Natural products in medicine: Transformational outcome of synthetic chemistry

Journal of Medicinal Chemistry

Volumn 57, Issue 22, 2014, Pages 9292-9308

  Szychowski, Janek ^a   Truchon, Jean François ^a   Bennani, Youssef L ^a  

^a VERTEX PHARMACEUTICALS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALISPORIVIR; AMIKACIN; ARTEMISININ; BUPRENORPHINE; BUTIROSIN; CASPOFUNGIN; CEFTRIAXONE; CYCLOPHILIN; DOCETAXEL; DUTASTERIDE; EPOTHILONE A; ESTRADIOL; FINASTERIDE; HABEKACIN; IXABEPILONE; KANAMYCIN B; MEVINOLIN; MIFEPRISTONE; NALOXONE; NATURAL PRODUCT; OXYCODONE; PACLITAXEL; PREDNISOLONE; PROGESTERONE; RIBOSTAMYCIN; SIMVASTATIN; TETRAHYDROLIPSTATIN; THEBAINE; ANTIINFECTIVE AGENT; BIOLOGICAL PRODUCT; MACROLIDE; NARCOTIC ANALGESIC AGENT; PEPTIDE; SOLVENT; STEROID; TAXOID;

CHEMICAL MODIFICATION; COMPLEX FORMATION; DRUG POTENCY; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; INFECTION; INFLAMMATION; MOLECULAR MODEL; NEOPLASM; REVIEW; ANIMAL; CHEMICAL STRUCTURE; CHEMISTRY; DRUG DESIGN; DRUG DEVELOPMENT; HUMAN; NEOPLASMS; SOLUBILITY; STRUCTURE ACTIVITY RELATION; SYNTHESIS; X RAY CRYSTALLOGRAPHY;

ANALGESICS, OPIOID; ANIMALS; ANTI-BACTERIAL AGENTS; BIOLOGICAL PRODUCTS; CHEMISTRY TECHNIQUES, SYNTHETIC; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; DRUG DISCOVERY; HUMANS; MACROLIDES; MODELS, MOLECULAR; MOLECULAR STRUCTURE; NEOPLASMS; PEPTIDES; SOLUBILITY; SOLVENTS; STEROIDS; STRUCTURE-ACTIVITY RELATIONSHIP; TAXOIDS;

EID: 84913555860     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm500941m     Document Type: Review

References (161)

1. Lam, K. S. New Aspects of Natural Products in Drug Discovery Trends Microbiol. 2007, 15, 279-289
2. Harvey, A. L. Natural Products in Drug Discovery Drug Discovery Today 2008, 13, 894-901
3. Feher, M.; Schmidt, J. M. Property Distributions: Differences between Drugs, Natural Products, and Molecules from Combinatorial Chemistry J. Chem. Inf. Comput. Sci. 2003, 43, 218-227
4. Newman, D. J.; Cragg, G. M. Natural Products as Sources of New Drugs over the 30 Years from 1981 to 2010 J. Nat. Prod. 2012, 75, 311-335
5. Lovering, F. Escape from Flatland 2: Complexity and Promiscuity Med. Chem. Commun. 2013, 4, 515-519
6. Clemons, P. A.; Bodycombe, N. E.; Carrinski, H. A.; Wilson, J. A.; Shamji, A. F.; Wagner, B. K.; Koehler, A. N.; Schreiber, S. L. Small Molecules of Different Origins Have Distinct Distributions of Structural Complexity That Correlate with Protein-Binding Profiles Proc. Natl. Acad. Sci. U.S.A. 2010, 107, 18787-18792
7. Hughes, J. D.; Blagg, J.; Price, D. A.; Bailey, S.; Decrescenzo, G. A.; Devraj, R. V.; Ellsworth, E.; Fobian, Y. M.; Gibbs, M. E.; Gilles, R. W.; Greene, N.; Huang, E.; Krieger-Burke, T.; Loesel, J.; Wager, T.; Whiteley, L.; Zhang, Y. Physiochemical Drug Properties Associated with in Vivo Toxicological Outcomes Bioorg. Med. Chem. Lett. 2008, 18, 4872-4875
8. Hamon, J.; Whitebread, S.; Techer-Etienne, V.; Le Coq, H.; Azzaoui, K.; Urban, L. In Vitro Safety Pharmacology Profiling: What Else beyond hERG? Future Med. Chem. 2009, 1, 645-665
9. Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J. Experimental and Computational Approaches To Estimate Solubility and Permeability in Drug Discovery and Development Settings Adv. Drug Delivery Rev. 1997, 23, 3-25
10. Walters, W. P.; Green, J.; Weiss, J. R.; Murcko, M. A. What Do Medicinal Chemists Actually Make? A 50-Year Retrospective J. Med. Chem. 2011, 54, 6405-6416
11. Vézina, C.; Kudelski, A.; Sehgal, S. N. Rapamycin (AY-22,989), a New Antifungal Antibiotic. I. Taxonomy of the Producing Streptomycete and Isolation of the Active Principle J. Antibiot. 1975, 28, 721-726
12. Sehgal, S. N. Sirolimus: Its Discovery, Biological Properties, and Mechanism of Action Transplant. Proc. 2003, 35, 7S-14S
13. Hay, N.; Sonenberg, N. Upstream and Downstream of mTOR Genes Dev. 2004, 18, 1926-1945
14. Faivre, S.; Kroemer, G.; Raymond, E. Current Development of mTOR Inhibitors as Anticancer Agents Nat. Rev. Drug Discovery 2006, 5, 671-688
15. Sehgal, S. N. Rapamune (RAPA, Rapamycin, Sirolimus): Mechanism of Action Immunosuppressive Effect Results from Blockade of Signal Transduction and Inhibition of Cell Cycle Progression Clin. Biochem. 1998, 31, 335-340
16. Sedrani, R.; Cottens, S.; Kallen, J.; Schuler, W. Chemical Modification of Rapamycin: The Discovery of SDZ RAD Transplant. Proc. 1998, 30, 2192-2194
17. Venkata, S. P.; Ekambaram, G.; Kothakonda, K. K.; Prasad, A. S. Processes for Preparation of Everolimus and Intermediate Thereof. WO 2012/066502 A1, 2012.
