CS354591A3 - Aminodiole derivatives, process of their preparation and their use - Google Patents

Description

uílíDr. Miíoá VŠETEČXA attorney at iM PtlAKA · “Rye 25 - 1 ra ^ ·‘ 1 <- C? · 0 '7-y. : i r rr ~

Aminodiol derivatives, process for their preparation and their use

Technical field

The present invention relates to novel aminodiol derivatives and to processes for their preparation. Further, the invention relates to the use of these novel compounds as medicaments.

SUMMARY OF THE INVENTION

New aminodiol derivatives of the general formula Ia and Ib were found

2 in which t is -C0-, -O-C0-, -SC1- or -NH-CO-,

Ra represents a hydrogen atom, an alkyl group having from 1 to 10 carbon atoms which is optionally one or two times unsaturated and which is optionally substituted with up to 3 identical non-boron substituents selected from the group consisting of hydroxy, alkoxy of 1 to 7 carbon atoms, alkanoyloxy of 1 C 7 -C 7 alkoxycarbonyl C 1 -C 7 alkoxycarbonyl C 1 -C 7 alkoxycarbonyl C 1 -C 7 alkylamino, C 1 -C 7 dialkylamino C 1-6 alkyloxycarbonylamino C 1 -C 5 -alkoxy and C 7 -C 15 -alkoxycarbonylamino means an cycloalkyl group having from 3 to 8 carbon atoms, a cycloalkyl-C 3 -C 8 -alkyl group in the cycloalkyl moiety and C 1 -C 6 alkyl, C 6 -C 14 aryl, optionally substituted substituted with 1 or 2 identical or different substituents selected from the group consisting of fluoro, chloro, bromo, iodo, hydroxy, alkoxy of 1-7 carbon atoms, alkyl of 1-7 carbon atoms, alkoxycarbonyl of 1-7 carbon atoms in the alkoxy moiety, an amino group, or an halogen group substituted by an anilino and a trifluoromethyl group, furthermore, an alkyl group having from 6 to 14 carbon atoms in the aryl moiety with from 1 to 6 carbon atoms in the alkyl moiety; wherein the aryl moiety is optionally substituted with 1 or 2 identical or different substituents selected from the group consisting of fluoro, chloro, bromo, iodo, hydroxy, C1-7 alkoxy, 1-7 alkyl carbon, C 1 -C 7 alkoxycarbonyl, alkoxy, C 1 -C 6 alkylamino, C 1-3 alkylamino C 1 -C 7 alkyl, carboxy, carboxymethoxy, C 1 -C 7 alkylamino, C 1 -C 7 alkylamino, C 1 -C 7 dialkylaminoalkyl, alkyl alkoxycarbonyl C 1 -C 7 alkoxy, carbamoyl, sulfamoyl, C 1 -C 7 alkoxy and sulfo, or is a 5- or 6-membered monocyclic or 9- or 10-membered bicyclic heterocycle with at least 1 carbon atom, 1 to 4 nitrogen atoms and / or 1 sulfur or oxygen atom as ring members which is optionally mono-, di- or tri-substituted with 1 or more substituents selected from the group consisting of it consists of a fluorine, chlorine, bromine, hydroxy, alkoxy group having 1 to 7 carbon atoms, an alkyl group of 1 to 7 carbon atoms, an alkoxycarbonyl group of 1 to 8 carbon atoms in the alkoxy moiety, amino and trifluoromethyl, 2 R represents a hydrogen atom or a hydroxyl group protecting group as described, for example, in TWGreene, " Protective Groups in Organic Synthesis ", A. Wiley-Interscience Publications New York-Chichester-Brisbane-Toronto-Singapore, 1981. Particularly suitable are benzyl, p-methoxybenzyl, methoxymethyl, methoxyethyl, benzyloxymethyl, acetyl, trimethylsilyl, tert-butyldimethylsilyl, and the like. -pina and tert-butyldiphenylsilyl group. 3 R is C 1 -C 12 alkyl, mono-, bi- or tricyclic C 3 -C 18 cycloalkyl, or C 3 -C 18 mono-, bi- or tricyclic-cycloalkylalkyl in C 1 -C 6 cycloalkyl in the alkyl moiety, wherein the cycloalkyl moiety is optionally optionally substituted by a C 1 -C 6 alkyl group, 4 R 4 and R 5 are the same or different substituents and represent a hydrogen atom, a C 1 -C 12 alkyl group, a C 3 -C 12 cycloalkyl group , a cycloalkylalkyl group having from 3 to 12 carbon atoms in the cycloalkyl moiety of 1 to 6 carbon atoms, an arylalkyl group having from 6 to 14 carbon atoms in an aryl moiety with from 1 to 6 carbon atoms in the alkyl moiety, the aryl moiety being substituted by one, two or three identical or different substituents selected from the group consisting of C1-6 alkyl and halogen, Het or Het-alkyl have 1 to 6 carbon atoms in the alkyl moiety, Het being a 5-, 6- or 7-membered heterocyclic ring optionally containing an annealed benzene ring and is aromatic, partially hydrogenated or fully hydrogenated, and as the heteroelement contains one or two identical non-compartmental moieties selected from the group consisting of N, O, S, NO, SO and SC 2, and which is optionally substituted with one or two identical or different the substituents selected from the group consisting of alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 4 carbon atoms and halogen, 7 R and R are the same or different and are hydrogen, alkyl of 1 to 12 carbon atoms, C 3 -C 12 cycloalkyl, C 3 -C 12 cycloalkyl C 1 -C 6 cycloalkyl C 1 -C 6 alkyl the aryl moiety is each optionally substituted with one, two or three identical or different substituents selected from the group consisting of an alkyl group having from 1 to 1 carbon atoms in the aryl moiety and from 1 to 6 carbon atoms in the alkyl moiety; Carbon atoms, (C 1 -C 4) alkoxy and halogen, or (5) R and R are taken together with the carbon atom to which the C 3 -C 12 cycloalkyl group is attached. Further, new salts of the compounds of general formula Ia and Ib were also found.

