Azalides from azithromycin to new azalide derivatives

Journal of Antibiotics

Volumn 60, Issue 2, 2007, Pages 85-122

  Mutak, Stjepan ^a  

^a PLIVA Research Institute Ltd   (Croatia)

Author keywords

8a and 9a lactams; Azalide N,O substituted derivatives; Azalides; Azithromycin; Bicyclic azalides; Descladinosyl azalides; Ketoazalides

Indexed keywords

4' DEMCAROSYL 20 DEOXO 20 (N,N DIBENZYLAMINO) 8A AZA 8A HOMOTYLOSIN; 6 O METHYLAZITHROMYCIN; 9 DIHYDRO 9 DEOXO 8A AZA 8A HOMOERYTHROMYCIN; 9 DIHYDRO 9 DEOXO 8A METHYL 8A AZA 8A HOMOERYTHROMYCIN; 9 DIHYDRO 9A AZA 9A HOMOERYTHROMYCIN DERIVATIVE; AZALIDE DERIVATIVE; AZITHROMYCIN; CLARITHROMYCIN; EP 13420; ERYTHROMYCIN; ERYTHROMYCIN ACISTRATE; ERYTHROMYCIN ESTOLATE; LINCOSAMIDE; MACROLIDE; NARBOMYCIN; PIKROMYCIN; STREPTOGRAMIN; TELITHROMYCIN; TULATHROMYCIN; UNCLASSIFIED DRUG; ANTIINFECTIVE AGENT; BICYCLO COMPOUND; DRUG DERIVATIVE; DYES, REAGENTS, INDICATORS, MARKERS AND BUFFERS;

ANTIBACTERIAL ACTIVITY; ANTIBIOTIC RESISTANCE; BECKMANN REARRANGEMENT; CYCLIZATION; DRUG BIOAVAILABILITY; DRUG CONFORMATION; DRUG DISTRIBUTION; DRUG HALF LIFE; DRUG MECHANISM; DRUG METABOLISM; DRUG STABILITY; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TISSUE LEVEL; DRUG TOLERABILITY; GASTROINTESTINAL SYMPTOM; HUMAN; NONHUMAN; PRIORITY JOURNAL; RESPIRATORY TRACT DISEASE; RESPIRATORY TRACT INFECTION; REVIEW; STRUCTURE ACTIVITY RELATION; BACTERIUM; CHEMISTRY; DRUG EFFECT; MICROBIOLOGICAL EXAMINATION; SYNTHESIS;

ANTI-BACTERIAL AGENTS; AZITHROMYCIN; BACTERIA; BICYCLO COMPOUNDS; INDICATORS AND REAGENTS; MACROLIDES; MICROBIAL SENSITIVITY TESTS;

EID: 34249661567     PISSN: 00218820     EISSN: None     Source Type: Journal    
DOI: 10.1038/ja.2007.10     Document Type: Review

References (121)

1. Ōmura S. Macrolide antibiotics. Chemistry, biology and practice, Second Edition, Academic Press Inc., San Diego, London (2002)
2. Kirst HA. Structural modification of macrolide antibiotics, Recent progress in the chemical synthesis of antibiotics. Springer-Verlag, Berlin-Heidelberg, pp. 39-63 (1990)
3. Kirst HA. Introduction to the macrolide antibiotics, In Macrolide Antibiotics. Ed., Schoenfeld W, Kirst HA, pp. 1-12, Birkhauser Verlag, Basel (2002)
4. Neu HC, Young LS, Zinner SH, Acar JF. New macrolides, azalides and streptogramins in clinical practice. Ed. Marcel Dekker, New York (1995)
5. Bryskier AJ, Agouridas C, Chantot J-F. New insights into the structure-activity relationship of macrolides and azalides; In: Bryskier AJ, Butzler J-P, Neu HC, Tulkens PM, Macrolides: Chemistry, pharmacology and clinical uses. Ed Arnette Blackwell, pp. 3-30, Paris (1993)
6. Schoenfeld W, Mutak S. Azithromycin and novel azalides, In Macrolide antibiotics. Ed., Schoenfeld W, Kirst HA, pp. 96 Birkhauser Verlag, Basel (2002)
7. Yang BV, Goldsmith M, Rizzi A. A novel product from Beckmann rearrangement of erythromycin A 9(E) oxime. Tetrahedron Lett 55: 3025-3028 (1994)
8. Fattori R, Pelacini F, Romagnano S, Fronza G, Rallo R. Unusual isoxaline formation by intramolecular cyclization of (9E)-erythromycin oxime. J Antibiot 49: 938-940 (1996)
