Antibiotic AA 896 analogs

1. A compound of the formula

wherein:

m is an integer of 0 to 2;

n is an integer of 0 to 13;

p is an integer of 0 to 2;

q is an integer of 0 to 5;

J is F, Cl or Br;

R 1 , R 2 , R 3 , and R 4 are independently

H;

alkyl of 1 to 10 carbon atoms optionally substituted with 1 to 3 substituents selected from the group consisting of -J, —R 16 , -aryl, —OR 14 , —OR 16 , —OR 15 R 16 , —Oaryl, —OR 15 OR 14 , —OCH 2 OR 16 , —OR 15 OR 15 aryl, —OR 15 Oaryl, —C(O)OR 14 , —C(O)OR 16 , —C(O)OR 15 R 16 , C(O)R 14 , —C(O)R 16 , —C(O)R 15 R 16 , —C(O)aryl, —C(O)R 15 aryl, silyl substituted with three groups independently selected from R 14 , R 15 , and R 16 , —O-silyl substituted with three groups independently selected from R 14 , R 15 , and R 16 ;

cycloalkyl of 3 to 10 carbon atoms optionally substituted with one to three alkyl groups of 1 to 6 carbon atoms;

silyl substituted with three groups independently selected from R 14 , R 15 , and R 16 ;

—C(O)R 14 , —C(O)R 15 R 16 , —C(O)R 16 , —C(O)aryl, —C(O)R 15 aryl;

allyl optionally substituted with one to three moieties independently selected from R 14 , R 15 , and R 16 ;

R 15 aryl;

aryl;

R 14 is a monovalent group independently selected from alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, and alkynyl of 2 to 6 carbon atoms;

R 15 is a divalent alkyl group of 1 to 6 carbon atoms; optionally when two of R 15 are substituted on a nitrogen atom together with the nitrogen to which they are attached, form a ring selected from morpholine, piperazine or piperidine;

R 16 is aryl optionally substituted with 1 to 4 substituents selected from the group consisting of: -J, —NO 2 , —NH 2 , —OH, —SH, —CN, —COOH, —CONH 2 , —NHC(O)NH 2 , —CF 3 , —OCF 3 , —R 14 , —OR 14 , —NHR 14 , —NR 14 R 14 , —S(O) m R 14 , —NHSO 2 R 14 , —R 15 OH, —R 15 OR 14 , —R 15 NH 2 , —R 15 NHR 14 , —R 15 NR 14 R 14 , —R 15 SH, R 15 S(O) m R 14 , —NHR 15 OH, —NHR 15 OR 14 , —N(R 14 )R 15 OH, —N(R 14 )R 15 OR 14 , —NHR 15 NH 2 , —NHR 15 NHR 14 , —NHR 15 NR 14 R 14 , —N(R 14 )R 15 NH 2 , —N(R 14 )R 15 NHR 14 , —N(R 14 )R 15 NHR 14 R 14 , —OR 15 OH, —OR 15 OR 14 , —NHC(O)R 14 , —NHC(O)NHR 14 , —OR 15 C(O)R 14 , —NHR 15 C(O)R 14 , —C(O)R 14 , —C(O)R 14 , —C(O)NHR 14 , —C(O)NR 14 R 14 , —R 14 C(O)R 14 , —R 15 C(O)OH, —R 15 C(O)OR 14 , —R 15 C(O)NH 2 , —R 15 C(O)NHR 14 , —R 15 C(O)NR 14 R 14 , —R 15 OC(O)R 14 , —R 15 OC(O)NH 2 , —R 15 OC(O)NHR 14 , and —R 15 OC(O)NR 14 R 14 ;

aryl may optionally be substituted by —V-aryl, —V—R 16 or —V—R 17 ;

V is selected from C(O), C(O)O, OC(O), C(O)NH, NHC(O), NHSO 2 , SO 2 NH, C(OH)H, O(CR 18 R 18 ) q , S(O) m″ (CR 18 R 18 ) q , NH(CR 18 R 18 ) q , NR 19 (CR 18 R 18 ) q , (CR 18 R 18 ) q , (CR 18 R 18 ) q O, (CR 18 R 18 ) q S(O) m , (CR 18 R 18 ) q NH, (CR 18 R 18 ) q NR 15 , alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms and cycloalkyl of 3 to 10 carbon atoms;