The compounds of formulas Ia and Ib are enantiomers.

The invention relates both to optically pure compounds and to their stereoisomeric mixtures as racemates.

The alkyl group may have a straight or branched chain. The same applies to groups derived from an alkyl group such as an alkoxy group.

By cycloalkyl is meant, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl.

The residue designated Het preferably has one of the following meanings: pyridyl, thiazolyl, thienyl, pyranyl, benzofuryl, isobenzofuryl, furyl, pyrrolyl, imidazolyl, pyrazinyl, indazolyl, quinolyl, isoquinolyl, phthalazinyl, pyrimidinyl, pyrazinyl, indolizinyl, isoindolyl, indolylphenylquinolinyl, cinnolinyl, oxazolyl, isoxazolyl and isothiazolyl. These radicals may be aromatic, may be partially hydrogenated or fully hydrogenated. They may also be substituted by one or two identical or different substituents selected from the group consisting of an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 4 carbon atoms and a halogen atom.

C 6 -C 14 aryl is understood to mean, for example, phenyl, naphthyl or biphenylyl. A phenyl group is preferred.

The halogen atom is fluorine, chlorine, bromine or iodine.

Suitable salts are, in particular, mineral acid salts such as hydrochloric acid, sulfuric acid and phosphoric acid, to which the compounds of formula (Ia) and (Ib) are converted, for example, for storage reasons. Preferred are compounds of formula (Ia) and (Ib) wherein W is as defined above,

Ra represents a hydrogen atom, an alkyl group having from 1 to 10 carbon atoms which is optionally unsaturated once or twice, and a cycloalkyl group having from 3 to 8 carbon atoms, a cycloalkylalkyl group having from 3 to 8 carbon atoms in the cycloalkyl group and from 1 to 6 carbon atoms on the alkyl group a (C 14-Catom,) aryl group, (C 14-C 14ryry) aralkyl group having from 1 to 6 carbon atoms in the alkyl moiety, or a residue of a 5- or 6-membered homonocyclic or 9- or 10-membered bicyclic heterocycle with at least one carbon atom, 1 to 4 nitrogen atoms and / or one sulfur atom or oxygen atom as ring members, 2 R is as defined above, R 1 is C 1 -C 6 alkyl, mono-, bi- or tricyclic cycloalkyl with 3 to 18 carbon atoms or a mono-, bi- or tricyclic cycloalkylalkyl group having 3 to 18 carbon atoms in the cycloalkyl moiety and having 1 to 3 carbon atoms R 6 and R 8 are the same or different from each other and are hydrogen, alkyl of 1 to 12 carbon atoms, cycloalkyl of 3 to 12 carbon atoms , a C 3 -C 12 cycloalkyl group having from 1 to 6 carbon atoms in the cycloalkyl moiety, or both together with the carbon atom to which they are attached, a C 3 -C 12 cycloalkyl group as well as and salts thereof.

