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1. WO2006101859 - PIPERIDINYL SUBSTITUTED CYCLOHEXANE-1,4-DIAMINES

Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

[ EN ]

What is claimed is:
1. A compound of Formula (I)



or a pharmaceutically acceptable form thereof, wherein
Ri is selected from the group consisting of
(1) aryl,
(2) aryl-CLsalkyl,
(3) Cs-scycloalkyl,
(4) C3-8cycloalkyl-Ci.8alkyl,
(5) heteroaryl,
(6) heteroaryl-C1.8alkyl,
(7) heterocyclyl, and
(8) heterocyclyl-Q.galkyl,
wherein each aryl, C3.8cycloalkyl, heteroaryl and heterocyclyl is optionally substituted
with one, two, three or four substituents independently selected from the group
consisting of
(i) C^alkyl,
(ϋ) C1-8alkoxy,
(iii) Ci-Salk:oxy-C1.8alkyl,
(iv) halo-Ci-8alkyl,
(v) halo-C1-8alkoxy,
(vi) hydroxy-Ci.8alkyl,


(viii) SO2 substituted with a substituent selected from the group consisting of Ci-8alkyl,

Ca-gcycloalkyl, aryl, heteroaryl, and heterocyclyl,
(ix) amino optionally mono- or di-substituted with Ci-8alkyl,
(x) cyano,
(xi) halogen,
(xii) hydroxy, (xiϋ) nitro,
(xiv) amino-C1-8alkyl optionally mono- or di-substituted on amino with Ci.8alkyl, (xv) aryl-Ci-8alkyl,
(xvi) aryl-Ci.8alkoxy,
(xvii) heteroaryl-Ci.8alkyl,
(xvϋi) heterocyclyl-C1-8alkyl;
(xix) C(O) substituted with a substituent selected from the group consisting of
hydrogen, Ci-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(xx) S(O) substituted with a substituent selected from the group consisting of C1-8alkyl, Ca-scycloalkyl, aryl, heteroaryl, and heterocyclyl,
(xxi) C(O)N substituted on nitrogen with two substituents selected from the group consisting of hydrogen, Ci-8alkyl, C3.8cycloalkyl, aryl, heteroaryl, and
heterocyclyl,
(xxii) SO2N substituted on nitrogen with two substituents selected from the group
consisting of hydrogen, Ci-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and
heterocyclyl,
(xxiϋ) NHSO2 substituted on sulfur with a substituent selected from the group consisting of Ci-8alkyl, C3.8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(xxiv) NHC(O) substituted on carbonyl with a substituent selected from the group
consisting of hydrogen, Ci-8alkyl, C3.8cycloalkyl, aryl, heteroaryl, and
heterocyclyl,
(xxv) NHSO2N substituted on nitrogen with two substituents selected from the group consisting of hydrogen, Ci.8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and
heterocyclyl,
(xxvi) NHC(O)N substituted on nitrogen with two substituents selected from the group consisting of hydrogen, C1-8alkyl, C^scycloalkyl, aryl, heteroaryl, and
heterocyclyl,
(xxvϋ) C3.8cycloatkyl,
(xxviii) aryl,
(xxix) heteroaryl, and
(xxx) heterocyclyl;
R2 is selected from the group consisting of hydrogen and Ci-8alkyl;
R3 is one, two, three or four optionally present substituents independently selected from the group consisting of
(1) C1-8alkyl,
(2) Ci-8alkoxy, (3) C1-8alkoxy-C1-8alkyl,
(4) halo-C1-8alkyl,
(5) halo-Ci.galkoxy,
(6) hydroxy-C1-8alkyl,
(7) Ci-salkoxy-carbonyl,
(8) SO2 substituted with a substituent selected from the group consisting of Ci-8alkyl, C3-8CyClOaIlCyI, aryl, heteroaryl, and heterocyclyl,
(9) amino optionally mono- or di-substituted with Ci_8alkyl,
(10) cyano,
(11) halogen,
(12) hydroxy,
(13) nitro,
(14) amino-Ci-8alkyl optionally mono- or di-substituted on amino with C1-8alkyl,