R 17 is cycloalkyl of 3 to 7 carbon atoms optionally substituted with one or more alkyl groups of 1 to 6 carbon atoms or R 14 ;

R 18 is independently H or R 14 ;

R 5 , R 6 , R 7 and R 10 are independently

H;

alkyl of 1 to 10 carbon atoms optionally substituted with 1 to 3 substituents selected from the group consisting of -J, —R 16 , -aryl, —OR 14 , —OR 16 , —OR 15 R 16 , —Oaryl, —OR 15 OR 14 , —OCH 2 OR 16 , —OR 15 OR 15 aryl, —OR 15 Oaryl, —C(O)OR 14 , —C(O)OR 16 , —C(O)OR 15 R 16 , —C(O)Oaryl, —C(O)OR 15 aryl, —C(O)R 14 , —C(O)R 16 , —C(O)R 15 R 16 , —C(O)aryl, —C(O)R 15 aryl, silyl substituted with three groups independently selected from R 14 , R 15 , and R 16 , —O-silyl substituted with three groups independently selected from R 14 , R 15 , and R 16 ;

cycloalkyl of 3 to 10 carbon atoms optionally substituted with one to three alkyl groups of 1 to 6 carbon atoms;

—C(O)R 14 , —C(O)R 15 R 16 , —C(O)R 16 , —C(O)aryl, or —C(O)R 15 aryl;

—C(O)OR 14 , —C(O)OR 15 R 16 , or —C(O)OR 16 ;

allyl optionally substituted with one to three groups independently selected from R 14 , R 15 , and R 16 ;

R 15 aryl;

aryl;

R 8 , R 9 are independently

H;

alkyl of 1 to 10 carbon atoms optionally substituted with 1 to 3 substituents selected from the group consisting of —R 16 , —OH, —C(O)OH, CONH 2 , —NHC(O)NH 2 , —OR 14 , —OR 16 , —OR 15 R 16 , —Oaryl, —OR 15 aryl, —OR 15 OR 14 , —OR 15 OR 16 , —OR 15 OR 15 R 16 , —OR 15 OR 15 aryl, —OR 15 Oaryl, —C(O)OR 14 , —C(O)OR 16 , —C(O)OR 15 R 16 , —C(O)Oaryl, —C(O)OR 15 aryl, —C(O)R 14 , —C(O)R 16 , —C(O)R 15 R 16 , —C(O)aryl, —C(O)R 15 aryl, —S(O)pR 14 , —S(O)pR 16 , —S(O)pR 16 R 16 , —S(O)paryl, —S(O)pR 15 aryl, C(O)aryl, —C(O)R 15 aryl, —S(O)pR 14 , —S(O)pR 16 , —S(O)pR 15 R 16 , —S(O)paryl, —S(O)pR 15 aryl, NHC(═NH)NH 2 , —NHC(═NH)NH(NO 2 ), —N-optionally substituted with three groups independently selected from R 14 , R 15 , and R 16 , silyl substituted with three groups independently selected from R 14 , R 15 , and R 16 , —O-silyl substituted with three groups independently selected from R 14 , R 15 , and R 16 ;

allyl optionally substituted with one to three groups independently selected from R 14 , R 15 , and R 16 ;

aryl;

cycloalkyl group of 3 to 10 carbon atoms, which may be optionally substituted with one or more alkyl groups of 1 to 6 carbon atoms;

R 11 is independently

H;

alkyl of 1 to 10 carbon atoms optionally substituted with 1 to 3 substituents selected from the group consisting of -J, —R 16 , -aryl, —OR 14 , —OR 16 , —OR 15 R 16 , —Oaryl, —OR 15 OR 14 , —OCH 2 OR 16 , —OR 15 OR 15 aryl, —OR 15 Oaryl, —C(O)OR 14 , —C(O)OR 16 , —C(O)OR 15 R 16 , —C(O)Oaryl, —C(O)OR 15 aryl, —C(O)R 14 , —C(O)R 16 , —C(O)R 15 R 16 , —C(O)aryl, —C(O)R 15 aryl, —N-optionally substituted with three groups independently selected from R 14 , R 15 , and R 16 , -silyl substituted with three groups independently selected from R 14 , R 15 , and R 16 , —O-silyl substituted with three groups independently selected from R 14 , R 15 , and R 16 ;