Particularly preferred are compounds of formula I and Ib wherein W is -CO- or -O-CO-

R a represents a hydrogen atom, a C 1 -C 10 alkyl group which is optionally unsaturated once or twice, a C 3-8 cycloalkyl group, a C 3-8 cycloalkylalkyl group in a cycloalkyl group and a C 1-6 carbon atom; an alkyl moiety, an aryl group having from 6 to 14 carbon atoms, an aryl-alkyl group having from 6 to 14 carbon atoms in an aryl moiety having from 1 to 6 carbon atoms in the alkyl moiety, an unnamed 5- or 6-membered monocyclic or 9- or 10-membered bicyclic heterocycle having at least one carbon atom, 1 to 4 nitrogen atoms and / or one sulfur atom or oxygen atom as ring members, 2 R is as defined above, 3 R is methyl, ethyl, n-propyl, n-butyl a group, 2-methylpropyl group, 2-ethylbutyl group, cyclopentylmethyl group, cyclohexylmethyl group or cycloheptylmethyl group; amy a6 7 R and R are the same and are hydrogen or C1 -C4 alkyl, or both together with the carbon atom to which they are attached are C5 -C7 cycloalkyl and salts thereof.

Particularly preferred are compounds of formula Ia and Ib, wherein R 'and R' are as defined above, R 4 is methyl, ethyl, n-propyl, n-butyl, 2-methyl-8 propyl, 2-ethylbutyl, cyclopentylmethyl, cyclohexylmethyl or cycloheptylmethyl, and are the same or different from each other to represent a hydrogen atom, a C 1 -C 4 alkyl group, a C 5 -C 7 cycloalkyl group, a 5-7 cycloalkylalkyl group carbon atoms in the cycloalkyl moiety of 1 to 3 carbon atoms in the alkyl moiety, phenyl, benzyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-thienyl, 3-thienyl, 1-methylimidazol-2-yl, 1-methylimidazol-4-yl or 1-methylimidazol-5-ylovous and R and R are the same and represent a hydrogen atom, an alkyl group having 1 to 4 carbon atoms, or together with the carbon atom to which they are attached, a cycloalkyl group having 5 to 7 carbon atoms, as well as salts thereof.

The invention furthermore relates to a process for the preparation of compounds of general formula Ia or Ib, which comprises reacting a compound of formula IIa or IIb 9

in which R, R, R, R and Rz are as defined above,

with phosphorane of formula III

(III) wherein R 4 and R 5 are as defined above and g and R are both the same or different aryl groups, preferably phenyl. For the preparation of a compound of formula (IIa), if desired, the compounds of formula (IIa) are suitably protected from amino acid derivatives. These compounds provide compounds of formula (IIa) optionally with a double reaction with a nucleophilic formyl equivalent of 2-trimethylsilylthiazole (TST) (cf. Scheme 1) (A. Oondoni et al., 3. Org. Chem. 1990, 55, 1439) in an inert solvent. to this nucleophilic agent, such as diethyl ether, MT8, dichloromethane, DIP, THF, tetrahydropyran or DME at a temperature between -40 ° C and the boiling point of the solvent, preferably at a temperature of between -40 ° C and + 25 ° C. The first addition takes place with high-susceptibility, the second addition with high anti-selection. The resulting hydroxyl function is protected in the next reaction step using methods known in the literature. The release of the formyl group can be carried out by the following reaction sequence: 1) N-alkylation with a suitable alkylating agent, such as dimethyl sulphate or solvent free methyl iodide or in an inert inert solvent such as acetonitrile, tetrahydrofuran, MTB, DIP, EE at a temperature of between 25 ° C. ° C and the boiling point of the corresponding solvent. 2) Reduction with a hydride transfer agent such as sodium borohydride in a solvent suitable for this type of reaction, such as in methanol, ethanol at temperatures between -25 ° C and 25 ° C, preferably at temperatures between -20 ° C and Low: 1 ° C. 3) Release of the aldehyde group by thioacetal cleavage reagents (cf. Tamura et al., Synthesis 312 (1973), Seebach et al., Ibid. 357 (1977) and the references cited therein), preferably by treatment with N-bromosuccinimide in acetone and water, preferably at 0 ° C to 30 ° C. 11