(15) aryl,
(16) aryl-d-galkyl,
(17) aryl-Ci.8alkoxy, '
(18) C3-8cycloallcyl,
(19) C3.8cycloalkyl-Ci-8alkyl,
(20) C3.8cycloalkyl-Ci-8alkoxy,
(21)1 heteroaryl,
(22) heteroaryl-C1-8alkyl,
(23) heterocyclyl,
(24) heterocyclyl-Ci-salkyl,
(25) C(O) substituted with a substituent selected from the group consisting of
hydrogen, Ci.8alkyl, C3-8CyClOaIlCyI, aryl, heteroaryl, and heterocyclyl,
(26) S(O) substituted with a substituent selected from the group consisting of Ci-gatkyl, C3.8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(27) SO2 substituted with a substituent selected from the group consisting of Ci-8alkyl, C3.8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(28) C(O)N substituted on nitrogen with two substituents selected from the group consisting of hydrogen, Ci-8alkyl, C3.8cycloallcyl, aryl, heteroaryl, and
heterocyclyl,
(29) SO2N substituted on nitrogen with two substituents selected from the group
consisting of hydrogen, Ci-8alkyl, C3.8cycloalkyl, aryl, heteroaryl, and
heterocyclyl, (30) NHSO2 substituted on sulfur with a substituent selected from the group consisting of Ci-8alkyl, C3.8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(31) NHC(O) substituted on carbonyl with a substituent selected from the group
consisting of hydrogen, Ci.8alkyl, C3.8cycloalkyl, aryl, heteroaryl, and
heterocyclyl,
(32) NHSO2N substituted on nitrogen with two substituents selected from the group
consisting of hydrogen, C1-8alkyl, C^cycloalkyl, aryl, heteroaryl, and
heterocyclyl,
(33) NHC(O)N substituted on nitrogen with two substituents selected from the group consisting of hydrogen, Ci.8alkyl, C3.8cycloalkyl, aryl, heteroaryl, and
heterocyclyl, and
(34) C3-8CyClOaIkOXy;
wherein each aryl, C3.8cycloalkyl, heteroaryl and heterocyclyl is optionally substituted
with one or two substituents independently selected from the group consisting of (i) CI-8alkyl,
(ii) Ci-8alkoxy,
(in) Ci-8alkoxy-Ci.8atkyl,
(iv) halo-C1-8alkyl,
(v) halo-C1-8alkoxy,
(vi) hydroxy-C^alkyl,
(vϋ) Ci-salkoxy-carbonyl,
(viii) C1-8alkyl-sulfonyl,
(ix) amino optionally mono- or di-substituted with Ci-8alkyl,
(x) cyano,
(xi) halogen,
(xϋ) hydroxy,
(xiii) nitro, and
(xiv) amino-Ci.8alkyl optionally mono- or di-substituted on amino with Ci-8alkyl; and

R4 and R5 is each selected from hydrogen or are one or two optionally present substituents independently selected from the group consisting of Ci.8alkyl, Ci.8alkoxy, amino,

C1-8alkyl-amino, cyano, halogen, oxo and nitro.

2. A compound of Formula (I) or a pharmaceutically acceptable form thereof, wherein Ri is selected from the group consisting of
(1) aryl, and
(2) heterocyclyl, wherein each is optionally substituted with one, two, three or four substituents
independently selected from the group consisting of
(i) C1-8alkyl,
(ii) Ci-Salkoxy,
(iii) halo-Ci-8alkoxy, and
(iv) halogen.

3. A compound of Formula (I) or a pharmaceutically acceptable form thereof, wherein Ri is selected from the group consisting of
(1) aryl optionally substituted with one, two, three or four substituents independently selected from the group consisting of
(i) C1-galkyl,
(ii) C1-Salkoxy,
(iii) halo-C1-8alkoxy, and
(iv) halogen, and
(2) heterocyclyl.

4. A compound of Formula (I) or a pharmaceutically acceptable form thereof wherein R2 is hydrogen.

5. A compound of Formula (I) or a pharmaceutically acceptable form thereof wherein R3 is one, two, three or four optionally present substituents independently selected from the group consisting of
(1) C1-8alkyl,
(2) C1-8alkoxy,
(3) halo-Ci-8alkoxy, and
(4) C3.8cycloalkyl-Ci-8alkoxy.

