Searching Medicinal Chemical Literature - ACS Publications

Searching Medicinal Chemical Literature C. R. ADDINALL and P. G. STECHER Merck & Co., Inc., Rahway, N. J.

The technical information department of the re­ search and development division of a manufac­

Downloaded by UNIV OF MELBOURNE on March 29, 2016 | http://pubs.acs.org Publication Date: January 1, 1961 | doi: 10.1021/ba-1961-0030.ch014

turer of fine chemicals has many interesting prob­ lems in searching for information in the medicinal chemical literature and that of pertinent and allied fields.

Three such representative problems have

been selected for presentation.

•knowledge of somewhat obscure sources of botanical drug information is necessary i n answering such queries as those concerned w i t h a folk remedy k n o w n only b y its vernacular name, the determination of the scientific nomenclature of a popular plant name i n some dialect or foreign language, the active pharmaco­ logical principles of a specific drug, or the occurrence i n plant materials of certain active principles of a predetermined chemical or biological character. Searching the Botanical Drug Literature M a n y suggestions of folk remedies k n o w n only b y vernacular names have been inspired b y awakened interest i n synthetic organicals w i t h activity i n the treatment of rheumatoid arthritis. O n e such example was the report that a local drug named bawang is valued i n the Philippines for the treatment of rheumatism. Books have been published on the folk remedies of almost every country and geo­ graphical area i n the w o r l d , and the Philippines are no exception. In 1901, Tavero (15) published an interesting but n o w out-of-date volume on the medicinal plants of the Philippines. Often an o l d compilation of this k i n d is far more valu­ able for such a search than new publications written w h e n the o l d knowledge is lost i n the splendor of the new, and for this reason they should be jealously guarded and treasured. In Tavero's work bawang, under a slightly different spelling, is described, and the miracle d r u g is exposed as ordinary garlic. Often, however, the information available is so indefinite that the search is hopeless from the beginning. The folklore that rheumatism can be cured b y infusion of "rheumatism root" or "rheumatism w e e d " suggests the identification of this herb w i t h a v i e w to further investigation. Clute (3) has listed a l l such vernacular descriptive plant designations. Rheumatism root may be Chelone glabra (Scrophulariaceae), Chimaphûa macuhta (Ericaceae), Apocynum cannabinum (Apocynaceae), Jeffersonia diphylla (Berberidaoeae), or etfen Dioscorea 121 SEARCHING THE CHEMICAL LITERATURE Advances in Chemistry; American Chemical Society: Washington, DC, 1961.

Downloaded by UNIV OF MELBOURNE on March 29, 2016 | http://pubs.acs.org Publication Date: January 1, 1961 | doi: 10.1021/ba-1961-0030.ch014