—C(O)(CR 19 R 20 )NHC(O)NH(CR 21 R 22 )COOR 23 ;

cycloalkyl of 3 to 10 carbon atoms optionally substituted with one to three alkyl groups of 1 to 6 carbon atoms;

—C(O)R 14 , —C(O)R 15 R 16 , —C(O)R 16 , —C(O)aryl, —C(O)R 15 aryl;

allyl optionally substituted with one to three groups independently selected from R 14 , R 15 , and R 16 ;

R 15 aryl;

aryl;

R 19 , R 20 , R 21 and R 22 are independently

H;

alkyl of 1 to 10 carbon atoms optionally substituted with 1 to 3 substituents selected from the group consisting of —R 16 , —OH, —C(O)OH, CONH 2 , —NHC(O)NH 2 , —OR 14 , —OR 16 , —OR 15 R 16 , —Oaryl, —OR 15 aryl, —OR 15 OR 14 , —OR 15 OR 16 , —OR 15 OR 15 R 16 , —OR 15 OR 15 aryl, —OR 15 Oaryl, —C(O)OR 14 , —C(O)OR 16 , —C(O)OR 15 R 16 , —C(O)Oaryl, —C(O)OR 15 aryl, —C(O)R 14 , —C(O)R 16 , —C(O)R 15 R 16 , —C(O)aryl, —C(O)R 15 aryl, —S(O)pR 14 , —S(O)pR 16 , —S(O)pR 15 R 16 , —S(O)paryl, —S(O)pR 15 aryl, NHC(═NH)NH 2 , —NHC(═NH)NH(NO 2 ), —N-optionally substituted with three groups independently selected from R 14 , R 15 , and R 16 , silyl substituted with three groups independently selected from R 14 , R 15 , and R 16 , —O-silyl substituted with three groups independently selected from R 14 , R 15 , and R 16 ;

allyl optionally substituted with one to three groups independently selected from R 14 , R 15 , and R 16 ;

aryl;

cycloalkyl group of 3 to 10 carbon atoms, which may be optionally substituted with one or more alkyl groups of 1 to 6 carbon atoms;

R 23 is

H;

alkyl of 1 to 10 carbon atoms optionally substituted with 1 to 3 substituents selected from the group consisting of -J, —R 16 , -aryl, —OR 14 , —OR 16 , —OR 15 R 16 , —Oaryl, —OR 15 OR 14 , —OCH 2 OR 16 , —OR 15 OR 15 aryl, —OR 15 Oaryl, —C(O)OR 14 , —C(O)OR 16 , —C(O)OR 15 R 16 , —C(O)Oaryl, —C(O)OR 15 aryl, —C(O)R 14 , —C(O)R 16 , —C(O)R 15 R 16 , —C(O)aryl, —C(O)R 15 aryl;

silyl substituted with three groups independently selected from R 14 , R 15 , and R 16 ;

cycloalkyl of 3 to 10 carbon atoms optionally substituted with one to three alkyl groups of 1 to 6 carbon atoms;

—C(O)R 14 , —C(O)R 15 R 16 , —C(O)R 16 , —C(O)aryl, —C(O)R 15 aryl;

allyl optionally substituted with one to three groups independently selected from R 14 , R 15 , and R 16 ;

R 15 aryl;

aryl;

R 12 and R 13 are independently

H;

F;

an alkyl group of 1 to 10 carbon atoms including their branches;

allyl optionally substituted with one to three groups independently selected from R 14 , R 15 , and R 16 ;

aryl;

or a pharmaceutically acceptable salt thereof.

2. A compound according to claim 1 wherein:

R 3 , R 12 and R 13 are H;

m is an integer of 1 or 2;

R 1 and R 2 are silyl substituted with three groups independently selected from R 14 , R 15 , and R 16 .

3. A compound according to claim 1 wherein:

R 3 , R 6 , R 7 , R 12 and R 13 are H;

m is an integer of 1 or 2;

R 1 and R 2 are silyl substituted with three groups independently selected from R 14 , R 15 , and R 16.