9. Djokic S, Tamburasev Z. Erythromycin study: 9-amino-3 -O-cladinosyl-6,11,12-trihydroxy-2,4,6,8,10,12-hexamethylpentadecane-13- olide. Tetrahedron Lett 17: 1645-1647 (1967)
10. Kobrehel G, Djokic S (PLIVA). Nouveaux derives de l'erythromycine A, procede pour leur preparation et leur utilisation comme substances antibacteriennes. BE. 892 357, July 1 (1982)
11. Kobrehel G, Djokic S (PLIVA). 11-Methyl-11-aza-4-O-cladinosyl- 6-O-desosaminyl-15-ethyl-7,13,14-trihydroxy-3,5,7,9,12, 14-hexamethyl-oxacyclopentadecane-2-one and derivatives thereof. US 4 517 359, May 14 (1985)
12. Kobrehel G, Radobolja G, Tamburasev Z, Dokic S. (PLIVA). 11-Aza-10-deoxo-10-dihydroerythromycin A and derivatives thereof as well a process for their preparation. US 4 328 334 (1982)
13. Djokic S, Kobrehel G, Lazarevski G, Lopotar N, Tamburasev Z, Kamenar B, Nagl A, Vickovic I. Erythromycin series. Part 11. Ring expansion of erythromycin A oxime by the Beckmann rearrangement. J Chem Soc Perkin Trans I 1881-1990 (1986)
14. Djokic S, Kobrehel G, Lopotar N, Kamenar B, Nagl A, Mrvos D. Erythromycin series. Part 13. Synthesis and structure elucidation of 10-dihydro-10-deoxo-11- methyl-11-azaerythromycin A. J Chem Research (S): 152-153 (1988)
15. Labro MT. Anti-inflamatory activity of macrolides: a new therapeutic potential? J Antimicrob Chemother 41 (Suppl. B): 37-46 (1998)
16. Labro MT. Macrolide antibiotics: current and future uses, Expert Opin. Pharmacother 5(3): 541-550 (2004)
17. Amsden GW. Anti-inflamatory effects of macrolides-an underappreciated benefit in the treatment of community-aquired respiratory tract infections and chronic inflammatory pulmonary conditions? J Antimicrob Chemother 55: 10-21 (2005)
18. Culic O, Erakovic V, Parnham MJ. Anti-inflammatory effects of macrolide antibiotics. Eur J Pharmacol 429: 209-229 (2001)
19. Sassa K, Mizushima Y, Fujishita T, Oosaki R, Kobayashi M. Therapeutic effect of clarithromycin on a transplanted tumor in rats. J Antimicrob Chemother 43: 67-72 (1999)
20. Wilkening RR, Ratcliffe RW, Doss GA, Mosley RT, Ball RG. Novel transanular rearrangements of azalide iminoethers. Tetrahedron 53: 16923-16944 (1997)
21. Wilkening RR, Ratcliffe RW, Doss GA, Bartizal KF, Graham AC, Herbert CM. The synthesis of novel-8a-aza-8a-homoerythromycin derivatives via the Beckmann rearrangement of (9Z)-erythromycin A oxime. Bioorg Med Chem Lett 3: 1287-1292 (1993)
22. Heck JV, Leanza WJ, Ratcliffe RW, Salzmann TN, Wilkening RR, Szymonifka MJ, Shankaran K. (Merck & Co). 9-Deoxo-8a-aza-8a-homoerythromycin a derivatives modified at 4″- and 8a-positions. Eur Pat. 0 508 699 A1, Oct. 14 (1992)
23. Lazarevski G, Vinkovic M, Kobrehel G, Djokic S, Metelko B. Conformational analysis of 9-deoxo-9a-aza-9a- and 9-deoxo-8a-aza-8a-homoerythromycin A 6,9-cyclic iminoethers. Tetrahedron 50: 12201-12210 (1994)
24. Bright GM (Pfizer). Antibacterial N-methyl 11-aza-10-deoxo-10-dihydro- erythromycin A and pharmaceutically acceptable acid addition salts thereof, intermediates therefore, and processes for their preparation. USP 4 474 768, Oct. 2 (1984)