6. A compound of Formula (Ia):



or a pharmaceutically acceptable form thereof, wherein
Ri is selected from the group consisting of (1) aryl,
(2) aryl-C1-8alkyl,
(3) C3-8cycloalkyl,
(4) C3.8cycloalkyl-Ci.8alkyl,
(5) heteroaryl,
(6) heteroaryl-Ci-8aIkyl,
(7) heterocyclyl, and
(8) heterocyclyl-C1-8alkyl,
wherein each aryl, C3.8cycloalkyl, heteroaryl and heterocyclyl is optionally
substituted with one, two, three or four substituents independently selected from the group consisting of
(i) C1-8OIlCyI,
(ii) Ci-8alkoxy,
(iϋ) C1-8alkoxy-Ci-8alkyl,
(iv) halo-Ci-8alkyl,
(v) halo-Ci-8alkoxy,
(vi) hydroxy-Ci.8alkyl,
(vii) Ci-galkoxy-carbonyl,
(viii) SO2 substituted with a substituent selected from the group consisting of Ci-8alkyl, C3.8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(ix) amino optionally mono- or di-substituted with Ci-8alkyl,
(x) cyano,
(xi) halogen,
(xii) hydroxy,
(xϋi) nitro,
(xiv) amino-Ci-8alkyl optionally mono- or di-substituted on amino with Ci-8alkyl,

(xv) aryl-Ci-8alkyl,
(xvi) aryl-Ci-8alkoxy,
(xvii) heteroaryl-Ci-8alkyl,
(xviii) heterocyclyl-C1-8allcyl;
(xix) C(O) substituted with a substituent selected from the group consisting of
hydrogen, Ci.8alkyl, C3.8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(xx) S(O) substituted with a substituent selected from the group consisting of Ci.8alkyl, C3-8CyClOaIlCyI, aryl, heteroaryl, and heterocyclyl, (xxi) C(O)N substituted on nitrogen with two substituents selected from the group consisting of hydrogen, C1-8alkyl, C3.8cycloalkyl, aryl, heteroaryl, and
heterocyclyl,
(xxϋ) SO2N substituted on nitrogen with two substituents selected from the group consisting of hydrogen, Ci-Salkyl, C3.8cycloalkyl, aryl, heteroaryl, and
heterocyclyl,
(xxiii) NHSO2 substituted on sulfur with a substituent selected from the group consisting of Ci-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(xxiv) NHC(O) substituted on carbonyl with a substituent selected from the group
consisting of hydrogen, Ci-8alkyl, C3.8cycloalkyl, aryl, heteroaryl, and
heterocyclyl,
(xxv) NHSO2N substituted on nitrogen with two substituents selected from the group consisting of hydrogen, Ci-8alkyl, C3.8cycloalkyl, aryl, heteroaryl, and
heterocyclyl,
(xxvi) NHC(O)N substituted on nitrogen with two substituents selected from the group consisting of hydrogen, Ci.8alkyl, C3.8cycloalkyl, aryl, heteroaryl, and
heterocyclyl,
(xxvϋ) C3.8cycloalkyl,
(xxviii) aryl,
(xxix) heteroaryl, and
(xxx) heterocyclyl;
R2 is selected from the group consisting of hydrogen and Ci.8alkyl; and
R3 is one, two, three or four optionally present substituents independently selected from the group consisting of
(1) C^alkyl,
(2) C1-8alkoxy,
(3) C1-8alkoxy-C1-8alkyl,
(4) halo-C1-8alkyl,
(5) halo-Ci-8alkoxy,
(6) hydroxy-CLsalkyl,


(8) SO2 substituted with a substituent selected from the group consisting of Ci.8alkyl, C3.8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(9) amino optionally mono- or di-substituted with Ci-8alkyl,
(10) cyano,
(11) halogen, (12) hydroxy,
(13) nitro,
(14) amino-Ci.8alkyl optionally mono- or di-substituted on amino with Ci-8alkyl,

