [1,5-a] purin-9-one 2-cyclopentyl-4-ethyl-6- (3-pyridylmethyl) - 1,2,4-triazolo [1,5-a] purin-9-one 2,4-diethyl-6- (3-pyridylmethyl) -1,2,4triazolo- [1,5-a] purin-9-one 6-Benzyl-1,4-diethyl-2- (2-phenyl) -1,2,4-triazolo [1,5-a] purin-9-one Melting point ° C 272-274 260-262 294-297 243-244 343–345 261-263 225-227 187-189 CD QL 1 9 9 9 ' 9 9 9 9 LD CL ' 1 1 1 T 1 1 1 1 Article 1 n-propyl ethyl n-propyl 4— »Φ > » 4— · Φ ethyl and >> M— · Q) 1 <D 1 CM Article 1 CM WHAT  about. from 9 Q 1 T 9 9 > with H— ¹ Φ about v- O CO CĹ Φ CĹ 05 T 1 X X x t 1 x x 1 X 1 ethyl Example No .: 65 99 67 68 69 70 r- 72

, .- 1-11 «

> ο N ‘OJ C 1,2,4-triazolo- in-9-one ethyl-1,2,4-triazolo in-9-one 4 cm ’in- t>. Φ Ό 1 M · cm ’ ] Purin-9-one 1, N b c Φ Cl O >, O 1 CM 1,5-a] purin-9-one 1 tX5_ τ- ι o o N ra 4 cm ’ 9-one 1 about o N ra c - + - <4cm ’ 1>. in-9-one 1 xr CN in- 1 § Φ> x C £ 1 CD ] Purin-9-one n-propyl-2- (3- 1 IX5_ τ- ι O O N 05 * 1— 1 McM ’ what 1 05 >>> j ±: o φ E CL5 CL 1 n- 1 □ CL 2? ro 1 1X5 1 1 O τι t-f CD C Έ> ra CL 1 >> 05 1 1X5 4 1 Vt C E φ JC >> 1 LO >. »Φ E ^ 1 ro 1 1X5 Φ E >> in- 1 o Φ E>, o N 05 Σ3 Q. 05 C r ** 'i 05 1 ΙΌ Φ 1 XT 1 IN" 1 o >. c Φ >. c ro ra 05 ABOUT CL - > with X X (D o N x φ 1 N · c Ä CD 1 >, c o N Q. O O «4o WHAT CD X 4 * Φ JC o o š (U '4— » ; x: Ό • 0 «í>> * 'about CN 1 M · 1 CD 1 >> 3— »Q) Φ TJ 1 'sr O CL O AT >> ra • 4 » O i CD · L. Ό >. jC 05 L- M 1 M ^- o cô CD CD 1 Φ 1 n · cm ABOUT 1 CM Φ 4-4 (0 > ABOUT about CM M ^- WHAT M ABOUT ra WHAT WHAT WHAT R - 00 05 05 o CL φ ABOUT 0 what what CM CM WHAT CM CM CM C Φ n 00 1 00 1 ABOUT . 1 WHAT BCM 1 CN 1 CM 1 CD H Q CM CM WHAT r- 00 05 00 4 ' WHAT WHAT CM CM CM CM CM WHAT ť FROM 1 1 C Ύ r Cl C Article 5 JJ 9 J WITH J with J 9 and CL ' 1 1 1 1 1 1 1 ΤΓ a >> >> > ϊ > ϊ >. >. >. about Φ Φ Φ Φ Φ Φ Φ CL C 1 R-1 ΓΛ _r o CM cr Έ T 1 >> 4 — i Φ 1 9 T 1 Γ -ethyl 9 9 about Article _Q Φ WHAT Article T T 1 T 1 T 1 T 1 I 1 T 1 T 1 ra Ό ra WHAT M LO CD; b- 00 05 about > About h- r- b- b- b- 00 CL  !

- 112 -

-114-

Chemical name 6-cyklohexylmetyi-4-ethyl-2- (5- 1 in ó o N ro * 1— 1 sr CM 1 g CM C d) C ΟΟ -Q ΙΟ C a] purin-9-one 3-benzyl-2-cyclopentyl-4-ethyl-6- ethyloxy methyl 1-1,2,4-triazolo- [1,5-a] purine- c • o σ> 2-cyclopentyl-4-ethyl-6-etyloxymetyl- What 1 CD 1 C  'C □ ^ Q. OJ 1 in in- 1 O O N ra 1 M CM T " <é i | >> (D * - C ω Q. 1 t OJ 1 j (benzyloxymethyl) -1,2,4-triazolo [1,5- a] purin-9-one 2-cyclopentyl-4-ethyl-6- (Benzyloxymethyl) -1,2,4-triazolo [1,5- a] purin-9-one 3-benzyl-2-cyclopentyl-4-ethyl-6- methyloxymethyl-1,2,4-triazolo [1,5- a] purin-9-one > about WHAT m CD what nj 'c CD TJ CM CM WHAT _about ABOUT CM 05 CM 1 ol F Pulse (D Q. ABOUT 58 N O 20 24 00 CO ABOUT X " 4 · CM CM CM <n I d o o j ro (D CC 1 9 m r CM O o k o = V_7 0 ς o = y o ς - ^ OCH m 01 l 1 F T 1 1 g · >% > > » > » saith 1 Φ 1 Φ 1 • w Φ 1 «4—» 1 Φ Φ 1 CM ή n Γ , r Λ r λ r oL 1 τ J 9 in > with / with > T ABOUT The Ίι F 01 n o WHAT CC T WITH· J T 1 e T 1 'r ra J TJ Tt ID WHAT r- 00 CD > About about CD CD CD CD CD nn

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1 >> · ♦ - »φ C 1 ο ο t CD 1 o o 1 o o J.> O ι-9-one Olo- ·> yloxymethyl Ό 1 CD 1 C ’C 1 CM I Ν N ro 4 C t >> 4— »Φ 1 T C N .55 ‘u. · + - * C CD —L N 05 i_ 1 M C o q = 73M; at ’1_ D Q. 05 OJ 1 >> N C N .55 ’k_ Μ-» 1 xr C ο N * (0 φ Ε ZJ Q. 1 '^ ω c φ X) of 'ABOUT 1 σ> 1 oi about 1 o 1 »- »Φ CM > the 1 σ> 1 what 1 CD ιό J. Xi J. pole •about 1 CD C '>> ώ 1 1 ΙΌ 1 L. * Ο z -x * c ’l_ Φ Q. *> \ c ’k_ >> z — s >> C * L · - b 1 O * o _D ">, C ' Λί > χ C ABOUT 4 * □ 4-J Σ3 Φ 1 about WHAT about Ο Ε φ • -J- * 5 = WHAT Q. in Φ Q. C Φ Q. N 73 Q. Φ 1 1 ο ο I WITH/ what - * - » ^{11 11} '»05 m >. about < E o c Γ-Ί 05 1 LD Φ Οο E o c 05 2 m η · 05 • 4 » l sf co c CO • 4— * WHAT ABOUT -C Ν WHAT C CM -X - F M * C - Ο 4- * C φ CL Ο <2 ’C Μ—» 1 WHAT E L_-U N E 05 T ~ > 1 o 1 T 05 Ľ Cľ of ώ 05 E 4 οί φ 4 05 73 CO C Φ JO > » -4- »Φ O1 No * Φ o> » T >> • tΦ 05 73 05 τ ~ U. o 1 CO E E about >. N M l_ o ο C 73 73 OJ C C οι Φ XI > οο r- CD r- 05 what 'c φ ο OJ CD T " • 4— »Ο Ο. Φ Ο 0 οι 1 CD WHAT CD 1 224 - ra m OJ OJ 14 - 2 5-3 H ο 24 OJ CO CD OJ IN" WHAT rt u. r τ ' LL LL Á u. 1 ω r ο about T nf υ CO T T j "-Ύ 01 ο ς 1 v · << from- about from ς -about r L r m 01 1 1 and >> >. >> > » > ϊ Ί >> 01 4- »Φ 1 in M— »Φ 1 Φ Φ Φ ΟΙ Γ ' \ r C λ C ) I7 ³ s 01 1 ϊ ) > Ύ with from T C Ο f ' Ϊ1 01 η φ 00 01 τ 1 r 1 with 'J T t T 1 I 1 C0 J σ CX3 ο OJ what Ό m > ο ο about about about ABOUT about ν- T " t IN" IN" T " 0_

-116-

Chemical name 3-Benzyl-2-cyclopentyl-4-ethyl-6- (N-morpholino-methyl) -1,2,4-triazolo [1,5- a] purin-9-one 2-cyclopentyl-4-ethyl-6- (N-morpholinomethyl) -1,2,4-triazolo [1,5-a] purin-9-one 6-benzyl-4-ethyl-2- (noradamantan-3-yl) - 1,2,4-triazolo [1,5-a] purin-9-one 4-ethyl-2- (noradamantan-3-yl) -6- (3-pyridyl-methyl) -1,2,4-triazolo [1,5-a] purin-9-one 3-benzyl-2-cyclopentyl-4-ethyl-6- (methyl-3pyridylkarbonyloxy) -1,2,4triazolo- [1,5-a] purin-9-one 3-benzyl-6-carboxy-2-cyclopentyl-4-ethyl-1,2,4-triazolo [1,5-a] purin-9-one 3-Benzyl-6-kyrboxymetyl-2-cyclopentyl- 4-ethyl-1,2,4-triazolo [1,5-a] purin-9-one Melting point ° C 1 00 x- 320-322 330-332 1 157- 158 155-157 <0 qí 1 (Τ'N- \ 0 i i k. 9 oP o 9 -C00H CO T o o o t m ° r 1 - 1 1 1 x 1 >> Φ 1 >> + - »Φ 1 ">» 4- »Φ 1 4— »Φ 1 ~> A »- »Φ > » > 4— »Φ 1 • 4— * Φ 1 Ol trí 9 9 9 9 9 9 about v- Γ) n et al 05 9 T 1 T 1 I 1 9 9 9 Example No .: CO o about 00 o CD O T " about - CM

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The structures of the synthesized compounds I (a) to (Id) were confirmed by @ 1 H NMR spectrometry and are given as examples.

NMR-spectrometric data of selected compounds:

Example 3 ¹ H NMR (DMSO-d 6) δ = 14.10 (1H, s,

H, m, aryl-H); 4.12 (2H, t, J = 7.5 Hz, N-CH ₂ CH ₂ CH _3); 4.09 (2H, s, CH, -phenyl); 1.73 (2H, m, N- CH, CH, CH 2); 0.89 (3H, t, J = 7.5Hz, N-CH, CH, CH 2).

broad, NH); 8.24 (1 H, s, H 2); 7.35 - 7.14 (5

Example 4 ¹ H NMR (DMSO-d 6) δ = 13.28 (1H, s, broad, NH); 8.24 (1H, s, H _2); 7.35-7.14 (5H, m, aryl-H); 4.15 (2H, t, J = 7.5 Hz; N-CH, CH, CH, CH 2); 1.68 (2H, m, NCH ₂ CH, CH, CH,); 1.32 (2H, m, N-CH, OH, CH, CH 2); 0.90 (3H, t, J = 7.5Hz, NCH ₂ CH ₂ CH ₂ CH ₃ ). |

Example 5 ¹ H NMR (DMSO-d 6) δ = 13.22 (1H, s, broad, NH); 8.25 (1 H, s, _H2); 7.35-7.14 (5H, m, aryl-H); 5.33 (1H, m, CH-isopropyl); 4.09 (2H, s, CH, -phenyl); 1.55 (6H, d, J = 7.0 Hz, _{(CH3) 2} isopropyl).

Example 6

Ή NMR (DMSO-d 6) δ = 13.66 (1H, s, broad, NH); 7.35-7.14 (5H, m, aryl-H); 4.11 (2H, t, J = 7.5 Hz, N-CH, CH, CH 2); 4.07 (2H, s, _CH2-phenyl); 2.79 (2H, q, J = 7.5 Hz, -CH, CH 2); 1.71 (2H, m, N-CH, CH, CH 2); 1.29 (3H, t, J = 7.5Hz, --CH, CH3); 0.90 (3H, t, J = 7.5 Hz, N-CH ₂ CH ₂ CH _3).

Example 7 ¹ H NMR (DMSO-d 6) δ = 13.70 (1H, s, broad, NH); 7.43-7.14 (5H, m, aryl-H); 4.09 (2H, t, J = 7.5 Hz, N-CH, CH, CH 2); 4.07 (2H, s, _CH2-phenyl); 2.75 (2H, t, J = 7.5Hz,

119-CH, CH ₂ H ₃ ); 1.74 (4H, m, N-CH ₂ CH ₂ CH ₃ CH, CH, CH,); 0.92 (6H, m, NCH, CH, CH 2).

Example 8

Δ NMR (DMSO-d 6) δ = 7.34-7.12 (5H, m, aryl-H); 4.07 (2H, s, _CH2-phenyl); 3.55 (3H, s, _N-CH3); 3.23 (1H, m, CH-cyclopentyl); 2.14 to 1.52 (8H, m, CH ₂ -cyclopentyl).

Example 9

Δ NMR (DMSO-d 6) δ = 13.68 (1H, s, broad, NH); 7.40-7.14 (5H, m, aryl-H); 4.19 (2H, q, J = 7.5 Hz, N-CH, CH 2); 4.09 (2H, s, _CH2 -aryl); 3.24 (1H, m, CH cyclopentyl); 2.26 to 1.50 (8H, m, _{CH2-cyclopentyl);} 1.26 (3H, t, J = 7.5Hz, CH, CH 2).

Example 10 ¹ H NMR (DMSO-d 6) δ = 13.65 (1H, s, broad, NH); 7.38-7.14 (5H, m, aryl-H); 4.11 (2H, t, J = 7.5 Hz, N-CH ₂ CH ₂ CH _3); 4.08 (2H, s, _CH2-phenyl); 3.23 (1H, m, CH cyclopentyl); 2.14 -1.49 (10H, m, _{CH2-cyclopentyl,} N-CH, CH, CHJ, 0.89 (3H, t, J = 7.5 Hz, N-CH ₂ CH ₂ CH ₃ ).

and

Example 11 ¹ H NMR (DMSO-d 6) δ = 13.85 (1H, s, broad, NH); 7.62-7.33 (5H, m, aryl-H); 4.34 (2H, t, J = 7.5 Hz, N-CH3); 4.28 (2H, s, _CH2-phenyl); 3.43 (1H, m, CH-cyclopentyl);

2.33 to 1.38 (12 H, m, _{CH2-cyclopentyl,} N-CH, -CH, -CH,); 1.10 (3H, t, J = 7.5 Hz, N (CH _{2) 3} CH _3). ;

I

Example 12 ¹ H NMR (DMSO-d 6) δ = 12.58 (1H, s, broad, NH); 7.52-7.14 (10H · m, aryl-H);

5.52 (2H, s, N-CH, -aryl); 4.18 (2H, s, _CH2 -aryl); 3.31 (1H, m, CH-cyclopentyl);

j

2.21 -1.50 (8H, m, CH ₂ -cyclopentyl).

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Example 13 ¹ H NMR (DMSO-d 6)? = 12.38 (1H, s, broad, NH); 7.34-7.14 (5H, m, aryl-H); 4.08 (2H, t, J = 7.5 Hz, N-CH, CH, _CH); 4.06 (2H, s, _CH2-phenyl); 3.69, 3.59 (8H, m, morpholine-H); 1.70 (2H, m, N-CH, CH, _CH); 0.88 (3H, t, J = 7.5 Hz, N CH ₂ CH ₂ CH _3).

Example 14 ¹ H NMR (DMSO-d 6)? = 12.26 (1H, s, broad, NH); 7.38-7.14 (10H, m, aryl-H); 4.08 (2H, t, J = 7.5 Hz, N-CH ₂ CH ₂ CH _3); 4.06 (2H, s, _CH2-phenyl); 3.57, 2.46 (8H, m, piperazine-CH2-); 3.52 (2H, s, N-CH ₂ -phenyl); 1.70 (2H, m, N-CH, -CH, CH 2); ® 0.88 (3H, t, J = 7.5 Hz, N-CH, CH, _CH).

in

Example 15 ¹ H NMR (DMSO-d 6) δ = 7.40-7.14 (5H, m, aryl-H); 4.76 (3H, s, br, NH, _NH2); 4.08 (2H, t, J = 7.5 Hz, N-CH ₂ CH ₂ CH _3); 4.06 (2H, s, -CH 2 -phenyl); 3.48, 2.79 (8H, 2m, piperazine-CH2-); 1.90 (3H, s, CH ₃ COOH); 1.70 (2H, m, N-CH, -CH, CH ₃ ); 0.88 (3H, t, J = 7.5 Hz, N - CHoCHoCH3).