25. Bright GM, Nagel AA, Bordner J, Desai KA, Dibrino JN, Nowakowska J, Vincent L, Watrous RM, Sciavolino FC, English AR, Retsema JA, Anderson MR, Brennan LA, Borovoy RJ, Cimochowski CR, Faiella JA, Girard AE, Girard D, Herbert C, Manousos M, Mason R. Synthesis, in vitro and in vivo activity of novel 9-deoxo-9a-aza-9a-homoerythromycin A derivatives; a new class of macrolide antibiotics, the azalides. J Antibiot 41: 1029-1047 (1988)
26. Allen DJM, Nepveux KM (Pfizer). Non-hygroscopic, azithromycin (9-deoxo-9a-aza-9a-methyl-9a-homoerythromycin) dihydrate and a process therefor. US 87 01612, Jan. 26 (1989)
27. 3). 10th Meeting of chemists of Croatia, Feb. 16-18, Zagreb, Croatia, Abstr. p. 29 (1987)
28. Djokic S, Kobrehel G, Lazarevski G. Erythromycin series XII. Antibacterial in vitro evaluation of 10-dihydro-10-deoxo-11- azaerythromycin A: synthesis and structure activity relationship of its acyl derivatives. J Antibiot 40: 1006-1015 (1987)
29. Bucar D, Cincic D, Danilovski A, Dumbovic A, Dumic M, Filic D, Knezevic Z, Lazarevski G, Lazaric K, Mestrovic E, Oresic M, Vinkovic M. (PLIVA). Novel amorphous 9-deoxo9a-aza-9a-methyl-9a-homoerythromycin A. Process for preparing the same, and use thereof. WO 2004/009608, Jan. 29 (2004)
30. Djokic S, Vajtner Z, Lopotar N, Mrvos-Sermek D, Kamenar D, Nagl A. Complexes of azithromycin with some divalent metal ions. Croatica Chemica Acta 68: 375-381 (1995)
31. Retsema J, Girard A, Schelkly W, Manousos M, Anderson M, Bright G, Borovoy R, Brenan L, Mason R. Spectrum and mode of action of azithromycin (CP-62,993), a new 15-membered-ring macrolide with improved potency against Gram-negative organisms. Antimicrob Agent Chemother 31: 1939-1947(1987)
32. Fiese EF, Steffen SH. Comparism of the acid stability of azithromycin and erythromycin A. J Antimicrob Chemother 25: 39-47 (1990)
33. Girard AE, Girard D, English AR, Gotz TD, Cimochowski CR, Faiella JA, Haskell SL, Retsema JA. Pharmacokinetic and in vivo studies with azithromycin (CP-62,993), a new macrolide with an extended half life and excellent tissue distribution. Antimicrob Agent Chemother 31: 1948-1954 (1987)
34. Foulds G, Shepard RM, Johnson RB. The pharmacokinetics of azithromycin in human serum and tissues. J Antimicrob Chemother 25: 73-82 (1990)
35. Schonwald S, Skerk V, Petricevic I, Car V, Majerus-Misic L, Gunjaca M. Comparism of three-day and five-day courses of azithromycin in the treatment of atypical pneumonia. Eur J Clin Microbiol Infect Dis 10: 877-880 (1991)
36. Lazarevski G, Vinkovic M, Kobrehel G, Djokic S, Metelko B, Vikic-Topic D. Conformational analysis of azithromycin by nuclear magnetic resonance spectroscopy and molecular modelling. Tetrahedron 49: 721-730 (1993)
37. Schlutzen F, Harms JM, Franceschi F, Hansen AS, Bartels H, Zarivach R, Yonath A. Structural basis for the antibiotic activity of ketolides and azalides. Structure 11: 329-338 (2003)