5 12

1. TST 2. Protection \ t

3. "Me +" Z 4. Ή - "

5. eg MBS

Ha, IIb

Wittig reaction with the appropriate phosphorous in an inert solvent such as diethyl ether, di-n-butyl ether, methyl tert-butyl ether, diisopropyl ether, tetrahydrofuran, 1,2-dimethoxyethane, dioxane at -30 ° C until the boiling point of the solvent, preferably at temperatures between 0 ° C and 30 ° C, affords the title compounds of formula (Ia) or (Ib). Likewise, the aldehyde of formula (IIa) or (IIb) can be reacted with the anion of the appropriate phosphinoxide to give the title compound (Horner; cf. Krauch, Kunz, Reactionion of Organism Chemistry, Huthig Verlag Heidelberg, 1976, p. 241).

The compounds of formula (Ia) and (Ib) are valuable intermediates in the manufacture of pharmaceuticals, in particular renin and proteazyHIV inhibitors. Inhibitors for which these compounds can be advantageously used are described, for example, in FE3S Lett. St. 230.30 (1930), J. Med. Chem. St. 31, 2264 (1938), ibid. 2277, Sio-chem. Biophys. Res. Commun. St. 146, 959 (1987) and ΕΡ-Λ-370,454.

List of abbreviations used: DC thin layer chromatography 0CI desorption by chemical ionization DIP di isopropyl ether DME 1,2-dimethoxyethane EE ethyl acetate FAB fast atom bombardment 13

Hep n-heptane M molecular peak

MeOH methanol MS mass spectrum MTB methyl tert-butyl ether

EtzO diethyl ether R.T. room temperature THF tetrahydrofuran NBS N-bromosuccinimide TST trimethylsilylthiazole

Red-Al sodium bis- (2-methoxyethoxy) dihydroaluminate

The following examples serve to illustrate the present invention. However, the examples are not intended to limit the invention. Example 1 (2S, 1RS) -2-tert-butyloxycarbonylamino-3-cyclohexyl-1- (2-thiazolyl) propanol 3.14 g (10 mmol) of N-Boc-L-cyclohexylalanine N, O-dimethylamide dissolved in 30 ml of absolute tetrahydrofuran and the resulting solution was cooled to 0 ° C. 5.7 ml (20 mmol) of sodium bis- (2-methoxyethoxy) dihydroaluminate (70 µl in toluene) were added dropwise to the cooled solution. After stirring for 2 hours at 0 ° C, the mixture is poured into 200 ml of ice-water and extracted three times with ethyl acetate. The combined organic phases are washed with saturated sodium chloride solution, dried over sodium sulfate and concentrated. There were obtained 2.6 g of N-Boc-L-cyclohexylalanine, which was dissolved as crude product in 30 ml of absolute methylene chloride and 3.13 g (20 mmol) of 2-trimethylsilyl thiazole were added to the obtained solution at -30 DEG. The reaction mixture was left in a refrigerator at -25 ° C for 14 hours. After concentration, the residue is dissolved in a mixture of 30 ml of tetrahydrofuran and 5 ml of water and 3 g (20 mmol) of fluoride is added to the solution. After refluxing for 7 hours, the reaction mixture was diluted with ethyl acetate and washed twice with saturated sodium chloride solution. After drying over sodium sulfate, the residue is concentrated.

The product is separated from the small amounts of unreacted aldehyde on silica gel (solvent system: ethyl acetate / n-heptane 1: 2). 1.83 g (54% of theory) of the title compound are obtained. According to the NMR spectrum, it is a mixture of R- and S-configurations on the carbon atom of Cl at a ratio of 5: 1.

