I" Stavudine S 1901 1.211 2. H~N"-"CH~ 3. ion exchange v- 2. butylamine Stovudine 1 Zn 2 H~N-CH~ 3 ion exchonge 1,2-0-isopropylidene- benzoyl a-D-xylofuronose chloride 1 -2.3-tri-0-acetyl-5- 0-benzoyl-a-I-xylo- furonose (VIII) 0 ,T~~ 1 SnCI4. CH3CN 2 H2S04. CH3CN. 65-77 "C 0 - Vlll + NyH3 Trns, ,I.!, 0 N' 0 H bts(trlmethy1- (x) s~lyl)thym~ne (IX) 2. Nal. H3C\O~~\CH3 , 100-1 50 "C 3. CH30No. CH30H XCI b Stavudine 1902 S Stavudine OH thymidine thymine tBuOK Stavudine 1. hexamethyldisilazane 2.3.5-tri-0-benzoyl- a-D-ribofuranosyl acetate tert-butyldiphenyl- v 2. lithium diisopropylomide 3. diphenyl sulfide y-valerolactone silyl chloride I. H3C'T"~~/\rCH3 , toluene CH3 H CH3 2. (H3C-CO)20. 0 3. IX . SnCI4. CH2C12 b mn 1. diisobutylalurninum hydride Stavudine S 1903 1. No104, THF/HZO 2. toluene, Q , A 3. Bu,N4F-, THF 1. sodium periodate Stovudine El Reference(s): synthesis: EP334 368 (Bristol-Myers Squibb; appl. 27.9.1989; USA-prior. 24.3.1988). EP 653 436 (Bristol-Myers Squibb; appl. 17.5.1995; USA-prior. 15.1 1.1993, 3.1 1.1994, 23.9.1994). RU 2 047 619 (Institut Organicheskoj Khimii Ufimskogo Nauchnogo Tsentra Ran.; appl. 10.1 1 .I 995; RU-prior. 14.4.1993). JP 07 278 178 (Nippon Tobacco Sangyo; appI. 24.1.1995; J-prior. 1.4.1994). EP501 511 (Bristol-Myers Squibb; appl. 2.9.1992; USA-prior. 2.9.1992). JP04 054 193 (Nippon Tobacco Sangyo; appl. 20.2.1992; J-prior. 25.5.1990). WO 9 202 516 (Japan Tobacco Inc.; appl. 26.6.1991; J-prior. 27.7.1990,30.11 .I 990). WO 9 209 599 (Yamasa Shoyu; appl. 11.6.1992; J-prior. 30.1 1.1990). EP 519 464 (Ajinomoto Co.; appl. 23.12.1992; J-prior. 19.6.1991). JP 04 226 976 (Japan Tobacco Inc.; appl. 17.8.1992; J-prior. 5.6.1990). US 5 175 267 (University of Georgia Res. Found.; appl. 29.12.1992; USA-prior. 2.3.1990). Honvitz, J.P. et al.: J. Org. Chem. (JOCEAH) 31, 205 (1966). Herdewijn, P. et al.: J. Med. Chem. (JMCMAR) 30 (8), 1270 (1987). Lin, T.3. et al.: J. Med. Chem. (JMCMAR) 30 (2), 440 (1987). pharmaceutical compositions: EP 273 277 (Yale University; appl. 6.7.1988; USA-prior. 17.12.1986). JP 63 107 924 (Yamasa Shoyu Co.; appl. 12.5.1988; J-prior. 25.10.1986). JP04 038 727 (Yamasa Shoyu Co.; appl. 25.6.1992; J-prior. 25.10.1986). in combination with porphyrin and phthalocyanine: WO 8 911 277 (Georgia State Univ. Found.; appl. 30.1 1.1989; USA-prior. 23.5.1988) nucleoside derivatives: WO 9 01 1 081 (Oncogene;-appl. 16.3.1990; USA-prior. 22.3.1989, 17.3.1989). EP 631 783 (Mitsubishi Kasei; appl. 31 S.1994; J-prior. 3.6.1993). quinoxalines: EP 657 166 (Hoechst AG; appl. 5.12.1992; D-prior. 