38. Jones AB, Herbert CM. Assessment of the biological value of the 11-hydroxy group of the azalides. Bioorg Med Chem Lett 3: 1999-2004 (1993)
39. 7. Zeitschrift für Kristallographie 211: 415-417 (1996)
40. Markovic S, Mercep M, Mesic M, Tomaskovic L (PLIVA). Novel Compounds, compositions as carriers for steroid/non-steroid anti-inflammatory, antineoplastic and antiviral active molecules. WO 2004/005313, January 15 (2004)
41. Makaruha O, Markovic S, Mercep M, Mesic M, Poljak y Tomaskovic L. (PLIVA). New compounds, compositions and methods for treatment of inflammatory diseases and conditions. WO 2004/005310 A2, January 15 (2004)
42. Mercep M, Mesic M, Hrvacic B, Elenkov IJ, Malnar I, Markovic S, Simicic L, Cempuh-Klonkay A, Filipovic A (PLIVA). Substituted furochromene compounds of antiinflammatory action. US2006148890, July 6 (2006)
43. Mercep M, Mesic M, Tomaskovic L, Komac M, Hrvacic B, Markovic S (PLIVA). Conjugates of immune cell specific macrolide compounds with anti-inflammatory compounds for improved cellular targeting of anti-inflamatory therapy. WO 02/055531, July 18 (2002)
44. Kujundzic N, Kobrehel G, Banic Z, Kelneric Z, Kojic-Prodic B. Azalides: Synthesis and antibacterial activity of novel 9a-N-(N′-substituted carbamoyl and thiocarbamoyl) derivatives of 9-deoxo-9a-aza-9a-homoerythromycin A. Eur J Med Chem 30: 455-462 (1995)
45. Sheldrick GM, Kojic-Prodic B, Banic Z, Kobrehel G, Kujundzic N. Structure of 9-deoxo-9a-N-(N′-(4′-pyridyl)-carbamoyl)-9a-aza-9a- homoerythromycin A and conformational analysis of analogous 9a-aza 15-membered azalides in solid state. Acta Cryst B51: 358-366 (1995)
46. Marusic-Istuk Z, Kujundzic N, Kobrehel G, Mutak S, Marsic N (PLIVA). Halo derivatives of 9-deoxo-9a-aza-9a-homoerythromycin A. WO 00/66603, Nov. 9 (2000)
47. Brajsa K., Bukvic Krajacic M. Kujundzic N (PLIVA). Substituted 9a-N-(N′-(4-(sulfonyl)phenylcarbamoyl derivatives of 9-deoxo-9-dihydro-9a-aza-9a-homoerythromycin A and 5-O-desosaminyl-9- deoxo-9-dihydro-9a-aza-9a-homoerythronolide A. WO 2004/043985, May 27 (2004)
48. Kujundzic N, Bukvic Krajacic M, Dumic M, Hasenohrl A (PLIVA). 9a-N-[N′-(Phenylsulfonyl)carbamoyl] derivatives of 9-deoxo-9-dihydro-9a-aza-9a-homoerythromycin A and of 5-O-desosaminyl-9- deoxo-9-dihydro-9a-aza-homoerythronolide A. US 2004/0077558, April 22 (2004)
49. Bukvic Krajacic M, Kujundzic N, Dumic M, Cindric M, Brajsa K, Metelko B, Novak P. Synthesis, characterization and in vitro antimicrobial activity of novel sulfonylureas of 15-membered azalides, J Antibiot 58: 380-389 (2005)
50. Kujundzic N, Pavlovic D, Kobrehel G, Lazarevski G, Kelneric Z (PLIVA). Beta,beta-disubstituted derivatives of 9-deoxo-9a-N-ethenyl-9a-aza-9a- homoerythromycin A. EP 0 927 722 B1, March 12 (2003)
51. Alihodzic S, Lazarevski G, Derek M, Mutak S, Stimac V, Marusic-Istuk Z, Berdik A, Marsic N, Rusic-Pavletic J, Erakovic y Schoenfeld W, Pétrone M. Synthesis and antibacterial activity of 4″-O-substituted 8a-aza-8a-homoerythromycins. 43rd Intersci Conf on Antimicrob Agents Chemother, ICAAC, Chicago, USA, September 14-17, 2001, F-1185 (2003).
