Lysine based compounds
View Patent ↗The present invention provides lysine based compounds of the formula; and when the compound of formula I comprises an amino group, pharmaceutically acceptable ammonium salts thereof, wherein R 1 may be, for example, (HO) 2 P(O)—, (NaO) 2 P(O)—, alkyl-CO— or cycloalkyl-CO—, wherein X may be, for example, F, Cl, and Br, and wherein R 2 and R 3 are as defined herein.
1. A compound of formula I
or a pharmaceutically acceptable salt thereof,
wherein n is 3 or 4,
wherein X and Y, the same or different, are selected from the group consisting of H, a straight alkyl group of 1 to 6 carbon atoms, a branched alkyl group of 3 to 6 carbon atoms, a cycloalkyl group of 3 to 6 carbon atoms, F, Cl, Br, I, —CF 3 , —OCF 3 , —CN, —NO 2 , —NR 4 R 5 , —NHCOR 4 , —OR 4 , —SR 4 , —COOR 4 , —COR 4 , and —CH 2 OH or X and Y together define an alkylenedioxy group selected from the group consisting of a methylenedioxy group of formula —OCH 2 O— and an ethylenedioxy group of formula —OCH 2 CH 2 O—,
wherein R 6 is selected from the group consisting of a straight alkyl group of 1 to 6 carbon atoms, a branched alkyl group of 3 to 6 carbon atoms and a cycloalkylalkyl group having 3 to 6 carbon atoms in the cycloalkyl part thereof and 1 to 3 carbon atoms in the alkyl part thereof,
wherein R 3 is selected from the group consisting of H, a straight alkyl group of 1 to 6 carbon atoms, a branched alkyl group of 3 to 6 carbon atoms, a cycloalkyl group of 3 to 6 carbon atoms, and a group of formula R 3A —CO—, R 3A being selected from the group consisting of a straight or branched alkyl group of 1 to 6 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, a cycloalkylalkyl group having 3 to 6 carbon atoms in the cycloalkyl part thereof and 1 to 3 carbon atoms in the alkyl part thereof, an alkyloxy group of 1 to 6 carbon atoms, tetrahydro-3-furanyloxy, —CH 2 OH, —CF 3 , —CH 2 CF 3 , —CH 2 CH 2 CF 3 , pyrrolidinyl, piperidinyl, 4-morpholinyl, CH 3 O 2 C—, CH 3 O 2 CCH 2 —, Acetyl-OCH 2 CH 2 —, HO 2 CCH 2 —, 3-hydroxyphenyl, 4-hydroxyphenyl, 4-CH 3 OC 6 H 4 CH 2 —, CH 3 NH—, (CH 3 ) 2 N—, (CH 3 CH 2 ) 2 N—, (CH 3 CH 2 CH 2 ) 2 N—, HOCH 2 CH 2 NH—, CH 3 OCH 2 O—, CH 3 OCH 2 CH 2 O—, C 8 H 5 CH 2 O—, 2-pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl-, 2-pyrazinyl, 2-quinolyl, 3-quinolyl, 4-quinolyl, 1-isoquinolyl, 3-isoquinolyl, 2-quinoxalinyl, a phenyl group of formula
a picolyl group selected from the group consisting of
a picolyloxy group selected from the group consisting of
a substituted pyridyl group selected from the group consisting of
and a group of formula
wherein X′ and Y′, the same or different, are selected from the group consisting of H, a straight alkyl group of 1 to 6 carbon atoms, a branched alkyl group of 3 to 6 carbon atoms, a cycloalkyl group of 3 to 6 carbon atoms, F, Cl, Br, I, —CF 3 , —NO 2 , —NR 4 R 5 , —NHCOR 4 , —OR 4 , —SR 4 , —COOR 4 , —COR 4 and —CH 2 OH,
wherein R 4 and R 5 , the same or different, are selected from the group consisting of H, a straight alkyl group of 1 to 6 carbon atoms, a branched alkyl group of 3 to 6 carbon atoms, and a cycloalkyl group of 3 to 6 carbon atoms,
wherein R 2 is selected from the group consisting of a diphenylmethyl group of formula IV
a naphthyl-1-CH 2 — group of formula V
a naphthyl-2-CH 2 — group of formula VI
a biphenylmethyl group of formula VII
and an anthryl-9-CH 2 — group of formula VIII
and wherein R 1 is selected from the group consisting of (HO) 2 P(O), (MO) 2 P(O) and a group of formula R 1A —CO—, wherein M is an alkali metal or alkaline earth metal,