Rf (solvent system: 1: 1 mixture of ethyl acetate and n-heptane) = 0.21. MS (DCI) = 341 (M + 1). Example 1a (45,5R) -3-tert-Butyloxycarbonyl-4-cyclohexylmethyl-2,2-dimethyl-5- (2-thiazolyl-oxazolidine 23 g of the title compound of Example 1 (67.6 mmol) in 250 ml of toluene was boiled refluxing together with 40 ml of 2,2-dimethoxypropane and 2.5 g of p-toluenesulfonic acid for 48 hours, after cooling the mixture was washed with 1N sodium bicarbonate solution, dried over magnesium sulfate and concentrated. Purification on silica using 1: 1 mixture of ethyl acetate and cyclohexane as eluent gave 12.5 g of the title compound.

R1 (solvent system: 1: 1 mixture of ethyl acetate and n-heptane) = 0.55. MS (DCI) = 381 (M + 1).

Melting point: 89-91 ° C. [.alpha.] D @ 20 = -67.9 DEG (c = 1, CH-OH). Example 1b (4S, 5R, 1R) -3-tert-butyloxycarbonyl-4-cyclohexylmethyl-2,2-dimethyl-5- (1,1-hydroxy-1 '- (2-thiazolyl) methyl) oxazolidine 15 12, 5 g (32.8 mmol) of the title compound are dissolved in 70 ml of acetonitrile. Dimethyl sulphate (3.9 ml, 1.25 equivalents) was added and the mixture was heated to boiling for 7 hours. The mixture is left to stand overnight at room temperature and then concentrated to dryness. The solid residue was dissolved in 150 mL of methanol. Sodium borohydride (4.3 g, 0.013 mol) was added portionwise to the resulting solution, while the temperature was not allowed to rise above -10 ° C. After 30 minutes of further stirring at 0 ° C, 40 ml of acetone are added. After concentration, the residue is taken up in 500 ml of ethyl acetate and washed with 200 ml of saturated sodium chloride solution. After drying over sodium sulfate, the solution is concentrated and the crude product is pre-purified by filtration through a small amount of silica gel to give 14 g of the product (compound 5, scheme 1). This product was dissolved in a mixture of 250 ml of acetone and water (95: 5) and 16.5 g of N-bromosuccinimide (25 ° C) was added to the solution over 10 minutes. After the addition was complete, the mixture was cooled and 500 ml of saturated sodium sulfite solution (&lt; 25 ° C, strongly exothermic!) Was added in small portions. After dilution with 500 ml of water, the mixture is extracted three times with diethyl ether. The combined extracts were washed twice with water and washed once with saturated sodium chloride solution, dried over sodium sulfate and concentrated. Azeotroping by rotary evaporation with toluene removes the water. 5.9 g of the aldehyde (compound 6, scheme 1) are obtained, which is immediately dissolved in 80 ml of methylene chloride and cooled to -40 DEG C. with a methylene chloride solution. 5.88 g (37.4 mmol) of trimethylsilyl thiazole are added to the cooled solution by means of a spray. The mixture was slowly warmed to room temperature overnight. After concentration, the residue is taken up in 80 ml of tetrahydrofuran and 11.8 g (37.4 mmoles) of tetrabutylammonium fluoride trihydrate are added. After 2 hours, the mixture was diluted with ethyl acetate, washed twice with water and once with saturated sodium chloride solution, dried over sodium sulfate and concentrated. The crystalline crude product is recrystallized from acetonitrile to give 4.7 g of the title compound.

Rf (DIP) = 0.4. MS (DCI) = 411 (M + 1).

Melting point: 176 DEG-178 DEG C. [.alpha.] D @ 20 = + 35.7 DEG (c = 1, CH-OH). Example 1c (4S, 5R, 1'R) -3-tert-Butyloxycarbonyl-4-cyclohexylmethyl-2,2-dimethyl-5- (1'-benzyloxy-1 '- (2-thiazolyl) methyl) oxazolidine 5, The title compound (4 g, 13.2 mmol) was dissolved in tetrahydrofuran (100 ml) and 0.7 g sodium borohydride (50% in oil, washed twice with n-heptane) in 20 ml of tetrahydrofuran was added dropwise to the resulting solution. After 20 minutes at reflux, the reaction mixture was cooled to 50 ° C and 0.5 g of tetrabutylammonium iodide and 1.76 ml of benzyl bromide were added. After stirring for 3 hours at room temperature, the mixture is taken up in about 500 ml of saturated sodium chloride solution. After being extracted twice with ethyl acetate, the solution is dried over sodium sulfate and then concentrated to give 5 g of the title compound which can be used without further purification for the next reaction.