122

ADVANCES I N CHEMISTRY SERIES

villosa (Dioscoreaceae), whereas the name rheumatism weed has been assigned to another species of Apocynum. Clute's invaluable compilation is restricted to American usage. There are, however, many polyglot compilations of this type. Thus, i n L y o n s ' book ( 9 ) , L a t i n , English, French, G e r m a n , and Spanish are represented. E v e n more com­ prehensive is the illustrated polyglotic dictionary b y Bedevian ( I ) . After definite identification of a supposed d r u g plant, it is necessary to deter­ mine the active principles k n o w n to occur i n the drug and to consider the known biological activity of these principles w i t h reference to the alleged curative prop­ erties. F o r such a search W e h m e r s three-volume work (16) is invaluable. I n condensed style, consisting mainly of literature references and cross references, this magnificent compilation lists the content of plants and the source of the informa­ tion. Thus (Volume 1, page 3 2 7 ) , Jeffersonia diphylla, one of the above-men­ tioned rheumatism roots, contains berberine, as was shown b y G o r d i n ( 5 ) . Wehmer covers the literature u p to 1934 only and a similar up-to-date compilation w o u l d b e a welcome addition to the library files. W e h m e r also gives preliminary answers to the question of what species might be suitable sources of a definite compound or product—the type of question that arises when substitute raw materials must be found i n times of economic stress or dislocation. Thus, he gives 31 references to the occurrence of berberine i n differ­ ent plants. A p a r t from sources familiar to a l l chemists, such as abstract journals, additional references for information of this type can be found i n monographs on alkaloids (6, 12). Considerably more difficult than the search for a definite compound such as berberine is that for plants yielding a material w i t h given definite biological activ­ ity, because the required effect may be provided b y various substances of like or unlike chemical nature. Thus, compiling a list of d r u g plants having digitalis-like physiological activity might be required. M u c h preliminary information can be gleaned from texts dealing w i t h the chemical class of compound under investiga­ tion. Its steroid and glycosidal nature suggests a study of the many available texts on steroids, particularly that b y Fieser and Fieser (4) and of monographs on gly­ cosides (14) or the chapter on glycosides b y Lebeau and Courtois ( 7 ) . I n con­ tinuation of the search, reference w o u l d then be made to books on medicinal plants w i t h indexes of therapeutic applications. Thus, Madaus (11) lists seven species alleged to have digitalis-like action on the heart, one such plant being the beautiful mountain laurel, Kalmia latijolia L . F i n a l l y , purely medical compilations w i l l be consulted. Thus, the " C u m u l a t i v e Quarterly Index M e d i c u s " lists numerous papers on "heart insufficiency" a n d some of these deal w i t h vegetable drugs other than those of the digitalis species. Sufficient information, however, may be gleaned to round out this most difficult of all searches into the botanical drug literature. Interpreting the Foreign Prescription T h e postwar scarcity of drugs i n Europe, particularly of previously w e l l established specialties of the prewar d r u g concerns, the shifting of large popula­ tions, a n d the entry of many displaced persons into the U n i t e d States made the tracking down a n d identification of prescription specialties, and of chemicals indicated i n obscurely written foreign prescriptions, a matter of much concern and significance. A s many European countries do not insist on prescription forms w i t h printed letterheads, initial difficulty i n deciphering the text prior to its translation may be SEARCHING THE CHEMICAL LITERATURE Advances in Chemistry; American Chemical Society: Washington, DC, 1961.

ADDINALL AND

STEC HER

Medicinal Chemical Literature

123

due to doubt as to the country of origin. Once a clear text has been obtained, the problems that interest the worker i n the chemical literature field are mainly those of the identification of a European specialty or drug, the establishment of its cor­ rect chemical name, and the identification of its American equivalent. T o illustrate these problems, a recent Polish prescription is given: Asthma! 7 - l - 4 9 r Rp. Coramini liq. 50,0

Downloaded by UNIV OF MELBOURNE on March 29, 2016 | http://pubs.acs.org Publication Date: January 1, 1961 | doi: 10.1021/ba-1961-0030.ch014