Example 16 ¹ H NMR (DMSO-d 6) δ = 13.82 (1H, s, broad, NH); 7.34-7.14 (5H, m, aryl-H); 4.19 φ (2H, q, J = 7.0 Hz, N-CH ₂ CH ₃ ); 4.08 (2H, s, -CH, -phenyl); 3.93 3.43 (4H, 2 m, 2 CH ₂ O); 3.09 (1H, m, -CH-THF); 2.00 to 1.68 (4H, m, 2 _CH2-THF); 1.25 (3H, t, J = 7.0 Hz, N-CH ₂ CH _3).

Example 17 ¹ H NMR (DMSO-d 6)? = 13.84 (1H, s, broad, NH); 7.34-7.14 (5H, m, aryl-H);

4.18 (2H, q, J = 7.0 Hz, N-CH, _CH?): 4.08 (2H, s, _CH2-phenyl); 4.08 to 3.74 (4H, m, CH 2 _-O-2 3THF); 3.62 (1H, m, -CH-3THF); 2.29 (2H, m, _CH2 -3THF); 1.25 (3H, t, J = 7.0 Hz, -N-CH 2 -CH 2).

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Example 18;

^{@ 1} H NMR (DMSO-d6) .delta. = 13.64, 12.76 (2H, 2 s, broad, 2 NH); 7.35-7.14 (5H, m, aryl-H); 4.02 (2H, s, CH, -phenyl): 3.23 (1H, add _F, CH-Cyclopentyl); 2.14 to 1.50 (8H, m, CH ₂ -cyclopentyl) .η

Example 19 ¹ H NMR (DMSO-d 6)? = 13.42, 13.20 (2H, 2 s, broad, 2 NH); 8.24 (1H, s, H2);

3.20 (1H, m, -CH-cyclopentyl); 2.17 1.50 (1H, m, CH ₂ -cyclopentyl).

Example 20 ¹ H NMR (DMSO-d 6) δ = 13.86 (1H, s broad, NH); 8.22 (1 H, s, H 2); 3.58 (3H, s, NCH ₃ ); 3.23 (1H, m, -CH-cyclopentyl); 2.14 1.52 (8H, m, CH ₂ -cyclopentyl).

Example 21 ^{@ 1} H NMR (DMSO-d6) .delta. = 14.04 (1H, s, broad, 1H); 8.24 (1H, s, H _2); 4.13 (2H, t, J =

7.5 Hz, N-CH ₂ CH ₂ CH ₃ ); 3.21 (1H, m, -CH-cyclopentyl); 2.14 to 1.52 (10 H, m, CH ₂ -cyclopentyl); 0.90 (3H, t, J = 7.5Hz, N-CH, C'H, CH 3).

Example 22

Ή NMR (DMSO-d 6) δ = 13.68 (1H, s, broad, NH); 4.12 (2H, t, J = 7.5 Hz, NCH ₂ CH ₂ CH ₃ ); 3.20 (1H, m, -CH-cyclopent 11); 2.12 to 1.52 (10 H, m, CH ₂ -cyclopentyl); 0.69 (3H, t, J = 7.5 Hz, N-CH ₂ CH ₂ CH _3).

and

Example 23 ¹ H NMR (DMSO-d 6) δ = 13.64 (1H, s, broad, NH); 4.12 (2H, t, J = 7.5 Hz, NCH ₂ CH ₂ CH ₃ ); 3.20 (1H, m, CH-Cyclopentyl); '2.80 (2H, q, J = 7.5 Hz, CH ₂ CH _3);

2.13-1.52 (10 H, m, CH ₂ -cyclopentyl, N -CH, CH, CH 3; 1.29 (3 H, t, J = 7.5 Hz, CH ₂ -CH ₃ ); 90 (3H, t, J = 7.5 Hz, N-CH ₂ CH ₂ CH _3).

..1 ι

Example 122 ¹ H NMR (DMSO-d 6) δ = 13.88 (1H, s, broad, NH); 7.35-7.14 (5H, m, aryl-H); 4.13 (2H, s, _CH2-phenyl); 4.11 (2H, t, J = 7.5 Hz, N-CH ₂ CH ₂ CH _3); 3.19 (1H, m, -CH-cyclopentyl); 2.09 to 1.52 (10 H, m, CH-cyclopentyl, N-CH ₂ CH ₂ CH _3); 0.89 (3H, t, J = 7.5 Hz, N-CH ₂ CH ₂ CH _3). '

Example 25 ¹ H NMR (DMSO-d 6) δ = 13.60 (1H, s, broad, NH); 7.43-7.14 (5H, m, aryl-H);

4.36 (2H, t, J = 7.5 Hz, CH ₂ N (CH _{2) 3} CH _3); 4.19 (2H, s, _CH2-phenyl); 3.40 (1H, m, CH-cyclopentyl); 2.31 -1.24 (14H, m, _{CH2-cyclopentyl,} N-CH, _(CH2), CHJ, 0.89 (3H, m, N - (CH, VCH).

Example 26 ¹ H NMR (DMSO-d 6) δ = 13.85 (1H, s, broad, NH); 8.16 (1H, s, H6); 7.35-7.14 (5H, m, aryl-H); 4.15 (2H, s, CH, -phenyl); 3.59 (3H, s, _N-CH3).

/ j ·

Example 27

Δ NMR (DMSO-d 6) δ = 14.02 (1H, s, broad, NH); 8.19 (1H, s, H6); 7.35 - 7.14 (5

I

H, m, aryl-H); 4.18 (2H, s, CH, -phenyl); 4.15 (2H, t, J = 7.5 Hz, N-CH, CH, CH ₃ );

1.75 (2H, m, N-CH, CH, CH 3; 0.93 (3 H, t, J = 7.5 Hz, N-CH, CH, CH ₃ )).

Example 28 ¹ H NMR (DMSO-d 6) δ = 13.50, 12.92 (2H, 2 s, broad, 2 NH); 8.10 (1H, s, H6);

3.24 (1H, m, -CH-cyclopentyl); 2.17 1.52 (8H, m, CH ₂ -cyclopentyl).

Example 29

Δ NMR (DMSO-d 6) δ = 13.70 (H, s, broad, NH); 8.18 (1H, s, H6); 3.59 (3H, s, -C1)

CH ₃ ); 3.25 (1H, m, CH-cyclopentyl); 2.15 to 1.52 (8H, m, CH ₂ -cyclopentyl).

-123Example 30 ¹ I

@ 1 H-NMR (DMSO-d6) .delta. = 13.70 (H, s, broad, NH1); 8.20 (1H, s, H6); 4.25 (2H, q, J = 7.0 Hz, N-CH ₂ -CH _3); 3.27 (1H, m, CH-cyclopentyl); 2.21 to 1.52 (8H, m, CH ₂ -cyclopentyl); 1.29 (3H, t, J = 7.0 Hz, N-CH ₂ CH _3).

I '

Example 31

@ 1 H NMR (DMSO-d6) .delta. = 13.74 (H, s, broad, NH); 8.18 (1H, s, H6); 4.14 (2H, t, J =

7.5 Hz, N-CH, -CH, CH 2); 3.25 (1H, m, CH-cyclopentyl); 2.15 -1.54 (10H, m, CH ₂ - and

cyclopentyl, N-CH, -CH, CH ₃ ); 0.90 (3H, t, J = 7.5 Hz, N-CH, CH, -CH 2).

and

I

Example 33 j

@ 1 H-NMR (DMSO-d6) .delta. = 13.62 (H, s, broad, NH); 4.11 (2H, t, J = 7.5 Hz, N-CH, CH ₂ CH ₃ ); 3.23 (1H, m, CH-cyclopentyl); 2.37 | (3H, s, -CH ₃ ); 2.14 to 1.50 (10 H, m, _{CH2-cyclopentyl,} N-CH, CH, .CH,); 0.90 (3H, t, J = 7.5Hz, N-CH, CH, -CH 2).

i i

i:

(2H, t, J = 7.5 Hz, N-CH ₂ CH ₂ CH _3);

iin, N-CH, -CH, CH 2); 1.29 (3H, t, J = 7.5Hz, N-CH, CH, -CH 2).

ľ i

I

I ·

Example 34 ¹ H NMR (DMSO-d 6) δ = 8.22 (1H, s,); 4.13

2.75 (2H, q, J = 7.5 Hz, CH ₂ CH _3); 1.74 (2H,

7.5 Hz, CH, CH 3); 0.92 (3H, t, J)

Example 35 ¹ H NMR (DMSO-d 6) δ = 13.62 (H, s, broad, NH); 4.12 (2H, t, J =

CH ₂ CH ₃ ); 3.25 (1H, m, CH-cyclopentyl); 2.74 (2H, q, J = 7.5 Hz, -CH, CH 2); 2.17

- 1.51 (10 H, m, _{CH2-cyclopentyl,} N-CH, CH, .CH,); 1.29 (3H, t, J = 7.5Hz, CH, CH 3); 0.90 (3H, t, J = 7.5Hz, N-CH, CH, -CH 3).

7.5 Hz, N-CH, Example 36;

^{@ 1} H NMR (DMSO-d6) .delta. = 13.58 (H, s, broad, NH); 4.12 (2H, t, J = 7.5 Hz, N-CH, CH ₂ CH ₃ ); 3.24 (1H, m, CH-cyclopentyl); 2.69 (2H, t, J = 7.5 Hz, -CH, -CH, CH 2);

-1Ž42.15-1.50 (12H, m, CH ₂ -cyclopentyl, (CH ₂ -CH ₂ CH ₃ ) ₂ ); 0.90 (6H, two t, J = 7.5 Hz, (CH ₂ CH ₂ CH _{3) 2).} and,

I j

Example 37 ¹

@ 1 H-NMR (DMSO-d6) .delta. = 13.62 (H, s, broad, NH); 4.13 (2H, t, J = 7.5 Hz, N-CH, CH ₂ CH _3); 3.24 (1H, m, CH-cyclopentyl); 3.05 (1H, m, CH-isopropyl); 2.14 to 1.50 (10 H, m, _{CH2-cyclopentyl,} N-CH, CH, .CH _3); 1.32 (6H, d, J = 7.5 Hz, _CH3 of isopropyl); 0.90 (3H, t, J = 7.5Hz, CH, CH, --CH2).

Example 38

^{@ 1} H NMR (DMSO-d6) .delta. = 13.62 (H, s, broad, NH); 4.12 (2H, t, J = 7.5 Hz, N-CH, CH ₂ CH ₃ ); 3.24 (1H, m, CH-cyclopentyl); 2.70 (2H, t, J = 7.5 Hz, -CH, CH, CH, CH 2); 2.15 to 1.26 (14 H, m, _{CH2-cyclopentyl,} N-CH, CH, .CH "TA CH CH, CH,); 0.90 (6H, m, N-CH ₂ CH ₂ CH _3, (CH _{2) 3} CH _3).

Example 39 ¹ H NMR (DMSO-d 6) δ = 4.36 (2H, t, J = 7.5 Hz, N-CH, -CH, CH 2); 3.40 (1H, m, CH-cyclopentyl); 2.32 to 1.63 (10 H, m, _{CH2-cyclopentyl,} N-CH, CH, .CH,); 1.48 (9H, s, C _{(CH3) 3);} 1.02 (3H, t, J = 7.5 Hz, N-CH ₂ CH ₂ CH _3).

Example 40 ¹ H NMR (DMSO-d 6) δ = 14.28 (1H, s, broad, NH); 8.26-7.45 (5H, m, aryl-H); 4.14 (2H, t, J = 7.5 Hz, N-CH ₂ CH, _CH); 2.71 (2H, t, J = 7.5 Hz, CH ₂ CH ₂ CH _3); 1.76 (4H, m, (CH ₂ CH ₂ CH ₃ ) ₂ ); 0.98, 0.93 (6H, 2t, (CH, CH, CH3)).

Example 41 ^{@ 1} H NMR (DMSO-d6) .delta. = 7.44-7.05 (4H, m, aryl-H); 4.13 (2H, s, _CH2-phenyl); 4.11 (2H, t, J = 7.5Hz, N-CH, CH, CHJ; 2.68 (2H, t, J = 7.5Hz, CH, CH, CHJ: 1.74 ( 4 H, m, (CH, CH, CH 2), 0.95, 0.89 (6 H, 2H, J = 7.5 Hz, (CH ₂ CH ₂ -CH ₃ ) ₂ ).

Example 42 ^{@ 1} H NMR (DMSO-d6) .delta. = 13.64 (1H, s, broad, NH); 4.12 (2H, t, J = 7.5 Hz, NCH, _CH? CH); 2.76 (4H, m, (CH, CH3)); 1.73 (2H, m, N-CH, CH, CH 2); 2.29 (6H, m, (CH, CH3)); 0.90 (3H, t, J = 7.5Hz, N-CH, CH, CH 2).

Example 43 ¹ H NMR (DMSO-d 6) δ = 14.19 (1H, s, broad, NH); 8.31 (1H, s, H _2); 8.16 - 7.38 (5

H, m, aryl-H); 4.21 (2H, t, J = 7.5 Hz, N-CH ₂ CH ₂ CH _3); 1.83 (2H, m, N-CH ₂ CH ₂ CH _3); “Í

0.98 (3H, t, J = 7.5 Hz, N-CH, CH, CH _3).

Example 44

@ 1 H-NMR (DMSO-d6) .delta. = 13.78 (1H, s, broad, NH); 8.19-7.43 (5H, m, aryl-H); 4.21 (2H, t, J = 7.5 Hz, N-CH ₂ CH ₂ CH _3); 2.83 (2H, q, J = 7.5 Hz, -CH, CH 2);

1.81 (2H, m, N-CH, CH, CH 2); 1.33 (3H, t, J = 7.5Hz, --CH, CH3); 0.95 (3H, t, J = 7.5Hz, NCH, CH, CH 2).

Example 45 ¹ H NMR (DMSO-d 6) δ = 13.70 (1H, s, broad, NH); 8.19-7.38 (5H, m, aryl-H); 4.21 (2H, t, J = 7.5 Hz, N-CH ₂ CH ₂ CH _3); 3.28 (1H, m, CH-cyclopentyl); 2.19 to 1.50 (10 H, m, _{CH2-cyclopentyl,} N-CH ₂ CH ₂ CH _3); 0.94 (3H, t, J = 7.5 Hz, N-CH ₂ CH ₂ CH _3).

Example 46

@ 1 H-NMR (DMSO-d6) .delta. = 8.26 (1H, s, H2); 7.84, 7.10, 6.69 (3H, 3m, furyl-H); 4.10 (2H, t, J = 7.5 Hz, N-CH ₂ CH ₂ CH _3); 1.81 (2H, m, N-CH 3 -CH 2 CH 2); 0.98 (3H, t, J =

7.5 Hz, N-CH, CH, -CH 2).

Example 47 ¹ H NMR (DMSO-d 6)? = 13.56 (1H, s, broad, NH); 7.70, 6.91, 6.50 (3H, 3 m, furyl H); 4.00 (2H, t, J = 7.5Hz, N-CH, CH, CH 2); 2.66 (2H, q, J = 7.5 Hz, -CH, CH 2);

-126-

1.61 (2H, m, N-CH, CH, CH 2); 1.14 (3H, t, J = 7.5 Hz, N-CH ₂ CH ₂ CH _3); 0.77 (3H, t, J = 7.5Hz, --CH, CH3).

Example 48 ^{@ 1} H NMR (DMSO-d6) .delta. = 13.84 (1H, s, broad, NH); 8.00, 7.18, 6.78 (3H, 3m, furanH); 4.26 (2H, t, J = 7.5 Hz, N-CH ₂ CH ₂ CH _3); 3.37 (1H, m, CH-cyclopentyl); 2,28 -

1.62 (10 H, m, _{CH2-cyclopentyl,} N-CH, CH, CH,); 1.04 (3H, t, J = 7.5 Hz, NCH, CH, _CH).