18. Atkins, M. B.; Yasothan, U.; Kirkpatrick, P. Everolimus Nat. Rev. Drug Discovery 2009, 8, 535-536
19. Shaw, C.-C.; Sellstedt, J. H.; Noureldin, R.; Cheal, G. K.; Fortier, G. Regioselective Synthesis of Rapamycin Derivatives. WO 01/23395, 2001.
20. Skotnicki, J. S.; Leone, C. L.; Schiehser, G. A. Rapamycin Hydroxyesters as Immunosuppressive, Antiinflammatory, Antifungal, Antiproliferative, and Antitumor Agents. US 5,362,718, 1994.
21. Hudes, G. R.; Berkenblit, A.; Feingold, J.; Atkins, M. B.; Rini, B. I.; Dutcher, J. Clinical Trial Experience with Temsirolimus in Patients with Advanced Renal Cell Carcinoma Semin. Oncol. 2009, 36 (Suppl. 3) S26-S36
22. Borel, J. F.; Kis, Z. L.; Beveridge, T. The History of the Discovery and Development of Cyclosporine (Sandimmune). In The Search for Anti-Inflammatory Drugs; Merluzzi, V. J.; Adams, J., Eds.; Birkhäuser: Boston, MA, 1995; pp 27-63.
23. Borel, J. F. History of the Discovery of Cyclosporin and of Its Early Pharmacological Development Wien. Klin. Wochenschr. 2002, 114, 433-437
24. Teraoka, S.; Mishiro, S.; Ebihara, K.; Sanaka, T.; Yamaguchi, Y.; Nakajima, I.; Kawai, T.; Yagisawa, T.; Honda, H.; Fuchinoue, S.; Takahashi, K.; Toma, H.; Agishi, T.; Ota, K. Effect of Cyclosporine on Proliferation of Non-A, Non-B Hepatitis Virus Transplant. Proc. 1988, 20, 868-876
25. Hubler, F.; Ru, T.; Patiny, L.; Muamba, T.; Guichou, Ë.; Mutter, M.; Wenger, R. Synthetic Routes to NEtXaa4-Cyclosporin A Derivatives as Potential Anti-HIV I Drugs Tetrahedron Lett. 2000, 41, 7193-7196
26. Paeshuyse, J.; Kaul, A.; De Clercq, E.; Rosenwirth, B.; Dumont, J.-M.; Scalfaro, P.; Bartenschlager, R.; Neyts, J. The Non-Immunosuppressive Cyclosporin DEBIO-025 Is a Potent Inhibitor of Hepatitis C Virus Replication in Vitro Hepatology 2006, 43, 761-770
27. Papageorgiou, C.; Borer, X.; French, R. R. Calcineurin Has a Very Tight-Binding Pocket for the Side Chain of Residue 4 of Cyclosporin Bioorg. Med. Chem. Lett. 1994, 4, 267-272
28. Scalfaro, P.; Dumont, J.-M.; Vuagniaux, G.; Mauvernay, R.-Y. Use of [D-MeAla]3-[EtVal]4-Cyclosporin for the Treatment of Hepatitis C Infection and Pharmaceutical Composition Comprising Said [D-MeAla]3-[EtVal]4-Cyclosporin. WO 2006/038088 Al, 2006.