4. A compound according to claim 1 wherein:

R 1 , R 2 , R 3 , R 12 and R 13 are H;

m is an integer of 1 or 2.

5. A compound according to claim 1 wherein:

R 1 , R 2 , R 3 , R 6 , R 7 , R 12 and R 13 are H;

m is an integer of 1 or 2.

6. A compound according to claim 1 wherein:

R 3 , R 12 and R 13 are H;

m is an integer of 1 or 2;

R 1 and R 2 are —C(O)R 14 , —C(O)R 15 R 16 , —C(O)aryl, —C(O)R 15 aryl.

7. A compound according to claim 1 wherein:

R 3 , R 6 , R 7 , R 12 and R 13 are H;

m is an integer of 1 or 2;

R 1 and R 2 are —C(O)R 14 , —C(O)R 15 R 16 , —C(O)R 16 , —C(O)aryl, or —C(O)R 15 aryl.

8. A pharmaceutical composition comprising a compound according to claim 1 in association with a pharmaceutically acceptable carrier.

9. A method for the treatment of bacterial infections in warm-blooded animals which comprises providing to said warm-blooded animals an antibacterially effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof.

10. The compound according to claim 1 which is tert-Butyl (2S,3S)-2-[(3-{[(2S,3S)-2-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]-3-hydroxypropanoate or a pharmaceutically acceptable salt thereof.

11. The compound according to claim 1 which is tert-Butyl (2S,3S)-2-[(3-{[(2S,3S)-2-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]-3-hydroxypropanoate or a pharmaceutically acceptable salt thereof.

12. The compound according to claim 1 which is tert-Butyl (2S,3R)-2-[(3-{[(2S,3S)-2-amino-3-hydroxy-4-methylpetanoyl]amino}propyl)amino]-3-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]-3-hydroxypropanoate or a pharmaceutically acceptable salt thereof.

13. The compound according to claim 1 which is (2S,6S,9S,16S)-6-(3-{[Amino(imino)methyl]amino}propyl)-16-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-9-[(1S)-1-hydroxy-2-methylpropyl]-2-isopropyl-19,19-dimethyl-4,7,10,17-tetraoxo-18-oxa-3,5,8,11,15-pentaazaicosan-1-oic acid or a pharmaceutically acceptable salt thereof.

14. The compound according to claim 1 which is tert-Butyl (2S,3R)-2-[(3-{[(2S)-2-amino-4-methylpentanoyl]amino}propyl)amino]-3-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]-3-hydroxypropanoate or a pharmaceutically acceptable salt thereof.

15. The compound according to claim 1 which is (3S)-3-Amino-4-[(3-{[(1S,2S)-2-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]-1-(tert-butoxycarbonyl)-2-hydroxyethyl]amino}propyl)amino]-4-oxobutanoic acid or a pharmaceutically acceptable salt thereof.

16. The compound according to claim 1 which is tert-Butyl (2S,3R)-2-[(3-{[(2S)-2-aminopropanoyl]amino}propyl)amino]-3-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]-3-hydroxypropanoate or a pharmaceutically acceptable salt thereof.

17. The compound according to claim 1 which is (2S,6S,9S,16S)-6-(3-{[Amino(imino)methyl]amino}propyl)-16-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-9-isobutyl-2-isopropyl-19,19-dimethyl-4,7,10,17-tetraoxo-18-oxa-3,5,8,11,15-pentaazaicosan-1-oic acid or a pharmaceutically acceptable salt thereof.

18. The compound according to claim 1 which is tert-Butyl (2S,3R)-3-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]-2-[(3-{[(2S)-2,6-diaminohexanoyl]amino}propyl)amino]-3-hydroxypropanoate or a pharmaceutically acceptable salt thereof.

19. The compound according to claim 1 which is tert-Butyl (4S)-4-amino-5-[(3-{[(1S,2R)-2-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]-1-(tert-butoxycarbonyl)-2-hydroxyethyl]amino}propyl)amino]-5-oxopentanoate or a pharmaceutically acceptable salt thereof.

20. The compound according to claim 1 which is tert-Butyl (2S,3R)-2-amino-3-[(2R,3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]-3-hydroxypropanoate or a pharmaceutically acceptable salt thereof.