Example 49!

^{@ 1} H NMR (DMSO-d6) .delta. = 12.84 (1H, s, broad, 1H); 8.26 (1H, s, H2); 4.32 (2H, t, J = 7.5 Hz, N-CH ₂ CH ₂ CH _3); 3.18 (1H, m, CH-cyclopentyl); 2.09 to 1.52 (10 H, m, _{CH2-cyclopentyl,} N-CH ₂ CH ₂ CH _3); 0.83 (3H, t, J = 7.5Hz, N-CH, CH, CH 2).

Example 50 ¹ H NMR (DMSO-d 6) δ = 8.28 (1H, s, H6); 8.15 (1H, s, H2); 13.35 (2H, s, broad).

s!

Example 51 i j

@ 1 H-NMR (DMSO-d6) .delta. = 13.74 (1H, s, broad, 1H); 8.34 (1H, s, H6); 4.63 (2H, q, J = 7.5 Hz, N-CH, _CH?): 3.33 (1H, m, CH-Cyclopentyl); 2.24 to 1.57 (8H, m, CH ₂ -cyclopentyl, CH ₂ N-CH ₂ CH _3); 1.47 (3H, t, J = 7.5Hz, N-CH, CH 3).

I ·

Example 52 ¹ H NMR (DMSO-d 6) δ = 13.72 (1H, s, broad, NH); 8.34 (1H, s, H6); 4.53 (2H, t, J = 7.5 Hz, N-CH ₂ CH ₂ CH _3); 3.34 (1H, m, CH-cyclopentyl); 2.20 to 1.57 (10 H, m, _{CH2-cyclopentyl);} 1.87 (2H, m, N-CH ₂ CH ₂ CH _3); 1.06 (3H, t, J = 7.5 Hz, NCH ₂ CH ₂ CH ₃ ). !

-127Príklad 53 ¹ H NMR (DMS0-d 6) θ = 8.19 (1H, s, H 6); 4.00 (3H, s, _N-CH3); 3.58 (3H, s, NCH ₃ ); 3.42 (1H, m, CH-cyclopentyl); 2.18 - _(1.57 (8 H, m, CH ₂ -cyclopentyl).

Example 54

Ή NMR (DMSO-d 6) δ = 14.12 (1H, s, broad, NH); 8.44 (1H, s, H2); 4.53 (2H, t, J = 7.5 Hz, N-CH, CH, CH 2 '); 3.26 (1H, m, CH-cyclopentyl); 2.17 to 1.55 (8H, m, CH ₂ -cyclopentyl); 1.87 (2H, m, N-CH, CH, CH 2); 1.05 (3H, t, J = 7.5 Hz, N-CH ₂ CH ₂ CH _3).

I

I

Example 56 ♦ ¹ H NMR (DMSO-d 6) δ = 8.28 (1H, s, H2); 4.36 (2H, t, J = 7.5 Hz, N-CH ₂ CH ₂ CH _3); 4.12 (2H, t, J = 7.5 Hz, N-CH, CH, CH ₃ ); 3.21 (1H, m, CH-cyclopentyl); 2,12 -

1.57 (12 H, m, CH ₂ -cyclopentyl, _(N-CH? CH, _CH?)?); 0.92, 0.87 (6H, 2H, J = 7.5 Hz, (N-CHoCHo-CH3)).

s

Example 57

Ή NMR (DMSO-d 6) δ = 8.02 (1H, s, H2); 4.45 (2H, t, J = 7.5 Hz, N-CH, CH, CH ₃ );

4.14 (2H, t, J = 7.5 Hz, N-CH ₂ CH ₂ CH _3); 3.24 (1H, m, CH-cyclopentyl); 2,14 -

1.57 (12 H, m, CH ₂ -cyclopentyl, (N-CH, CH, CH,),); 0.93, 0.89 (6H, two t, J = 7.5 Hz, (N-CH ₂ CH ₂ CH _{3) 2).}

I

The following table lists the receptor binding values of .alpha. (Human) and .beta

K, A ₂ (rat)

Table 20

Example number KA [nM] KA [nM] 7 8.1 158 8 1.9 363 9 1.4 422 10 1.7 730 11 8.3 345 13 5.2 82 25 10.3 1231 30 81.5 3292 36 5.8 731 37 6.4 307 38 6.4 532 39 6.0 539 48 11.4 4455

The following table lists the KA (human) receptor binding values

Table 21

Example number KA [nM] 3 4.7 4 2.3 6 2 12 20 19 3.8 23 2 25 26 38 22 65 3 68 30 78 5.3 82 25

The compounds having the general formula (I) can be used alone or in combination with other active substances of the invention, optionally also in combination with other pharmacologically active substances. Suitable dosage forms are, for example, tablets, capsules, suppositories, solutions, syrups and juices, emulsions, or dispersible powders. Tablets may be prepared, for example, by mixing the active ingredient with commonly known excipients, for example, inert diluents / carriers, such as calcium carbonate, calcium phosphate, or lactose, with tablet disintegrating agents such as corn starch or alginic acid, with binders, such as starch or gelatin, lubricants such as magnesium stearate or talc, and / or deposition aids such as carboxymethylcellulose, cellulose acetate phthalate, or polyvinyl acetate. Tablets may also be prepared from multiple layers in the form of layered tablets.

Similarly, dragees (coated tablets) may be prepared by coating the core, which is prepared similarly to tablets and then coated with a conventional coating coating, for example Kollidon, or shellac, gum arabic, talc, titanium dioxide, or sugar. To achieve a deposition effect or to prevent incompatibility, the core may also consist of multiple layers. Similarly, the dragee coating may consist of several layers to achieve the deposition effect, and the excipients mentioned in the tablets may be used.

The syrups of the active ingredients according to the invention or the combinations of the active ingredients mentioned may still contain a sweetening agent such as saccharin, cyclamate, glycerol or sugar, as well as a flavoring to improve the taste properties, for example flavoring agents such as vanillin or orange extract. In addition, they may contain a dispersant to facilitate the formation of a suspension or a thickening agent such as sodium carboxymethylcellulose, a wetting agent, for example, condensation products of fatty alcohols with ethylene oxide, or preservatives such as hydroxybenzoate.

Injectable solutions are prepared in a conventional manner with the addition of preservatives such as p-hydroxybenzoates, stabilizers such as the alkali salts of ethylenediaminetetraacetic acid and filling into injection bottles or ampoules.

- i & h

Capsules containing one or, optionally, a combination of a plurality of active ingredients according to the invention can be prepared, for example, by mixing the active ingredient with an inert carrier such as lactose or sorbitol, filling and encapsulating it in gelatin capsules.

Suitable suppositories may be prepared, for example, by mixing suitable carriers such as neutral fats or polyethylene glycol or derivatives thereof.

The therapeutically effective amount in a daily dose is between 1 to 800 mg, preferably 10 to 300 mg per adult.

The following are examples which are intended to illustrate the invention in more detail, but in no way limit the scope of the invention.

Examples of pharmaceutical formulations

A) Tablets

component quantity for tablet [Mg] Active substance 100 lactose 140 maize starch 240 polyvinylpyrrolidone 15 mg magnesium stearate 5 together 500

The finely divided active ingredient, lactose and a portion of the corn starch are mixed together. The mixture is sieved, moistened with a solution of polyvinylpyrrolidone in water, kneaded, wet granulated and dried. The sieved remaining portion of corn starch and magnesium stearate is added to the granulate and the ingredients mixed together. The mixture is then compressed to form tablets of suitable dimensions.

B) Tablets

- 13i -

component quantity for tablet [Mg] Active substance 80 lactose 55 maize starch 190 microcrystalline cellulose 35 polyvinylpyrrolidone 15 sodium salt carboxymethyl 23 magnesium stearate 2 together 400

The finely divided active ingredient, a portion of the corn starch, lactose, microcrystalline cellulose and polyvinylpyrrolidone are mixed with each other, sieved and the remaining portion of the corn starch and water are added. The mixture is processed to a granulate which is dried and sieved. The carboxymethyl starch sodium and magnesium stearate are then admixed with the mixture and compressed into tablets of suitable size.

C) Coated tablets (dragees)

component amount for dragees [mg] Active substance 5 lactose 30 maize starch 41.5 polyvinylpyrrolidone 3 magnesium stearate 0.5 together 80

-132-

The active ingredient, corn starch, lactose and polyvinylpyrrolidone are mixed well together and moistened with water. The wet mass is passed through a 1 mm sieve, dried at about 45 ° C and the granulate is prepared using the same sieve. After mixing the magnesium stearate, rounded dragee cores with a diameter of about 6 mm are pressed on a tabletting machine. The cores prepared in this way are coated in a known manner with a layer consisting essentially of sugar and talc. The finished coated tablets are polished with wax.

D) Capsules

component amount per capsule [mg] Active substance 50 maize starch 268.5 magnesium stearate 1.5

The active ingredient and corn starch are mixed and moistened with water. The wet mass is passed through a sieve and dried. The dry granulate is sieved and mixed with magnesium stearate. The finished mixture is filled into hard gelatin capsules of size 1.

E) Ampoule Solution

component Amount for ampoule [Mg] Active substance 50 sodium chloride 50 water for injections 5 ml

The active ingredient is dissolved in water at its own pH, or optionally at a pH of 5.5 to 6.5, and treated with sodium chloride as an isotonizing agent. The prepared solution is filtered to remove pyrogens, and the filtrate is filled to aseptic conditions

-1 ampoules, which are then sterilized and sealed. The ampoules contain 5 mg, 25 mg, or 50 mg of active ingredient.

F) Suppositories

component amount for suppository [mg] Active substance 50 Adeps solidus 1 650 together 1 700

The solid fat melts. The active ingredient is dispersed homogeneously into the fat at 40 ° C. The mixture was cooled to 38 ° C and poured into slightly chilled suppository molds.

G) Oral suspensions

component amount [mg] Active substance 50 hydroxyethyl 50 sorbic acid 5 sorbitol (70%) 600 glycerol 200 flavor 15 Water ad 5 ml

The distilled water is heated to 70 ° C. Hydroxyethylcellulose is dissolved in warm water. After addition of the sorbitol-glycerol solution, the solution is cooled to room temperature. Sorbic acid, flavor and the active ingredient are added at room temperature. To degas the suspension, the suspension is evacuated with stirring.

Claims (18)