52. Stimac V, Alihodzic S, Lazarevski G, Pavlovic D, Berdik A, Mutak S, Marsic N, Rusic-Pavletic J, Dominis Kramaric M, Erakovic V. Sinteza i antibakterijska aktivnost 6-O-alkil-4″-O-substituiranih 8a-aza-8a-homoeritromicina i 6-O-alkileritromicin 9(E)- i 9(Z)-oksima. V. Susret mladih kemijskih inzenjera, Febr. 19-20, Zagreb, Croatia, Abstr. p. 85 (2004)
53. Kobrehel G, Lazarevski G, Djokic S, Kolacni-Babic L, Kucisec-Tepes N, Cvrlje M. Synthesis and antibacterial activity of O-methylazithromycin derivatives. J Antibiot 45: 527-534 (1992)
54. Waddell ST, Santorelli GM, Blizzard TA, Graham A, Occi J. Synthesis and antibacterial activity of O-methyl derivatives of azalide antibiotics: I. 4″, 11 and 12-O-Me derivatives via direct methylation. Bioorg Med Chem Lett 8: 549-554 (1998)
55. Kamenar B, Kosutic-Hulita N, Vickovic I, Kobrehel G, Lazarevski G. 11,12,4″-Tri-O-methylazythromycin monohydrate. Acta Cryst C52: 2566-2568 (1996)
56. Waddell ST, Santorelli GM, Blizzard TA, Graham A, Occi J. Synthesis and antibacterial activity of O-methyl derivatives of azalide antibiotics: II: 6-O-Me derivatives via clarithromycin. Bioorg Med Chem Lett 8: 1321-1326 (1998)
57. Derek M, Kidemet D, Leljak M (PLIVA). Selective alkylation of macrolide and azalide derivatives comprises reacting an macrolide or azalide derivative having a vicinal hydroxyl system with diazoalkane in the presence of transition-metal halides and of boric acid. WO 2004/106353, Sept. 12 (2004)
58. Derek M, Kidemet D, Lazarevski G, Leljak M (PLIVA). Preparation of 11-alkoxy compounds useful as antibacterial agents involves reacting macrolide or azalide having vicinal hydroxyl system with diazoalkane in the presence of transition-metal halide or boric acid in inert organic solvent. WO 2004/106354, Sept. 12 (2004)
59. Denis A, Agouridas C. Synthesis of 6-O-methyl-azithromycin and its ketolide analogue via Beckmann rearrangement of 9(E)-6 -O-methyl-erythromycin oxime. Bioorg Med Chem Lett 8: 2427-2432 (1998)
60. Keyes RF, Ma Z, Or YS (Abbott). 9a-Azalides with antibacterial activity. US 6764996, July 20 (2004)
61. Wu YJ, Wons R, Durkin D, Goldsmith M, and others. Synthesis and in vitro activity of novel C-4 carbamates of 14- and 15-membered macrolides. 38th Interscience conference of antimicrobial agents and chemotheraphy, San Diego, California, Abstract F-123 (1998)
62. Cheng H, Letavic MA, Ziegler CB, Dutra JK, Bertinato P, Bronk BS (Pfizer). C11 Carbamates of macrolide antibacterials. EP 0 984 019 A1, Mar. 8 (2000)
63. Alihodzic S, Andreotti D, Berdik A, Biondi S, Ciraco, Damiani F, Derek M, Dumic M, Erakovic V, Hutinec A, Lazarevski G, Lociuro S, Marsic N, Mutak S, Paio A, Pavlovic D, Quaglia, Schoenfeld W, Stimac V, Tibasco J. (PLIVA & GSK). Macrolides. WO 03/042228 A1, May 22 (2003)
64. Hutinec A, Derek M, Stimac V, Alihodzic S, Mutak S, Erakovic V, Biondi S, Paio A. Synthesis and antibacterial activity of 4″-O-beta- aminopropionyl-8a- and 9a-aza-homo erythromycins. 2nd Brazilian Symposium on Medicinal Chemistry, Nov. 22-25, Rio de Janeiro, Brazil, SA-06 (2004)
65. Alihodzic S, Jarvest RL, Palej I (PLIVA & GSK). Novel 14 and 15-membered ring compounds. WO 2004101588, November 25 (2004)
66. Alihodzic S, Berdik A, Berge JM, Jarvest RL, Mutak S. (PLIVA & GSK). Macrolides substituted at 4″-position. WO 2004101585, November 25 (2004)