29. Huai, Q.; Kim, H.-Y.; Liu, Y.; Zhao, Y.; Mondragon, A.; Liu, J. O.; Ke, H. Crystal Structure of Calcineurin-Cyclophilin-Cyclosporin Shows Common but Distinct Recognition of Immunophilin-Drug Complexes Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 12037-12042
30. Inman, W. D.; Crews, P. Unraveling the Bastarane and Isobastarane Oximo Amide Configurations and Associated Macrocycle Conformations: Implications of Their Influence on Bioactivities J. Nat. Prod. 2011, 74, 402-410
31. Labute, P. LowModeMD-Implicit Low-Mode Velocity Filtering Applied to Conformational Search of Macrocycles and Protein Loops J. Chem. Inf. Model. 2010, 50, 792-800
32. Chen, I.-J.; Foloppe, N. Tackling the Conformational Sampling of Larger Flexible Compounds and Macrocycles in Pharmacology and Drug Discovery Bioorg. Med. Chem. 2013, 21, 7898-7920
33. Rowinsky, E. K. The Development and Clinical Utility of the Taxane Class of Antimicrotubule Chemotherapy Agents Annu. Rev. Med. 1997, 48, 353-374
34. Wang, M. C.; Taylor, H. L.; Wall, M. E.; Coggon, P.; McPhail, A. T. Plant Antitumor Agents. VI. The Isolation and Structure of Taxol, a Novel Antileukemic and Antitumor Agent from Taxus breoifolia J. Am. Chem. Soc. 1971, 93, 2325-2327
35. Denis, J.-N.; Greene, A. E.; Guénard, D.; Guéritte-Voegelein, F.; Mangatal, L.; Potier, P. A Highly Efficient, Practical Approach to Natural Taxol J. Am. Chem. Soc. 1988, 110, 5917-5919
36. Swindell, C. S.; Krauss, N. E.; Horwitz, S. B.; Ringel, I. Biologically Active Taxol Analogues with Deleted A-Ring Side Chain Substituents and Variable C-2′ Configurations J. Med. Chem. 1991, 1176-1184
37. Guéritte-Voegelein, F.; Sénilh, V.; David, B.; Guénard, D.; Potier, P. Chemical Studies of 10-Deacetyl Baccatin III: Hemisynthesis of Taxol Derivatives Tetrahedron 1986, 42, 4451-4460
38. Guéritte-Voegelein, F.; Guénard, D.; Lavelle, F.; Le Goff, M. T.; Mangatal, L.; Potier, P. Relationships between the Structure of Taxol Analogues and Their Antimitotic Activity J. Med. Chem. 1991, 34, 992-998
39. Manfredi, J. J.; Horwitz, S. B. Taxol: An Antimitotic Agent with a New Mechanism of Action Pharmacol. Ther. 1984, 25, 83-125
40. Cortes, J. E.; Pazdur, R. Docetaxel J. Clin. Oncol. 1995, 13, 2643-2655
41. Bollag, D. M.; Mcqueney, P. A.; Zhu, J.; Hensens, O.; Koupal, L.; Liesch, J.; Goetz, M.; Lazarides, E.; Woods, C. M. Epothilones, a New Class of Microtubule-Stabilizing Agents with a Taxol-like Mechanism of Action Cancer Res. 1995, 55, 2325-2333
42. Hoefle, G.; Bedorf, N.; Gerth, K.; Reichenback, H. Epothilones, Process for Preparing the Same and Their Use as Medicaments and as Plant Protecting Agents. WO1993010121 A1, 1993.
43. Lee, F. Y. F.; Borzilleri, R.; Fairchild, C. R.; Kim, S.; Long, B. H.; Reventos-suarez, C.; Vite, G. D.; Rose, W. C.; Kramer, R. A. BMS-247550: A Novel Epothilone Analog with a Mode of Action Similar to Paclitaxel but Possessing Superior Antitumor Efficacy Clin. Cancer Res. 2001, 7, 1429-1437
44. Lee, F. Y. F.; Borzilleri, R.; Fairchild, C. R.; Kamath, A.; Smykla, R.; Kramer, R.; Vite, G. Preclinical Discovery of Ixabepilone, a Highly Active Antineoplastic Agent Cancer Chemother. Pharmacol. 2008, 63, 157-166
45. Hunt, J. T. Discovery of Ixabepilone Mol. Cancer Ther. 2009, 8, 275-281
46. Nettles, J. H.; Li, H.; Cornett, B.; Krahn, J. M.; Snyder, J. P.; Downing, K. H. The Binding Mode of Epothilone A on Alpha,beta-Tubulin by Electron Crystallography Science 2004, 305, 866-869
47. Borzilleri, R. M.; Zheng, X.; Schmidt, R. J.; Johnson, J. A.; Kim, S.; Dimarco, J. D.; Fairchild, C. R.; Gougoutas, J. Z.; Lee, F. Y. F.; Long, B. H.; Vite, G. D. A Novel Application of a Pd(0)-Catalyzed Nucleophilic Substitution Reaction to the Regio- and Stereoselective Synthesis of Lactam Analogues of the Epothilone Natural Products J. Am. Chem. Soc. 2000, 122, 8890-8897