An imidazotriazolopyrimidinone derivative of the general formula (I) in which R ¹ or R ³ may be hydrogen, optionally substituted C ₁ -C ₁₀ -alkyl, C ₂ -C ₁₀ -alkenyl, or C ₂ -C ₁₀ -alkynyl, optionally substituted C ₃ -C ₈ -cycloalkyl, optionally substituted C ₄ -C ₈ -cycloalkenyl, or optionally substituted C ₆ -C ₈ -cycloalkynyl; R ¹ or R ³ can be substituted C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl-C ₂ -C ₆ -alkenyl, C ₆ -C ₁₀ -aryl-C ₂ -C ₆ -alkynyl, optionally substituted C ₆ -C ₁₀ -aryl-, or optionally substituted heteroaryl, optionally substituted with 5, 6, or 7-membered hetero ring containing one or more nitrogen, oxygen or sulfur atoms, wherein: said hetero ring is bonded via a ring carbon atom; R ¹ or R ³ may be substituted C ₁ -C ₁₀ -alkyloxycarbonyl, optionally substituted C ₂ -C ₁₀ -alkenyloxycarbonyl, optionally substituted C ₂ -C ₁₀ alkynyloxycarbonyl, optionally substituted C ₃ -C ₈ -cycloalkyloxycarbonyl, optionally substituted C ₆ -C ₁₀ -aryloxycarbonyl, optionally substituted C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyloxycarbonyl, AO-CO-, wherein A may be an optionally substituted 5, 6, or 7-membered heterocycle which: contains one or more nitrogen, oxygen or sulfur atoms, wherein A is attached via a carbon ring atom; -135- R ¹ or R ³ may be substituted C ₁ -C ₁₀ -alkylsulfonyl, C ₂ -C ₁₀ -alkenylsulfonyl, C ₂ -C ₁₀ alkynylsulfonyl, optionally substituted C ₃ -C ₈ -cycloalkylsulfonyl, optionally substituted C ₆ -C 10 _10- arylsulfonyl, optionally substituted C ₆ -C ₁₀ aryl-alkylsulfonyl, A-SO ₂ -, wherein A is as defined above and is bonded via a ring carbon atom; R ¹ or R ³ i denotes an optionally substituted radical C ₁ -C ₁₀ alkylcarbonyl, an optionally substituted C ₂ -C ₁₀ -alkenylkarbonyl, an optionally substituted C ₂ -C ₁₀ -alkinylkarbonyl, an optionally substituted C ₃ -C ₈ -cykloalkylkarbonyl optionally substituted zvyšokC ₆ - C ₁₀ -arylcarbonyl, optionally substituted C ₆ -C ₁₀ aryl-C 1 -C 8 -alkylcarbonyl, A-CO-, wherein A is as defined above; R ^{@ 1} or R ^{@ 3} may be a radical of formula ## STR3 ## in which hydrogen, phenyl, substituted phenyl, optionally substituted benzyl, optionally substituted C3 -C6 cycloalkyl, branched or unbranched C1 -C6 -alkyl-, preferably represents C 1 -C 4 alkyl-, C ₂ -C ₁₀ -alkenyl-, or C ₂ -C ₁₀ -alkynyl, which may be optionally substituted by hydroxy, phenyl, substituted by phenyl, amino, substituted by amino; R ² denotes hydrogen, hydroxyl, amino, halogen, nitro, _CF3, COOH, mercapto, C ^ -C-alkylmercapto, an optionally substituted C ^ C ^ alkyl, optionally substituted C ₂ -C ₁₀ -alkenyl, optionally substituted radical - C 36 C ₂ -C ₁₀ -alkynyl, optionally substituted C ₃ -C ₈ -cycloalkyl, optionally substituted C ₅ -C ₈ -cycloalkanone, optionally substituted C ₄ -C ₈ cycloalkenyl, optionally substituted C ₆ -C ₈ - cycloalkynyl, optionally substituted C ₆ -C ₁₀ -aryl, optionally substituted C ₆ -C ₁₀ -aryl-C ₆ -C ₈ alkyl, C ₆ -C ₁₀ -aryl-C ₂ -C ₆ -alkenyl, C ₆ -C ₁₀ -aryl -C ₂ -C ₆ -alkynyl, C ₃ -C ₈ -cycloalkyl-C ₂ -C ₆ alkyl, C ₃ -C ₈ -cycloalkyl-C ₂ -C ₆ -alkenyl, or C ₃ -C ₈ -cycloalkyl-C ₂ -C ₆ - alkynyl; R ² may be an optionally substituted 5, 6, or 7 membered heterocycle containing one or more nitrogen, oxygen or sulfur atoms, wherein the nitrogen may optionally be substituted and the heterocycle may be bonded directly through a carbon or nitrogen atom, or via a C 1 -C 6 -alkyl, a C ₂ -C ₆ -alkenyl, or a C ₂ -C ₆ -alkynyl bridge; R ² may be an optionally substituted C 1 -C 4 -alkylsulfonyl, C ₂ -C ₁₀ alkenylsulfonyl, or C ₂ -C ₁₀ -alkylsulfonyl radical, an optionally substituted C ₃ -C ₈ cycloalkylsulfonyl radical, an optionally substituted C ₆ -C ₁₀ -arylsulfonyl radical optionally substituted C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkylsulfonyl, or optionally substituted heteroarylsulfonyl; R ² denotes an optionally substituted C ₁ -C ₁₀ -alkylsulfonyloxy, C ₂ -C ₁₀ alkenylsulfonyloxy, or C ₂ -C ₁₀ -alkinylsulfonyloxy, an optionally substituted C ₃ -C ₈ -cykloalkylsulfonyloxy, an optionally substituted C ₆ -C ₁₀ -arylsulfonyloxy, optionally substituted C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkylsulfonyloxy, or optionally substituted heteroarylsulfonyloxy; R ² denotes an optionally substituted C ₁ -C ₁₀ alkylsulfonylamino, C ₂ -C ₁₀ alkanesulfonylamino, or C ₂ -C ₁₀ -alkinylsulfonylamino, an optionally substituted C ₃ -C ₈ -cykloalkylsulfonylamino, an optionally substituted C ₆ -C ₁₀ arylsulfonylamino, optionally substituted C 6 -C 6 -aryl-C 6 -C 8 -alkylsulfonylamino, or optionally substituted heteroarylsulfonylamino; - 1Í37R ² denotes an optionally substituted C ^ C ^ alkylaminocarbonyl, C _r C ₁₀ dialkylaminocarbonyl, C ₁ -C ₁₀ -alkyl-C ₂ -C ₁₀ -alkenylaminokarbonyl, C ₂ -C ₁₀ -alkenylaminokarbonyl, C ₂ -C ₁₀ -dialkenylaminocarbonyl, C ₂ -C ₁₀ -alkylaminocarbonyl, or C ₁ -C ₁₀ -alkyl-C ₂ -C ₁₀ -alkylaminocarbonyl, optionally substituted C ₃ -C ₈ cycloalkylaminocarbonyl, optionally substituted C ₆ -C ₁₀ -arylaminocarbonyl, optionally substituted C 8 -C 8 aryl-C 6 -C 8 -alkylaminocarbonyl, or optionally substituted heteroarylaminocarbonyl; R ² 'may be an optionally substituted C 1 -C 4 -alkyloxycarbonylamino radical; C ₂ -C ₁₀ -alkenyloxycarbonylamino or C ₂ -C ₁₀ -alkyloxycarbonylamino, optionally substituted C ₃ -C ₈ -cycloalkyloxycarbonylamino, optionally substituted C ₆ -C ₁₀ -aryloxycarbonylamino, optionally substituted C ₆ -C ₁₀ -aryl · C _6- alkyloxycarbonylamino, or an optionally substituted heteroaryloxycarbonylamino radical; ! R ² 'may be an optionally substituted C ₃ -C ₈ -alkylaminocarbonyloxy, C ₂ -C ₁₀ -alkenylaminocarbonyloxy, or C ₂ -C ₁₀ -alkylaminocarbonyloxy radical, an optionally substituted C ₃ -C ₈ -cycloalkylaminocarbonyloxy radical, optionally substituted C ₆ - C ₁₀ -arylaminocarbonyloxy, optionally substituted C ₆ -C ₁₀ -arylC ₁ -C ₆ -alkylaminocarbonyloxy, or optionally substituted heteroarylaminocarbonyloxy; R ² may be an optionally substituted C ₁ -C ₁₀ -alkyl-N-amidino, C ₂ -C ₁₀ alkenyl-N-amidino, or C ₂ -C ₁₀ -alkynyl-Nyamidino, optionally substituted radical i C ₃ -C ₈ -cycloalkyl-N-amidino, optionally substituted C ₆ -C ₁₀ -aryl-N-amidino, I optionally substituted C 8 -C 8 -aryl-C 8 -C 8 -alkyl-N-amidino, or optionally substituted heteroaryl-N-amidino; -138 - R ² can be an optionally substituted C ₁ -C 4 -alkyloxy, C ₂ -C ₁₀ -alkenyloxy, or C ₂ -C ₁₀ -alkyloxy radical, an optionally substituted C ₃ -C ₈ -cycloalkyloxy radical, an optionally substituted C ₆ -C ₁₀ -aryloxy radical , optionally substituted C 6 -C 6 -aryl-C 6 -C 8 -alkyloxy, or optionally substituted heteroaryloxy; R ² may be an optionally substituted C 1 -C 6 -alkyloxycarbonyl, C ₂ -C ₁₀ alkenyloxycarbonyl, or C ₂ -C ₁₀ -alkyloxycarbonyl radical, an optionally substituted C ₃ -C ₈ -cycloalkyloxycarbonyl radical, an optionally substituted C ₆ -C ₁₀ aryloxycarbonyl radical , optionally substituted C ₆ -C ₁₀ -aryloxycarbonyl, optionally substituted C ₆ -C 6 -aryl-C 1 -C 8 -alkyloxycarbonyl, or optionally substituted heteroaryloxycarbonyl; R ² may be an optionally substituted C ₆ -C ₁₀ -alkylcarbonyloxy, C ₂ -C ₁₀ alkenylcarbonyloxy, or C ₂ -C ₁₀ -alkynylcarbonyloxy, optionally substituted C ₃ -C ₈ -cycloalkylcarbonyloxy radical, optionally substituted C ₆ -C ₁₀ -arylcarbonyloxy radical, optionally a substituted C 8 -C 8 -aryl-C 1 -C 8 -alkylcarbonyloxy radical, or an optionally substituted heteroarylcarbonyloxy radical; R ² may be an optionally substituted C 1 -C 6 -alkylthio, C ₂ -C ₁₀ -alkenylthio, or C ₂ -C ₁₀ -alkynyl radical, an optionally substituted C ₃ -C 8 -cycloalkylthio radical, an optionally substituted C ₆ -C ₁₀ -alkyl radical arylthio, optionally substituted C ₆ -C ₁₀ -arylC 1 -C 6 -alkylthio, or optionally substituted heteroarylthio; R ² can be an optionally substituted amino group, preferably NR ⁸ R ⁹ ; R ² denotes an optionally substituted residue of formula -R ⁹ R ² may be an optionally substituted radical having the formula C _{r -C 6} -Alkyl C.rC ₆ -Alkyl wherein Y is a single bond or an alkyl, alkylene, or alkynyl group having up to 6, preferably up to 4 carbon atoms in the chain; R ² denotes an optionally substituted radical of the formula wherein Y is a single bond or an alkyl, alkylene, or alkynyl group having up to 6, preferably up to 4 carbon atoms in the chain; -140R ⁴ or R @ ⁵ denotes hydrogen, an optionally substituted C ₁ -C ₁₀ -alkyl, C ₂ -C ₁₀ alkenyl, or C ₂ -C ₁₀ -alkynyl, optionally substituted C ₃ -C ₈ -cycloalkyl, optionally substituted C ₄ -C ₈ -cycloalkenyl or optionally substituted C ₆ -C ₈ -cycloalkynyl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl, C ₆ -C ₁₀ -aryl-C ₂ -C ₆ -alkenyl C ₆ -C ₁₀ -aryl-C ₂ -C ₆ -alkynyl, optionally substituted C ₆ -C ₁₀ -aryl, or optionally substituted heteroaryl; R ⁴ or R ⁵ can be an optionally substituted 5, 6, or 7 membered hetero ring containing as heteroatoms one or more nitrogen, oxygen or sulfur atoms, the hetero ring being bonded through a carbon ring atom; • R ⁴ or R ⁵ may be optionally substituted C ₁₀ -C ₁₀ -alkyloxycarbonyl, optionally substituted C ₂ -C ₁₀ -alkenyloxycarbonyl, optionally substituted C ₂ -C ₁₀ -alkyloxycarbonyl, optionally substituted C ₃ -C ₈ -cycloalkyloxycarbonyl, optionally substituted C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyloxycarbonyl, optionally substituted C ₆ -C ₁₀ -aryloxycarbonyl; R ⁴ or R ⁵ may be A - O - CO - in which A represents an optionally substituted 5, 6, or 7 membered hetero ring containing one or more nitrogen, oxygen, or sulfur atoms as heteroatoms; R ⁴ or R ⁵ may be substituted C ₁ -C ₁₀ -alkylsulfonyl, C ₂ -C ₁₀ -alkenylsulfonyl, C ₂ -C ₁₀ alkynylsulfonyl, optionally substituted C ₃ -C ₈ -cycloalkylsulfonyl, optionally substituted C ₆ -C 10 _10- arylsulfonyl, A-SO ₂ -, wherein A is as defined above and is bonded via a ring carbon atom; R ⁴ or R ⁵ may be substituted C 1 -C 6 -alkylcarbonyl, optionally substituted C ₂ -C ₁₀ alkenylcarbonyl, optionally substituted C ₂ -C ₁₀ -alkynylcarbonyl, optionally substituted C ₃ -C ₈ -cyclalkylcarbonyl, optionally substituted radical C ₆ -C ₁₀ -arylcarbonyl, optionally substituted C ₆ -C ₁₀ -aryl-C 1-4 alkylcarbonyl, A-CO-, in which A has R ⁴ or R ⁵ as defined above; may be a residue having the general formula in which R represents hydrogen, phenyl, substituted phenyl, optionally substituted benzyl, optionally substituted cycloalkyl groups of 3 to 6 carbon atoms, branched or unbranched C ₁ -C ₁₀ -alkyl-, preferably C ₁ -C ₄ -alkyl-, C ₂ -C ₁₀ - alkenyl, or C ₂ C ₁₀ -alkynyl group which may be substituted by hydroxy, phenyl, substituted phenyl, amino or substituted amino; R ⁶ can be hydrogen, hydroxy, -CHO, amino, halogen, nitro, CF ₃ , COOH, mercapto, C ₁ -C ₈ -alkyl mercapto, optionally substituted C ₁ -C ₁₀ -alkyl, optionally substituted C ₂ -C ₁₀ -alkenyl, optionally substituted C ₂ -C ₁₀ -alkynyl, optionally substituted C ₃ -C ₈ -cycloalkyl, optionally substituted C ₅ -C ₈ -cycloalkanone, optionally substituted C ₄ -C ₈ -cycloalkenyl, optionally substituted C ₆ - C ₈ -cycloalkynyl, optionally substituted C ₆ -C ₁₀ -aryl, optionally substituted C ₆ -C 6 -aryl-C 6 -C 8 -alkyl, C ₆ -C ₁₀ -aryl-C ₂ -C ₆ -alkenyl, C ₆ -C ₁₀ aryl-C ₂ -C ₆ -alkynyl, C 3 -C 8 -cyclalkyl-C 1 -C 8 -alkyl, C ₃ -C ₈ -cycloalkyl-C ₂ -C ₆ -alkenyl, or C ₃ -C ₈ -cycloalkyl-C _{2 C6} alkynyl; R ⁶ may be an optionally substituted 5, 6, or 7 membered heterocycle containing one or more nitrogen, oxygen or sulfur atoms, wherein the nitrogen may optionally be substituted and the heterocycle may be bonded directly through A carbon or nitrogen atom, or via a C 1 -C 6 -alkyl, a C ₂ -C ₆ -alkenyl, or a C ₂ -C ₆ -alkynyl bridge; ^R6 denotes an optionally substituted C ^ C ^ alkylsulfonyl, C ₂ -C ₁₀ alkenylsulfonyl, or C 2 -C ₁₀ -alkynylsulfonyl, an optionally substituted C ₃ -C ₈ cycloalkylsulfonyl, optionally substituted C ₆ -C ₁₀ -arylsulfonyl, optionally substituted C ₆ -C ₁₀ -aryl-C ₁ -C 8 -alkylsulfonyl, or optionally substituted heteroarylsulfonyl; R ⁶ may be optionally substituted C 1 -C 6 -alkylsulfonyloxy, C ₂ -C ₁₀ alkenylsulfonyloxy, or C ₂ -C ₁₀ -alkylsulfonyloxy, optionally substituted C ₃ -C ₈ -cycloalkylsulfonyloxy, optionally substituted C ₆ -C _10- arylsulfonyloxy, optionally substituted C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkylsulfonyloxy, or optionally substituted heteroarylsulfonyloxy; ^R6 denotes an optionally substituted C ₁ -C ₁₀ alkylsulfonylamino, C ₂ -C ₁₀ alkanesulfonylamino, or C ₂ -C ₁₀ -alkinylsulfonylamino, an optionally substituted C ₃ -C ₈ -cykloalkylsulfonylamino, an optionally substituted C ₆ -C ₁₀ arylsulfonylamino, optionally substituted C 8 -C 6 -aryl-C 6 -C 6 -alkylsulfonylamino, or optionally substituted heteroarylsulfonylamino; φ R ⁶ denotes an optionally substituted C _r C ₁₀ alkylaminocarbonyl, C _r C ₁₀ dialkylaminocarbonyl, C ^ C ^ alkyl-C ^ C ^ -alkenylaminokarbonyl, C ₂ -C ₁₀ -alkenylaminokarbonyl, C ₂ -C ₁₀ -dialkenylaminokarbonyl , C ₂ -C ₁₀ -alkylaminocarbonyl, or C ₁ -C 4 -alkyl-C 1 -C 4 -alkylaminocarbonyl, optionally substituted C ₃ -C ₈ cycloalkylaminocarbonyl, optionally substituted C ₆ -C ₁₀ -arylaminocarbonyl, optionally substituted C ₆ -C ₁₀ -alkyl; -aryl-C 1 -C 8 -alkylaminocarbonyl, or an optionally substituted heteroarylaminocarbonyl radical; - 143 R ⁶ may be an optionally substituted C ₁ -C ₁₀ -alkylaminocarbonylamino, C ₂ -C ₁₀ -alkenylaminocarbonylamino, or C ₂ -C ₁₀ -alkylaminocarbonylamino, optionally substituted C ₃ -C ₈ -cycloalkylaminocarbonylamino radical, optionally substituted C ₆ -C ₁₀ -arylaminocarbonylamino, optionally substituted C 8 -C 8 -aryl-C 4 -C 8 -alkylaminocarbonylamino, or optionally substituted heteroarylaminocarbonylamino; R ⁶ may be an optionally substituted C ₆ -C ₁₀ -alkyloxycarbonylamino, C ₂ -C ₁₀ -alkenyloxycarbonylamino, or C ₂ -C ₁₀ -alkyloxycarbonylamino, optionally substituted C ₃ -C ₈ -cycloalkyloxycarbonylamino radical, optionally substituted C ₆ -C ₁₀ -aryloxycarbonylamino , optionally substituted C ₆ -C ₁₀ -aryl-C ₁ -C 8 -alkyloxycarbonylamino, or optionally substituted heteroaryloxycarbonylamino; R ⁶ may be optionally substituted C ₁ -C ₁₀ -alkylaminocarbonyloxy, C ₂ -C ₁₀ -alkenylaminocarbonyloxy, or C ₂ -C ₁₀ -alkylaminocarbonyloxy, optionally substituted C ₃ -C ₈ -cycloalkylaminocarbonyloxy, optionally substituted C ₆ -C 10 _10- arylaminocarbonyloxy, optionally substituted C ₆ -C ₁₀ -arylC 1 -C 8 -alkylaminocarbonyloxy, or optionally substituted heteroarylaminocarbonyloxy; R ⁶ may be optionally substituted C ₁ -C ₁₀ -alkyl-N-amidino, C ₂ -C ₁₀ alkenyl-N-amidino, or C ₂ -C ₁₀ -alkynyl-N-amidino, optionally substituted C ₃ -C _8- cycloalkyl-N-amidino, optionally substituted C ₆ -C ₁₀ -aryl-N-amidino, optionally substituted C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyl-N-amidino, or optionally substituted radical heteroaryl-N-amidino; R ⁶ may be an optionally substituted C ₃ -C ₈ -alkyloxy, C ₂ -C ₁₀ -alkenyloxy, or C ₂ -C ₁₀ -alkyloxy radical, an optionally substituted C ₃ -C ₈ -cycloalkyloxy radical, Ϊ 44 - an optionally substituted C ₆ -C ₁₀ -aryloxy radical, an optionally substituted C ₆ -C 6 -aryl-C 6 -C 8 -alkyloxy radical, or an optionally substituted heteroaryloxy radical; R ⁶ may be an optionally substituted C 1 -C ₈ -alkylcarbonyl, C ₂ -C ₁₀ alkenylcarbonyl, or C ₂ -C ₁₀ -alkynylcarbonyl, optionally substituted C ₃ -C ₈ -cycloalkylcarbonyl radical, optionally substituted C ₆ -C ₁₀ -arylcarbonyl radical optionally substituted C 8 -C 8 -aryl-C 1 -C 8 -alkylcarbonyl; R ⁶ may be A-CO in which A is as defined above; R ⁶ may be an optionally substituted C ₁ -C 4 -alkyloxycarbonyl, C ₂ -C ₁₀ alkenyloxycarbonyl, or C ₂ -C ₁₀ -alkyloxycarbonyl radical, optionally substituted C ₃ -C ₈ -cycloalkyloxycarbonyl radical, optionally substituted C ₆ -C ₁₀ aryloxycarbonyl radical, optionally substituted C ₆ -C ₁₀ -aryloxycarbonyl, optionally substituted C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkyloxycarbonyl, or optionally substituted heteroaryloxycarbonyl; R ⁶ may be optionally substituted C ₁ -C ₁₀ -alkylcarbonyloxy, C ₂ -C ₁₀ alkenylcarbonyloxy, or C ₂ -C ₁₀ -alkynylcarbonyloxy, optionally substituted C ₃ -C ₈ -cycloalkylcarbonyloxy, optionally substituted C ₆ -C ₁₀ arylcarbonyloxy, optionally substituted C ₆ -C ₁₀ -aryl-C ₁ -C ₆ -alkylcarbonyloxy, or optionally substituted heteroarylcarbonyloxy; R ⁶ can be an optionally substituted C ₁ -C 4 -alkylthio, C ₂ -C ₁₀ -alkenylthio, or C ₂ -C ₁₀ -alkynyl radical, an optionally substituted C ₃ -C ₈ -cycloalkylthio radical, an optionally substituted C ₆ -C ₁₀ -arylthio radical , optionally substituted C ₆ -C ₁₀ -arylC 1 -C 8 -alkylthio, or optionally substituted heteroarylthio; R ⁶ may be an optionally substituted C ₁₀ -C ₁₀ -alkylcarbonyloxy-C ₁ -C ₆ -alkyl radical, C ₆ -C 6 -alkenylcarbonyloxy-C 1 -C 6 -alkyl, or C ₂ -C ₁₀ -alkynylcarbonyloxy-C ₁ -C ₆ -alkyl, -45 optionally substituted C 1 -C 8 -cycloalkylcarbonyloxy-C ₁ -C ₆ -alkyl, optionally substituted C 8 -C 6 -arylcarbonyloxy-C 1 -C 6 -alkyl, C ₆ -C ₁₀ -aryl-C ₁ -C ₆ alkylcarbonyloxy-C ₁ -C ₆ -alkyl- alkyl, or an optionally substituted heteroarylcarbonyloxy-C 1 -C 8 -alkyl radical; R ⁶ may be an optionally substituted radical having the formula R ¹⁰ -O-B- (CH ₂ ) _n - wherein n = 1, 2, 3, or 4, wherein B may be C ₆ -C ₁₀ -aryl, or a single bond; R ⁶ can be an optionally substituted amino group, preferably NR ⁸ R ⁹ ; R ⁶ may be an optionally substituted radical having the formula R ⁶ may be an optionally substituted radical having the formula - 146- C 1 -C 8 -alkyl with C 1 -C 8 -alkyl I? wherein Y may be a single bond, or an alkyl, alkenyl or: i alkynyl group having up to 6, preferably up to 4, carbon atoms in the chain; R ⁶ may be an optionally substituted radical having the formula wherein Y may be a single bond, or an alkyl, alkenyl, or alkynyl group of up to 6, preferably up to 4, carbon atoms in the chain; R ⁸ can be hydrogen, optionally substituted cycloalkyl of 3 to 6 carbon atoms, branched or unbranched alkyl, alkenyl, or alkynyl of up to 10, preferably alkyl of 1 to 4 carbon atoms, which may optionally be substituted with hydroxy, phenyl, substituted - 147 phenyl, benzyl, substituted benzyl, amino, substituted amino, C, - to C ₈ alkyloxy, preferably C _r to C ₄ - alkyloxy, - (CH _{2) m} NHCOOR ¹⁰ m = 1, 2, 3 , or 4; R ⁸ may be, directly or through an alkyl chain of 1 to 4 carbon atoms, bonded via a carbon atom through a 5, 6, or 7 membered hetero ring containing one or more heteroatoms selected from nitrogen, oxygen or sulfur and optionally one or more times , preferably once, benzyl, optionally substituted benzyl, C 1 -C 4 alkyl, halogen, - OR ¹⁰ , - CN, - NO ₂ , - NH ₂ , - OH, = 0, - COOH, - SO ₃ H, - COOR ¹⁰ ; R ⁸ may be bicyclic, directly, or via an alkyl chain of 1 to 4 carbon atoms, through a carbon-bonded heterocycle containing one or more heteroatoms selected from nitrogen, oxygen or sulfur and optionally one or more times, preferably once, substituted benzyl, optionally substituted benzyl, C _r C ₄ alkyl, halogen, - oR ^10, - CN, - N0 _2, - NH _2, - OH, = 0, - COOH, - SO ₃ H, - COOR ^10; R ⁹ may be hydrogen, optionally substituted cycloalkyl of 3 to 6 carbon atoms, branched or unbranched alkyl, alkenyl, or alkynyl of up to 10, preferably alkyl of 1 to 4 carbon atoms, which may optionally be substituted with hydroxy, phenyl, substituted phenyl, benzyl, substituted benzyl, amino, substituted amino, C 1 -C ₈ -, preferably C 1 -C ₄ alkyloxy, - (CH ₂ ) _m -NHCOOR ¹⁰ m = 1.2 , 3, or 4; R ⁹ may be, directly or through an alkyl chain of 1 to 4 carbon atoms, bonded via a carbon atom through a 5, 6, or 7 membered heterocycle containing one or more heteroatoms selected from nitrogen, oxygen or sulfur and optionally one or more times , preferably once, substituted with benzyl, which may 148 be optionally substituted with benzyl, C 1 -C 4 alkyl, halogen, -OR ¹⁰ ,-CN, -NO ₂ , -NH ₂ , -OH, = O-COOH-SO ₃ H, -COOR ¹⁰ ; R ⁹ may be bicyclic, directly, or via an alkyl chain of 1 to 4 carbon atoms, through a carbon-linked heterocycle containing one or more heteroatoms selected from nitrogen, oxygen or sulfur and optionally one or more times, preferably once, substituted with benzyl, optionally substituted benzyl, O-O-alkyl, halogen, -OR ¹⁰ ,-CN, -NO ₂ , -NH ₂ , -OH, = O-COOH, -SO ₃ H, -COOR ¹⁰ ; or R ⁸ and R ⁹ together with the nitrogen may form a saturated or unsaturated 5 or 6 membered ring which may contain as further heteroatoms nitrogen, oxygen or sulfur, said hetero ring may be substituted by a branched or unbranched alkyl group having 1 to 4 carbon atoms, preferably methyl, or may bind the following groups - (CH ₂ ) _n -phenyl, - (CH ₂ ) _n -NH ₂ = O, ketal, preferably -O-CH ₂ -CH ₂ -O-, - (CH ₂ ) _n -NH-C 1 -C 6 -alkyl, - (CH ₂ ) _n -N - (C ₁ -C ₈ -alkyl) ₂ , - (CH ₂ ) _n -NH COOR ¹⁰ , (n = 1, 2, 3, 4), halogen, - OR ¹⁰ , - CN, - NO ₂ , - NH ₂ , - CH ₂ NR ⁸ R ⁹ , - OH, - COOH, - SO ₃ H, - COOR ¹⁰ , - CONR ⁸ R ⁹ , - SO ₂ - R ¹⁰ ; R ¹⁰ can be hydrogen, C 1 -C 4 alkyl, C ₂ -C ₄ -alkenyl, C ₂ -C ₄ -alkynyl, benzyl, or phenyl, optionally mono- or poly-substituted with OCH ₃ , optionally in the form of their racemates , enantiomers, diastereomers and mixtures thereof, optionally as pharmacologically acceptable acid addition salts thereof. -149 - 2. Imidazo triazolopyrimidinone derivatives of formulas (Ia) to (Id), in which: R ¹ or R ³ can be hydrogen, C 1 -C 4 alkyl, or benzyl; R ² can be hydrogen, C 1 -C 8 -alkyl, C ₂ -C ₈ -alkenyl, or C ₂ -C ₈ -alkynyl which is substituted with-CN, -CH ₂ NR ⁸ R ⁹ , OH (possibly multiple) - OR ¹⁰ , - NR ⁸ R ⁹ , - NHCOR ¹⁰ , - NHCONR ⁸ R ⁹ , - NHCOOR ¹⁰ , halogen, - OCOR ¹⁰ , - OCO-pyridyl, - OCH ₂ COOH, - OCH ₂ COR ¹⁰ , - SO ₂ R ⁷ , -SR ⁷ , - NHCONH-phenyl, - OCH 2 - CONR ⁸ R ⁹ , - O-CH ₂ -CH ₂ -OH, - SO ₂ CH ₂ -CH ₂ -OR ¹⁰ , - OCH ₂ -CH ₂ - NR ⁸ R ^9, -SO 2 CH ₂ .CH ₂ OH, -CONHSO ₂ R ^10, - ch ₂ conhso ₂ y ¹⁰ , - och ₂ ch ₂ or ¹⁰ y, -COOH, - coor ¹⁰ , - ⁸ y ⁹ , - cho, - SR ¹⁰ , - SOR ¹⁰ , - SO ₂ R ¹⁰ , - SO 3 H, - SO ₂ NR ⁸ R ⁹ , - OCH ₂ -CH ₂ OCOR ¹⁰ , - CH = ΝΟΗ, - CH = NOR ¹⁰ , = O, -COR ¹¹ , - CH (OH) R ¹¹ , - CH (OR ¹⁰ ) ₂ , - CH = CH-R ¹² , -OCONR ⁸ R ⁹ , 1,3-dioxolane, or 1,3-dioxane optionally mono- or poly-substituted with methyl; R ² -s .'j Λ 150 may be phenyl-C 1 -C 6 -alkyl, phenyl-C ₂ -C ₆ -alkenyl, or phenyl C ₂ -C ₆ -alkynyl, wherein the phenyl ring is optionally substituted by one, directly or through an alkylene bridge of 1 to 4 carbon atoms, or more of -C ₁ -C ₃ -alkyl, -CN, NR ⁸ R ⁹ , -NO 2, -OH, -OR ¹⁰ , -CH ₂ NH-SO ₂ R ¹⁰ , -NHCOR ¹⁰ , -NHCONR ⁸ R ⁹ , halogen , - OCOR ^10, - OCO-pyridyl, - -OCH2COOH, - OCH2COOR ^10, -CH2OCOR ^10, - SO 2 R ^7, -OCH 2 CONR ⁸ R ^9, -OCH2CH2OH, -OCH 2 CH 2 NR ⁸ R ^9, -CONHSO 2 R ^10, -och2CH2OR ¹⁰ , - COOH, -COOR ¹⁰ , -CF 3, cyclopropyl, -CONR ⁸ R ⁹ , -CH 2 OH, -CH 2 OR ¹⁰ , -CHO, -SR ¹⁰ , -SOR ¹⁰ , -SO ² R ¹⁰ , -SO 3 H, -SO 2 NR ⁸ R ⁹ , -OCH ₂ -CH ₂ OCOR ¹⁰ , -CH = NOH, -CH = NOR ¹⁰ , -COR ¹¹ , -CH (OH) R ¹¹ , -CH (OR ¹⁰ ) 2, -NHCOOR ¹⁰ , -CH 2 CONHSO ₂ R ¹⁰ , -CH = CH-R ¹² , -OCONR ⁸ R ⁹ , -CH 2 -O-CONR ⁸ R ⁹ , -CH 2 -CH ₂ -O-CONR ⁸ R ⁹ , optionally one or more times substituted with 1,3-dioxolane by methyl group or 1,3-dioxane; R ^2: may be C 1 -C ₆ cycloalkyl-C ₂ -C ₆ -alkyl-, C ₃ -C ₇ -cycloalkyl-C ₂ -C ₆ -alkenyl-, C ₃ -C ₇ cycloalkyl-C ₂ -C ₆ -alkynyl- wherein the cycloalkyl radical may be substituted, directly or through an alkylene bridge of 1 to 4 carbon atoms, by one or more of the radicals -CN, NR ⁹ R ⁸ , = O, -OH, -OR ¹⁰ , -NR ⁸ R ⁹ , -NHCOR ¹⁰ , -NHCONR ⁸ R ^9, halogen, -OCOR ^10, -OCO-pyridyl, -OCH 2 COOH, - OCH2COOR ^10, -CH2OCOR ^10, -SO 2 R ^7, -OCH 2 CONR ⁸ R ^9, -OCH2CH2OH, -OCH 2 CH 2 NR ⁸ R ⁹ , -OCH ₂ -CH ₂ -OR ¹⁰ , -COOH, -COOR ¹⁰ , -CONR ⁸ R ⁹ , -CH 2 OH, -CH 2 OR ¹⁰ , -CHO, -SR ¹⁰ , -SOR ¹⁰ , -SO ² R ¹⁰ , -SO 3 H, -SO 2 NR ⁸ R ⁹ , -OCH ₂ -CH ₂ OCOR ¹⁰ , -CH = NOH, -CH = NOR ¹⁰ , -COR ¹¹ , -CH (OH) R ¹¹ , -CONHSO ² R ¹⁰ , -CH (OR ¹⁰ ) 2, -NHCOOR ¹⁰ . -CH = CH-R ¹² , -OCONR ⁸ R ⁹ , -CH 2 -O-CONR ⁸ R ⁹ , -CH 2 -CH ₂ -O-CONR ⁸ R ⁹ , optionally substituted 1,3-dioxolane by methyl, or 1, 3-dioxane; R ² denotes a residue of the formula AC ₁ -C ₆ -alkyl-, A-CONHC 2 -C 6 -alkyl-, A-CONH-C ₂ -C ₆ -alkenyl-, A-CONH-C ₂ -C ₆ alkynyl, A-NH-CO-C C 1 -C 6 -alkyl-, A-NH-CO-C ₂ -C ₆ -alkenyl, A-NH-COC ₂ -C ₆ -alkynyl, AC ₂ -C ₆ -alkenylene, AC ₂ -C ₆ -alkynylene, or A - wherein A is a 5, 6, or 7 membered heterocycle bonded via carbon or nitrogen containing one or more nitrogen, oxygen or sulfur atoms and optionally - 15I may be mono- or polysubstituted, substituted benzyl, optionally substituted benzyl, C? -C? Alkyl, halo, -OR ^10, -CN, -NO _2, -NH _2, I -CH ₂ NR ⁸ R ⁹ , -OH, = O, ketal, ethylene ketal, -COOH, -SO 3 H, -COOR ¹⁰ , -CONR ⁸ R ⁹ , -COR ¹¹ , -SO ² R ¹⁰ , or -CONR ⁸ R ⁹ ; R ² can be C ₃ -C ₇ -cycloalkyl which is optionally substituted with = O, -OH, -OR ¹⁰ , OCOR ¹⁰ , or -OCO-pyridyl; R ² may be phenyl, which is optionally substituted with -OH, halogen, -OR ¹⁰ , C 1 -C 4 alkyl, -NH 2, -COOH, -SO 3 H, 9 -COOR ¹⁰ , -OCH ² COOR ¹⁰ , -CN, or -OCH ₂ CONR ⁸ R ⁹ group; ^R2 denotes norbornane, norbornene, C ₃ -C ₆ -dicykloalkyl-methyl, preferably dicyclopropylmethyl, adamantane or noradamantane group optionally substituted by C ^ C ^ alkyl; R ² may be -CH = CH-phenyl, wherein the phenyl ring is substituted one or more times with methoxy, hydroxy, or halogen; R ² may be a [3.3.0] -bicyclooctane; it may be a carbon-bonded piperidine or a furan; R ² may be an amino group having the formula NR ⁸ R ⁹ ; R ⁴ or R ⁵ j may be hydrogen, optionally branched C 1 -C 6 -alkyl, C ₂ -C ₈ -alkenyl, or C ₂ -C ₈ -alkynyl, which is substituted by - CN, - CH ₂ NR ⁸ R ⁹ , OH (possibly multiple) - OR ¹⁰ , - NR ⁸ R ⁹ , - NHCOR ¹⁰ , - NHCONR ⁸ R ⁹ , halogen, - OCOR ¹⁰ , - OCO-pyridyl, - OCH ² COOH, - OCH ² COOR ¹⁰ , - SO ² R ⁷ , - SR ⁷ , - NHCONH-phenyl, - OCH 2 L CONR ⁸ R ⁹ , - O-CH ₂ -CH ₂ -OH, - SO ₂ - CH ₂ - CH ₂ -52O-COR ¹⁰ , - och2-ch2-nr ⁸ r ⁹ , -so2- CH ₂ CH ₂ OH, -CONHSO ₂ R ^10, -ch2coNHSO2R ^10, - OCH 2 CH ₂ OR ¹ °, -COOH, -COOR ^10, - CONR ⁸ R ^9, - CHO, - SR ^10, - SOR ^10, -SO 2 R ^10, -SO 3 H, -SO ₂ NR ⁸ R ^9, - OCH ₂ CH ₂ OCOR ¹ ~, -CH = NOH, - CH = NOR ¹⁰ , -COR ¹¹ , -CH (OH) R ¹¹ , i - CH (OR ¹⁰ ) ₂ , - CH = CH-R ¹² , OCONR ⁸ R ⁹ , optionally mono- or poly-substituted with methyl 1, 3-dioxolane, or 1,3-dioxane; J R ⁴ or R ⁵ I may be phenyl-C 2 -C 6 -alkyl-, phenyl-C ₂ -C ₆ -alkenyl-, or phenyl-C ₂ -C ₆ -alkynyl, wherein the phenyl ring is optionally substituted directly or via an alkylene bridge of 1 to ₆ carbon atoms. 4 carbon atoms with one or more, preferably one, of the radicals C 1 -C 4 -alkyl, -CN, NR ⁸ R ⁹ , -NO 2, -OH, -OR ¹⁰ , -CH ₂ NH-SO ₂ R ¹⁰ , -NHCOR ¹⁰ , -NHCONR ⁸ R ⁹ , halogen, - OCOR ¹⁰ , -OCO-pyridyl, - OCH ² COOH, - OCH ² COOR ¹⁰ , -CH ² OCOR ¹⁰ , - SO ² R ⁷ , -OCH 2 -CONR ^? R ⁹ , -OCH 2 CH 2 OH, -OCH 2 -CH 2 -NR ⁸ R ⁹ , -CONHSO ² R ¹⁰ , -OCH 2 CH 2 OR ¹⁰ , - COOH, -COOR ¹⁰ , -CF 3, cyclopropyl, -CONR ⁸ R ⁹ , -CH 2 OH, -CH 2 OR ¹⁰ , - CHO, -SR ¹⁰ , -SOR ¹⁰ , -SO ² R ¹⁰ , -SO 3 H, -SO 2 NR ⁸ R ⁹ , -OCH ₂ CH ₂ OCOR ¹⁰ , -CH = NOH, -CH = NOR ¹⁰ , -COR ¹¹ , -CH (OH) R ¹¹ , -CH (OR ¹⁰ ) 2, -NHCOOR ¹⁰ , -CH 2 CONHSO ₂ R ¹⁰ , -CH = CH-R ¹² , -OCONR ⁸ R ⁹ , -CH 2 -O-CONR ⁸ R ⁹ , -ch ₂ CH ₂ -O- CONR ⁸ R ⁹ optionally substituted one or more times with a methyl group 1,3-dioxolane or 1,3-dioxane; R ⁴ or R ⁵ ! φ may be an optionally substituted C ₃ -C ₇ -alkyl radical; R ⁴ or R ⁵ may be C 1 -C ₆ -cycloalkyl-C ₁ -C ₈ -alkyl-, C ₃ -C ₇ -cycloalkyl-C ₂ -C ₆ -alkenyl-, C ₃ -C ₇ cycloalkyl-C ₂ -C ₆ -alkynyl- wherein the cycloalkyl radical may be substituted, directly or through a (C 1 -C 4) alkylene bridge, by -CN, NR ⁹ R ⁸ , = O, -OH, -OR ¹⁰ , -NR ⁸ R ⁹ , -NHCOR ¹⁰ , -NHCONR ⁸ R ^9, halo, - OCOR ^10, - OCOpyridyl, - OCH2COOH, - OCH2COOR ^10, -CH2OCOR ^10, - SO 2 R ^7, -OCH 2 CONR ⁸ R ^9, -OCH2CH2OH, -OCH 2 CH 2 NR ⁸ R ^9, - OCH 2 -CH ₂ -OR ¹⁰ , -COOH, -COOR ¹⁰ , -CONR ⁸ R ⁹ , -CH 2 OH, -CH 2 OR ¹⁰ , -CHO, -SR ¹⁰ , -SOR ¹⁰ , -SO ² R ¹⁰ , -SO 3 H, -SO 2 NR ⁸ R ⁹ , -OCH ₂ CH ₂ OCOR ¹⁰ , -CH = NOH, -CH = NOR ¹⁰ , -COR ¹¹ , -CH (OH) R ¹¹ , -CONHSO ² R ¹⁰ , -CH-153 (OR ¹⁰ ) 2, -nhcoor ¹⁰ , - ch = ch-r ¹² , -conr ⁸ R ⁹ , -ch 2 -o-conr ⁸ R ⁹ , -ch ₂ -ch ₂ -o CONON R ⁸ R ⁹ , optionally substituted 1,3-dioxolane, or 1,3-dioxane by a methyl group; R ⁴ or R ⁵ may be a radical having the formula A CRCG-alkyl, A-CONHCrCg-alkyl, A-CONH-C ₂ -C ₆ -alkenyl, A-CONH-C ₂ -C ₆ -alkynyl, A-NH-CO-C _r C ₆ -alkyl-, A-NH-CO-C ₂ -C ₆ -alkenyl, A-NH-COC ₂ -C ₆ -alkynyl, AC ₂ -C ₆ alkenyl, AC ₂ -C ₆ -alkynyl, or A-, wherein A is a heterocycle, bonded via carbon or nitrogen, which contains one or more nitrogen, oxygen or sulfur atoms and optionally can be mono- or poly-substituted by C 1 -C 4 alkyl, halogen, -OR ¹⁰ , -CN, -NO ₂ , -NH ₂₁ -CH ₂ NR ⁸ R ⁹ , -OH, = O, ketal, ethylene ketal, -COOH, -SO 3 H, -COOR ¹⁰ , -CONR ⁸ R ⁹ , -COR ¹¹ , -SO ² R ¹⁰ , or -CONR ⁸ R ⁹ ; R ⁶ may be hydrogen, optionally branched C 1 -C 8 -alkyl, C ₂ -C ₈ -alkenyl, or C ₂ -C ₈ -alkynyl, which is substituted with-CN, -CH ₂ NR ⁸ R ⁹ , OH (s) multiple substitution), - OR ¹⁰ , - NR ⁸ R ⁹ , - NHCOR ¹⁰ , - NHCONR ⁸ R ⁹ , halogen, - OCOŔ ¹⁰ , - OCO-pyridyl, - OCH ² COOH, - OCH ² COOR ¹⁰ , - SO ² R ⁷ , - SR ⁷ , - NHCONH-phenyl, - OCH 2 - CONR ⁸ R ⁹ , - O-CH ₂ -CH ₂ -OH, - SO ₂ - CH ₂ - CH ₂ O-COR ¹⁰ , - OCH 2 -CH 2 -NR ⁸ R ⁹ , -S02- CH ₂ CH ₂ OH, -CONHSO ₂ R ^10, -ch2coNHSO2R ^10, - OCH 2 CH ₂ OR ^10, - COOH, - COOR ^10, - CONR ⁸ R ^9, - CHO, - SR ^10, - SOR ¹⁰ , - SO ₂ R ¹⁰ '- SO 3 H, - SO ₂ NR ⁸ R ⁹ , - OCH ₂ -CH ₂ OCOR ¹⁰ , - CH = NOH, - CH = NOR ¹⁰ , - COR ¹¹ , - CH (OH) R ¹¹ , - CH (OR ¹⁰ ) ₂ , - CH = CH-R ¹² , OCONR ⁸ R ⁹ , one or more times substituted by a methyl group 1,3-dioxolane or 1,3-dioxane; R ⁶ may be phenyl-C 2 -C 6 -alkyl-, phenyl-C ₂ -C ₆ -alkenyl-, or phenyl-C ₂ -C ₆ -alkynyl, wherein the phenyl ring is optionally substituted directly or via an alkylene bridge of 1 up to 4 carbon atoms with one or more of -C 1 -C 8 -alkyl, -CN, NR ⁸ R ⁹ , -NO 2 -OH, -OR ¹⁰ , -CH ₂ NH-SO ₂ R ¹⁰ , -NHCOR ¹⁰ , -NHCONR ⁸ R ⁹ , halogen, <i -154- - OCOR ¹⁰ , - OCO-pyridyl, - OCH ² COOH, - OCH ² COOR ¹⁰ , -CH ² OCOR ¹⁰ , - SO ₂ R ⁷ , -OCH ₂ -CONR ⁸ R ⁹ , -OCH ₂ CH 2 OH, -och 2 -ch 2 -n ⁸ r ⁹ , -conhso ² r ¹⁰ , -och ² CH ² OR ¹⁰ , -COOH, -COOR ¹⁰ , -CF 3, cyclopropyl, -CONR ⁸ R ⁹ , - CH 2 OH, -CH 2 OR ^10, CHO, -SR ^10, -SOR ^10, -SO 2 R ^10, -SO3H | -SO 2 NR ⁸ R ^9, -OCH 2 -CH ₂ OCOR ^10, -CH = NOH, -CH = NOR ^10, -COR ^ ^1, -CH (OH) R ^11, -'CH (OR ¹⁰⁾ 2, -NHCOOR ¹⁰ , -CH2CONHSO ₂ R ¹⁰ , -CH = CH-R ¹² , -OCONR ⁸ R ⁹ , -CH 2 -O-CONR ⁸ R ⁹ , -CH 2 -CH ₂ -O-CONR ⁸ R ⁹ , -CO-R ¹⁰ , -COC ₁ -C ₄ - alkyl-NR ⁸ R ⁹ , optionally mono- or poly-substituted with methyl 1,3-dioxolane, or 1,3-dioxane; R ⁶ can be C ₃ -C ₇ -cycloalkyl-C ₁ -C ₆ -alkyl-, C ₃ -C ₇ -cycloalkyl-C ₂ -C ₆ -alkenyl-, C ₃ -C ₇ cycloalkyl-C ₂ -C ₆ -alkynyl, wherein the cycloalkyl radical may be substituted, directly or through an alkylene bridge of 1 to 4 carbon atoms, by one or more, -CN, NR ⁹ R ⁸ , = O, -OH, -OR ¹⁰ , -NR ⁸ R ⁹ , -NHCOR ¹⁰ , -NHCONR ⁸ R ⁹ , halogen, - OCOR ¹⁰ , - OCO-pyridyl, - OCH ² COOH, - OCH ² COOR ¹⁰ , -CH ² OCOR ¹⁰ , - SO ₂ R ⁷ , -OCH ₂ -CONR ⁸ R ⁹ , -OCH ₂ CH ₂ OH, -OCH ₂ -CH ₂ -NR ⁸ R ⁹ , -OCH ₂ -CH ₂ -OR ¹⁰ , -COOH, -COOR ¹⁰ , -CONR ⁸ R ⁹ , -CH 2 OH, -CH 2 OR ^10, CHO, -SR ^10, -SOR ^10, -SO 2 r ^10, -SO ₃ h -SO ₂ nR ⁸ r ^9, -OCH 2 ch2ocor ^10, -CH = NOH, -CH = NOR ¹⁰ , -cor ¹¹ , -ch (OH) R ¹¹ , -CONHSO ² R ¹⁰ , -CH (OR ¹⁰ ) 2, -NHCOOR ¹⁰ , -CH = CH-R ¹² , -conr ⁸ r ⁹ , -ch2O-CONR ⁸ R ⁹ , -CH ₂ -CH ₂ -O-CONR ⁸ R ⁹ , a 1,3-dioxolane optionally substituted by a methyl group, or 1,3-dioxane; R ⁶ may be a radical having the formula A-C ₁ -C ₆ -alkyl, A-CONHC ₁ -C ₆ -alkyl, A-CONH-C ₂ -C ₆ -alkenyl, A-CONH-C ₂ -C ₆ -alkynyl, A-NH-CO-C ₁ -C ₆ -alkyl- , A-NH-CO-C ₂ -C ₆ -alkenyl, A-NH-COC ₂ -C ₆ -alkynyl, AC ₂ -C ₆ alkenyl, AC ₂ -C ₆ -alkynyl, or A-, wherein A is 5 A carbon, nitrogen, 6 or 7 membered heterocycle containing one or more nitrogen, oxygen or sulfur atoms and optionally one or more times substituted by benzyl, optionally substituted by benzyl, C 1 -C 4 alkyl , halogen, -OR ¹⁰ , -CN, -NO ₂ , -NH ₂ , -CH ₂ NR ⁸ R ⁹ , -OH, -165 = O, ketal, ethylene ketal, -COOH, -SO ₃ H, -COOR ¹⁰ , -CONR ⁸ R ⁹ , -COR ¹¹ , -SO ₂ R ¹⁰ , or -CONR ⁸ R ⁹ ; R ⁶ can be -CHO, -COOR ¹⁰ , -CONR ⁸ R ⁹ ; R ⁶ may be C ₃ -C ₇ -cycloalkyl, which is optionally substituted with = O, -OH, -OR ¹⁰ , OCOR ¹⁰ , or -OCO-pyridyl; R ⁶ may be phenyl, which is optionally substituted with -OH, halogen, -OR ¹⁰ , C 1 -C 4 alkyl, -NH 2, -COOH, -SO 3 H, -COOR ¹⁰ , -OCH ² COOR ¹⁰ , -CN, or - OCH ₂ CONR ⁸ R ⁹ group; R ⁶ may be a norbornene, norbornene, C ₃ -C ₆ -dicycloalkylmethyl, preferably dicyclopropylmethyl, adamantane, or noradamantane radical, optionally substituted with a C 1 -C 6 alkyl group; R ⁶ may be -CH = CH-phenyl, wherein the phenyl ring may be substituted one or more times with methoxy, hydroxy, or halogen; R ⁶ can be [3,3,0] -bicyclooctane; it may be a carbon-bonded piperidine or a furan; R ⁷ can be C 1 -C 4 alkyl, optionally substituted with -OH, -OCOR ¹⁰ , -OCO-pyridyl, -NH 2, NR ⁸ R ⁹ , or NHCOR ¹⁰ , preferably -CH 2 -CH ₂ -OH, -CH ₂ -CH ₂ -OCOR ¹⁰ , -CH ₂ -CH ₂ -CH ₂ -OH, or CH ₂ -CH ₂ -CH ₂ -OCOR ¹⁰ ; R ⁸ may be hydrogen, optionally substituted cycloalkyl of 3 to 6 carbon atoms, branched or unbranched alkyl, alkenyl, or alkynyl of up to 10 carbon atoms, which may optionally be substituted Hydroxy, phenyl, substituted phenyl, benzyl, substituted benzyl, amino, substituted amino, C 1 -C ₈ -alkyloxy, preferably C 1 -C 4 alkyloxy, - (CH ₂ ) _m -NHCOOR ¹⁰ m = 1, 2, 3, or 4; R ⁸ may be, directly or through an alkyl chain of 1 to 4 carbon atoms, bonded via a carbon atom through a 5, 6, or 7 membered hetero ring containing one or more heteroatoms selected from nitrogen, oxygen or sulfur and optionally one or more times substituted with benzyl, optionally substituted benzyl, C 1 -C 4 alkyl, halogen, - OR ¹⁰ , - CN, - NO ₂ , - NH ₂ , - OH, = O, - COOH, - SO ₃ H, - COOR ¹⁰ ; R ⁸ may be bicyclic, directly or via a C 1 -C 4 alkyl chain, a carbon-linked heterocycle containing one or more heteroatoms selected from nitrogen, oxygen or sulfur, optionally one or more times, substituted with benzyl, optionally substituted benzyl, C 1 -C 4 alkyl, halogen, - OR ¹⁰ , - CN, - NO ₂ , - NH ₂ , - OH, = O, - COOH, - SO ₃ H, or - COOR ¹⁰ ; R ⁹ may be hydrogen, optionally substituted cycloalkyl of 3 to 6 carbon atoms, branched or unbranched alkyl, alkenyl, or alkynyl of up to 10 carbon atoms, which may optionally be substituted with hydroxy, phenyl, substituted phenyl, benzyl, substituted benzyl, amino, substituted amino, C _r to C ₈ alkyloxy, - (CH _{2) m} -NHCOOR ¹⁰ m = 1, 2, 3, or 4; R ⁹ may be, directly or through an alkyl chain of 1 to 4 carbon atoms, bonded via a carbon atom through a 5, 6, or 7 membered heterocycle containing one or more heteroatoms selected from nitrogen, oxygen or sulfur and optionally one or more times substituted benzyl, optionally substituted benzyl, C _r C ₄ -alkyl, halogen, - oR ^10, - CN, - NO _2, NH ₂ , OH, = O, COOH, SO ₃ H, or COOR ¹⁰ ; R ⁹ may be bicyclic, directly or through a C 1 -C 4 alkyl chain, a carbon-linked heterocycle containing one or more nitrogen, oxygen or sulfur heteroatoms optionally one or more times substituted with benzyl, optionally substituted with benzyl , C 1-6 alkyl, halogen, -OR ¹⁰ ,-CN, -NO ₂ , -NH ₂ , -OH, = O, -COOH, -SO ₃ H, or -COOR ¹⁰ , or R ⁸ and R ^{8 9} may form, together with the nitrogen, a saturated or unsaturated 5 or 6 membered ring which may contain as further heteroatoms nitrogen, oxygen or sulfur, said hetero ring may be substituted by a branched or unbranched alkyl group having 1 to 4 carbon atoms, or may bind the following groups - (CH ₂ ) _n -phenyl, - (CH ₂ ) _n -NH ₂ = O, ketal, preferably -O-CH ₂ -CH ₂ -O-, - (CH ₂ ) _n -NH-C 1 -C 6 -alkyl, - (CH ₂ ) _n -N - (C 1 -C 8 -alkyl) ,, - (CH ₂ ) _n -NH COOR ¹⁰ , (n = 1, 2, 3, 4), halogen, - OR ¹⁰ , - CN, - NO ₂ , - NH ₂ , - CH ₂ NR ⁸ R ⁹ , - OH, - COOH, - SO ₃ H, - COOR ¹⁰ , - CONR ⁸ R ⁹ , - SO ₂ - R ¹⁰ ; R ¹⁰ can be hydrogen, C ₁ -C ₄ -alkyl, C ₂ -C ₄ -alkenyl, C ₂ -C ₄ -alkynyl, benzyl, or phenyl, optionally mono- or poly-substituted with OCH ₃ ; R ¹¹ can be C 1 -C 4 alkyl, C ₂ -C ₄ -alkenyl, C ₂ -C ₄ -alkynyl, optionally substituted phenyl, optionally substituted benzyl, C ₃ -C ₆ -cycloalkyl; -isereR ¹² can be -COOR ¹⁰ , -CH ₂ OR ¹⁰ , -CONR ⁸ R ⁹ , hydrogen, C 1 -C 6 -alkyl, optionally I substituted phenyl, -CH ₂ NR ⁸ R ⁹ , optionally in the form of their racemates, their enantiomers, diastereomers and mixtures thereof, as well as their pharmacologically acceptable acid addition salts. 