Rf (DIP) = 0.45. MS (DCI) = 500 (M + 1).

Melting point 96 ° C. [.alpha.] D @ 20 = 146.3 DEG (c = 1, CH2 OH). Example 1d (4S, 5R, 1'R) -3-tert-butyloxycarbonyl-4-cyclohexylmethyl-2,2-dimethyl-5- (1'-benzyloxy-1'-formoxoxazolidine 17 2.1g (4.2 mmol) of the title compound are dissolved in 10 ml of acetonitrile and 0.55 ml of dimethyl sulphate is added to the obtained solution, and after 8 hours under reflux and after standing overnight at room temperature, the reaction mixture is concentrated to dryness. The solution was dissolved in methanol (15 ml) and sodium borohydride (0.5 g) was added in small portions to the solution and the solution was concentrated, the residue was taken up in ethyl acetate, washed with brine and dried over sodium sulfate. After concentration, the crude product is dissolved in a 25: 5 mixture of water and water in a ratio of 95: 5 and the solution obtained is added dropwise over 15 minutes at -10 ° C to 2.25 g of N-bromosuccinimide in 22 ml of an acetone mixture. water (95: 5), 80 mL of saturated was added slowly sodium sulphate solution so that the temperature does not exceed +20 DEG C. After dilution with 100 ml of water, the mixture is extracted three times with diethyl ether. The combined ether extracts were washed twice with water, dried over magnesium sulfate and concentrated to give 1.75 g (95% of theory) of the title compound which was used as a crude product.

Rf (DIP) = 0.4. MS (DCI) = 446 (M + 1). Example 1e (4S, 5R, 1S) -3-tert-Butyloxycarbonyl-4-cyclohexylmethyl-2,2-dimethyl-5- [1-benzyloxy-3- (2-pyridyl) prop-2-phenyl] oxazole -Line 1.72 g (4 mmol) of 2-picolyltriphenylphosphonium chloride is suspended in 30 ml of absolute tetrahydrofuran. Potassium tert-butoxide (0.43 g) was then added to the obtained suspension under argon. After 2 hours at room temperature, the docitron-yellow solution was added dropwise at -15 DEG C. to 0.85 g of the title compound of Example 1d in 5 ml of tetrahydrofuran. After standing overnight at room temperature, the mixture was diluted with water and extracted three times with ethyl acetate. 18

The ethyl acetate extract was washed with saturated sodium chloride solution, dried over sodium sulfate and concentrated. Chromatography on silica gel gave 0.11 g of the cis isomer and 0.4 g of the trans isomer of the title compound as an oil.

R f (DIP) = 0.45 (cis) 0.3 (trans). MS (OCI) = 521 (M + 1). [.alpha.] D @ 20 = + 26.8 DEG (c = 1, methanol, trans).

Claims (7)