67. Berge JM, Forrest AK, Jarvest RL (GSK). Novel 14 and 15 membered-ring compounds. WO 2004101589, November 25 (2004)
68. Mercep M, Mesic M, Tomaskovic L, Markovic S (PLIVA). Novel nonsteroidal antiinflamatory subtrances, composition and methods for their use. WO 2004005309, April 22 (2004)
69. Mercep M, Mesic M, Tomaskovic L, Markovic S, Makaruha O, Poljak V (PLIVA). New compounds, compositions and methods for treatment of inflammatory diseases and conditions. US 2004014685, January 22 (2004)
70. Kobrehel G, Lazarevski G, Kelneric Z, Djokic S. 9a,11-Cyclic carbamates of 15-membered azalides. J Antibiot 46: 1239-1245 (1993)
71. Blizzard TA, Waddell ST, Santorelli GM (Merck). 9a-Aza-3-ketolides, compositions containing such compounds and methods of treatment. WO 99/00125, Jan. 7 (1999)
72. Blizzard TA, Santorelli GM (Merck). 8a-Azalides, compositions containing such compounds and methods of treatment. WO 99/19331, Apr. 22 (1999)
73. Wang G, Peng Y, Wang Y, Phan LT, Or YS (ENANTA). 9a,11-3C-Bicyclic 9a-azalide derivatives, WO 2005/030227, April 7 (2005)
74. Shankaran K, Wilkening RR, Blizzard TA,, Bartizal KF, Ratcliffe RW, Heck JV, Graham AC, Herbert CM. Preparation and activities of 4″-epi and 4′-deoxy-α-amino analogs derived from 9-deoxo-8a-aza-8a- homoerythromycin A. Bioorg Med Chem Lett 4: 1111-1116 (1994)
75. Alihodzic S, Berdik A, Jarvest RL, Lazarevski G (PLIVA & GSK). Novel 14 and 15 membered-ring compounds. WO 2004/101590, May 11 (2004)
76. Bronk BS, Letavic MA, Bertsche CD, George DM, Hayashi SF, Kamicker BJ, Kolosko NL, Norcia LJ, Rushing MA, Santoro SL, Yang BV. Synthesis, stereochemical assignment and biological activity of a novel series of C-4″ modified aza-macrolides. Bioorg Med Chem Lett 13: 1955-1958 (2003)
77. Rafka RJ, Ragan CB, Allen DJM (Pfizer). New crystalline diphosphate salt of antibacterial and antiprotozoal agent, for parenteral administration to livestock. WO 200102414, Jan. 12 (2005)
78. Pesachovic M, Isaacs S, Singer C, Schwartz E, Berger E (TEVA). Degradation products of azithromycin and methods for their identification. WO 04/0087729, October 14 (2004)
79. Codony A, Diago J, Garcia R, Rifa J (Sandoz). Derivatives of azithromycin. WO 2004/09276, October 28 (2004)
80. Leclercq R, Courvalin P. Bacterial resistance to macrolide, lincosamide and streptogramin antibiotics in bacteria. Antimicrob Agents Chemother 35: 1267-1272 (1991)
81. Weisblum B. Erythromycin resistance by ribosome modification. Antimicrob Agents Chemother 39: 577-585 (1995)
82. Asaka TT, Misawa YT, Kashimura MT, Morimoto ST, Hatayama KT (Taisho). 5-O-Desosaminylerythronolide derivative. EP 0 619 320, Oct. 12 (1994)
83. Tanikawa T, Asaka T, Kashimura M, Suzuki K, Sugiyama H, Sato M, Kameo K, Morimoto S, Nishida A. Synthesis and antibacterial activity of a novel series of acylides: 3-O-(3-pyridyl)acetyl-erythromycin A derivatives. J Med Chem 46: 2706-2715 (2003)
84. Alihodzic S, Kobrehel G, Lazarevski G, Mutak S, Marsic N, Dominis-Kramaric M, Erakovic V, Schoenfeld W. Synthesis and antibacterial activity of isomeric 15-membered azalides. 41st Interscience conference of antimicrobial agents and chemotheraphy, ICAAC, September 22-25, Chicago, USA, F-1177 (2001)
85. Berdik-Fajdetic A, Kobrehel G, Lazarevski G, Stimac V, Mutak S. 3-O-Acyl derivatives of bridged-15-membered azalides: Synthesis, structural determination and antibacterial activity. Croatica Chemica Acta 78: 301-312 (2005)