3. Imidazo triazolopyrimidinone derivatives of formulas (Ia) to (Id) wherein R ¹ or R ³ can be hydrogen, C 1 -C 4 alkyl, benzyl; R ² denotes hydrogen, CPCG-alkyl, preferably CPCG-alkyl; R ² can be phenyl, which is optionally substituted with halogen, C 1 -C 4 alkyl, C 1 -C 4 alkyloxy, hydroxy, or NR ⁸ R ⁹ ; R ² can be phenyl-C 2 -C 6 -alkyl-, phenyl-C ₂ -C ₆ -alkenyl-, or phenyl-C ₂ -C ₆ -alkynyl, wherein the phenyl ring is optionally substituted with halogen, preferably fluorine or -159chlórom, C ^ C ^ alkyl, C ^ C ^ alkyloxy, hydroxy, or NR ⁸ R ^9; R ² can be an amine having the formula NR ⁸ R ⁹ ; R ² may optionally be either directly or through a C 1 -C 4 alkylene bridge, or a 6-membered heterocycle bonded via a carbon or nitrogen atom containing one or more nitrogen or oxygen heteroatoms and optionally substituted by benzyl or C 1 -C 4 alkyl; R ² may be a C ₃ -C ₆ -cycloalkyl group which may be optionally substituted with = O, hydroxy, C ₁ -C ₄ alkyl, or C ₁ -C ₄ alkyloxy; R ² may be norborane, norborene, adamantane, or noradamantane, optionally substituted with a C 1 -C 4 alkyl group; R ⁴ or R ⁵ may be hydrogen, C 1 -C 6 -alkyl, phenyl-C ₂ -C ₆ -alkyl, phenyl-C ₂ -C ₆ -alkenyl, or phenyl-C ₂ -C ₆ -alkynyl, the phenyl ring optionally being substituted halogen, hydroxy, C 1 -C 4 alkyl, C 1 -C 4 alkyloxy, or NR ⁸ R ⁹ ; R ⁶ may be hydrogen, C 1 -C 6 -alkyl, wherein the alkyl chain may be optionally substituted by halogen, hydroxy, = O, C 1 -C 6 alkyloxy, NR ⁸ R ⁹ , phenyloxy, -O-phenyl-C 1 -C 4 - alkyloxy, benzyloxy, -O-benzyl-O-C 1 -C 4 -alkyloxy, -OCO-C 1 -C 4 alkyl, -OCO-phenyl, -OCO-benzyl, -OCO-pyridyl, -O-C 2 -C 4 -alkylenyl, -CO-C 1 -C 4 -alkyl, -CHO, = NOH, -COOH, -COO-C 1 -C 4 -alkyl, -COO-phenyl, -COO-benzyl, -CONR ⁸ R ⁹ , -NHCOC 1 -C ₄ -alkyl, -NHCO-phenyl, -CO-C ₁ -C ₄ -alkyl-NR ⁸ R ⁹ , -SO ₂ OH, -SO 4 -C 1 -alkyl, or -SO ₂ -phenyl; R ⁶ may be phenyl, which may optionally be substituted with halogen, hydroxy, C 1 -C 4 alkyl, C 1 -C 4 alkyloxy, benzyloxy, phenyloxy, NR ⁸ R ⁹ , -OCO-C 1 -C 4 alkyl, -OCO- phenyl, -OCO-benzyl, -OCO-pyridyl, -O-C 2 -C 4 -alkylenyl, -CO-C 1 -C 4 -alkyl, -C 1 -C 4 -alkyl-NH 3, -C 1 -C 4 -alkyl-OH, - C 1 -C 8 -alkylhNOH, -COOH, -COO-C 1 -C 4 -alkyl, -COO-phenyl, -COO-benzyl, -CONR ⁸ R ⁹ , -CO-C 1 -C ₄ -alkyl-NH ₂ , -SO ₂ OH, - SO ₂ -C ₁ -C ₄ -alkyl, or -SO ₂ -phenyl; R ⁶ may be phenyl-C ₁ -C ₄ -alkyl-, phenyl-C ₂ -C ₆ -alkenyl, or phenyl-C ₂ -C ₆ -alkynyl, wherein the phenyl ring may be substituted by halogen, hydroxy, C 1 -C ₄ -alkenyl, C 1-4 alkyl, C 1-4 alkyloxy, benzyloxy, phenyloxy, NR ⁸ R ⁹ , -OCO-C 1-4 alkyl, -OCO-phenyl, -OCO-benzyl, -OCO-pyridyl, -O-C 2 -C 4 -alkylenyl , -CO-C ₁ -C ₄ alkyl, -C ₁ -C ₄ -alkyl-NR ⁸ R ⁹ , C 1 -C ₄ -alkyl-OH, -C ₁ -C ₄ -alkyl = NOH, -COOH, -COO-C 1-4 alkyl; C 1-6 alkyl, -COO-phenyl, -COObenzyl, -CONR ⁸ R ⁹ , -CO-C ₁ -C ₄ -alkyl-NH ₂ , -SO ₂ OH, -SO 4 -C 1-4 alkyl, or -SO ₂ phenyl; R ⁶ may be either directly or through a C 1 -C 4 alkylene bridge, or a 6 membered heterocycle bound via a carbon or nitrogen atom containing one, two or three heteroatoms from the nitrogen or oxygen group and may optionally be once , or multiple substituted with benzyl, or C 1 -C 4 alkyl; R ⁶ may be a C ₃ -C ₆ -cycloalkyl or a C 1 -C ₆ -cycloalkyl-C 1 -C 4 alkyl radical, which may optionally be substituted by = O, hydroxy, C 1 -C 4 alkyl, or a C ₁ -C ₄ -alkyloxy group ; R ⁶ may be norbomyl, norbornenyl, adamantyl, or noradamantyl, optionally substituted with a C 1 -C 4 alkyl group; -161 ^R6 denotes -CHO, -COOH, -COO-C _r C ₄ -alkyl, -COO-phenyl, -COO-benzyl, or CONR ⁸ R ^9; R ⁶ can be an amine having the formula NR ⁸ R ⁹ ; R ⁸ can be hydrogen, a branched or unbranched alkyl group having 1 to 4 carbon atoms; R ⁸ may be a 5 or 6 membered heterocycle bonded through a carbon atom containing one, two, or three heteroatoms selected from nitrogen, oxygen or sulfur and optionally substituted by benzyl, C 1 -C 4 alkyl, C 1 -C 4 alkyl; alkyloxy, halogen, -CN, -NO ₂ , -NH ₂ , -OH, or = O; R ⁹ can be hydrogen, a branched or unbranched alkyl group having 1 to 4 carbon atoms; R ⁹ may be a 5 or 6 membered heterocycle bonded through a carbon atom containing one, two, or three heteroatoms from the group nitrogen, oxygen or sulfur and which is optionally substituted by a benzyl group, a C 1 -C 4 alkyl group, a C 1-6 group C 1-4 alkyloxy, halogen, -CN, -NO ₂ , -NH ₂ , -OH, or = O; or R ⁸ and R ⁹ together with the nitrogen atom form a saturated or unsaturated 5 or 6 membered ring which, as further heteroatoms, may contain nitrogen or oxygen, said hetero ring may be substituted by a branched or unbranched alkyl group having 1 to 4 carbon atoms, preferably methyl, or - (CH ₂ ) ₁ . _4- phenyl, preferably benzyl, Optionally in the form of their racemates, enantiomers, in the form of diastereomers and mixtures thereof, and optionally in the form of their pharmacologically acceptable acid addition salts. 4. Imidazo triazolopyrimidinone derivatives of formulas (Ia) and (1b) in which R ¹ or R ³ can be hydrogen, C 1 -C 4 alkyl, benzyl; R ² denotes hydrogen, C ^ Cg alkyl, R ² denotes cyclopentyl, cyclohexyl, cyklopentatnón, cyclohexanone, hydroxycyclopentane or hydroxycyclohexane; ^R2 denotes a morpholine radical which is optionally substituted 0, - (^ alkyl group, a piperidino radical, a piperazinyl radical which is optionally substituted C ^ C ^ alkyl, pyridyl, tetrahydrofuranyl, tetrahydropyranyl or furyl; R ² may be a phenyl radical which is optionally substituted by a radical O, -O 4 alkyl, halogen, or hydroxy; -163R ² denotes phenyl-CrC ^ alkyl, wherein the phenyl ring is optionally substituted by halogen, preferably fluoro or chloro, a C _r C ₄ alkyl, C ^ alkyloxy, hydroxy, or NR ⁸ R ^9; R ² can be an amine having the formula NR ⁸ R ⁹ ; R ² may be norbornenyl, norbomyl, adamantyl, or noradamantyl, optionally substituted with a C 1 -C ₄ -alkyl group; R ⁴ may be hydrogen, C ₁ -C ₆ -alkyl, phenyl-C ₁ -C ₃ -alkyl, wherein the phenyl ring may be substituted with halogen, hydroxy, C 1 -C 4 alkyloxy, or NR ⁸ R ⁹ ; R ⁶ may be hydrogen, C 1 -C 6 -alkyl, wherein the alkyl chain may be optionally substituted by halogen, hydroxy, = O, C 1 -C 6 alkyloxy, NR ⁸ R ⁹ , phenyloxy, -O-phenyl-C 1 -C 6 alkyl; -alkyloxy, benzyloxy, -O-benzyl-OC 1 -C 4 alkyloxy, -OCO-C 1 -C 4 -alkyl, -OCO-phenyl, -OCO-benzyl, -OCO-pyridyl, -O-C 2 -C 4 -alkylene, - CO-C 1 -C 4 alkyl, -CHO, = NOH, -COOH, -COO-C 1 -C 4 -alkyl, -COO-phenyl, -COO-benzyl, -CONR ⁸ R ⁹ , -NHCO-C 1 -C 4 -alkyl, -NHCO-phenyl, -CO-CrC. alkyl-NR ^9, -SO 2 OH, -SO ₂ -C _r C ₄ alkyl, or _-SO2 -phenyl; may be phenyl, wherein the phenyl ring may be substituted with halogen, hydroxy, C 1 -C 4 alkyl, C 1 -C 4 alkyloxy, or NR ⁸ R ⁹ ; R ⁶ may be phenyl-C ₁ -C ₃ -alkyl-, wherein the phenyl ring may be substituted by halogen, preferably chlorine or fluorine, hydroxy, C 1 -C 4 alkyl, C 1 -C 4 alkyloxy, benzyloxy, phenyloxy, NR ⁸ R ⁹ , -OCO-C 1 -C 4 -alkyl, -OCO-phenyl, -OCO-benzyl, -OCO-pyridyl, -O-C 2 -C 4 -alkylenyl, -CO-C 1 -C 4 -alkyl, -C1- 4 alkyl-NR ⁸ R ^9, -C ₄ -all <ylOH, -C C-alkykNOH, -COOH, -COO-C ^ C-alkyl, -COO-phenyl, -COO-benzyl, - 164 CONR ⁸ R ^9, -CO-C 1 -C 4 alkyl-NR ⁸ R ^9, -SO 2 OH, -SO ₂ -C _r C ₄ alkyl "or -SO ₂ phenyl group; R ⁶ may be a single bond, or a cyclopentyl, cyclohexyl, cyclohexyl-C 1 -C 6 -alkyl, preferably cyclohexylmethyl, cyclopentanone, cyclohexanone, hydroxycyclopentane, or hydroxycyclohexane bonded via an alkylene bridge of 1 to 4 carbon atoms; R ⁶ may be a single bond, or via a C 1 -C 4 alkylene bridge bound furan, tetrahydrofuran, α-pyran, γ-pyran, dioxolane, tetrahydropyran, dioxane, thiophene, thiolane, dithiolane, pyrrole, pyroline, pyrrolidine, pyrazole, pyrazoline, imidazole, imidazoline, imidazolidine, triazole, pyridine, piperidine, pyridazine, pyrimidine, pyrazine, piperazine, triazine, morpholine, thiomotpholine, oxazole, isoxazole, oxazine, thiazole, isothiazole, thiadiazole, oxadiazole, or pyrazolidine; R ⁶ can be -CHO, -COOH, -COOC 1 -C 4 alkyl, -COO-phenyl, -COO-benzyl, -CONH-C ₁ -C ₄ alkyl, -CO-N (C ₁ -C ₄ -alkyl) ₂ , or - CO-NH-phenyl; R ⁶ can be an amine having the formula NR ⁸ R ⁹ ; R ⁸ can be hydrogen, a branched or unbranched alkyl group having 1 to 4 carbon atoms; R ⁸ may be a carbon-bonded pyrrole, pyroline, pyrrolidine, pyrazole, pyrazoline, imidazole, imidazoline, imidazolidine, triazole, pyridine, piperidine, pyridazine, pyrimidine, pyrazine, piperazine, morpholine, oxazole, isoxazole, thiazole, isothiazole, or thiazole, isothiazole, or thiazole, optionally substituted with chlorine, bromine, C 1 -C 4 alkyl, C 1 -C 4 alkyloxy, NO ₂ , NH ₂ , or OH; - Í65R ⁹ denotes hydrogen, a branched, or unbranched alkyl having 1 to 4 carbon atoms; R ⁹ may be a carbon-bonded pyrrole, pyroline, pyrrolidine, pyrazole, pyrazoline, imidazole, imidazoline, imidazolidine, triazole, pyridine, piperidine, pyridazine, pyrimidine, pyrazine, piperazine, morpholine, oxazole, isoxazole, thiazole, isothiazole, or thiazole, isothiazole, or thiazole; optionally substituted by chlorine, bromine, a C _r C ₄ alkyl, C, -C ₄ alkyloxy, NO _2, NH _2, or OH group, and • R ⁸ and R ⁹ together with the nitrogen atom a saturated or unsaturated 5, or a 6-membered ring which, as further heteroatoms, may contain nitrogen or oxygen, said heterocycle may be substituted by a branched or unbranched alkyl group having 1 to 4 carbon atoms, or by a - (CH ₂ ) ₁₁ -phenyl _radical , optionally in the form of their racemates , their enantiomers, in the form of diastereomers and mixtures thereof, optionally in the form of their pharmacologically acceptable acid addition salts. Imidazo triazolopyrimidinone derivatives of the general formula (Ib) in which R ² denotes hydrogen, C ^ C ^ alkyl, phenyl, benzyl, where the phenyl ring is optionally substituted by fluorine, pyridyl, piperidinyl, morpholinyl, piperazinyl, 4 -166 benzylpiperazinyl, furyl, tetrahydrofuranyl, tetrahydropyranyl, NR ⁸ R ⁹ , cyclopentyl, cyclohexyl, adamantyl, noradamantyl, norbornyl, or norbornenyl; R ³ : I may be hydrogen, C ₁ -C ₃ -alkyl, or benzyl; R ⁴ 'can be hydrogen, C 1 -C 6 -alkyl, or benzyl; R ⁶ may be hydrogen, C 1 -C 6 alkyl, optionally substituted by chlorine, fluorine, hydroxy, C 1 -C 6 alkyloxy, or NR ⁸ R ⁹ , furthermore denote -CHO, -COOH, -COO-CrC C 1-4 alkyl, phenyl, phenyl-C ₁ -C ₃ -alkyl optionally