(15) aryl,
(16) aryl-C1-8alkyl,
(17) aryl-Ci.8alkoxy,
(18) C3.8cycloalkyl,
(19) C3.8cycloalkyl-Ci-8alkyl,
(20) C3.8cycloalkyl-Ci-8alkoxy,
(21) heteroaryl,
(22) heteroaryl-Ci.8alkyl,
(23) heterocyclyl,
(24) heterocyclyl-CLsalkyl,
(25) C(O) substituted with a substituent selected from the group consisting of
hydrogen, C1-8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(26) S(O) substituted with a substituent selected from the group consisting of Ci.8alkyl, C3.8cycloaUcyl, aryl, heteroaryl, and heterocyclyl,
(27) SO2 substituted with a substituent selected from the group consisting of Ci-8alkyl, C3-Scycloalkyl, aryl, heteroaryl, and heterocyclyl,
(28) C(O)N substituted' on nitrogen with two substituents selected from the group consisting of hydrogen, Ci-8alkyl, C3.8cycloalkyl, aryl, heteroaryl, and
heterocyclyl,
(29) SO2N substituted on nitrogen with two substituents selected from the group
consisting of hydrogen, Ci-8alkyl, C3-8CyClOaIlSyI, aryl, heteroaryl, and
heterocyclyl,
(30) NHSO2 substituted on sulfur with a substituent selected from the group consisting of Ci-8atkyl, C3-8cycloalkyl, aryl, heteroaryl, and heterocyclyl,
(31) NHC(O) substituted on carbonyl with a substituent selected from the group
consisting of hydrogen, Ci-8alkyl, C3.8cycloalkyl, aryl, heteroaryl, and
heterocyclyl,
(32) NHSO2N substituted on nitrogen with two substituents selected from the group consisting of hydrogen, Ci.8alkyl, C3-8cycloalkyl, aryl, heteroaryl, and
heterocyclyl,
(33) NHC(O)N substituted on nitrogen with two substituents selected from the group consisting of hydrogen, Ci-8alkyl, C3.8cycloalkyl, aryl, heteroaryl, and
heterocyclyl, and (34) C3-8cycloalkoxy;
wherein each aryl, C3.scycloalkyl, heteroaryl and heterocyclyl is optionally substituted
with one or two substituents independently selected from the group consisting of

(1) C1-8alkyl,
(ii) Ci_galkoxy,
(iii) Ci.8alkoxy-Ci.8alkyl,
(iv) halo-Ci-8atkyl,
(v) halo-C1-8alkoxy,
(vi) hydroxy-Ci_8alkyl,
(vϋ) Ci.salkoxy-carbonyl,
(viii) C1-8alkyl-sulfonyl,
(ix) amino optionally mono- or di-substituted with Ci-8alkyl,
(x) cyano,
(xi) halogen,
(xϋ) hydroxy,
(xiii) nitro, and
(xiv) amino-Ci-8alkyl optionally mono- or di-substituted on amino with Ci-8alkyl.

7. A compound of formula of Formula (Ia) and pharmaceutically acceptable forms thereof, wherein Ri is selected from the group consisting of
(1) aryl, and
(2) heterocyclyl,
wherein each is optionally substituted with one, two, three or four substituents independently selected from the group consisting of
(i) C1-8alkyl,
(ii) Ci-8alkoxy,
(iii) halo-Ci-8alkoxy, and
(iv) halogen.

8. A compound a compound of Formula (Ia) and pharmaceutically acceptable forms thereof, wherein Ri is selected from the group consisting of
(1) aryl optionally substituted with one, two, three or four substituents independently selected from the group consisting of
(i) C,.8alkyl,
(ii) Ci.8alkoxy,
(iii) halo-Ci.8alkoxy, and
(iv) halogen, and (2) heterocyclyl.

9. A compound of Formula (Ia) or pharmaceutically acceptable form thereof, wherein R2 is hydrogen.

10. A compound of Formula (Ia) or a pharmaceutically acceptable form thereof, wherein R3 is one, two, three or four optionally present substituents independently selected from the group consisting of
(1) C^alkyl,
(2) Ci-8alkoxy,
(3) halo-Ci-8alkoxy, and
(4) C3.8cycloalkyl-Ci.8alkoxy.

11. A compound of Formula (Ib) :



or a pharmaceutically acceptable form thereof, wherein
R1 is selected from 3,4-(OCH3)2-phenyl, 3,4-F2-phenyl, 5-Cl-2-OCH3-phenyl, 5-C1-2-F- phenyl, 2,3-dihydro-benzo[l,4]dioxin-6-yl, 2,4-Q2-phenyl, benzo[l,3]dioxol-5- yl, 3-OCHF2-phenyl and 4-OCHF2-phenyl; and
R3 is selected from 2-OCH(CH3)2, 2-OCH2CF3, 2-cyclopropoxy, 2-O(CH2)3F, 2- OCH2CH(F2), 4-F-2-OCH(CH3)2 and 5-F-2-OCH(CH3)2.