9.12.1993) aminopy ridones: EP484 071 (Merck & Co.; appl. 6.5.1992; USA-prior. 1.1 l.l990,25.I.l99l). Fomulurion(s): cps. 15 mg, 20 mg, 30 mg 40 mg; powder 200 mg (oral sol.) Trade Name(s): D: Zerit (Bristol-Myers GB: Zerit (Bristol-Myers USA: Zerit (Bristol-Myers Squibb) Squibb) Squibb) F: Zerit (Bristol-Myers J: Zerit (Green Cross) Squibb) 1904 S Stepronin Stepronin (Prostenoglycine; Tenoglicine; Tiofacic) ATC: RO5CB11 Use: mucolytic, hepatic protectant RN: 72324-18-6 MF: C,,H,,NO,S, MW: 273.33 EINECS: 276-587-4 LD,,,: >I250 mglkg (M, i.v.); 3336 mglkg (M, p.0.); 1801 mgkg (R, i.m.); >I250 mglkg (R, i.v.); >2500 mgtkg (R, p.0.) CN: N-[1-oxo-2-[(2-thienylcarbonyl)thio]propyl]glycine sodium salt RN: 78 126-10-0 MF: C,,H,,NNaO,S, MW: 295.32 a-bromopropionyl- thiobenzoic a-(benzoy1thio)- glycine acid propionylglycine (I) - chloride (II) a-mercaptopropionyl- glycine Stepronin Z-rnercopto- propionic acid 2-(2-thenoylthi0)- propioni~ acid NoHS &3da I1 sodium 0 Stepronin hydrosulfide glycine Reference(s): a DE 2 913 21 1 (Mediolanum; appl. 3.4.1979; I-prior. 11.4.1978). US 4 242 354 (Mediolanum; 30.12.1980; appl. 4.4.1 979; I-prior. 11.4.1978, 12.2.1979). b DOS 3 120 592 (BTB Ind. Chimica: appl. 23.5.1981: I-prior. 3.6.1980). c 1T 1 193 195 (Mediolanum; appl. 20.7.1979). synthesis of a-mercaptopropionylglycine: JP 1 1 616 (Santen; appl. 1961); C.A. (CHABA8) 61,16155 (1962). US 3 246 025 (Santen; 1965; appl. 1962; J-prior. 1961). Fortizulation(s): cps. 420 mg; gran. 180 mg, 360 mg (as sodium salt); suppos. 180 mg, 360 mg, 720 rng (as sodium salt); vial 335 mg Streptokinase S 1905 Trade Name(s): I: Broncoplus (Sigma-Tau; Mucodil (Valeas; as lysine Tioten (Mediolanum; as 198 1 as sodium salt) salt) sodium salt) Masor (Fonenti; as lysine Tiase (Mediolanum) salt) Streptokinase ATC: BOl AD01 Use: fibrinolytic (plasminogen activator) RN: 9002-01-1 MF: unspecified MW: unspecified EINECS: 232-647-1 LD,,: 3700 mgkg (M, i.v.); >I0 glkg (M, p.0.); 2 g/kg (R, i.v.1 CN: streplokinase (enzyme-activating) Co-enzyme obtained from cultures of various strains of Streptococcus haemolyticus and capable of changing plasminogen into plasmin (complex enzyme mixture of streptokinase, streptodornase and streptolysin "0"). From fermentation liquors of hemolytic streptococci species (Streptococcus haemolyticus), e. g. H 46 A. Reference(s): US 2 666 729 (Merck & Co.; 1954; appl. 1 95 1). US 2 701 227 (American Cyanamid; 1955; appl. 1951). US 3 063 913 (Behringwerke; 13.1 1.1962; D-prior. 29.12.1959). US 3 063 914 (Behringwerke; 13.1 1.1962; D-prior. 