substituted by fluorine or benzyloxy, phenyloxy-C ₁ -C ₃ -alkyl optionally substituted by methoxy, benzyloxy-C ₁ -C ₃ -alkyl optionally substituted by methoxy, benzyloxybenzyl, benzoyloxymethyl, pyridylcarbonyloxymethyl, cyclopentyl, furyl, cyclohexylmethyl, pyridylmethyl, N-pyrrolylmethyl, or N-morpholinomethyl; R ⁸ can be hydrogen, C 1 -C 4 alkyl, or pyridyl; R ⁹ may be hydrogen, C 1 -C 4 alkyl, or pyridyl, optionally in the form of their racemates, their enantiomers, in the form of their diastereomers and mixtures thereof, optionally as their pharmacologically acceptable acid addition salts. An imidazotriazolopyrimidinone derivative of the general formula (Ia) in which I R ¹ can be hydrogen, C 1 -C 4 alkyl, or benzyl; R ² j II denotes hydrogen, C ₁ -C ₄ alkyl, phenyl, benzyl, wherein the phenyl ring is optionally substituted by fluorine, pyridyl, piperidinyl, morpholinyl, piperazinyl, 4 R, benzylpiperazinyl, furyl, tetrahydrofuranyl, tetrahydropyranyl, NR ⁸ R ⁹ , cyclopentyl, cyclohexyl, adamantyl, noradamantyl, norbornyl, or norbornenyl; R ⁴ ! can be hydrogen, C1-C6-alkyl, or benzyl; R ⁶ denotes hydrogen, C _r C ₄ -alkyl which is optionally substituted with chloro, fluoro, hydroxy, C ^ C ^ alkyloxy, NR ⁸ R ^9; denotes. " ii CHO, -COOH, -COO-C 1 -C 4 alkyl, phenyl, phenyl-C 1 -C 6 -alkyl, optionally substituted with fluoro, or benzyloxy, phenyloxy-C 1 -C 4 -alkyl, optionally substituted !.! methoxy, benzyloxy-C ₁ -C ₃ -alkyl optionally substituted with methoxy, benzyloxybenzyl, benzoyloxymethyl, pyridylcarbonyloxymethyl, cyclopentyl, furyl, cyclohexylmethyl, pyridylmethyl, N-pyrrolylmethyl, or N-morpholinomethyl; ^r8 [ee denotes hydrogen, C ^ C ^ alkyl, or pyridyl; R ⁹ can be hydrogen, C ₁ -C ₄ -alkyl, or pyridyl; optionally in the form of their racemates, their enantiomers, in the form of their diastereomers, and i mixtures thereof, optionally as pharmacologically acceptable acid addition salts thereof. ii i! I 7. Imidazotriazolopyrimidinone derivatives of formula (Ic) -168 - in which i R ¹ ! It may be hydrogen or C1-C6-alkyl; < R ² 'can be hydrogen, C 1 -C ₄ -alkyl, cyclopentyl, cyclopentanone, hydroxycyclopentane, furan, or benzyl; R ⁵ can be C 1 -C 6 -alkyl; R ⁶ may be hydrogen, benzyl, or cyclopentyl, optionally in the form of their racemates, their enantiomers, in the form of their diastereomers and mixtures thereof, optionally as their pharmacologically acceptable acid addition salts. Imidazo triazolopyrimidinone derivatives of the general formula (Id) in which R ¹ can be hydrogen, or C 1 -C 6 -alkyl; it may be hydrogen, C 1 -C 4 alkyl, cyclopentyl, cyclopentanone, hydroxy cyclopentane, furan, or benzyl; I R ⁵ can be C 1 -C 6 -alkyl; R ⁶ can be hydrogen, benzyl, or cyclopentyl, Optionally in the form of their racemates, their enantiomers, their diastereomers, and Mixtures thereof, optionally as pharmacologically acceptable acid addition salts thereof. [i 9. Imidazo triazolopyrimidinone derivatives of the general formula (Ib) ^R V AA R ⁶ XVR ² R ³ in which R ² can be hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, tert-butyl, phenyl, benzyl, 4-fluorobenzyl, pyridyl, N-piperidinyl, N-morpholinyl, N-piperazinyl, 4-benzylpiperazinyl, 2- furyl, 3-tetrahydrofuranyl; 4-tetrahydropyranyl, -NMe ₂ , cyclopentyl, cyclohexyl, adamantan-1-yl, noradamanten-3-yl, norboran-2-yl, or 5-norbornen-2-yl; ^; her R ³ can be hydrogen, methyl, ethyl, n-propyl, or benzyl; R ^4! it may be hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, tert-butyl, n-pentyl, or benzyl; R &lt; ⁶ &gt; can be hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, tert-butyl, phenyl, benzyl, cyclopentyl, 2-furyl, 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, cyclohexylmethyl , phenylethyl, N-morpholinomethyl, N-pyrrolylmethyl, (3-pyridyl) -NH-CH _{2, phenyl-CO-O-CH2} -, pyridyl-CO-O-CH _2, phenyl-O-CH ₂ -, ( 4-MeO-phenyl) -O-CH ₂ -, (4-MeOphenyl) -CH ₂ -O-CH ₂ -, (4-phenyl-CH ₂ -O-phenyl) -CH ₂ -, 4-F-phenyl-CH _2- , 3,4-F-phenyl-CH ₂ -, -COOH, -COOMe, -CH ₂ -OH, -CH ₂ -OMe, -CH ₂ -O-Et, or -CH ₂ -NMe ₂ ,. I -170-; f. optionally in the form of their racemates, their enantiomers, in the form of their diastereomers and mixtures thereof, optionally as their pharmacologically acceptable acid addition salts. ¹ ! I, i ' ^: ' I I Imidazotriazolopyrimidinone derivatives of the general formula (Ia) in which R ¹ can be hydrogen, methyl, ethyl, n-propyl, or benzyl; R ² I can be hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, tert-butyl, phenyl, benzyl, 4-fluorobenzyl, pyridyl, N-piperidinyl, N-morpholinyl, N-piperazinyl, 4-benzylpiperazinyl, 2 -furyl, 3-tetrahydrofuranyl, 4-tetrahydropyranyl, -NMe ₂ , Cyclopentyl, cyclohexyl, adamantan-1-yl, noradamantan-3-yl, norboran-2-yl, or 5-norbornen-2-yl; R ⁴ I may be hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, tert-butyl, n-pentyl, or benzyl; ! I R ⁶ ! can be hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, tert-butyl, phenyl, benzyl, cyclopentyl, 2-furyl, 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, cyclohexylmethyl, phenylethyl, morfplínometyl N, N-pyrrolylmethyl, (3-pyridyl) -NH-CH _{2, phenyl-CO-O-CH2} -, _{pyridyl-CO-O-CH2} -, phenyl-O-CH ₂ -, (4 MeO-phenyl) -O-CH ₂ -, (4-MeOphenyl) -CH ₂ -O-CH ₂ , (4-phenyl-CH ₂ -O-phenyl) -CH ₂ -, 4-F-phenyl-CH ₂ -, 3,4-F-phenyl-CH ₂ , -COOH, -COOMe, -CH ₂ -OH, -CH ₂ -QMe, -CH ₂ -O-Et, or -CH ₂ -NMe ₂ , optionally in the form of their racemates , their enantiomers, in the form of their diastereomers and mixtures thereof, optionally also as their pharmacologically acceptable acid addition salts. ! The imidazotriazolopyrimidinone derivatives of the general formula (Ib) in which R ² I f. n-propyl, i-propyl, n-butyl, tert-butyl, phenyl, N-piperazinyl, 44-tetrahydropyranyl, -NMe ₂ , I! can be hydrogen, methyl, jetyl, benzyl, 4-fluorobenzyl, pyridyl, N-piperidinyl, N-morpholinyl, benzylpiperazinyl, 2-furyl, 3-etrahydrofuranyl, cyclopentyl, cyclohexyl, adamantari-1-yl, noradamantan-3-yl , norboran-2-yl, or 5-norbornen-2-yl; ! R ³ 'can be hydrogen; R ⁴ í 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, may be hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, tert-butyl, n-pentyl or benzyl; R ⁶ denotes hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, t-butyl, phenyl, benzyl, cyclopentyl, 2-furyl, cyclohexylmethyl, 2-phenylethyl, N-morpholinomethyl, N-pyrrolylmethyl, ( 3-pyridyl) -NH-CH ₂ , phenyl-CO-O-CH ₂ -, 3-pyridyl-CO-O-CH ₂ , phenyl-O-CH ₂ -, (4-MeO-phenyl) -O-CH ₂ -, (4- 4-F-phenyl-CH ₂ -, 3,4-F-phenyl-CH ₂ -, -CH ₂ -OH, -CH ₂ -OMe, or -COOH, MeO-phenyl) -CH ₂ -O-CH ₂ , -CH ₂ -O-Et, -CH ₂ -NMe ₂ , -COOMe, I Optionally in the form of their racemates, their enantiomers, in the form of their diastereomers and mixtures thereof, optionally also as their pharmacologically acceptable acid addition salts. An imidazotriazolopyrimidinone derivative of the general formula (Ia) in which R ¹ can be hydrogen; R ² i. Can be hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, tert-butyl, phenyl, I Benzyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, N-piperidinyl, N-morpholinyl, N-piperazinyl, 4-benzylpiperazinyl, 3-tetrahydrofuranyl, 4-tetrahydropyranyl, -NMe ₂ , cyclopentyl, cyclohexyl, adamantan-1-yl, noradamantane 3-yl, norboran-2-yl, or 5-norbenzyl 2-yl; ! R * n-propyl, i -propyl, n -butyl, tert -butyl, phenyl, 3-pyridylmethyl, 4-pyridylmethyl, may be hydrogen, methyl, ethyl, or benzyl; R ⁶ can be hydrogen, methyl, ethyl, benzyl, cyclopentyl, 2-furyl, 2-pyridylmethyl cyclohexylmethyl, phenylethyl, N-morpholinomethyl, N-pyrrolylmethyl, (3-pyridyl) -NH-CH ₂ -, phenyl-CO-O -CH ₂ -, 3-pyridyl-CO-O-CH. MeO-phenyl) -CH ₂ -O-CH ₂ , 4-F-phenyl-CH ₂ -, OH, -CH ₂ -OMe, -CH ₂ -O-Et, or -CH ₃ -NMe ₂ ,; phenyl-O-CH ₂ -, (4-MeO-phenyl) -O-CH ₂ -, (4; 3,4-F-phenyl-CH ₂ , -COOH, -COOMe, -CH ₂ f 173 optionally in the form of their racemates, their enantiomers, in the form of their diastereomers and their mixtures, optionally also as their pharmacologically acceptable acid addition salts. A process for the preparation of imidazo triazolopyrimidinone derivatives having the general formula (I) wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ are as defined in claims 1 to 12, 1. characterized in that: (a) a compound having the general formula (9) O) or tautomers thereof, wherein R ² , R ⁴ and R ⁶ are as defined above, in a suitable organic solvent or solvent mixture in a basic medium with a suitable alkylating agent having the general formula R ¹ -X, or R ³ - X, wherein R ¹ and R ³ have the same meaning as defined above and X represents a exchangeable group, or (b) a compound having the general formula (16) (16) -174- or tautomers thereof, wherein R ² , R ⁵ and R ⁶ are as defined above, in a suitable organic solvent or solvent mixture in a basic environment with a suitable alkylating agent having the general formula R ¹ -X, or R ³ - X, wherein R ¹ and R ³ have the same meaning as defined above and X represents I replaceable group, or c) for R ⁴ = R ^{1, a} compound of the formula or tautomers thereof, wherein R ² and R ⁶ are as defined above, in a suitable organic solvent or in a mixture of solvents in a basic environment with a suitable alkylating agent having the general formula R ¹ - X, or R ³ -X, are reacted to an amino-alkylated compound (9), or directly to a dialkylated compound (I), wherein R ¹ and R ³ have the same meaning as defined above and X is a removable group. A process for the preparation of imidazo triazolopyrimidinone derivatives of the general formula (9) or tautomers thereof, wherein R ² , R ⁴ and R ⁶ are as defined in claims 1 to 12, characterized in that: (a) a compound of the general formula - 175- or in which R ² , R ⁴ and R ⁶ are as defined above, reacts in a basic, acidic or neutral environment to the cyclic derivatives of the imidazotriazolopyrimidinones of the general formula (9), or (b) for R ² = H, a diamine of the formula wherein R ⁴ and R ⁶ are as defined above, is converted to the imidazole-thiazolopyrimidinone derivative of the general formula (9) by heat treatment with formamide; or c) for R ² = NR ⁸ R ⁹ , wherein R ⁸ and R ⁹ are as defined above, the nitroso compound of the formula wherein R ⁴ and R ⁶ are as defined above in a dehydration medium with N-formylamine reacts to imidazole triazolopyrimidinone derivatives with (9). -176- A process for the preparation of imidazotriazolopyrimidinone derivatives of general formula (16) (16) or tautomers thereof, wherein R ² , R ⁵ and R ⁶ are as defined in claims 1 to 12, characterized in that: (a) a compound of the general formula in which R ² , R ⁵ and R ⁶ are as defined above, is reacted by cyclisation in an alkaline, acidic or dehydrating medium to give the tricyclic imidazotriazolopyrimidinone derivatives of the general formula (16), or b) for R ² = H, a diamine of the general formula ABOUT -177 wherein R ⁵ and R ⁶ are as defined above, are converted to imidazotriazolopyrimidinone derivatives of general formula (16) by heat treatment with formamide, or c) for R ² = NR ⁸ R ⁹ , wherein R ⁸ and R ⁹ are as defined above, the nitroso compound of the formula wherein R ⁵ and R ⁶ is as defined above under dehydration conditions with Nformylamine to imidazotriazolopyrimidinone derivatives of general formula (16). A pharmaceutical composition comprising as active ingredient one or more imidazotriazolopyrimidinone derivatives according to any one of claims 1 to 12, or a physiologically acceptable acid addition salt thereof, in combination with conventional excipients and / or carriers. The imidazotriazolopyrimidinone derivatives according to any one of claims 1 to 12 for use as a medicament. The imidazotriazolopyrimidinone derivatives of any one of claims 1 to 12 for use as an adenosine antagonist.