48. Egerton, N. Optimizing Ixabepilone Treatment Schedules in Patients with Advanced or Metastatic Breast Cancer Cancer Chemother. Pharmacol. 2010, 66, 1005-1012
49. Hamad, B. The Antibiotics Market Nat. Rev. Drug Discovery 2010, 9, 675-676
50. Barriere, L.; Flaherty, J. F. Third-Generation Cephalosporins: A Critical Evaluation Clin. Pharm. 1984, 3, 351-373
51. Bijie, H.; Kulpradist, S.; Manalaysay, M.; S, A. In Vitro Activity, Pharmacokinetics, Clinical Efficacy, Safety and Pharmacoeconomics of Ceftriaxone Compared with Third and Fourth Generation Cephalosporins: Review J. Chemother. 2005, 17, 3-24
52. Klein, N. C.; Cunha, B. A. Third-Generation Cephalosporins Med. Clin. North Am. 1995, 79, 705-719
53. Waxman, D. J.; Strominger, J. L. Penicillin-Binding Proteins and the Mechanism of Action of B-Lactam Antibiotics Ann. Rev. Biochem. 1983, 52, 825-869
54. Tipper, D. J. Mode of Action of B-Lactam Antibiotics Pharmacol. Ther. 1985, 27, 1-35
55. Patel, I. H.; Chen, S.; Parsonnet, M.; Hackman, M. R.; Brooks, M. A.; Konikoff, J.; Kaplan, S. A. Pharmacokinetics of Ceftriaxone in Humans Antimicrob. Agents Chemother. 1981, 20, 634-641
56. Abraham, E. P. Isolation of Cephalosporin C, a Penicillin-like Antibiotic Containing d -α-Aminoadipic Acid Biochem. J. 1956, 62, 651-658
57. Abraham, E. P.; Newton, G. G. F. The Structure of Cephalosporin C Biochem. J. 1961, 79, 377-393
58. Nikolov, A.; Danielsson, B. Enzymatic Transformation of Cephalosporin C to 7-Amino-cephalosporanic Acid. Part II: Single-Step Procedure Using a Coimmobilized Enzyme System Enzyme Microb. Technol. 1994, 16, 1037-1041
59. Montavon, M.; Reiner, R. Thiazolylacelamide Cephalosporins. U.S. Patent 4,327,210, 1982.
60. Kwang, H. L.; Seung, S. C.; Myeong, S. Y. Process for Preparing Cephem Derivative. US 5,700,932, 1996.
61. Reiner, R. Correlation between Structure and Biological Properties of Cephalosporins: The Discovery of Ceftriaxone Drugs Exp. Clin. Res. 1986, 12, 299-302
62. Fedarovich, A.; Nicholas, R. A.; Davies, C. The Role of the β5-α11 Loop in the Active-Site Dynamics of Acylated Penicillin-Binding Protein A from Mycobacterium tuberculosis J. Mol. Biol. 2012, 418, 316-330
63. Brownstein, M. J. Review A Brief History of Opiates, Opioid Peptides, and Opioid Receptors Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 5391-5393
64. Eddy, N. B. The Chemopharmacological Approach to the Addiction Problem Public Health Rep. 1963, 78, 673-680
65. Kalso, E. Oxycodone J. Pain Symptom Manage. 2005, 29, S47-S56
66. Kleemann, A.; Engel, J. Pharmaceutical Substances: Syntheses, Patents, Applications, 4 th ed.; Thieme: Stuttgart, Germany, 2001.
67. Campbell, N. D.; Lovell, A. M. The History of the Development of Buprenorphine as an Addiction Therapeutic Ann. N.Y. Acad. Sci. 2012, 1248, 124-139
68. Jasinski, D. R.; Pevnick, J. S.; Griffith, J. D. Human Pharmacology and Abuse Potential of the Analgesic Buprenorphine Arch. Gen. Psychiatry 1978, 35, 501-516
69. Likar, R. Transdermal Buprenorphine in the Management of Persistent Pain-Safety Aspects Ther. Clin. Risk Manage. 2006, 2, 115-125
70. Bentley, K. W.; Hardy, D. G. Novel Analgesics and Molecular Rearrangements in the Morphine-Thebaine Group. I. Ketones Derived from 6,14- endo -Ethenotetrahydrothebaine J. Am. Chem. Soc. 1967, 89, 3267-3273
71. Bentley, K. W. Thebaine and Oripavine Derivatives. U.S. Patent 3,433,791, 1969.
72. Mendelson, J. Clinical and Pharmacological Evaluation of Buprenorphine and Naloxone Combinations: Why the 4:1 Ratio for Treatment? Drug Alcohol Depend. 2003, 70, S29-S37