22.12.1959). purification: US 2 753 291 (American Cyanamid; 1956; appl. 1954). US 3 016 337 (Ortho Pharmac. Corp.; 9.1.1962; appl. 27.4.1959). US 3 042 586 (Merck & Co.; 3.7.1962; appl. 29.9.1959). US 3 107 203 (Merck & Co.; 15.10.1963; appl. 24.1 1,1961). US 3 138 542 (Behringwerke; 23.6.1964; D-prior. 3 1.12.1959). Formulation(s): vial 100000 iu, 250000 iu, 600000 iu, 750000 iu, 1500000 iu. Trade Narnefs): D: Kabikinase (Pharmacia & Upjohn) Streptase (Hoechst) Streptokinase (BIBraun) Varidase (Leder1e)-comb. F: Kabikinase (Pharmacia & Upjohn) Streptase (Hoechst) GB: Kabikinase (Pharmacia & Upjohn) S treptase (Hoechst) Varidase (Wyeth)-comb. I: Streptase (Hoechst Marion Roussel) Varidase (Wyeth-Leder1e)- comb. J: Belsiene (Misshin- Yamagata) Ceoluase (Maruko) Gospelaze (Takeshima) Pesiron (Towa) Reoplase (Tabishi) Screptase (Tenyo-Towa) Seori tase (Choseido-Ni hon Garen) Stochemidaze (Chemix) Twmnase (Taisho) Varidase (Takeda) USA: Streptase (Astra) - Streptomycin ATC: ~07~~04; JOIGAOI Use: antibiotic RN: 57-92-1 MF: C21H3,N7012 MW: 581.58 EINECS: 200-355-3 LD,,: 90.2 mgkg (M, i.v ); 500 mg/kg (M, p.0.); 175 mgkg (R, i.v.); 9 gkg (R, p.0.) CN: 0-2-deoxy-2-(methylamino)-a-~-glucopyranosyl(1+2)-0-5-deoxy-3-C-formyl-a-~- lyxofuranosyl(l~4)-N,hr-bis(aminoiminomethyl)-~-streptamine sulfate (2:3) RN: 38 10-74-0 MF: C,,H,,N,O,Z. 3/2H,S04 MW: 1457.39 EINECS: 223-286-0 LD,,,: 90.2 mglkg (M, i.v.); 430 mglkg (M, p.0.); 430 mglkg (R, p.0.) Streptomycin I From fermentation solutions of Streptomvces griseus. Kefcrence(s): US 2 449 866 (Kutgers Res. Found; 1948; prior. 1945). Ehrhart, Ruschig IV, 3 17. purification: US 2 765 302 (Olin Mathieson; 1956; appl. 1953). US 2 868 779 (Olin Mathieson; 1959; appl. 1956). Fortizulation(s): amp. I g (as sulfate) Trade Narne(s): D: Strepto-Fatol (Fatol) GB: Orastrep (Dista): wfm J: Streptomycin Sulfate Streptomycin-Hefa (Hefa Streptaguaine (Dista): wfm (Banyu; Dainippon; Kaken; Phar-ma) - Streptotriad (May & Kyowa; Meiji; Nikken; generics Baker)-comb.; wfm Sankyo; Sanwa; Taito F: Streptomycine Diamant 1: Streptocol (Molteni) Pfizer; Takeda; Toyo Jozo) (Diamant); wfm Streptomicina Solfato USA: Streptomycin Sulfate generics; wfm (Fisiopharma: ISF) (Pfizer) S trep toniazid (Streptonicozid) ATC: D08; JWA Use: tuberculostatic RN: 4480-58-4 MF: C,,H,N,,O,, MW: 700.71 LD,,,: 81.9 mglkg (M, route unreported) CN: 4-pyridinecarboxylic acid hydrazide', hydrazone with 0-2-deoxy-2-(methylamino)-a-L-glucopyranosyl. (1+2)-0-5-deoxy-3-C-formyl-a-~-lyxofuranosyl-l(l+4)-N,~-bis(aminoiminomethyl)-~-strept~1~ne sulfate (2:3) RN: 5667-71-0 MF: C2,H,NloO1,. 