wherein R 1A is selected from the group consisting of a straight or branched alkyl group of 1 to 6 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, a cycloalkylalkyl group having 3 to 6 carbon atoms in the cycloalkyl part thereof and 1 to 3 carbon atoms in the alkyl part thereof, an alkyloxy group of 1 to 6 carbon atom, —CH 2 OH, CH 3 OC—, CH 3 O 2 CCH 2 , Acetyl-OCH 2 CH 2 —, HO 2 CCH 2 —, 2-hydroxyphenyl, 3-hydroxyphenyl, 4-hydroxyphenyl, (CH 3 ) 2 NCH 2 —, (CH 3 ) 2 CHCH(NH 2 )—, HOCH 2 CH 2 NH—, CH 3 OCH 2 O—, CH 3 OCH 2 CH 2 O—, 2-pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 1-methyl-1,4-dihydro-3-pyridyl, 2-pyrazinyl, 2-quinolyl, 3-quinolyl, 4-quinolyl, 1-isoquinolyl, 3-isoquinolyl, 2-quinoxalinyl, a phenyl group of formula
a picolyl group selected from the group consisting of
a picolyloxy group selected from the group consisting of
a substituted pyridyl group selected from the group consisting of
and a group of formula,
2. A compound of formula II,
or a pharmaceutically acceptable salt thereof,
wherein n is 3 or 4,
wherein X and Y, the same or different, are selected from the group consisting of H, a straight alkyl group of 1 to 6 carbon atoms, a branched alkyl group of 3 to 6 carbon atoms, a cycloalkyl group of 3 to 6 carbon atoms, F, Cl, Br, I, —CF 3 , —OCF 3 , —CN, —NO 2 , —NR 4 R 5 , —NHCOR 4 , —OR 4 , —SR 4 , —COOR 4 , —COR 4 , and —CH 2 OH or X and Y together together define an alkylenedioxy group selected from the group consisting of a methylenedioxy group of formula —OCH 2 O— and an ethylenedioxy group of formula —OCH 2 CH 2 O—,
wherein R 6 is selected from the group consisting of a straight alkyl group of 1 to 6 carbon atoms, a branched alkyl group of 3 to 6 carbon atoms and a cycloalkylalkyl group having 3 to 6 carbon atoms in the cycloalkyl part thereof and 1 to 3 carbon atoms in the alkyl part thereof,
wherein R 3 is selected from the group consisting of H, a straight alkyl group of 1 to 6 carbon atoms, a branched alkyl group of 3 to 6 carbon atoms, a cycloalkyl group of 3 to 6 carbon atoms, and a group of formula R 3A —CO—, R 3A being selected from the group consisting of a straight or branched alkyl group of 1 to 6 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, a cycloalkylalkyl group having 3 to 6 carbon atoms in the cycloalkyl part thereof and 1 to 3 carbon atoms in the alkyl part thereof, an alkyloxy group of 1 to 6 carbon atoms, tetrahydro-3-furanyloxy, —CH 2 OH, —CF 3 , —CH 2 CF 3 , —CH 2 CH 2 CF 3 , pyrrolidinyl, piperidinyl, 4-morpholinyl, CH 3 O 2 C—, CH 3 O 2 CCH 2 —, Acetyl-OCH 2 CH 2 —, HO 2 CCH 2 —, 3-hydroxyphenyl, 4-hydroxyphenyl, 4-CH 3 OC 6 H 4 CH 2 —, CH 3 NH—, (CH 3 ) 2 N—, (CH 3 CH 2 ) 2 N—, (CH 3 CH 2 CH 2 ) 2 N—, HOCH 2 CH 2 NH—, CH 3 OCH 2 O—, CH 3 OCH 2 CH 2 O—, C 6 H 5 CH 2 O—, 2-pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl-, 2-pyrazinyl, 2-quinolyl, 3-quinolyl, 4-quinolyl, 1-isoquinolyl, 3-isoquinolyl, 2-quinoxalinyl, a phenyl group of formula
a picolyl group selected from the group consisting of
a picolyloxy group selected from the group consisting of
a substituted pyridyl group selected from the group consisting of
and a group of formula
wherein X′ and Y′, the same or different, are selected from the group consisting of H, a straight alkyl group of 1 to 6 carbon atoms, a branched alkyl group of. 3 to 6 carbon atoms, a cycloalkyl group of 3 to 6 carbon atoms, F, Cl, Br, I, —CF 3 , —NO 2 , —NR 4 R 5 , —NHCOR 4 , —OR 4 , —SR 4 , —COOR 4 , —COR 4 and —CH 2 OH,