21. The compound according to claim 1 which is tert-Butyl (5S,12S)-12-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-isobutyl-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate or a pharmaceutically acceptable salt thereof.

22. The compound according to claim 1 which is tert-Butyl (2S,3R)-2-[(3-{[(2S)-2-amino-4-methylpentanoyl]amino}propyl)amino]-3-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]-3-hydroxypropanoate or a pharmaceutically acceptable salt thereof.

23. The compound according to claim 1 which is tert-Butyl (2S,3R)-2-[(11-aminoundecanoyl)amino]-3-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]-3-hydroxypropanoate or a pharmaceutically acceptable salt thereof.

24. The compound according to claim 1 which is tert-Butyl (2S,3R)-2-({3-[(11-aminoundecanoyl)amino]propyl}amino)-3-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]-3-hydroxypropanoate or a pharmaceutically acceptable salt thereof.

25. The compound according to claim 1 which is (4S,8S,11S,18S)-18-[(R)-[(3S,4R,5R)-3,4-Dihydroxy-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-8-(3-{[(2,2-dioxido-2lambda˜1˜diazanyl)(imino)methyl]amino}propyl)-11-isobutyl-4-isopropyl-3,6,9,12-tetraoxo-1-phenyl-2-oxa-5,7,10,13,17-pentaazanonadecan-19-oic acid or a pharmaceutically acceptable salt thereof.

26. The compound according to claim 1 which is (2S,6S,9S,16S)-6-(3-{[Amino(imino)methyl]amino}propyl)-16-[(R)-[(3S,4R,5R)-3,4-dihydroxy-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)-methyl]-9-isobutyl-2-isopropyl-4,7,10-trioxo-3,5,8,11,15-pentaazaheptadecane-1,17-dioic acid or a pharmaceutically acceptable salt thereof.

27. The compound according to claim 1 which is tert-Butyl (2S,3R)-2-[(3-{[(2S)-2-amino-4-methylpentanoyl]amino}propyl)amino]-3-[(3S,4R,5R)-3,4-dihydroxy-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]-3-hydroxypropanoate or a pharmaceutically acceptable salt thereof.

28. The compound according to claim 1 which is Ethyl (5S)-12-[(R)-[(2R,3R,4R,5R)-3,4-bis(acetyloxy)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl](hydroxy)methyl]-3,6-dioxo-1-phenyl-5-[(1S)-1-(tetradecanoyloxy)ethyl]-2-oxa-4,7,11-triazatridecan-13-oate or a pharmaceutically acceptable salt thereof.

29. The compound according to claim 1 which is tert-Butyl (5S,12S)-12-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-[(1S)-1-hydroxy-2-methylpropyl]-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate or a pharmaceutically acceptable salt thereof.

30. The compound according to claim 1 which is tert-Butyl (5R,12S)-12-[(S)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-[(1S)-1-hydroxy-2-methylpropyl]-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate or a pharmaceutically acceptable salt thereof.

31. The compound according to claim 1 which is tert-Butyl (5S,12S)-12-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-isobutyl-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate or a pharmaceutically acceptable salt thereof.

32. The compound according to claim 1 which is tert-Butyl (5S,12S)-12-[(S)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-[(1S)-1-hydroxyethyl]-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate or a pharmaceutically acceptable salt thereof.

33. The compound according to claim 1 which is tert-Butyl (5S,12S)-12-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-[(1S)-1-hydroxyethyl]-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate or a pharmaceutically acceptable salt thereof.

34. The compound according to claim 1 which is tert-Butyl (2S,3R)-2-[(3-{[(2S,3S)-2-amino-3-hydroxybutanoyl]amino}propyl)amino]-3-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]-3-hydroxypropanoate or a pharmaceutically acceptable salt thereof.

35. The compound according to claim 1 which is tert-Butyl (5S,12S)-5-benzyl-12-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate or a pharmaceutically acceptable salt thereof.

36. The compound according to claim 1 which is tert-Butyl (2S,3R)-2-[(3-{[(2S)-2-amino-3-phenylpropanoyl]amino}propyl)amino]-3-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]-3-hydroxypropanoate or a pharmaceutically acceptable salt thereof.

37. The compound according to claim 1 which is tert-Butyl (5S,12S)-12-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-methyl-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate or a pharmaceutically acceptable salt thereof.