19 - PATENT REQUIREMENTS 1D Aminodiol Derivatives of Formula Ia fla) (Ib) j____ i λΛΒΓΟΟνλΖΞΤ. D OtdI αν ^ η I ---- 16 IX 7 3I ® £ οα where RM / is -C0-, -O-CO-, -SO2- or -NH-CO-, 20 is hydrogen, alkyl with 1 to 10 carbon atoms which is optionally unsaturated one or two times and which is optionally substituted with up to 3 identical non-compartmental substituents selected from the group consisting of hydroxy, alkoxy of 1-7 carbon, alkanoyloxy of 1-7 carbon atoms, C 1 -C 7 alkoxycarbonyl, halo, amino, C 1 -C 7 alkylamino, C 1 -C 7 dialkylamino, C 1 -C 5 alkoxycarbonylamino, and C 1 -C 5 alkoxycarbonylamino. alkoxy and aralkoxycarbonylamino. 7 to 15 carbon atoms in the aralkoxy moiety, furthermore, a C 3 -C 8 cycloalkyl group, a C 3 -C 8 cycloalkyl-alkyl group having 1 to 6 carbon atoms in the alkyl moiety, an aryl group having 6 up to 14 carbon atoms optionally substituted by 1 or 2 identical or different substituents selected from the group consisting of fluorine, chlorine, bromine, iodine, hydroxy, alkoxy of 1-7 carbon atoms, alkyl of s1 C 7 -C 7 alkoxycarbonyl, C 1-7 C 1-6 alkoxy, amino, anilino or trifluoromethyl substituted C 2 -C 6 haloalkyl, C 6 -C 14 aryl-alkyl in the aryl moiety with from 1 to 6 carbon atoms in the alkyl moiety, wherein the aryl moiety is optionally substituted with 1 or 2 identical or different substituents selected from the group consisting of it consists of fluorine, chlorine, bromine, iodine, hydroxy, C 1 -C 7 alkoxy, C 1 -C 7 alkyl, C 1 -C 7 alkoxycarbonyl, amino, alkylamino C 1 -C 7 -alkyl, C 1 -C 7 -alkylamino, C 1-7 alkylamino, C 1 -C 7 alkyl amino, C 1 -C 7 alkylamino-alkyl, dialkylaminoalkyl (C 1 -C 7) carbonyl, (C 1 -C 7) alkoxycarbonyl, (C 1 -C 7) alkoxycarbonyl, sulfamoyl, (C 1 -C 7) alkoxysulfonyl and sulfo, or is -5- or A 6-membered monocyclic or 9- or 10-membered bicyclic heterocycle having at least 1 carbon atom, 1 to 4 nitrogen atoms and / or 1 sulfur or oxygen atom as members a ring optionally mono-, di- or tri-substituted with 1 or more substituents selected from the group consisting of fluoro, chloro, bromo, hydroxy, alkoxy of 1-7 carbon, alkyl C 1 -C 7 alkoxycarbonyl, C 1 -C 3 alkoxycarbonyl, amino and trifluoromethyl, R 2 is hydrogen or hydroxyl protecting group, R 1 is C 1 -C 12 alkyl , a C 3 -C 18 mono-, bi- or tricyclic cycloalkyl group, or a C 3 -C 18 mono-, bi- or tricyclic-cycloalkylalkyl group in a cycloalkyl moiety with from 1 to 6 carbon atoms in the alkyl moiety, wherein the cycloalkyl moiety is in each case optionally sub- substituted by C 1-6 alkyl, R 4 and R 5 are the same or different substituents and represent a hydrogen atom, an alkyl group having 1 to 12 carbon atoms cycloalkyl of 3 to 12 carbon atoms, cycloalkylalkyl of 3 to 12 carbon atoms, cycloalkyl of 3 to 12 carbon atoms, arylalkyl of 6 to 14 carbon atoms in the aryl moiety of 1 to 6 carbon atoms in the alkyl moiety. the moiety, wherein the aryl moiety may be substituted by one, two or three identical or different substituents selected from the group consisting of alkyl of 1 to 6 carbon atoms and a halogen atom, further referred to as Het or Het-alkyl of 1 to 6 carbon atoms in the alkyl moiety, wherein Het is a 5-, 6- or 7-membered heterocyclic ring which optionally contains a fused benzene ring and is aromatic, partially hydrogenated or fully hydrogenated, and the heteroelement contains one or two identical non-boron groups. selected from the group consisting of N, O, S, NO, SO and SO2 and which is optionally substituted with one or two identical or different substituents selected from the group consisting of alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 4 carbon atoms and halogen, g 7 R and R are the same or different and are hydrogen, alkyl with s C 1 -C 12, C 3 -C 12 cycloalkyl, C 3 -C 12 cycloalkylalkyl, C 1 -C 6 cycloalkyl, C 6 -C 14 arylalkyl. carbon atoms in the alkyl moiety, wherein the aryl moiety is each optionally substituted by one, two or three identical or different substituents selected from the