73. Martin, W. R. Naloxone Ann. Intern. Med. 1976, 85, 765-768
74. Lewenstein, M. J. Improvements in or Relating to Morphine Derivatives. US 3254088, 1966.
75. Manglik, A.; Kruse, A. C.; Kobilka, T. S.; Thian, F. S.; Mathiesen, J. M.; Sunahara, R. K.; Pardo, L.; Weis, W. I.; Kobilka, B. K.; Granier, S. Crystal Structure of the μ-Opioid Receptor Bound to a Morphinan Antagonist Nature 2012, 485, 321-326
76. Yuan, Y.; Zaidi, S. A.; Elbegdorj, O.; Aschenbach, L. C. K.; Li, G.; Stevens, D. L.; Scoggins, K. L.; Dewey, W. L.; Selley, D. E.; Zhang, Y. Design, Synthesis, and Biological Evaluation of 14-Heteroaromatic-Substituted Naltrexone Derivatives: Pharmacological Profile Switch from Mu Opioid Receptor Selectivity to Mu/Kappa Opioid Receptor Dual Selectivity J. Med. Chem. 2013, 56, 9156-9169
77. Imperato-McGinley, J.; Guerrero, L.; Gautier, T.; Peterson, R. E. Steroid 5a-Reductase Deficiency in Man. An Inherited Form of Male Pseudohermaphroditism Science 1974, 186, 1213-1215
78. Peterson, R. E.; Imperato-McGinley, J.; Gautier, T.; Sturla, E. Male Pseudohermaphroditism Due to Steroid 5-Alpha-Reductase Deficiency Am. J. Med. 1977, 62, 170-191
79. Allen, W. M. The Isolation of Crystalline Progestin Science 1935, 82, 89-93
80. Pauli, G. F.; Friesen, J. B.; Gödecke, T.; Farnsworth, N. R.; Glodny, B. Occurrence of Progesterone and Related Animal Steroids in Two Higher Plants J. Nat. Prod. 2010, 73, 338-345
81. Rasmusson, G. H.; Reynolds, G. F.; Steinberg, N. G.; Walton, E.; Pate, G. F.; Liang, T.; Cascieri, M. A.; Cheung, A. H.; Brooks, J. R.; Berman, C. Azasteroids: Structure-Activity Relationships for Inhibition J. Med. Chem. 1986, 2298-2315
82. Rasmusson, G. H.; Reynolds, G. F. 17B-N-Monosubstituted Carbamoyl-4-Aza-5a-androst- l -en-3-ones Which Are Active as Testosterone 5a-Reductase Inhibitors. U.S. Patent 4,760,071, 1988.
83. Frye, S. V. Discovery and Clinical Development of Dutasteride, a Potent Dual 5alpha-Reductase Inhibitor Curr. Top. Med. Chem. 2006, 6, 405-421
84. Keam, S. J.; Scott, L. J. Dutasteride: A Review of Its Use in the Management of Prostate Disorders Drugs 2008, 68, 463-485
85. Schwartz, R. E.; Sesin, D. F.; Joshua, H.; Wilson, K. E.; Kempf, A. J.; Goklen, K. A.; Kuehner, D.; Gailliot, P.; Gleason, C.; White, R.; Inamine, E.; Bills, G.; Salmon, P.; Zitano, L. Pneumocandins from Zalerion arboricola I. Discovery and Isolation J. Antibiot. 1992, 45, 1853-1866
86. Hensens, O. D.; Liesch, J. M.; Zink, D. L.; Smith, J. L.; Wichmann, C. F.; Schwartz, R. E. Pneumocandins from Zalerion arboricola III. Structure Elucidation J. Antibiot. 1992, 45, 1875-1885
87. Morris, M.; Villmann, M. Echinocandins in the Management of Invasive Fungal Infections, Part 1 Am. J. Health-Syst. Pharm. 2006, 63, 1693-1703
88. Morris, M.; Villmann, M. Echinocandins in the Management of Invasive Fungal Infections, Part 2 Am. J. Health-Syst. Pharm. 2006, 63, 1813-1820
89. Chen, S. C.; Slavin, M. A.; Sorrell, T. C. Echinocandin Antifungal Drugs in Fungal Infections: A Comparison Drugs 2011, 71, 11-41
90. Balkovec, J. M.; Hughes, D. L.; Masurekar, P. S.; Sable, C. A.; Schwartz, R. E.; Singh, S. B. Discovery and Development of First in Class Antifungal Caspofungin (CANCIDAS)-A Case Study Nat. Prod. Rep. 2014, 31, 15-34
91. Bouffard, F. A.; Zambias, R. A.; Dropinski, J. F.; Balkovec, J. M.; Hammond, M. L.; Abruzzo, G. K.; Bartizal, K. F.; Marrinan, J. A.; Kurtz, M. B.; McFadden, D. C. Synthesis and Antifungal Activity of Novel Cationic Pneumocandin B0 Derivatives J. Med. Chem. 1994, 37, 222-225
92. Leonard, W. R.; Belyk, K. M.; Conlon, D. A.; Bender, D. R.; DiMichele, L. M.; Liu, J.; Hughes, D. L. Synthesis of the Antifungal Beta-1,3-Glucan Synthase Inhibitor CANCIDAS (Caspofungin Acetate) from Pneumocandin B0 J. Org. Chem. 2007, 72, 2335-2343
93. Wimberly, B. T.; Brodersen, D. E.; Clemons, W. M., Jr.; Morgan-Warren, R. J.; Carter, A. P.; Vonrhein, C.; Hartsch, T.; Ramakrishnan, V. Structure of the 30S Ribosomal Subunit Nature 2000, 407, 327-339
94. Carter, A. P.; Clemons, W. M.; Brodersen, D. E.; Morgan-Warren, R. J.; Wimberly, B. T.; Ramakrishnan, V. Functional Insights from the Structure of the 30S Ribosomal Subunit and Its Interactions with Antibiotics Nature 2000, 407, 340-348
95. Shomura, T.; Ezaki, N.; Tsuruoka, T.; Niwa, T.; Akita, E.; Niida, T. Studies on Antibiotic SF-733, a New Antibiotic. I. Taxonomy, Isolation and Characterization J. Antibiot. 1970, 23, 155-161
96. Woo, P. W. K.; Dion, H. W.; Bartz, Q. R. Butirosins A and B, Aminoglycoside Antibiotics. I. Structural Units Tetrahedron Lett. 1971, 28, 2617-2620
97. Umezawa, H.; Ueda, M.; Maeda, K.; Yagishita, K.; Kondo, S.; Okami, Y.; Utahara, R.; Osato, Y.; Nitta, K.; Takeuchi, T. Production and Isolation of a New Antibiotic, Kanamycin J. Antibiot. 1957, 10A, 181-188
98. Kawaguchi, H.; Naito, T.; Nakagawa, S.; Fujisawa, K.-I. BB-K 8, a New Semisynthetic Aminoglycoside Antibiotic J. Antibiot. 1972, 25, 695-708
99. Kondo, S.; Iinuma, K.; Yamamoto, H.; Ikeda, Y.; Maeda, K.; Umezawa, H. Synthesis of (S)-4-Amino-2-Hydroxybutyryl Derivatives of 3′,4′-Dideoxykanamycin B and Their Antibacterial Activities J. Antibiot. 1973, 26, 705-707
100. Umezawa, H.; Umezawa, S. 3′,4′-Dideoxy-Kanamycin B Active against Kanamycin-Resistant Escheria coli and Pseudomonas aeruginosa J. Antibiot. 1971, 24, 485-487
101. Weinstein, M.; Luedemann, G. Gentamicin: A New Broad-Spectrum Antibiotic Complex Antimicrob. Agents Chemother. 1963, 161, 1-7
102. Magnet, S.; Blanchard, J. S. Molecular Insights into Aminoglycoside Action and Resistance Chem. Rev. 2005, 105, 477-498
103. Perlin, M. H.; Brown, S. A.; Dholakia, J. N. Developing a Snapshot of the ATP Binding Domain(s) of Aminoglycoside Phosphotransferases Front. Biosci. 1999, 4, 63-71
104. Edson, R. S.; Terrell, C. L. The Aminoglycosides Mayo Clin. Proc. 1999, 74, 519-528
105. Hotta, K.; Sunada, A.; Ikeda, Y. Double Stage Activity in Aminoglycoside Antibiotics J. Antibiot. 2000, 53, 1168-1174
106. Nikolaidis, I.; Favini-Stabile, S.; Dessen, A. Resistance to Antibiotics Targeted to the Bacterial Cell Wall Protein Sci. 2014, 23, 243-259
107. Li, Y.; Wu, Y.-L. An over Four Millennium Story behind Qinghaosu (Artemisinin)-A Fantastic Antimalarial Drug from a Traditional Chinese Herb Curr. Med. Chem. 2003, 10, 2197-2230
108. Klayman, D. L. Qinghaosu (Artemisinin): An Antimalarial Drug from China Science 1985, 228, 1049-1055
109. Miller, L. H.; Su, X. Artemisinin: Discovery from the Chinese Herbal Garden Cell 2011, 146, 855-858
110. Luo, X. D.; Shen, C. C. The Chemistry, Pharmacology, and Clinical Applications of Qinghaosu (Artemisinin) and Its Derivatives Med. Res. Rev. 1987, 7, 29-52
111. Shandilya, A.; Chacko, S.; Jayaram, B.; Ghosh, I. A Plausible Mechanism for the Antimalarial Activity of Artemisinin: A Computational Approach Sci. Rep. 2013, 3, 2513
112. Singh, C.; Tiwari, P. One-Pot Synthesis of Antimalarial Drug Artemether from Artemisinin Indian J. Chem. 2002, 41B, 2185-2186
113. Sulzberger, M. B.; Sauer, G. C.; Herrmann, F.; Baer, R. L.; Milberg, I. L. Effect of Adrenocorticotropic Hormone and Cortisone on Diseases and Physiological Functions of the Skin. I. Effects of ACTH J. Invest. Dermatol. 1951, 16, 323-327
114. Sulzberger, M. B.; Witten, V. H. The Effect of Topically Applied Compound F in Selected Dermatoses J. lnvest. Dermatol. 1952, 19, 101-102
115. Herzog, H.; Oliveto, E. P. A History of Significant Steroid Discoveries and Developments Originating at the Schering Corporation (USA) since 1948 Steroids 1992, 57, 617-623
116. Oliveto, E. P.; Gerold, C.; Hershberg, E. B. The Acylation of 11β-Hydroxy Steroids: The Synthesis of Δ4-Pregnene-11β,17α-21-triol-3,20-dione 11,21-diacetate (Compound F 11,21-Diacetate) Arch. Biochem. Biophys. 1953, 43, 234-235
117. Herzog, H. L.; Payne, C. C.; Hughes, M. T.; Gentles, M. J.; Hershberg, E. B.; Nobile, A.; Charney, W.; Federbush, C.; Sutter, D.; Perlman, P. L. Microbiological Transformation of Steroids-X. I-Dehydro Analogs of Cortical Steroids Tetrahedron 1962, 18, 581-589
118. Fried, J.; Thoma, R. W.; Klinsberg, A. Microbiological Transformation of Steroids-X. I-Dehydro Analogs of Cortical Steroids J. Am. Chem. Soc. 1953, 75, 5764-5765
119. Nobile, A.; Charney, W.; Perlman, P. L.; Herzog, H. L.; Payne, C. C.; Tully, M. E.; Jevnik, M. A.; Hershberg, E. B. Microbiological Transformation of Steroids. I. Δ1,4-Diene-3-ketosteroids J. Am. Chem. Soc. 1955, 77, 4184
120. Cooney, W. P. Compound F: The History of Hydrocortisone and Hand Surgery J. Hand Surg. Am. 2013, 38, 774-778
121. Mason, H.; Hoehn, W.; Kendall, E. Chemical Studies of the Suprarenal Cortex: IV. Structures of Compounds C, D, E, F, and G J. Biol. Chem. 1938, 124, 459-474
122. Herzog, H. L.; Nobile, A.; Tolksdorf, S.; Charney, W.; Hershberg, E. B.; Perlman, P. L.; Pechet, M. M. New Antiarthritic Steroids Science 1955, 121, 3136
123. Czock, D.; Keller, F.; Rasche, F. M.; Häussler, U. Pharmacokinetics and Pharmacodynamics of Systemically Administered Glucocorticoids Clin. Pharmacokinet. 2005, 44, 61-98
124. Newton, R.; Holden, N. S. Separating Transrepression and Transactivation: A Distressing Divorce for the Glucocorticoid Receptor? Mol. Pharmacol. 2007, 72, 799-809
125. Rhen, T.; Cidlowski, J. A. Antiinflammatory Action of Glucocorticoids-New Mechanisms for Old Drugs N. Engl. J. Med. 2005, 353, 1711-1723
126. Corner, G. W. The Early History of Progesterone Gynecol. Invest. 1974, 5, 106-112
127. Milgrom, E.; Atger, M.; Baulieu, E.-E. Progesterone in Uterus and Plasma. IV-Progesterone Receptor(s) in Guinea Pig Uterus Cytosol Steroids 1970, 16, 741-754
128. Baulieu, E. E.; Raynaud, J. P. A "Proportion Graph" Method for Measuring Binding Systems Eur. J. Biochem. 1970, 13, 293-304
129. Teutseh, G.; Ojasoo, T.; Raynaud, J. P. 11β-Substituted Steroids, an Original Pathway to Antisteroids J. Steroid Biochem. 1988, 31, 549-565
130. Bélanger, A.; Philibert, D.; Teutsch, G. Regio and Stereospecific Synthesis of 11β-Substituted 19-Norsteroids: Influence of 11β-Substitution on Progesterone Receptor Affinity Streroids 1981, 37, 361-382
131. Beaulieu, E.-E. Contragestion and Other Clinical Applications of RU 486, an Antprogesterone at the Receptor Science 1989, 245, 1351-1357
132. Teutsch, G.; Costerousse, G.; Deraedt, R. 17α-Alkynyl-11β,17-dihydroxyandrostane Derivatives: A New Class of Potent Glucocorticoids Steroids 1981, 38, 651-665
133. Dryden, H. I., JR; Webber, G. M.; Burtner, R. R.; Cella, J. A. The Use of Sodium Metal in the Birch Reduction of Aromatic Compounds1 J. Org. Chem. 1961, 26, 3237-3245
134. Nelson, N. A.; Wilds, A. L. The Facile Synthesis of 19-Nortestosterone and 19-Norandrostenedione from Estrone J. Am. Chem. Soc. 1953, 75, 5366-5369
135. Merck & Co.: Procédé de Préparation de Composés Stéroïdes et Produits Ainsi Obtenus. BE 651 812, 1965.
136. Merck & Co.: Procédé de Préparation de Composés Stéroïdes et Produits Ainsi Obtenus. BE 651 813, 1965.
137. Teutsch, J. G.; Torelli, V.; Philibert, D. Steroid Derivatives. US 4634695, 1987.
138. Cadepond, F.; Ulmann, A.; Baulieu, E. E. RU486 (Mifepristone): Mechanisms of Action and Clinical Uses Annu. Rev. Med. 1997, 48, 129-156
139. Williams, S. P.; Sigler, P. B. Atomic Structure of Progesterone Complexed with Its Receptor Nature 1998, 393, 392-396
140. Raaijmakers, H. C. A.; Versteegh, J. E.; Uitdehaag, J. C. M. The X-ray Structure of RU486 Bound to the Progesterone Receptor in a Destabilized Agonistic Conformation J. Biol. Chem. 2009, 284, 19572-19579
141. Bledsoe, R. K.; Madauss, K. P.; Holt, J. A.; Apolito, C. J.; Lambert, M. H.; Pearce, K. H.; Stanley, T. B.; Stewart, E. L.; Trump, R. P.; Willson, T. M.; Williams, S. P. A Ligand-Mediated Hydrogen Bond Network Required for the Activation of the Mineralocorticoid Receptor J. Biol. Chem. 2005, 280, 31283-31293
142. Hadvary, P.; Hochuli, E.; Lengsfeld, H.; Weibel, E. K. Leucine Derivatives. US 4,598,089, 1986.
143. Weibel, E. K.; Hadvary, P.; Kupfer, E.; Lengsfeld, H.; Hochuli, E. Lipstatin, an Inhibitor of Pancreatic Lipase, Produced by Streptomyces toxytricini I. Producing Organism, Fermentation, Isolation and Biological Activity J. Antibiot. 1987, 40, 1081-1085
144. Hochuli, E.; Kupfer, E.; Maurer, R. Lipstatin, an Inhibitor of Pancreatic Lipase, Produced by Streptomyces toxytricini II. Chemistry and Structure Elucidation J. Antibiot. 1987, 40, 1086-1091
145. Stalder, H.; Schneider, P. R.; Oesterhelt, G. Tetrahydrolipstatin: Thermal and Hydrolytic Degradation Helv. Chim. Acta 1990, 73, 1022-1036
146. Hadvary, P.; Lengsfeld, H.; Wolfer, H. Inhibition of Pancreatic Tetrahydrolipstatin in Vitro by the Covalent Inhibitor Biochem. J. 1988, 256, 357-361
147. Hadváry, P.; Sidler, W.; Meister, W.; Vetter, W.; Wolfer, H. The Lipase Inhibitor Tetrahydrolipstatin Binds Covalently to the Putative Active Site Serine of Pancreatic Lipase J. Biol. Chem. 1991, 266, 2021-2027
148. Endo, A. The Discovery and Development of HMG-CoA Reductase Inhibitors Atheroscler. Suppl. 2004, 5, 67-80
149. Endo, A.; Kuroda, M. Citrinin, an Inhibitor of Cholesterol Synthesis J. Antibiot. 1976, 29, 841-843
150. Endo, A.; Tsujita, Y.; Kuroda, M.; Tanzawa, K. Inhibition of Cholesterol Synthesis in Vitro and in Vivo by ML-236A and ML-236B, Competitive Inhibitors of 3-Hydroxy-3-methylglutaryl-coenzyme A Reductase Eur. J. Biochem. 1977, 77, 31-36
151. Brown, A.; Smale, T.; King, T. Crystal and Molecular Structure of Compactin, a New Antifungal Metabolite from Penicillium brevicompactum J. Chem. Soc., Perkin Trans. 1 1976, 1165-1170
152. Alberts, A. W.; Chen, J.; Kuron, G.; Hunt, V.; Huff, J.; Hoffman, C.; Rothrock, J.; Lopez, M.; Joshua, H.; Harris, E.; Patchett, A.; Monaghan, R.; Currie, S.; Stapley, E.; Albers-Schonberg, G.; Hensens, O.; Hirshfield, J.; Hoogsteen, K.; Liesch, J.; Springer, J. Mevinolin: A Highly Potent Competitive Inhibitor of Hydroxymethylglutaryl-coenzyme A Reductase and a Cholesterol-Lowering Agent Proc. Natl. Acad. Sci. U.S.A. 1980, 77, 3957-3961
153. Istvan, E. S.; Deisenhofer, J. Structural Mechanism for Statin Inhibition of HMG-CoA Reductase Science 2001, 292, 1160-1164
154. Tobert, J. A. Lovastatin and beyond: The History of the HMG-CoA Reductase Inhibitors Nat. Rev. Drug Discovery 2003, 2, 517-526
155. Rosegay, A.; Vickers, S.; Duncan, C. A.; Duggan, D. E. Metabolic Disposition Studies on Simvastatin, a Cholesterol Lowering Prodrug Drug Metab. Dispos. 1990, 18, 138-145
156. Hoffman, W. F.; Alberts, A. W.; Anderson, P. S.; Chen, J. S.; Smith, R. L.; Willardt, A. K. 3-Hydroxy-3-methylglutaryl-coenzyme A Reductase Inhibitors. 4. Side Chain Ester Derivatives of Mevinolin J. Med. Chem. 1986, 29, 849-852
157. Group, H. P. S. C. MRC/BHF Heart Protection Study of Cholesterol Lowering with Simvastatin in 20 536 High-Risk Individuals: A Randomised Placebocontrolled Trial Lancet 2002, 360, 7-22
158. Sarver, R. W.; Bills, E.; Bolton, G.; Bratton, L. D.; Caspers, N. L.; Dunbar, J. B.; Harris, M. S.; Hutchings, R. H.; Kennedy, R. M.; Larsen, S. D.; Pavlovsky, A.; Pfefferkorn, J.; Bainbridge, G. Thermodynamic and Structure Guided Design of Statin Based Inhibitors of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase J. Med. Chem. 2008, 51, 3804-3813
159. Carvalho, A.; Trincão, J.; Romão, M. X-ray Crystallography in Drug Discovery. In Ligand-Macromolecular Interactions in Drug Discovery; Roque, A. C. A., Ed.; Methods in Molecular Biology, Vol. 572; Springer: New York, 2010; pp 31-56.
160. Howard, J. A. K.; Probert, M. R. Cutting-Edge Techniques Used for the Structural Investigation of Single Crystals Science 2014, 343, 1098-1102
161. Garman, E. F. Developments in X-ray Crystallographic Structure Determination of Biological Macromolecules Science 2014, 343, 1102-1108