38. The compound according to claim 1 which is tert-Butyl (5S,12S)-5-[2-(benzyloxy)-2-oxoethyl]-12-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate or a pharmaceutically acceptable salt thereof.

39. The compound according to claim 1 which is tert-Butyl (9S,16S)-9-{[(benzyloxy)carbonyl]amino}-16-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-3,10-dioxo-1-phenyl-2-oxa-4,11,15-triazaheptadecan-17-oate or a pharmaceutically acceptable salt thereof.

40. The compound according to claim 1 which is tert-Butyl (5S,12S)-12-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-[3-(tert-butoxy)-3-oxopropyl]-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate or a pharmaceutically acceptable salt thereof.

41. The compound according to claim 1 which is 1-Benzyl 17-(tert-butyl)(2S,6S,9S,16S)-16-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-6-(3-{[(2,2-dioxido-2lambda˜1˜diazanyl)(imino)methyl]amino}propyl)-9-[(1S)-1-hydroxy-2-methylpropyl]-2-isopropyl-4,7,10-trioxo-3,5,8,11,15-pentaazaheptadecane-1,17-dioate or a pharmaceutically acceptable salt thereof.

42. The compound according to claim 1 which is (2S,6S,9S,16S)-6-(3-{[Amino(imino)methyl]amino}propyl)-16-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-9-[(1S)-1-hydroxy-2-methylpropyl]-2-isopropyl-19,19-dimethyl-4,7,10,17-tetraoxo-18-oxa-3,5,8,11,15-pentaazaicosan-1-oic acid or a pharmaceutically acceptable salt thereof.

43. The compound according to claim 1 which is 1-Benzyl 17-(tert-butyl)(2S,6S,9S,16S)-16-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-6-(3-{[(2,2-dioxida-2lambda˜1˜diazanyl)(imino)methyl]amino}propyl)-9-isobutyl-2-isopropyl-4,7,10-trioxo-3,5,8,11,15-pentaazaheptadecane-1,17-dioate or a pharmaceutically acceptable salt thereof.

44. The compound according to claim 1 which is (2S,6S,9S,16S)-6-(3-{[Amino(imino)methyl]amino}propyl)-16-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-9-isobutyl-2-isopropyl-19,19-dimethyl-4,7,10,17-tetraoxo-18-oxa-3,5,8,11,15-pentaazaicosan-1-oic acid or a pharmaceutically acceptable salt thereof.

45. The compound according to claim 1 which is 1-Benzyl 17-(tert-butyl)(2S,6S,9S,16S)-16-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-6-(3-{[(2,2-dioxido-2lambda˜1˜diazanyl)(imino)methyl]amino}propyl)-9-[(1S)-1-hydroxyethyl]-2-isopropyl-4,7,10-trioxo-3,5,8,11,15-pentaazaheptadecane-1,17-dioate or a pharmaceutically acceptable salt thereof.

46. The compound according to claim 1 which is Ethyl (5S)-12-[(R)-[(2R,3R,4R,5S)-3,4-bis(acetyloxy)-5-(2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-[(1S)-1-hydroxyethyl]-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate or a pharmaceutically acceptable salt thereof.

47. The compound according to claim 1 which is Ethyl (5S)-12-[(R)-[(2R,3R,4R,5R)-3,4-bis(acetyloxy)-5-(2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-[(1S)-1-hydroxyethyl]-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate or a pharmaceutically acceptable salt thereof.

48. The compound according to claim 1 which is Ethyl (3R)-2-[(3-{[(2S,3S)-2-amino-3-hydroxybutanoyl]amino}propyl)amino]-3-(2R,3R,4R,5S)-3,4-bis(acetyloxy)-5-(2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]-3-hydroxypropanoate or a pharmaceutically acceptable salt thereof.

49. The compound according to claim 1 which is Ethyl (3R)-2-[(3-{[(2S,3S)-2-amino-3-hydroxybutanoyl]amino}propyl)amino]-3-[(2R,3R,4R,5R)-3,4-bis(acetyloxy)-5-(2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]-3-hydroxypropanoate or a pharmaceutically acceptable salt thereof.