wherein R 4 and R 5 , the same or different, are selected from the group consisting of H, a straight alkyl group of 1 to 6 carbon atoms, a branched alkyl group of 3 to 6 carbon atoms, and a cycloalkyl group of 3 to 6 carbon atoms,
wherein R 2 is selected from the group consisting of a diphenylmethyl group of formula IV
a naphthyl-1-CH 2 — group of formula V
a naphthyl-2-CH 2 — group of formula VI
a biphenylmethyl group of formula VII
and an anthryl-9-CH 2 — group of formula VIII
and wherein R 1 is selected from the group consisting of (HO) 2 P(O), (MO) 2 P(O) and a group of formula R 1A —CO—,
wherein M is an alkali metal or alkaline earth metal,
wherein R 1A is selected from the group consisting of a straight or branched alkyl group of 1 to 6 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, a cycloalkylalkyl group having 3 to 6 carbon atoms in the cycloalkyl part thereof and 1 to 3 carbon atoms in the alkyl part thereof, an alkyloxy group of 1 to 6 carbon atoms, —CH 2 OH, CH 3 O 2 C—, CH 3 O 2 CCH 2 —, Acetyl-OCH 2 CH 2 —, HO 2 CCH 2 —, 2-hydroxyphenyl 3-hydroxyphenyl, 4-hydroxyphenyl, (CH 3 ) 2 NCH 2 —, (CH 3 ) 2 CHCH(NH 2 )—, HOCH 2 CH 2 NH—, CH 3 OCH 2 O—, CH 3 OCH 2 CH 2 O—, 2-pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 1-methyl-1,4-dihydro-3-pyridyl, 2-pyrazinyl, 2-quinolyl, 3-quinolyl, 4-quinolyl, 1-isoquinolyl, 3-isoquinolyl, 2-quinoxalinyl, a phenyl group of formula
a picolyl group selected from the group consisting of
a picolyloxy group selected from the group consisting of
a substituted pyridyl group selected from the group consisting of
a group of formula,
3. A compound as defined in claim 2 , wherein R 6 is iso-butyl and n is 3.
4. A compound as defined in claim 2 , wherein R 6 is iso-butyl and n is 4.
5. A compound as defined in claim 4 , wherein R 1 is (HO) 2 P(O) or (NaO) 2 P(O).
6. A compound as defined in claim 4 , wherein R 1 is selected from the group of CH 3 CO, 3-pyridyl-CO, (CH 3 ) 2 NCH 2 CO and (CH 3 ) 2 CHCH(NH 2 )CO.
7. A compound as defined in claim 5 , wherein R 3 is selected from the group consisting of CH 3 CO, CH 3 O—CO, (CH 3 ) 2 N—CO, 3-pyridyl-CO, 4-pyridyl-CO and 4-morpholine-CO.
8. A compound as defined in claim 6 , wherein R 3 is selected from the group consisting of CH 3 CO, CH 3 O—CO, (CH 3 ) 2 N—CO, 3-pyridyl-CO, 4-pyridyl-CO and 4-morpholine-CO.
9. A compound as defined in claim 7 , wherein X is 4-NH 2 and Y is H or F.
10. A compound as defined in claim 8 , wherein X is 4-NH 2 and Y is H or F.
11. A compound as defined in claim 9 , wherein R 2 is selected from the group consisting of a diphenylmethyl group of formula IV, a naphthyl-1-CH 2 — group of formula V, a naphthyl-2-CH 2 — group of formula VI, a biphenylmethyl group of formula VII and an anthryl-9-CH 2 — group of formula VIII.
12. A compound as defined in claim 10 , wherein R 2 is selected from the group consisting of a diphenylmethyl group of formula IV, a naphthyl-1-CH 2 — group of formula V, a naphthyl-2-CH 2 — group of formula VI, a biphenylmethyl group of formula VII and an anthryl-9-CH 2 — group of formula VIII.
13. A compound as defined in claim 11 , wherein R 2 is selected from the group consisting of a diphenylmethyl group of formula IV, a naphthyl-1-CH 2 — group of formula V, and a naphthyl-2-CH 2 — group of formula VI.
14. A compound as defined in claim 12 , wherein R 2 is selected from the group consisting of a diphenylmethyl group of formula IV, a naphthyl-1-CH 2 — group of formula V, and a naphthyl-2-CH 2 — group of formula VI.
15. A compound as defined in claim 13 , wherein X′ and Y′ is H.
16. A compound as defined in claim 14 , wherein X′ and Y′ is H.
17. A compound of formula IIa
or a pharmaceutically acceptable salt thereof,
wherein X and Y, the same or different, are selected from the group consisting of H, a straight alkyl group of 1 to 6 carbon atoms, a branched alkyl group of 3 to 6 carbon atoms, a cycloalkyl group of 3 to 6 carbon atoms, F, Cl, Br, I, —CF 3 , —OCF 3 , —CN, —NO 2 , —NR 4 R 5 , —NHCOR 4 , —OR 4 , —SR 4 , —COOR 4 , —COR 4 , and —CH 2 OH or X and Y together define an alkylenedioxy group selected from the group consisting of a methylenedioxy group of formula —OCH 2 O— and an ethylenedioxy group of formula —OCH 2 CH 2 O—,
wherein X′ and Y′, the same or different, are selected from the group consisting of H, a straight alkyl group of 1 to 6 carbon atoms, a branched alkyl group of 3 to 6 carbon atoms, a cycloalkyl group of 3 to 6 carbon atoms, F, Cl, Br, l, —CF 3 , —NO 2 , —NR 4 R 5 , —NHCOR 4 , —OR 4 , —SR 4 , —COOR 4 , —COR 4 and —CH 2 OH,
wherein n is 3 or 4,
wherein R 6 is selected from the group consisting of a straight alkyl group of 1 to 6 carbon atoms, branched alkyl group of 3 to 6 carbon atoms and a cycloalkylalkyl group having 3to 6 carbon atoms in the cyoloalkyl part thereof and 1 to 3 carbon atoms in the alkyl part thereof,
wherein R 3 is selected from the group consisting of H, a straight alkyl group of 1 to 6 carbon atoms, a branched alkyl group of 3 to 6 carbon atoms, a cycloalkyl group of 3 to 6 carbon atoms, and a group of formula R 3A —CO—, R 3A being selected from the group consisting of a straight or branched alkyl group of 1 to 6 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, a cycloalkylalkyl group having 3 to 6 carbon atoms in the cycloalkyl part thereof and 1 to 3 carbon atoms in the alkyl part thereof, an alkyloxy group of 1 to 6 carbon atoms, tetrahydro-3-furanyloxy, —CH 2 OH, —CF 3 , —CH 2 CF 3 , —CH 2 CH 2 CF 3 , pyrrolidinyl, piperidinyl, 4-morpholinyl, CH 3 O 2 C—, CH 3 O 2 CCH 2 —, Acetyl-OCH 2 CH 2 —, HO 2 CCH 2 —, 3-hydroxyphenyl, 4-hydroxyphenyl, 4-CH 3 OC 8 H 4 CH 2 —, CH 3 NH—, (CH 3 ) 2 N—, (CH 3 CH 2 ) 2 N—, (CH 3 CH 2 CH 2 ) 2 N—, HOCH 2 CH 2 NH—, CH 3 OCH 2 O—, CH 3 OCH 2 CH 2 O—, C 6 H 5 CH 2 O—, 2-pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl-, 2-pyrazinyl, 2-quinolyl, 3-quinolyl, 4-quinolyl, 1-isoquinolyl, 3-isoquinolyl, 2-quinoxalinyl, a phenyl group of formula
a picolyl group selected from the group consisting of
a picolyloxy group selected from the group consisting of
a substituted pyridyl group selected from the group consisting of
and a group of formula
wherein R 4 and R 5 , the same or different, are selected from the group consisting of H, a straight alkyl group of 1 to 6 carbon atoms, a branched alkyl group of 3 to 6 carbon atoms, and a cycloalkyl group of 3 to 6 carbon atoms,
and wherein R 1 is selected from the group consisting of (HO) 2 P(O), (MO) 2 P(O) and a group of formula R 1A —CO—,
wherein M is an alkali metal or alkaline earth metal,
wherein R 1A is selected from the group consisting of a straight or branched alkyi group of 1 to 6 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, a cycloalkylalkyl group having 3 to 6 carbon atoms in the cycloalkyl part thereof and 1 to 3 carbon atoms in the alkyl part thereof, an alkyloxy group of 1 to 6 carbon atoms, —CH 2 OH, CH 3 O 2 C—, CH 3 O 2 CCH 2 —, Acetyl-OCH 2 CH 2 —, HO 2 CCH 2 —, 2-hydroxyphenl, 3-hydroxyphenyl, 4-hydroxyphenyl, (CH 3 ) 2 NCH 2 —, (CH 3 ) 2 CHCH(NH 2 )—, HOCH 2 CH 2 NH—, CH 3 OCH 2 O—, CH 3 OCH 2 CH 2 O—, 2-pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 1-methyl-1,4-dihydro-3-pyridyl, 2-pyrazinyl, 2-quinolyl, 3-quinolyl, 4-quinolyl, 1-isoquinolyl, 3-isoqtuinolyl, 2-quinoxalinyl, a phenyl group of formula
a picolyl group selected from the group consisting of
a picolyloxy group selected from the group consisting of
a substituted pyridyl group selected from the group consisting of
and a group of formula.
18. A compound as defined in claim 17 , wherein R 6 is iso-butyl.
19. A compound as defined in claim 18 , wherein n is 4.
20. A compound as defined in claim 19 , wherein R 1 is (HO) 2 P(O) or (NaO) 2 P(O).
21. A compound as defined in claim 19 , wherein R 1 is selected from the group of CH 3 CO, 3-pyridyl-CO, (CH 3 ) 2 NCH 2 CO and (CH 3 ) 2 CHCH(NH 2 )CO.
22. A compound as defined in claim 20 , wherein R 3 is selected from the group consisting of CH 3 CO, CH 3 O—CO, (CH 3 ) 2 N—CO, 3-pyridyl-CO, 4-pyridyl-CO and 4-morpholine-CO.
23. A compound as defined in claim 21 , wherein R 3 is selected from the group consisting of CH 3 CO, CH 3 O—CO, (CH 3 ) 2 N—CO, 3-pyridyl-CO, 4-pyridyl-CO and 4-morpholine-CO.
24. A compound as defined in claim 22 , wherein X is 4-NH 2 and Y is H or F.
25. A compound as defined in claim 23 , wherein X is 4-NH 2 and Y is H or F.
26. A compound as defined in claim 22 , wherein X is 4-NH 2 , Y is H, X′ is H, Y′ is H and R 3 is CH 3 O—CO.
27. A compound as defined in claim 26 , wherein R 1 is (HO) 2 P(O).
28. A compound as defined in claim 26 , wherein R 1 is (NaO) 2 P(O).
29. A compound as defined in claim 22 , wherein X is 4-NH 2 , Y is 3-F, X′ is H, Y′ is H and R 3 is CH 3 O—CO.
30. A compound as defined in claim 29 , wherein R 1 is (HO) 2 P(O).
31. A compound as defined in claim 29 , wherein R 1 is (NaO) 2 P(O).
32. A compound as defined in claim 22 , wherein X is 4-NH 2 , Y is H or 3-F, X′ is H, Y′ is H and R 3 is CH 3 CO.
33. A compound as defined in claim 32 , wherein R 1 is (HO) 2 P(O).
34. A compound as defined in claim 32 , wherein R 1 is (NaO) 2 P(O).
35. A compound as defined in claim 22 , wherein X is 4-NH 2 , Y is H or 3-F, X′ is H, Y′ is H and R 3 is 4-morpholine-CO.
36. A compound as defined in claim 23 , wherein X is 4-NH 2 , Y is H, X′ is H, Y′ is H and R 3 is CH 3 O—CO.
37. A compound as defined in claim 36 , wherein R 1 is 3-pyridyl- CO.
38. A compound as defined in claim 36 , wherein R 1 is (CH- 3 ) 2 NCH 2 CO.
39. A compound as defined in claim 36 , wherein R 1 is (CH 3 ) 2 CHCH(NH 2 )CO.
40. A compound as defined in claim 36 , wherein R 1 is CH 3 CO.
41. A compound as defined in claim 23 , wherein X is 4-NH 2 . Y is 3-F, X′ is H, Y′ is H and R 3 is CH 3 O—CO.
42. A compound as defined in claim 41 , wherein R 1 is 3-pyridyl-CO.
43. A compound as defined in claim 41 , wherein R 1 is (CH 3 ) 2 NCH 2 CO.
44. A compound as defined in claim 41 , wherein R 1 is (CH 3 ) 2 CHCH(NH 2 )CO.
45. A compound as defined in claim 23 , wherein X is 4-NH 2 , Y is H or 3-F. X′ is H, Y′ is H and R 3 is CHCO.
46. A compound as defined in claim 23 , wherein X is 4-NH 2 , Y is H or 3-F, X′ is H, Y′ is H and R 3 is 4-morpholine-CO.