Jurasthmol, scat. orig. V I Dehydrit vel Euphyllin, amp X V A d manus medici! Dr. Adelmann Because this prescription for asthma is Polish i n origin (as suggested by the date l i n e ) , the European specialties prescribed must be sought i n the various excellent répertoria and codices of medicinal drugs. A c c o r d i n g to L u d w i g (8), Coramin ( C i b a ) (pyridin-^-karbonsàure-diâthylamid) is made available i n Europe as a 2 5 % aqueous solution for oral use. I n the index of Chemical Abstracts C o r amine is listed under Ν,Ν-diethylnicotinamide, and from " N e w and Nonofficial Remedies" w e learn that the compound is officially designated as Nikethamide i n the U n i t e d States and is sold b y numerous companies under the official designation "Solution Nikethamide 2 5 % w / v . " A l t h o u g h the index of Chemical Abstracts is extremely helpful i n giving the chemical name of Coramine and thus immediately m a k i n g the search for an A m e r i ­ can equivalent of the European d r u g relatively simple, it w o u l d not have been so simple to identify the w e l l k n o w n drug, Caronamide (now Carinamide® ). In the index to Chemical Abstracts, V o l u m e 42 ( 1 9 4 8 ) , several references are given under the heading Caronamide. The same references are given under the heading Benzoic acid, p-(benzylsulfonamido), but the references are not cross-indexed. A c c o r d i n g to Bernoulli and L e h m a n n ( 2 ) , Jurasthmol is a powder for the treatment of bronchial asthma and contains antipyrine, acetanilide, citrated caf­ feine, and lobeline sulfate, together w i t h minute amounts of digitalin and strophanthin. B y reference to the " M o d e r n D r u g E n c y c l o p e d i a " (13), the pharmacist can select a corresponding American proprietary remedy and adjust the prescription to fit the number of powders to the requirement of the demand for six original packages (of 15 powders each). T h e Polish proprietary medicine Dehydrit is described i n Gehe's Codex (3rd supplement, 1950) as the sodium salt of o-[(3-hydroxymercuri-2-methoxypropyl) carbamyl]phenoxyacetic acid dissolved i n aqueous theophylline solution. This preparation is known i n the U . S. Pharmacopeia as Mersalyl and theophylline i n ­ jection, and i n the U . S. Dispensatory (page 700, 24th edition) the pharmacist is informed of the U n i t e d States equivalent i n the form of Salyrgan-Theophylline Ampuls ( W i n t h r o p ) . T h e compendia cited give the composition of drugs and the chemical identity of their ingredients. Especially useful for this purpose are " T h e American D r u g Index" and " T h e M e r c k Index," the latter being international i n scope. Another source is the monthly publication Unlisted Drugs, edited b y the Pharmaceutical Section of the Special Libraries Association. This listing attempts to be truly international i n scope and has become a trustworthy tool for workers in SEARCHING THE CHEMICAL LITERATURE Advances in Chemistry; American Chemical Society: Washington, DC, 1961.

124

ADVANCES I N CHEMISTRY SERIES

the field of medicinal chemical literature whose labors carry them into the field of prescription translation.

Downloaded by UNIV OF MELBOURNE on March 29, 2016 | http://pubs.acs.org Publication Date: January 1, 1961 | doi: 10.1021/ba-1961-0030.ch014

Identifying

Merck

References

A somewhat difficult problem encountered b y librarians of pharmaceutical houses a n d other institutions concerned w i t h research o n medicinal problems is that of tracing and identifying references to M e r c k literature. H e i n r i c h E m a n u e l M e r c k , intimate friend of Justus v o n L i e b i g , a n d founder of the first factory of the enterprise, E . M e r c k , Darmstadt ( G e r m a n y ) , h a d as his main objective the preparation of pure alkaloids. H i s many achievements included the original commercial manufacture of morphine ( 1 8 2 7 ) , codeine (1836), a n d cocaine ( 1 8 6 2 ) . F o l l o w i n g the scientific tradition established b y the founder, t h e C h e m i c a l Works of E . M e r c k , Darmstadt, u p to the beginning of W o r l d W a r II, serially issued various types of pharmaceutical publications including, among others, the following important reference material: " E . Merck's Jahresbericht" (1887-1946: Vols. 1 to 60). In German, though some early began publication of original communications on natural products with the article "Neue Alkaloide aus Sabadillsamen," Vol. 4 ( 1890 ). Contains many valuable communications, particularly on alkaloidal investigations, not elsewhere available. " E . Merck's Annual Report on the Advancements of Pharmaceutical Chemistry and Thera­ peutics" (1887-1940). English, French, Spanish, Portuguese, and Italian (1930) editions. Contains original articles of general and scientific interest, a pharmacotherapeutic review, and medical opinions regarding E . Merck products. Originally a transla­ tion of E . Merck's Jahresbericht but later a different and more popular publication. " E . Merck's Wissenschaftliche Abhandlungen aus den Gebieten der Pharmakotherapie, Pharmazie und verwandter Disziplinen" (Nos. 1-42; 1890-1929). N o translations or foreign editions known. Published to provide the busy practitioner with information not readily available i n the international literature concerning old and new therapeutic or diagnostic useful preparations. Includes monograph N o . 22, "Nicht offizinelle Alkaloide" (480pages). "Merck's Index" [1897, 1902, 1910, 1914 (in French), 1927, 1928 (in 1930 i n Spanish), 1935 ( i n French)]. A collective index of preparations, drugs, and minerals listed by E . Merck with descriptions of their chemical composition, physical properties, and medical, technical, and other uses. "Merck's Reagenzien-Verzeichnis" (1903, 1907, 1913. 1916, 1924, 1928, 1932, 1936), i n German. Useful reagents and reactions listed according to author's name. Afterwards appeared serially i n translation i n American Merck's Report and Merck Report and reproduced i n Merck Index ( 5th edition ). T h e A m e r i c a n house of M e r c k , established i n 1887 i n N e w York and organized i n 1891 as M e r c k & C o . b y George M e r c k , grandson of H e i n r i c h E m a n u e l M e r c k , was incorporated i n 1908 i n N e w York a n d i n 1919 became a n independent American enterprise, consolidated w i t h Powers-Weightman-Rosengarten C o . of Philadelphia, P a . , i n 1927 to form M e r c k & C o . , Inc. D u r i n g the gradual development from a n offshoot of E . M e r c k , Darmstadt, to the present independent American corporation, the enterprise published works w i t h titles originally identical and later more or less similar to those of the publica­ tions of E . M e r c k , Darmstadt. I n the course of time, these publications became entirely different a n d individually distinct works. A brief résumé is accordingly given of the publications of M e r c k & C o . a n d of M e r c k & C o . , Inc., to lighten the difficulties arising from the similarity of their titles to those of the original a n d often contemporaneous publications of the entirely distinct German organization. Merck's Bulletin (Merck & Co., 1888-1891).