50. The compound according to claim 1 which is 16-Benzyl 2-ethyl (1R,9S,12S,16S)-1-[(2R,3R,4R,5S)-3,4-bis(acetyloxy)-5-(2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]-12-(3-{[(2,2-dioxido-2lambda˜1˜-diazanyl)(imino)methyl]amino}propyl)-1-hydroxy-9-[(1S)-1-hydroxyethyl]-17-methyl-8,11,14-trioxo-3,7,10,13,15-pentaazaoctadecane-2,16-dicarboxylate or a pharmaceutically acceptable salt thereof.

51. The compound according to claim 1 which is 16-Benzyl 2-ethyl (1R,9S,12S,16S)-1-[(2R,3R,4R,5R)-3,4-bis(acetyloxy)-5-(2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]-12-(3-{[(2,2-dioxido-2lambda˜1˜-diazanyl(imino)methyl]amino}propyl)-1-hydroxy-9-[(1S)-1-hydroxyethyl]-17-methyl-8,11,14-trioxo-3,7,10,13,15-pentaazaoctadecane-2,16-dicarboxylate or a pharmaceutically acceptable salt thereof.

52. The compound according to claim 1 which is Ethyl (5S)-12-[(R)-[(2R,3R,4R,5R)-3,4-bis(acetyloxy)-5-(2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-[(1S)-1-hydroxy-2-methylpropyl]-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate or a pharmaceutically acceptable salt thereof.

53. The compound according to claim 1 which is 16-Benzyl 2-ethyl (1R,9S,12S,16S)-1-[(2R,3R,4R,5R)-3,4-bis(acetyloxy)-5-(2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]-12-(3-{[(2,2-dioxido-2lambda˜1˜-diazanyl)(imino)methyl]amino}propyl)-1-hydroxy-9-[(1S)-2-methylpropyl]-17-methyl-8,11,14-trioxo-3,7,10,13,15-pentaazaoctadecane-2,16-dicarboxylate or a pharmaceutically acceptable salt thereof.

54. The compound according to claim 1 which is Ethyl (5S)-12-{(R)-(acetyloxy)[(2R,3R,4R,5S)-3,4-bis(acetyloxy)-5-(2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]methyl}-5-isobutyl-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate or a pharmaceutically acceptable salt thereof.

55. The compound according to claim 1 which is Ethyl (5S)-12-{(R)-(acetyloxy)[(2R,3R,4R,5R)-3,4-bis(acetyloxy)-5-(2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]methyl}-5-isobutyl-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate or a pharmaceutically acceptable salt thereof.

56. The compound according to claim 1 which is Ethyl (3R)-3-(acetyloxy)-2-[(3-{[(2S)-2-amino-4-methylpentanoyl]amino}propyl)amino]-3-[(2R,3R,4R,5S)-3,4-bis(acetyloxy)-5-(2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]propanoate or a pharmaceutically acceptable salt thereof.

57. The compound according to claim 1 which is Ethyl (3R)-3-(acetyloxy)-2-[(3-{[(2S)-2-amino-4-methylpentanoyl]amino}propyl)amino]-3-[(2R,3R,4R,5R)-3,4-bis(acetyloxy)-5-(2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]propanoate or a pharmaceutically acceptable salt thereof.

58. The compound according to claim 1 which is 19-Benzyl 5-ethyl (4R,12S,15S,19S)-4-[(2R,3R,4R,5S)-3,4-bis(acetyloxy)-5-(2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]-15-(3-{[(2,2-dioxido-2lambda˜1˜diazanyl)(imino)methyl]amino}propyl)-12-isobutyl-20-methyl-2,11,14,17-tetraoxo-3-oxa-6,10,13,16,18-pentaazahenicosane-5,19-dicarboxylate or a pharmaceutically acceptable salt thereof.

59. The compound according to claim 1 which is 1-Benzyl 17-ethyl (2S,6S,9S)-16-{(R)-(acetyloxy)[(2R,3R,4R,5R)-3,4-bis(acetyloxy)-5-(2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]methyl}-6-(3-{[(2,2-dioxido-2lambda˜1˜diazanyl)(imino)methyl]amino}propyl)-9-isobutyl-2-isopropyl-4,7,10-trioxo-3,5,8,11,15-pentaazaheptadecane-1,17-dioate or a pharmaceutically acceptable salt thereof.