group consisting of an alkyl group having from 1 to 6 carbon atoms, an alkoxy group having from 1 to 4 carbon atoms and a halogen atom, and / or being taken together with a carbon atom to which the C 3 -C 12 cycloalkyl group is bonded as well as its salts. A compound of formula (Ia) or (Ib) according to claim 1, wherein R a represents a hydrogen atom, an alkyl group having from 1 to 10 carbon atoms which is not saturated once or twice, and a cycloalkyl group having from 3 to 8 carbon atoms, a cycloalkylalkyl group having from 3 to 8 carbon atoms in the cycloalkyl moiety and from 1 to 6 carbon atoms in the alkyl moiety, an aryl group having from 6 to 14 carbon atoms, an arylalkyl group having from 6 to 14 carbon atoms in the aryl moiety and from 1 to 6 carbon atoms in the alkyl moiety, or a residue of 5 or a 6-membered homonocyclic or 9- or 10-membered bicyclic heterocycle with at least one carbon atom, 1 to 4 nitrogen atoms, and / or one sulfur atom or oxygen atom as ring members, r 3 is an alkyl group having 1 to 6 carbon atoms, mo-mon -, a bi- or tricyclic cycloalkyl group having from 3 to 18 carbon atoms or a mono-, bi- or tricyclic cycloalkylalkyl group of from 3 to 18 carbon atoms per ring C 1-6 alkyl having 1 to 3 carbon atoms in the alkyl moiety, R 6 and R 7 are the same or different and are hydrogen, C 1 -C 12 alkyl, C 3 -C 12 cycloalkyl, cycloalkylalkyl C 3 -C 12 carbon atoms in the cycloalkyl moiety with 1 to 6 carbon atoms in the alkyl moiety, or both together with the carbon atom to which they are attached represent a C 3 -C 12 cycloalkyl moiety, and the other substituents are as defined in and the salts thereof. Compound of formula (Ia) or (Ib) according to claim 1 or 2, wherein W represents a group -CQ-, -Q-CO-, 24 Ra represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms which is not once or twice unsaturated C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkylalkyl, C 1 -C 6 cycloalkyl, C 6 -C 14 aryl, C 6 -C 14 aryl-alkyl in an aryl moiety of about up to 6 carbon atoms in the alkyl moiety, a 5- or 6-membered monocyclic or 9- or 10-membered bicyclic heterocycle having at least one carbon atom, 1 to 4 nitrogen atoms and / or one sulfur atom or an oxygen atom as member ring, 3 ·, R is methyl, ethyl, n-propyl, n-butyl, 2-methylpropyl, 2-ethylbutyl, cyclopentylmethyl, cyclohexylmethyl, R 7 and R 8 are the same and are hydrogen or C 1 -C 4 alkyl or both together with the carbon atom to which they are attached represent a C 5 -C 7 cycloalkyl group, and the other substituents are as defined in claim 1, as well as salts thereof. A compound of formula Ia or Ib according to one of claims 1 to 3, wherein: and have the meanings defined in claim 3, R 1 and R 5 are the same or different and are hydrogen, C 1 -C 4 alkyl, C 5 -C 7 cycloalkyl, C 5 -C 7 cycloalkylalkyl C 1 -C 3 -alkyl, phenyl, benzyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl a 2-thienyl group, a 3-thienyl group, a 1-methylimidazol-2-yl group, a 1-methylimidazol-4-yl group, or a 1-methylimidazol-5-yl group, and 6 7 R and R are the same and is a hydrogen atom, an alkyl group having 1 to 4 carbon atoms or together with the carbon atom to which they are attached, is a cycloalkyl group having 5 to 7 carbon atoms, and the other substituents are as defined in claim 1, as well as their salts . 5. A process for the preparation of compounds of the formula Ia and Ib according to one of claims 1 to 4, characterized in that the compound of formula IIa or IIb - 26 - wherein R 1, R 2, R 2, R 6 and R 7 are as defined in claim 1, reacted with a phosphorane of the formula III, R 9 (XR 5 (III), 10 in which R 1 and R 6 are as defined in claim 1 and R 8, R 6 and RIG represent the same or different aryl groups, and the compounds obtained are optionally converted to their salts. A compound of formula IIa or IIb wherein r 1, r 2, r 7 are as defined in claim 1. Use of a compound according to one of claims 1 to 4 in the production of renin inhibitors and HIV protease. Represents: