Merck Review

Spitz, Diamines and Higher Amines, Aliphatic in Kirk-Othmer Encyclopedia of Chemical Technology vol. 7 (Wiley-Interscience, New York. 3rd ed., 1979) pp 580-602. Orphan drug developed by Merck. Review. J. M. Walshe, Orphan Drugs, F. E. Karch, Ed. (Marcel Dekker, New York, 1982) Pp 57-71-... 

Acknowledgment The authors wish to express their gratitude to Dr. J. Edwards of Syntex Research who provided the experimental procedure utilizing silver carbonate on Celite. We are also indebted to the Synthetic Chemical Research Department of Merck Sharp Dohme Research Laboratories for providing time to complete this review and also to Miss Joanna Mohr for her patience and care in preparing the manuscript. 

The author would like to thank the SERM team members in Merck Process Research, who were the coauthors for the original publications reviewed in this chapter, for their original contributions to the work. 

Only 1,3,5,7-tetraazaadamantane is known. It is also called hexamethylenetetramine (93) (HMT), hexamine, aminoform, ammoform, cyctamin, cystogen, formin, uritone, urotropin, and methenamine. It is listed by the last name in the Merck Index. It is prepared from formaldehyde and ammonia. The chemistry of this well-known compound is not discussed in this review. 

Griseofulvin is listed in the following compendia The United States Pharmacopia (1) The British Pharmacoepia (2) The Europeon Pharmacoepia (3) and the Merck Index (4). A previously published review (5) is a good source for physical and chemical data, production, use, occurrence and biological information. 

This chapter is dedicated to Dr. James T. Stewart on the occasion of his 70th birthday. Formerly a professor at the University of Georgia s College of Pharmacy and my PhD advisor, Dr. Stewart is now retired. My thanks also to Dr. Wu Du of the Merck Research Laboratories and Dr. Mark Arnold of BMS for their reviews and comments. 

Gaboxadol (9) is a selective extrasynaptic GABA receptor agonist in late-stage investigation for the treatment of insomnia. The action of this compound was extensively reviewed in Chebib et al. [13] and updated in Wafford et al. [23]. Nevertheless, the sponsor companies Merck Co., Inc., and H. Lundbeck A/S announced in March 2007 that the results from recently completed clinical studies do not support further development and announced the discontinuation of their joint development program for gaboxadol. 

In some circumstances, the FDA processes drug reviews under the accelerated scheme. This mechanism is to review and approve drugs speedily for cases where effective therapies are lacking or in situations of rare diseases. One of the fastest approval times to date is the case of imatinib mesylate (Gleevec, Novartis—Exhibit 7.3) for the treatment of chronic myeloid leukemia (CML) it was approved in less than 3 months after the filing of an NDA with the FDA. Another example is the new AIDS drug indinavir (Crixivan, Merck), which was approved in a mere 42 days. 

Storm, P.F. Review of Bulking Episode at the Merck and Co., Inc., Elkton, Virginia Wastewater Treatment Pilot Plant, Merck Co., Inc. Elkton, VA, 1981. 

Simons, John. The Lortune 500 Lrom Scandal to Stardom How Merck Healed Itself. Fortune 157, no. 3 (February 18, 2008) 94—96, 98. This article reviews the recent downs and ups of one major drug company. Since 2006, Merck has received approval for many new and promising drugs, won important court cases involving its drug Vioxx, and enjoyed increases in stock prices. 

There is also continuous interaction throughout the review process. For example, over roughly six years, the sponsor, Merck Research Laboratories of West Point, Pa., and the FDA had several face-to-face meetings and about 28 teleconferences regarding the asthma drug Singulair (montelukast sodium). 

For an excellent review about process research at Merck, see E. J. J. Grabowski, ACS Symposium Series 2004, 870 (Chemical Process Research), 1—21. 

The authors would like to thank Drs. Anjum Muzzafar, Herman H. J. C. Yeh, and Ernest Hamel from the National Institutes of Health in Bethesda, Maryland, for their profound interest in the topic discussed and for splendid collaboration. We also would like to thank Drs. Hans-Ekart Radunz from the Pharmaceutical Division of E. Merck Co., Inc., in Darmstadt, Germany, and Dr. Bernhard Witkop, Institute Scholar, for their help in finalizing this review. 

Special thanks are due to Dr. Tom Perun of the IUPAC Medicinal Chemistry Subcommittee, Dr. Hanns Wurziger (Merck KGaA, Darmstadt), Dr. Derek Buckle (DRB Associates), and Dr. Stefan Jaroch (Schering AG, Berlin) for their help in the final preparation and review of the manuscript... 

Biesterveld, N. (2002), Nasal vaccine delivery, vaccine delivery adjuvants, Merck Company, West Point, PA, a Literature review submitted to the Department of Chemistry, Lehigh University, Aug. 2002. 

The advantage of bureaucracy, though, is that any project gets a thorough review. One reason Merck hasn t had products killed by the FDA is probably that it kills them early itself. 

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