86. Berdik A, Kobrehel G, Lazarevski G, Mutak S (PLIVA). New 3-decladinosyl derivatives of 9-deoxo-9a-aza-9a-homoerythromycin A 9a-11-cyclic carbamate useful for treating bacterial infections. WO-200429067, Apr. 29 (2004)
87. Sakya SM, Bertinato P, Prat B, Suarez-Contreras M, Lundy KM, Minich ML, Cheng H, Ziegler CB, Kamicker BJ, Haxashi SF, Santoro SL, George DM, Bertsche CD. Azalide 3,6-ketals: antibacterial activity and structure-actiivity relationships of aryl and hetero aryl substituted analogues. Bioorg Med Chem Lett 13: 1373-1375 (2003)
88. Kujundzic N, Mutak S, Marusic-Istuk Z (PLIVA). New 3-decladinosyl derivatives of 9a,N-(thio)carbamoyl-9-deoxo-9-dihydro-9a-aza-9a- homoerythromycin A useful in the treatment of bacterial infections. WO 2004/101591, 25.11.2004, prior. HR 14.05.2003 (2004)
89. Mereu A, Morazzoni G, Moriggi E, Napoletano M, Ornaghi F, Pellacini F. New 9a-azalide derivatives having anti-inflammatory activity useful for the treatment of e.g. inflammatory pathologies and respiratory pathologies. WO 2004/039821, October 28 (2003)
90. Corbaz L, Ettlinger L, Gauman E, Keller W, Kradolfer F, Kyburz E, Neipp L, Prelog V, Reusser R, Zahner H. Stoffwechselprodukte von Actinomyceten. Narbomycin. Helv Chim Acta 35: 935-942 (1955)
91. Brockmann H, Henkel W. Picromycin, ein bitter schmeckendes Antibioticum aus Actinomyceten. Chem Ber 84: 284-288 (1951)
92. Allen N. Macrolide resistance in Staphylococcus aureus: inducers of macrolide resistance. Antimicrob Agents Chemother 11: 669-674 (1977)
93. Agouridas C, Denis A, Auger J-M, Beneddeti Y, Bonnefoy A, Bretin F, Chantot J-F, Dussarat A, Fromentin C, D'Ambriéres SG, Lachaud S, P.Laurin, Le Martret O, Loyau V, Tessot N. Synthesis and antibacterial activity of ketolides (6-O-methyl-3-oxoerythromycin derivatives): A new class of antibacterials highly potent against macrolide-resistant and -susceptible respiratory pathogens. J Med Chem 41: 4080 (1998)
94. Kobrehel G, Lazarevski G, Vinkovic M (PLIVA). Novel 3,6-hemiketals from the class of 9a-azalides. WO-09920639, Apr. 29 (1999)
95. Denis A, Agouridas C, Auer J-M, Beneddeti Y, Bonnefoy A, Bretin F, Chantot J-F, Dussarat A, Fromentin C, D'Ambrieres SG, Lashaud S, Laurin P, Le Martret O, Loyau V, Tessot N, Pejac J-M, Perron S. Synthesis and antibacterial activity of HMR 3647, a new ketolide highly potent against erythromycin- resistant and susceptible pathogens. Bioorg Med Chem Lett 9: 3075-3080 (1999)
96. Ma Z, Nemoto PA. Discovery and development of ketolides as a new generation of macrolide antimicrobial agents. Curr Med Chem-Anti-infective Agents 1: 15-34 (2002)
97. Lazarevski G, Kobrehel G, Kelneric Z (PLIVA). 15-Membered lactams ketolides with antibacterial activity. WO 99/51616, Oct. 14 (1999)
98. Niu D, Wang G, Vo NH, Kim H, Xu G, Peng Y, Wang Y, Busuyek M, Amsler K, Polemeropoulos A, Scorneaux B, Phan LT, Or YS. Synthesis and antibacterial activities of novel 2-fluoro-6,11-bridged oxime ketolides. 43rd Interscience conference of antimicrobial agents and chemotheraphy, September 14-17, Chicago, USA, F-1196 (2003)
99. Busuyek M, Or JS, Phan LT, Wang G (ENANTA). 6,11-3C-Bicyclic 9A-azalide derivatives. US 6645941 B1, Nov. 11 (2003)
100. Phan LT, Wang G, Or JS (ENANTA). 6,11-4C-Bicyclic 9a-azalide derivatives of erythromycin useful for controlling bacterial infection. US. 6764998 B1, July 20 (2004)