12. A compound of Formula (Ic):



H
or a pharmaceutically acceptable form thereof, wherein R1 is selected from 3,4-(OCH3)2-ρhenyl, 3,4-F2-phenyl, 5-Cl-2-OCH3-phenyl, 5-C1-2-F- phenyl, 2,3-dihydro-benzo[l,4]dioxin-6-yl, 2,4-Cl2-ρhenyl, benzo[l,3]dioxol-5- yl, 3-OCHF2-ρhenyl and 4-OCHF2-phenyl; and
R3 is selected from 2-OCH(CH3)2, 2-OCH2CF3, 2-cyclopropoxy, 2-O(CH2)3F, 2- OCH2CH(F2), 4-F-2-OCH(CH3)2 and 5-F-2-OCH(CH3)2.

13. A compound as claimed in claim 1 wherein the compound is selected from the group consisting of :
N-cis- { 4-[4-(2-isopropoxy-phenyl)-piperidin- 1 -yl]-cyclohexyl } -3 ,4-dimethoxy- benzenesulfonamide,
3 ,4-difluoro-N-cw- { 4-[4-(2-isopropoxy-phenyl)-piperidin- 1 -yl]-cyclohexyl } - benzenesulfonamide,
3,4-difluoro-N-ϊraλi5-{4-[4-(2-isopropoxy-phenyl)-piperidin-l-yl]-cyclohexyl}- benzenesulfonamide,
3 ,4-dimethoxy-N-cz5-(4- { 4-[2-(2,2,2-trifluoro-ethoxy)-phenyl]-piperidin- 1 -yl } - cyclohexyl)-benzenesulfonamide,
3 ,4-dimethoxy-N-ϊrøns-(4- { 4-[2-(2,2,2-trifluoro-ethoxy)-phenyl]-piperidin- 1 -yl } - cyclohexyl)-benzenesulfonamide,
N-cw-{4-[4-(2-cyclopropoxy-phenyl)-piperidin-l-yl]-cyclohexyl}-3,4-dimethoxy- benzenesulfonamide,
5-chloro-N-cώ-{4-[4-(2-cyclopropoxy-phenyl)-ρiperidin-l-yl]-cyclohexyl}-2- methoxy-benzenesulfonamide,
5-chloro-N-cω- { 4- [4-(2-cyclopropoxy-phenyl)-piperidin- 1 -yl] -cyclohexyl } -2-fmoro- benzenesulfonamide,
2,3-dihydro-benzo[l,4]dioxine-6-sulfonic acid cω-(4-{4-[2-(2,2,2-trifluoro-ethoxy)- phenyl] -piperidin- 1 -yl } -cyclohexyl)-amide,
5-chloro-2-methoxy-Ν-cw-(4- { 4- [2-(2,2,2-trifluoro-ethoxy)-phenyl] -piperidin- 1 -yl } - cyclohexyl)-benzenesulfonamide,
5-chloro-2-methoxy-N-f rans-{A- { 4- [2-(2,2,2-trifluoro-ethoxy)-phenyl]-piperidin- 1 -yl } - cyclohexyl)-benzenesulfonamide,
5-chloro-2-fluoro-N-c/5-(4-{4-[2-(2,2,2-trifluoro-ethoxy)-phenyl]-piperidin-l-yl}- cyclohexyl)-benzenesulfonamide,
5-chloro-2-fluoro-N-f rans-(4- { 4-[2-(2,2,2-trifluoro-ethoxy)-phenyl] -piperidin- 1 -yl } - cyclohexyl)-benzenesulfonamide,
3-difluoromethoxy-N-c/5-(4-{4-[2-(2,2,2-trifluoro-ethoxy)-phenyl]-piperidin-l-yl}- cyclohexyl)-benzenesulfonamide,
N-ds-(4- { 4-[2-(2-fluoro-ethoxy)-phenyl] -piperidin- 1 -yl } -cyclohexyl)-3 ,4-dimethoxy- benzenesulfonamide,
N-trans-(4- { 4- [2-(2-fluoro-ethoxy)-phenyl]-piperidin- 1 -yl } -cyclohexyl)-3 ,4- dimethoxy-benzenesulfonamide,
N-c/5-(4-{4-[2-(2,2-difluoro-ethoxy)-phenyl]-piperidin-l-yl}-cyclohexyl)-3,4- dimethoxy-benzenesulfonamide,
N-cw-{4-[4-(4-fluoro-2-isopropoxy-phenyl)-piperidin-l-yl]-cyclohexyl}-3,4- dimethoxy-benzenesulfonamide, N-cis- { 4-[4-(5-fluoro-2-isopropoxy-ρhenyl)-ρiperidin- 1 -yl] -cyclohexyl } -3 ,4- dimethoxy-benzenesulfonamide, and
N-trans- { 4-[4-(5-fluoro-2-isopropoxy-phenyl)-piperidin- 1 -yl] -cyclohexyl } -3 ,4- dimethoxy-benzenesulfonamide.
14. The compound of any of claim 1 to 13, wherein the compound is an cxia/otid
adrenoreceptor modulator.