47. A compound of formula IIb
or a pharmaceutically acceptable salt thereof,
wherein X and Y, the same or different, are selected from the group consisting of H, a straight alkyl group of 1 to 6 carbon atoms, a branched alkyl group of 3 to 6 carbon atoms, a cycloalkyl group of 3 to 6 carbon atoms, F, Cl, Br, I, —CF 3 , —OCF 3 , —CN, —NO 2 , —NR 4 R 5 , —NHCOR 4 , —OR 4 , —SR 4 , —COOR 4 , —COR 4 , and —CH 2 OH or X and together define an alkylenedioxy group selected from the group consisting of a methylenedioxy group of formula —OCH 2 O— and an ethylenedioxy group of formula —OCH 2 CH 2 O—,
wherein X′ and Y′, the same or different, are selected from the group consisting of H, a straight alkyl group of 1 to 6 carbon atoms, a branched alkyl group of 3 to 6 carbon atoms, a cycloalkyl group of 3 to 6 carbon atoms, F, Cl, Br, I, —CF 3 , —NO 2 , —NR 4 R 5 , —NHCOR 4 , —OR 4 , —SR 4 , —COOR 4 , —COR 4 and —CH 2 OH,
wherein n is 3 or 4,
wherein R 6 is selected from the group consisting of a straight alkyl group of 1 to 6 carbon atoms, a branched alkyl group of 3 to 6 carbon atoms and a cycloalkylalkyl group having 3to 6 carbon atoms in the cyoloalkyl part thereof and 1 to 3 carbon atoms in the alkyl part thereof,
wherein R 3 is selected from the group consisting of H, a straight alkyl group of 1 to6 carbon atoms, a branched alkyl group of 3 to 6 carbon atoms, a cycloalkyl group of 3 to 6 carbon atoms, and a group of formula R 3A —CO—, R 3A being selected from the group consisting of a straight or branched alkyl group of 1 to 6 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, a cycloalkylalkyl group having 3 to 6 carbon atoms in the cycloalkyl part thereof and 1 to 3 carbon atoms in the alkyl part thereof, an alkyloxy group of 1 to 6 carbon atoms, tetrahydro-3-furanyloxy, —CH 2 OH, —CF 3 , —CH 2 CF 3 , —CH 2 CH 2 CF 3 , pyrrolldinyl, piperidinyl, 4-morpholinyil, CH 3 O 2 C—, CH 3 O 2 CCH 2 —, Acetyl-OCH 2 CH 2 —, HO 2 CCH 2 CCH 2 —, 3-hydroxyphenyl, 4-hydroxyphenyl, 4-CH 3 OC 6 H 4 CH 2 —, CH 3 NH—, (CH 3 ) 2 N—, (CH 3 CH 2 ) 2 N—, (CH 3 CH 2 CH 2 ) 2 N—, HOCH 2 CH 2 NH—, CH 3 OCH 2 O—, CH 3 OCH 2 CH 2 O—, C 6 H 5 CH 2 O—, 2-pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl-, 2-pyrazinyl, 2-quinolyl, 3-quinolyl, 4-quinolyl, 1-isoquinolyl, 3-isoquinolyl, 2-quinoxalinyl, a phenyl group of formula
a picolyl group selected from the group consisting of
a picolyloxy group selected from the group consisting of
a substituted pyridvl group selected from the group consisting of
and a group of formula
wherein R 4 and R 5 , the same or different, are selected from the group consisting of H, a straight alkyl group of 1 to 6 carbon atoms, a branched alkyl group of 3 to 6 carbon atoms, and a cycloalkyl group of 3 to 6 carbon atoms,
and wherein R 1 is selected from the group consisting of (HO) 2 P(O), (MO) 2 P(O) and a group of formula R 1A —CO—,
wherein M is an alkali metal or alkaline earth metal,
wherein R 1A is selected from the group consisting of a straight or branched alkyl group of 1 to 6 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, a cycloalkylalkyl group having 3 to 6 carbon atoms in the cycloalkyl part thereof and 1 to 3 carbon atoms in the alkyl part thereof, an alkyloxy group of 1 to 6 carbon atoms, —CH 2 OH, CH 3 O 2 C—, CH 3 O 2 CCH 2 —, Acetyl-OCH 2 CH 2 —, HO 2 CCH 2 —, 2-hydroxphenyl, 3hydroxyphenyl, 4-hydroxyphenyl, (CH 3 ) 2 NCH 2 —, (CH 3 ) 2 CHCH(NH 2 )—, HOCH 2 CH 2 NH—, CH 3 OCH 2 O—, CH 3 OCH 2 CH 2 O—, 2-pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 1-methy1,4-dihydro-3-pyridyl, 2-pyrazinyl, 2-quinolyl, 3-quinolyl, 4-quinolyl, 1-isoquinolyl, 3-isoquinolyl, 2-quinoxalinyl, a phenyl group of formula
a picolyl group selected from the group consisting of
a picolyioxy group selected from the group consisting of
a substituted pyridyl group selected from the group consisting of
and a group of formula,
48. A compound as defined in claim 47 wherein R 6 is iso-butyl.
49. A compound as defined in claim 48 , wherein n is 4.
50. A compound as defined in claim 49 , wherein R 1 is (HO) 2 P(O) or (NaO) 2 P(O).
51. A compound as defined in claim 49 , wherein R 1 is selected from the group of CH 3 CO, 3-pyridyl-CO. (CH 3 ) 2 NCH 2 CO and (CH 3 ) 2 CHCH(NH 2 )CO.