A periodical record of new discoveries,

SEARCHING THE CHEMICAL LITERATURE Advances in Chemistry; American Chemical Society: Washington, DC, 1961.

Downloaded by UNIV OF MELBOURNE on March 29, 2016 | http://pubs.acs.org Publication Date: January 1, 1961 | doi: 10.1021/ba-1961-0030.ch014

ADDINALL AND STECHER

Medicinal Chemical Literature

125

Merck's Archives of the Materia Medica and Its Uses (Merck & Co., 1899-1901; Vols. 1-3). The Merck Report ( 1892-, issued quarterly). Merck's Market Report and Pharmaceutical Journal (Merck & C o . ) , (1892-96; Vols. I to V ) . Merck's Report (Merck & Co., 1897-1927; Merck & Co., Inc., 1927-34). A practical journal of pharmacy, materia medica, and chemistry, with a section of each quarterly devoted to current price lists. The Merck Report (Merck & Co., Inc., 1934-, V o l . 4 3 - ) . For many years Theo. Holm contributed a series of articles on "Medicinal Plants of North America" with figures drawn from nature. This extensive series, covering 99 plants, has never been repro­ duced elsewhere and is often cited by botanists and pharmacognosists. "The Merck Index." First American edition ( E . Merck, 1889); Merck's 1896 Index ( Merck & Co. ) ; Merck's 1907 Index ( Merck & Co. ) ; Merck's Index, 4th ed. ( Merck & Co., Inc., 1930); The Merck Index, 5th ed. (Merck & Co., Inc., 1940); The Merck Index, 6th ed. (Merck & Co., Inc., 1952); The Merck Index 7th ed. (Merck & Co., Inc., 1960 ). A n encyclopedia for the chemist, pharmacist, physician, dentist, and veterinar­ ian. "The Merck Manual." "Merck's Manual of Materia Medica" ( 1st English éd., E . Merck, 1899); "Merck's 1901 Manual" (Merck & C o . ) ; "Merck's Manual" (Merck & Co., 1905, 1911, and 1923); "The Merck Manual" (Merck & Co., Inc., 1934, 1940, 1950, 1956; 6th, 7th, 8th, and 9th eds. ). First five editions were counterparts of the original first English edition prepared for British physicians. N o German edition seems to exist and no translation of the original E . Merck publication of 1899 is known. In 1934, "The Merck Manual" appeared as a newly revised sixth edition, and extensive revision and enlarge­ ments were continued in the subsequent editions. Conclusions Although the problems discussed are but a f e w of those facing workers i n the literature of the fine chemical field, they are probably of concern to many others because of the widespread interest due to recent advances i n medicinal chemistry. T h e discussion of the M e r c k literature seems of particular importance at this time, because no study has previously been published of this source of so many papers in the fields of alkaloid chemistry, pharmacognosy, and related disciplines. Bibliography