15. The compound of claim 14, wherein the compound is a prodrug form thereof.

16. The compound of any of claim 1 to 15, wherein the compound is an isolated form thereof.

17. An as αia/αid adrenoreceptor modulator characterized in that it is a compound as
claimed in claim 1.

18. An as a\Jan adrenoreceptor antagonist characterized in that it is a compound as
claimed in claim 1.

19. The compound of claim 16, wherein the compound is a metabolite form thereof.

20. The compound of any of claim 1 to 16, wherein the compound is labeled with a ligand for use as a marker, and wherein the ligand is a radioligand selected from deuterium or tritium.

21. A pharmaceutical composition, comprising a therapeutically effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier.

22. A process for preparing a pharmaceutical composition according to claim 21,
comprising the step of intimately mixing a compound according to claim 1 with a pharmaceutically acceptable carrier.

23. Use of the compound of any of claim 1 to 19 as an αia/ocid adrenoreceptor antagonist comprising contacting one or both of the a or a^ adrenoreceptors with the
compound.

24. The use of claim 23, wherein the use further comprises use of the compound in a pharmaceutical composition, medicine or medicament for the treatment of an ccia/αid adrenoreceptor mediated disease.

25. Use of the compound of any of claim 1 to 16 for the manufacture of a medicament for treating an (Wαid adrenoreceptor mediated disease.

26. Use of the compound of any of claim 1 to 16 as a medicine for treating an 0Cia/αid adrenoreceptor mediated disease.

27. A method for treating an αia/αid adrenoreceptor mediated disease, comprising administering to a patient in need of such a treatment an effective amount of a compound as claimed in claim 1.

28. The method of claim 27, wherein the effective amount is in a range of from about 0.001 mg/kg to about 300 mg/kg of body weight per day.

29. A method of treating LUTS comprising administering to a patient in need of such treatment an effective amount of a compound as claimed in claim 1.

30. The method of claim 29, wherein the effective amount is in a range of from about 0.001 mg/kg to about 300 mg/kg of body weight per day.

31. A method of treating BPH comprising administering to a patient in need of such treatment an effective amount of a compound as claimed in claim 1.

32. The method of claim 31, wherein the effective amount is in a range of from about 0.001 mg/kg to about 300 mg/kg of body weight per day.

33. A process for preparing a compound as claimed in claim 1, comprising the steps of a) reacting an intermediate of formula Al with an intermediate of formula A2, resulting in an intermediate of formula A3:



b) transforming an intermediate of formula A3 in an intermediate of formula A4 which is in turn transformed into an intermediate of formula A5;


c) reacting an intermediate of formula A5 with an intermediate of formula A6, thus forming an intermediate of formula A7:



HN-Boc ;

d) transforming an intermediate compound of formula A7 into an intermediate compound of formula A8 and reacting the intermediate compound of formula A8 with an intermediate compound of formula A9, thus forming a compound of formula AlO:



e) transforming the compounds of formula AlO into compounds of formula All:


f) optionally separating the isomeric forms, resulting in compounds of formula A12 andA13:



optionally, the resulting compounds can be converted into one another by using art-known functional group transformations, salts can be formed by adding the appropriate acid or base.