52. A compound as defined in claim 50 , wherein R 3 is selected from the group consisting of CH 3 CO, CH 3 O—CO, (CH 3 ) 2 N—CO, 3-pyridyl-CO, 4-pyridyl-CO and 4-morpholine-CO.
53. A compound as defined in claim 51 , wherein R 3 is selected from the group consisting of CH 3 CO, CH 3 O—CO, (CH 3 ) 2 N—CO, 3-pyridyl-CO, 4-pyridyl-CO and 4-morpholine-CO.
54. A compound as defined in claim 52 , wherein X is 4-NH 2 and Y is H or F.
55. A compound as defined in claim 53 , wherein X is 4-NH 2 and Y is H or F.
56. A compound as defined in claim 52 , wherein X is 4-NH 2 , Y is H or 3-F, X′ is H, Y′ is H and R 3 is CH 3 O—CH.
57. A compound as defined in claim 52 , wherein X is 4-NH 2 , Y is H or 3-F. X′ is H, Y′ is H and R 3 is CH 3 CO.
58. A compound as defined in claim 52 , wherein X is 4-NH 2 , Y is H or 3-F, X′ is H, Y′ is H and R 3 is 4-morpholine-CO.
59. A compound as defined in claim 56 , wherein the naphthyl group is a naphthyl-2-CH 2 group.
60. A compound as defined in claim 59 , wherein Y is H and R 1 is (HO) 2 P(O).
61. A compound as defined in claim 58 , wherein the naphthyl group is a naphthyl-1-CH 2 group.
62. A compound as defined in claim 61 , wherein Y is H and R 1 is (HO) 2 P(O).
63. A compound as defined in claim 53 , wherein X is 4-NH 2 , Y is H or 3-F, X′ is H, Y′ is H and R 3 is CH 3 O—CO.
64. A compound as defined in claim 53 , wherein X is 4-NH 2 , Y is H or 3-F, X′ is H, Y′ is H and R 3 is CH 3 CO.
65. A compound as defined in claim 53 , wherein X is 4-NH 2 , Y is H or 3-F, X′ is H, Y′ is H and R 3 is 4-morpholine-CO.
66. A compound as defined in claim 65 , wherein the naphthyl group is a naphthyl-1-CH 2 group.
67. A compound of formula IIc
or a pharmaceutically acceptable salt thereof,
wherein X and Y, the same or different, are selected from the group consisting at H, a straight alkyl group of 1 to 6 carbon atoms, a branched alkyl group of 3 to 6 carbon atoms, a cycloalkyl group of 3 to 6 carbon atoms F, Cl, Br, I, —CF 3 , —OCF 3 , —CN, —NO 2 , —NR 4 R 5 , —NHCOR 4 , —OR 4 , —SR 4 , —COOR 4 , —COR 4 , and —CH 2 OH or X and together define an alkylenedioxy group selected from the groups consisting of a methylenedioxy group of formula —OCH 2 O— and an ethylenedioxy group of formula —OCH 2 CH 2 O—,
wherein X′ and Y′, the same or different, are selected from the group consisting of H, a straight alkyl group of 1 to 6 carbon atoms, a branched alkyl group 3 to 6 carbon atoms, a cycloalkyl group of 3 to 6 carbon atoms, F, Cl, Br, I, —CF 3 , —NO 2 , —NR 4 R 5 , —NHCOR 4 , —OR 4 , —SR 4 , —COOR 4 , —COR 4 and —CH 2 OH,
wherein n is 3 or 4
wherein R 6 is selected from the group consisting of a straight alkyl group of 1 to 6 carbon atoms, a branched alkyl group of 3 to 6 carbon atoms and a cycloalkylalkyl group having 3 to 6 carbon atoms in the cycloalkyl part thereof and 1 to 3 carbon atoms in the alkyl part thereof,
wherein R 3 is selected from the group consisting of H, a straight alkyl group of 1 to 6 carbon atoms, a branched alkyl group of 3 to 6 carbon atoms, a cycloalkyl group of 3 to 6 carbon atoms, and a group of formula R 3A —CO—, R 3A being selected from the group consisting of a straight or branched alkyl group of 1 to 6 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, a cycloalkylalkyl group having 3 to 6 carbon atoms in the cycloalkyl part thereof and 1 to 3 carbon atoms in the alkyl part thereof, an alkyloxy group of 1 to 6 carbon atoms, tetrahydro-3-furanyloxy, —CH 2 OH, —CF 3 , —CH 2 CF 3 , —CH 2 CH 2 CF 3 , pyrrolidinyl, piperidinyl, 4-morpholinyl, CH 3 O 2 C—, CH 3 O 2 CCH 2 —, Acetyl-OCH 2 CH 2 —, HO 2 CCH 2 —, 3-hydroxyohenyl, 4-hydroxyphenyl, 4-CH 3 OC 5 H 4 CH 2 —, CH 3 NH—, (CH 3 ) 2 N—, (CH 3 CH 2 ) 2 N—, (CH 3 CH 2 CH 2 ) 2 N—, HOCH 2 CH 2 NH—, CH 3 OCH 2 O—, CH 3 OCH 2 CH 2 O—, C 6 H 5 CH 2 O—, 2- pyrrolyl, 2-pyridyl, 3-pyridvl, 4-pyridyl-, 2-pyrazinyl, 2-quinolyl, 3-quinolyl, 4-quinolyl, 1-isoquinolyl, 3-isoquinolyl, 2-quinoxalinyl, a phenyl group of formula
a picolyl group selected from the group consisting of
a picolyloxy group selected from the group consisting of
a substituted pyridyl group selected from the group consisting of
and a group of formula
wherein R 4 and R 5 , the same or different, are selected from the group consisting of H, a straight alkyl group of 1 to 6 carbon atoms, a branched alkyl group of 3 to 6 carbon atoms, and a cyoloalkyl group of 3 to 6 carbon atoms,
and wherein R 1 is selected from the group consisting of (HO) 2 P(O), (MO) 2 P(O) and group of formula R 1A —CO—,
wherein M is an alkali metal or alkaline earth metal,
wherein R 1A is selected from the group consisting of a straight or branched alkyl group of 1 to 6 carbon atoms, a cycloalkyl group having 3 to 6 carbon atoms, a cycloalkylalkyl group having 3 to 6 carbon atoms in the cycloalkyl part thereof and 1 to 3 carbon atoms in the alkyl part thereof, an alkyloxy group of 1 to 6 carbon atoms, —CH 2 OH, CH 3 O 2 C—, CH 3 O 2 CCH 2 —, Acetyl-OCH 2 CH 2 —, HO 2 CCH 2 —, 2-hydroxyphenyl, 3-hydroxyphenyl, 4-hydroxyphenyl, (CH 3 ) 2 NCH 2 —, (CH 3 ) 2 CHCH(NH 2 )—, HOCH 2 CH 2 NH—, CH 3 OCH 2 O—, CH 3 OCH 2 CH 2 O—, 2-pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 1-methyl-1,4-dihydro-3-pyridyl, 2-pyrazinyl, 2-quinolyl, 3-quinolyl, 4-quinolyl, 1-isoquinolyl, 3-isoquinolyl, 2-quinoxalinyl, a phenyl group of formula
a picolyl group selected from the group consisting of
a picolyloxy group selected from the group consisting of
a substituted pyridyl group selected from the group consisting of
and a group of formula,
68. A compound as defined in claim 67 , wherein R 6 is iso-butyl.
69. A compound as defined in claim 68 , wherein n is 4.
70. A compound as defined in claim 69 , wherein R 1 is (HO) 2 P(O) or (NaO) 2 P(O).
71. A compound as defined in claim 69 , wherein R 1 is selected from the group of CH 3 CO, 3-pyridyl-CO, (CH 3 ) 2 NCH 2 CO and (CH 3 ) 2 CHCH(NH 2 )CO.
72. A pharmaceutical composition comprising at least one compound as defined in claim 1 and a pharmaceutically acceptable carrier.
73. A method of treating or reducing an HIV infection comprising administering at least one compound as defined in claim 1 to a mammal in thereof.
74. A compound as defined in claim 20 , which is:
(1S,5S)-(1-{5-[(4-amino-benzenesulfonyl)-isobutyl-amino]-6-phosphonooxy-hexacarbomoyl}-2,2-diphenyl-ethyl)-carbamic acid methyl ester or a pharmaceutically acceptable salt thereof; or
(1S,5S)-(1-{5-[(4-amino-3fluoro-benzenesulfonyl)-isobutyl-amino]-6phosphonooxy-hexacarbomoyl}-2,2-diphenyl-ethy)-carbamic acid methyl ester or a pharmaceutically acceptable salt thereof.
75. A compound as defined in claim 74 , which is(1S,5S)-(1-{5-[(4-amino-benzenesulfonyl)-isobutyl-amino]6phosphonooxy-hexacarbomoyl}-2,2-diphenyl-ethyl)-carbamic acid methyl ester sodium salt.
76. A compound as defined in claim 74 , which (1S,5S)-(1-{5-[(4-amino-3-fluoro-benzenesulfonyl)-isobutyl-amino]-6-phosphonooxy-hexacarbomoyl}-2,2-diphenyl-ethyl)-carbamic acid methyl ester.