60. The compound according to claim 1 which is (2S,6S,9S)-6-(3-{[Amino(imino)methyl]amino}propyl)-16-[(R)-[(2R,3R,4R,5R)-3,4-bis(acetyloxy)-5-(2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-9-[(1S)-1-hydroxy-2-methylpropyl]-2-isopropyl-4,7,10,17-tetraoxo-18-oxa-3,5,8,11,15-pentaazaicosan-1-oic acid or a pharmaceutically acceptable salt thereof.

61. The compound according to claim 1 which is tert-Butyl (5S,12S)-12-[(R)-[(3S,4R,5R)-3,4-dihydroxy-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-[(1S)-1-hydroxyethyl]-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate or a pharmaceutically acceptable salt thereof.

62. The compound according to claim 1 which is tert-Butyl (2S,3R)-2-[(3-{[(2S,3S)-2-amino-3-hydroxybutanoyl]amino}propyl)amino]-3-[(3S,4R,5R)-3,4-dihydroxy-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)-tetrahydro-2-furanyl]-3-hydroxypropanoate or a pharmaceutically acceptable salt thereof.

63. The compound according to claim 1 which is (5S,12S)-12-[(R)-[(3R,4R,5R)-4-{[tert-butyl(dimethyl)silyl]oxy}-3-hydroxy-5-(3-(4-methoxy-benzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-[(1S)-1-hydroxyethyl]-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oic acid or a pharmaceutically acceptable salt thereof.

64. The compound according to claim 1 which is (2S,3R)-2-[(3-{[(2S,3S)-2-Amino-3-hydroxybutanoyl]amino}propyl)amino]-3-{(3R,4R,5R)-4-{[tert-butyl(dimethyl)silyl]oxy}-5-[3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl]tetrahydrofuran-2-yl}-3-hydroxypropanoic acid or a pharmaceutically acceptable salt thereof.

65. The compound according to claim 1 which is (4S,8S,11S,18S)-18-[(R)-[(3S,4R,5R)-3,4-Dihydroxy-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-8-(3-{[(2,2-dioxido-2lambda˜1˜diazanyl)(imino)methyl]amino}propyl)-11-isobutyl-4-isopropyl-3,6,9,12-tetraoxo-1-phenyl-2-oxa-5,7,10,13,17-pentaazanonadecan-19-oic acid or a pharmaceutically acceptable salt thereof.

66. The compound according to claim 1 which is tert-Butyl (5S,12S)-12-[(R)-[(3S,4R,5R)-3,4-dihydroxy-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-isobutyl-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate or a pharmaceutically acceptable salt thereof.

67. The compound according to claim 1 which is (5S,12S)-12-[(R)-[(3S,4R,5R)-3,4-Dihydroxy-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-isobutyl-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oic acid or a pharmaceutically acceptable salt thereof.

68. The compound according to claim 1 which is (2S,3R)-2-[(3-{[(2S)-2-Amino-4-methylpentanoyl]amino}propyl)amino]-3-[(3S,4R,5R)-3,4-dihydroxy-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]-3-hydroxypropanoic acid or a pharmaceutically acceptable salt thereof.

69. The compound according to claim 1 which is (5S,12S)-12-[(R)-[(3S,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-1(2H)-pyrimidinyl)-3,4-dihydroxy-tetrahydro-2-furanyl](hydroxy)methyl]-5-isobutyl-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oic acid or a pharmaceutically acceptable salt thereof.

70. The compound according to claim 1 which is tert-Butyl (5R,12S)-12-[(R)-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl](hydroxy)methyl]-5-isobutyl-3,6-dioxo-1-phenyl-2-oxa-4,7,11-triazatridecan-13-oate or a pharmaceutically acceptable salt thereof.

71. The compound according to claim 1 which is tert-Butyl (2S,3R)-2-[(3-{[(2R)-2-amino-4-methylpentanoyl]amino}propyl)amino]-3-[(3R,4R,5R)-3,4-bis{[tert-butyl(dimethyl)silyl]oxy}-5-(3-(4-methoxybenzyl)-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-2-furanyl]-3-hydroxypropanoate or a pharmaceutically acceptable salt thereof.