3/2HlS04 MW: 1695.65 EINECS: 227-128-1 Streptozocin S 1907 HCI streptomycin hydrochloride isoniozid (9. v.) (4. v.) ~ehington. F.C. et al.: J. Am. Chem. Soc. (JACSAT) 75, 2261 (1953). DE 1 OY69 618 (Pfizer; appl. 1953; USA-prior. 1953, 1952). use as tuberculnstatic: US 3 035 044 (Olin Mathieson; 15.5.1962; prior. 4.5.1956, 1.3.1952). alternative synthesis: FR 1 058 441 (Rh6ne-Poulcnc; appl. 1952). Trade Name(s): F: Streptoniacide "LcBrun" 1: Nicost~eptil Atral USA. Streptohydrazid (Pfi7er); (LeBrun); wfrn (Mastroeni); wfm wfm Streptozocin (S treptozotocin) ATC: LOIAD04 Use: antineoplastic RN: 72521-89-2 MF: C,H,SN,07 MW: 265.22 CN: 2-deoxy-2-[[(rnethylnitrosoarnino)carbonyl]amino]-~-glucopyrmose open-chain tautomer RN: 18883-66-4 MF. C8Ht5N307 MW' 265.22 EINECS: 242-646-R LDSb: 275 mglkg (M, i.~.); 138 mglkg (R, i.v.); 50 rnglkg (dog, i.v.1 From cultures of S~reptonl~ces uchronloge~zes var. streptozoticus I Streptorocin I Reference(s): Vavra, J.J. et al.: Antibiot. Annu. (ABANAE). 1959-60,230. DE 1 090 823 (Upjohn; appl. 29.7.1960; USA-prior. 1.8.1958). US 3 027 300 (Upjohn; 27.3.1962; prior. 1.8.1958). Fornzulation(s): vial I g Trade Na~ne(s): F: Zanosar (Pharmacia & USA: Zanosar (Pharmacia & Upjohn) Upjohn) g-Strophanthin (g-Strophantoside; Ouabain) ATC: COl ACOl Use: cardiac glycoside RN: 630-60-4 MF: C,,H,O,, MW: 584.66 EINECS: 211-139-3 LDs,,: 2200 pglkg (M, i.v.); 5 mglkg (M, p.0.); 14 rnglkg (R, i.v.) CN: (1 P,3P,@,I la)-3-[(6-deoxy-a-L-mannopyranosyl)oxy]-1 ,5,11,14,19-pentahydroxycard-20(22)-enolide a From Strophantus gratus b From Acnkmthera ouabaio Cathcl. Reference(s): a Arnaud, A.: C. R. Hebd. Seances Acad. Sci. (COREAF) 106, 1011 (1888); 107, 1162 (1888). Mannich, C.; Siewert, G.: Ber. Dtsch. Chem. Ges. (BDCGAS) 75,737 (1942). Reichstein, T. et a1 : Helv. Chim. Acta (HCACAV) 50, 179 (1967). b Arnaud, A,: C. R. Hebd. Seances Acad. Sci. (COREAF) 106,101 1 (1888); 107, 1162 (1888). review: Podolsky, E.: Am. Prof. Pharm. (APPTAZ) 8,293 (1942). Fieser, L.F.; Fieser, M.: Steroide, 845 (Weinheim 1961). Ullmanns Encykl. Tech. Chem., 4. Auf., Vol. 12, 617. Fonnulation(s): cps. 3 mg, 6 mg Trude Narne(s): D: Strodival (Herbert) Ouabai'ne Aguettant GB: Ouhaine Arnaud (Wilcox); F: Antally Ouabai'ne (Bai1ly)- (Aguettant); wfm wfm comb.; wfm Ouabai'ne-Arnaud J: Uabanin (Takeda) Digibai'ne (Deg1audc)- (Nativelle); wfm comb.; wfm ATC: COl AC Use: cardiac glycoside RN: 11 005-63-3 MF: unspecified MW: unspecified CN: strophanthin RN: 560-53-2 MF: C36Hs40,4 MW: 710.81 EINECS: 209-210-9 