of Drug

Compendia

American Drug Index, C . O. Wilson and T. E . Jones, eds., Lippincott, Philadelphia. Published annually. "American Druggist Blue Book," American Druggist, 250 West 55th St., New York 19, Ν. Y . Published every spring. "Apotekens Register over Standardforpackade Lakemedel," Apotekarsocietetens Informationsavdelning, Stockholm, Sweden. Published annually. 'Apotekens Specialitetsregister," Apotekens Kontrol-laboratorium, Kronobergsgatan 27, Stockholm, Sweden. Published annually. "Austria Codex," Ôsterreichischer ApothekenverLag, Vienna I X , Austria, 1959. Bernoulli, E . , Lehmann, H . , "Ubersicht der gebrauchlichen und neueren Arzneimittel," 9th Auflage, Benno Schwabe & Co., Basel, Switzerland, 1959. 555 pages. Revised every 2 to 3 years. Council on Pharmacy and Chemistry, American Medical Association, " N e w and Nonofficial Drugs," J. B. Lippincott Co., Philadelphia, Pa. Annual publication œntaining descrip­ tions of articles accepted by council. "Drug Topics Red Book," Topics Publishing Co., Inc., 10 East 15th St., New York 3, Ν. Y . Published annually. Fumi, R., "Repertorio Terapeutico" (Elenco Générale délie Specialità Medicinali Com­ merciale in Italia), Aracne, Milan, Italy. Annual publication. "Gehes Codex der pharmazeutischen Spezialprâparate mit Angaben iiber Zusammensetzung, Indikationen, Zubereitungsformen und Hersteller." 9th edition. Wissenschaftliche Verlagsgesellschaft, Stuttgart, 1960. Helwig, B., 'Moderne Arzneimittel," Wissenschaftliche Verlagsgesellschaft, Stuttgart, 1956. 772 pages. Supplement 1958. Jalander, Y . W . , Helsinki, Finland, "Farmaseutisia ja kemiallisia Synonymeja," 1948. 570 pages plus 1949 supplement of 47 pages. Kaplan, Α., "Manual de Especialidades Médicinales," Lopez & Etchegoyen, S.R.L., Junin 863, Buenos Aires, 1951. 777 pages and supplements. Ludwig, H , "Repertorium pharmazeutischer Snezialprâparate, Sera und Impfstoffe," 1st Ausgabe, Verlagsgesellschaft Beobachter A . G . , Basel, Switzerland, 1946. 1308 pages. Supplement, Ausgabe 1947, 331 pages. 2nd supplement, 1950. SEARCHING THE CHEMICAL LITERATURE Advances in Chemistry; American Chemical Society: Washington, DC, 1961.

Downloaded by UNIV OF MELBOURNE on March 29, 2016 | http://pubs.acs.org Publication Date: January 1, 1961 | doi: 10.1021/ba-1961-0030.ch014