101. Or YS, Qiu YL, Wang G, Niu D, Phan LT. Novel bicyclic 9a-azalide derivatives. US 2006/0069048 A1, March 30 (2006)
102. Rafka RJ, Morton BJ, Ragan CB, Bertinato P, Dirlam JP, Blize AE, Ziegler CB (Pfizer). 13-Membered azalides and their use as antibiotic agents. WO 00/31097, June 2 (2000)
103. Bartizal KF, Hammond ML, Schmatz DM, Wilkening RR. (Merck). 6,11-3C-Bicyclic 8a-azalide derivatives. WO 2005/072204, November 8 (2005)
104. Clark R, Djuric SMZ, Wang Z (Abbott). 11-Deoxy azalide antibacterials. WO 03/090679 A2, November 6 (2003)
105. O'Connell TN, Morse BK, McArthur HAI, Dirlam JP (Pfizer). Azalides and methods of making same. US 6,270,768, Aug. 7(2001)
106. Deshpande P, Sindkhedkar MD, Desai V, Gupte SV, Yeole RD, Patel MV, De Souza NJ (Wockhard Chem. Centre). Azalides and azaketolides having antimicrobial activity. WO 2004/108744 A2, December 16 (2004)
107. Ajito K, Kurihara K, Miura T, Yoshida T (Meji Seika). Novel 15-membered cyclic azalide, novel 16-membered cyclic diazalide derivative, and process for production these. WO 03/072589 A1, Febr. 25 (2003)
108. Naranda A, Suskovic B, Kelneric Z, Djokic S. Structure-activity relationship among polyhydro derivatives of tylosin. J Antibiot 47: 581-587 (1994)
109. Naranda A, Kelneric Z, Kolacni-Babic L, Djokic S. 10,11,12,13-Tetrahydro derivatives of tylosin. Synthesis, antibacterial activity and tissue distribution of 4′-deoxy-10,11,12,13-tetrahydrodesmycosin. J Antibiot 48: 284-253 (1995)
110. Lopotar N, Djokic S (PLIVA). Tylosine derivatives. EP 0410433B1, Febr. 28 (1996)
111. Naranda A, Lopotar N, Kelneric Z. Synthesis of novel dihydro and tetrahydro desmycosin derivatives. Fourth International Conference on the Macrolides, Azalides, Streptogramins and Ketolides, ICMASK 4, Barcelona, Spain, Abstr. 1.29 (1998)
112. Lopotar N, Naranda A, Vela V, Derek M, Marsic N. Synthesis and microbiological activity of 17-membered azalides. Fifth International Conference on the Macrolides, Azalides, Streptogramins, Ketolides and Oxazolidinones, Seville, Spain, Abstr. 1.01 (2000)
113. Grdisa M, Lopotar N, Pavelic K. Effect of a 17-member azalide on tumor cell growth. Chemotherapy 44: 331 (1998)
114. Lopotar N, Narandja A, Mutak S. Derivatives of 4′-demycarosyl-8a- aza-8a-homotylosin. WO 00/77016, Dec. 12 (2000)
115. LeMahieu RA, Carson M, Kerstead RW, Fern LM, Grundberg DE. Glycoside cleavage on erythromycin A. Preparation of erythronolide A. J Med Chem 17: 953-956 (1974)
116. Jones AB, ActionIII JJ, Doss GA. Selectivity in the dehydration of 15-membered azalides. Tetrahedron Lett 31: 4913-4916 (1993)
117. Waddell ST, Blizard. Chimeric azalides with simplified western portions. Tetrahedron Lett 34: 5385-5388 (1993)
118. Waddell ST, Blizard. Base catalysed ring opening reactions of erythromycin A. Tetrahedron Lett 33: 7827-7830 (1992)
119. Waddell ST, Blizard. Semisynthesis of linear fragments corresponding to the eastern portion of azalide antibiotics. Bioorg Med Chem Lett 3: 1757-1760 (1993)
120. Lazarevski G, Kobrehel G, Naranda A, Banic-Tomisic Z, Metelko B. Acid catalyzed ring opening reactions of 6-deoxy-9-deoxo-9a-aza-9a-homoerythromycin 6,9-cyclic imino ether. J Antibiot 51: 893-896 (1998)
121. Lazarevski G, Kobrehel G, Metelko B, Duddeck H. Ring opening reactions of 6-deoxy-9-deoxo-9a-aza-9a-homoerythromycin 6,9-cyclic imino ether. J Antibiot 49: 1066-1069 (1996)