LDs,,: 1071 pgkg (M, i.p.); 213 pglkg (M, s.c.) CN: (~~,~~)-~-[(2,6-dideoxy-4-O-~-~-gluco~~ranosyl-3-O-meth~l ~-ibo-hexo~~ranos~l)ox~]-5,14- dihydroxy- 19-oxocard-20(22)-enolide RN: 33279-57-1 MF: C,,H,O,, MW: 872.96 CN: ~3~,~~)-3-[(0-~-~-glucopyranosyl-(1+6)-O-~-gucopyranosyl-(1+4)-2,6-dideoxy-3-0-methyl-~-~- ribo-hexopyranosyl)oxy]-5,14-dihydroxy-l9-oxocard-20(22)-enolide From Stropbanthus kombe' and other Strophanthus species (preparation of k-strophanthin-a, q. v.). Reference(s): DRP 721 001 (Sandoz; appl. 1937; CH-prior. 1937). DRP 737 540 (Sandoz; appl. 1937; CH-prior. 1937). Ullmanns Encykl. Tech. Chem., 3. Aufl., Vol. 8, 232. Ullmanns Encykl. Tech. Chem., 4. Aufl.; Vol. 12, 617. Formulation(s): amp. 0.125 mg, 0.25 mg Trade Name(s): D: Kombetin (Boehringer 1: Kombetin (Boehringer USA: Pasanol (Tilden Yates)- Mannh.) Biochemia) comb.; wfm k-Strophanthin-a (Cymarin) ATC: COIAC03 Use: cardiac glycoside RN: 508-77-0 MF: C3,,H,0, MW: 548.67 EINECS: 208-087-9 LD,,,: 2800 pglkg (M, i.v.); 20 mglkg (R, i.v.) CN: (3~,5~)-3-[(2.6-dideoxy-3-O-methy1-~opyranosyl)oxy]-5,14-dihydroxy-l9-oxocard-20(22)- enolide a From Strophanthus kombe'. _____, - glucose HO k-strophanthin-7 (k-strophonthoside) enzymatic hydrolysis [~tro~honthobiase] 1 4 b From Casrilloa elasrica Cerv. c From Apocynum cannabium. Kejerence(s): a Stoll, A. et al.: Helv. Chim. Acta (HCACAV) 20, 1484 (1937). DRP 721 001 (Sandoz; appl. 1937; CH-prior. 1937). DRP 737 540 (Sandoz; appl. 1937; CH-prior. 1937). Ullmanns Encykl. Tech. Chem., 3. Aufl Vol. 8, 232. DE 1 920 177 (G6decke; appl. 21.4.1969). DOS 2 050 457 (GOdecke; appl. l4.lO.l972). b GB 972 91 7 (Wellcome Foundation; appl. 20.4. I96 1). c DD 35 688 (W. Grundmann. R. Giessner, appl. 26.3.1964). DD 43 401 (W. Grundmann: R. Giessner; appl. 25.1.1965). OH k-strophonthin-8 (I) alternative syntheses: The Merck Index, 12th Ed., 1512 (1996). . ~-ibo-hexo~~ranos~l)ox~ ]-5 ,1 4- dihydroxy- 19-oxocard-20(22)-enolide RN: 3327 9-5 7-1 MF: C,,H,O,, MW: 872.96 CN: ~3~,~~ )-3 -[ ( 0-~ -~ -glucopyranosyl-(1+6)-O-~-gucopyranosyl-(1+4 )-2 ,6-dideoxy- 3-0 -methyl- ~-~ - ribo-hexopyranosyl)oxy ]-5 ,14-dihydroxy-l9-oxocard-20(22)-enolide. p.0.) CN: 0-2 -deoxy- 2-( methylamino)-a-~-glucopyranosyl(1+2 )-0 -5 -deoxy-3-C-formyl-a- ~- lyxofuranosyl(l~4)-N,hr-bis(aminoiminomethyl )-~ -streptamine sulfate (2:3) RN: 38 1 0-7 4-0 MF: C,,H,,N,O,Z H~N" ;-& quot;CH~ 3. ion exchange v- 2. butylamine Stovudine 1 Zn 2 H~N-CH~ 3 ion exchonge 1, 2-0 -isopropylidene- benzoyl a-D-xylofuronose chloride 1 -2 .3-tri-0-acetyl- 5- 0-benzoyl-a-I-xylo-