126

ADVANCES IN CHEMISTRY SERIES

Martindale, "The Extra Pharmacopoeia," V o l . I, 24th edition, 1958; V o l . II, 23rd edition, 1955. Pharmaceutical Press, 17 Bloomsbury Square, London W . C . 1. "The Merck Index," P. G . Stecher, M . J. Finkel, Ο. H . Siegmund, Β. M . Szafranski, eds., 7th ed., Merck & Co., Inc., Rahway, N . J., I960. 1642 pages. "'Modern Drug Encyclopedia and Therapeutic Index," 7th ed., Drug Publications, Inc., 11 East 36th St., New York 16, Ν. Y. Published every 3 years. Publishers issue supplementary service every 2 months under tide of "Modern Drugs," which contains descriptions of new preparations as they appear on the market. Negwer, M . , "Organisch-Chemische Arzneimittel und ihre Synonyma," Akademie-Verlag, Berlin, 1959. "Ôsterreichisches Spezialitatenverzeichnis," Hauptverband der osterreichischen Sozialversicherungstrager, Hegelgasse 8, Vienna. Osol, Α., et al., "Dispensatory of the United States of America," 25th éd., J. B. Lippincott Co., Philadelphia, 1955. 2134 pases. "Physicians' Desk Reference to Pharmaceutical Specialties and Biologicals," Medical Economics, Inc., Oradell, N . J. Published annually. "Rote Liste Verzeichnis pharmazeutscher Spezialprâparate," Herausgeber: "Bundesverband der Pharmazeutische Industrie," Editio Cantor, Aulendorf in Wurttemberg, Germany. Vidal, L . , "Dictionnaire des spécialités pharmaceutiques," Office de Vulgarisation phar­ maceutique, 11, rue Quentin-Bauchart, Paris ( V i l l e ) . Published annually.

Literature Cited (1) Bedevian, A . K., "Illustrated Polyglotic Dictionary of Plant Names in the Latin, Arabic, Armenian, English, French, German, Italian, and Turkish Languages," Cairo, Egypt, 1936. Published by the author, represented in the United States exclusively by Stechert-Hafner, Inc., 31 East 10th St., New York 3, Ν. Y. (2) Bernoulli, E . , Lehmann, H., "Ubersicht der Gebräuchlichen und Neueren Arznei­ mittel," Benno Schwabe & Co., Basel, 1959. (3) Clute, W . N., "American Plant Names," Willard N. Clute & Co., Indianapolis, Ind., 1940. (4) Fieser, L. F., Fieser, M., "Chemistry of Natural Products Related to Phenanthrene," 3rd ed., Reinhold, New York, 1949. New edition named "Steroids" (1959) omits phenanthrene. (5) Gordin, H. M., Arch. Pharm. 239, 638 (1901). (6) Henry Τ. Α., "Plant Alkaloids," 4th ed. J. & A. Churchill, London, 1949. (7) Lebeau, P., Courtois, G . , "Traité de Pharmacie chimique," 4th ed., Masson & Cie., Paris, 1955-56. 5 vols. (8) Ludwig, H., "Repertorium pharmazeutischer Spezialpräparate," Verlagsgesellschaft Beobachter A . G . , Basel, Switzerland, 1946. 2 supplements, 1947 and 1950. (9) Lyons, A . B., "Plant Names, Scientific and Popular," Nelson, Baker & Co., Detroit, Mich, 1900. (10) McIlroy, R. J., "The Plant Glycosides," Edwin Arnold, London, 1951. (11) Madaus, Gerhard, "Lehrbuch der biologischen Heilmittel," G . Thieme, Leipzig, 1938 (12) Manske, R. H. F., Holmes, H. L . , "The Alkaloids," Academic Press, New York, 1949-55. 5 vols. Two supplemental vols. published in 1960. (13) "Modern Drug Encyclopedia." See above bibliography. (14) Rijn, J. J. L . van, "Die Glykoside," Gebrüder Borntraeger, Berlin, 1931. (15) Tavero, Pardo de, "Medicinal Plants of the Philippines," Blakiston's, Philadelphia, 1901. (16) Wehmer, C., "Die Pflanzenstoffe," Gustav Fischer, Jena, J. W . Edwards, A n n Arbor, Mich., 1946 (reprint). BASED on paper presented before the Division of Chemical Literature, Symposium on Searching the Chemical Literature, 117th Meeting, A C S , Detroit, Mich., April 1950. Revised 1960.

SEARCHING THE CHEMICAL LITERATURE Advances in Chemistry; American Chemical Society: Washington, DC, 1961.