Diflucortolone valerate 641 CH3 1. CH,COOK, C,H,OH 2. H2F2. CHCl, I * 11 N,N'-dibromo-5.5- dimethylhydontoin pyridine + (I LcH3 + F] voleryl Diflucortalone valerote chloride Reference(s): DE 1 21 1 194 (Schering; 27.7.1963) continuation of DE 1 169 444. DE 1 169 444 (Schering; 22.2.196 1). Kieslich, K. et al.: Arzneim Forsch. (ARZNAD) 26, 1462 (1976). (alternative syntheses described) Fonnularion(s): cream 0.1 %; ointment 0.1 % Dude Nnme(s): D: Neribas (Schering) Nerisona (Schering) Nerisona C (Schering)- comb. Travocort (Schering)-comb. F: Nerisone (Schering; as valerate) Nerisone C (Schering; as valerate)-comb. GB: Nerisone (Schering) I: Cortical (Cabcr) Cortifluoral (Schering)- comb. Dermaflogil (Nuovo Cons. Sanit. Naz.)-comb. Derrneval (Firma) J: Derrnobios (Biotekfarma)- comb. Dcrvin (Boniscontro & Gazzone) Dicortal (Medici) Flu-Cortanest (Piam) Impetex (Roche)-comb. Nerisona (Schering) Nerisona C (Schedng)- comb. Temetex (Roche) several combination preparations Afusona (Toyama) Arusona (Hotta) Dertron (Sankyo) Lizatlone (Kaken) Lorizon (Shinshin) Neridalon (Taiyo) Nerisona (Nippon Schcring) Sawatolone (Sawai) Texrneten (Roche) Youtolon (Tatsumi) 642 D Diflunisal Diflunisal ATC: N02BA11 Use: anti-inflammatory, analgesic, antipyretic RN: 22494-42-4 MF: C,,H,F,O, MW: 250.20 EINECS: 245-034-9 LD,,: 439 mgtkg (M, p.0.); 392 mglkg (R, p.0.) CN: 2',4'-difluoro-4-hydroxy[l ,I '-biphenyl]-3-carboxylic acid 2.4-difluoro- onisole aniline Reference(s): Hannah, J. et at.: J. Med. Chem. (JMCMAR) 21,1093 (1978) DE 1 61 8 663 (Merck & Co.; appl. 3.3.1967; USA-prior. 8.9.1966). DAS 2 532 559 (Merck & Co.; appl. 21.7.1975; USA-prior. 22.7.1974, 16.4.1975, 1.5.1975). US 3 674 870 (Merck & Co.; 4.7.1972; appl. 9.6.1970; USA-prior. 23.12.1964, 8.9.1966, 19.1.1968). US 3 68 1 445 (Merck & Co.; 1.8.1972; appl. 19.1.1968; USA-prior. 23.12.1964, 8.9.1966). US 3 714 226 (Merck & Co.; 30.1.1973; appl. 9.6.1970; prior. 23.12.1964, 8.9.1966, 19.1.1968). 4-(2,4-difluoro- alternative syntheses: US 3 992 459 (Merck & Co.; 16.1 1.1976; appl. 1.5.1975). US 4 131 618 (Merck & Co.; 26.12.1978; appl. 29.12.1977). US 4 225 730 (Merck & Co,; 30.9.1980; appl. 11.5.1978; prior. 22.7.1974, 16.4.1975) Diflunisal Formulation(s): tabl. 250 mg, 500 mg phenyl)phenol (1) Trade Name(s): D: Fluniget (Ferlux; 1982); Artrodol (AGIPS) Reuflos (Roussel) wfrn Difludol (Edmond) J: Dolobid (Merck-Banyu; F: Dolobis (Merck Sharp & Diflusan (Leben's) 1984) Dohme-Chibret: 198 1) Dolisal (Guidotti) USA: Dolobid (Merck; 1982) GB: Dolobid (Morson; 1978) Dolobid (Merck Sharp & I: Adomal (Malesci) Dohme; 1979) Aflogos (Biomedica Fluodonil (Biologici Italia) Foscama; as arginine salt) Hustar (Firma) Difuprednate D 643 ATC: D07AC19 Use: topical glucocorticoid RN: 23674-86-4 MF: C2,H3,F207 MW: 508.56 EINECS: 245-815-4 LD,: >4 glkg (M, p.0.); >4 glkg (R, PO.) CN: (6a,11~)-21-(acetyloxy)-6,9-difluoro-11-hydroxy- 17-(1-oxobutoxy)pregna- I ,4-diene-3,20-dione 6a.9-difluoro- trimethyl prednisolone orthobutyrate 1 1. oxalic acld Difluprednote I US 3 780 177 (Warner-Lambcrt; 18.12.1973; I-prior. 6.6.1967). ZA 6 803 686 (Warner-Lambert; appl. 21.5.1968; I-prior. 16.6.1967). Gardi, R. et al.: J. Med. Chem. (JMCMAR) 15, 556 (1972). Fonnulation(s): gel 0.05 % Tmde Name(s): F: Epilopic (Gerda) J: Myser (Mitsubishi Chem Tokyo Tanabe) Digitoxin ATC: COlAA04 Use: cardiac glycoside, cardiotonic RN: 71-63-6 MF: C4,HMOI3 MW: 764.95 EINECS: 200-760-5 LD,,: 0.18 mglkg (cat, p.0.) CN: (3~,5~)-3-[(0-2,6-dideoxy-~-ribo-hexopyranosy-(l+4)-0-2,6-dideoxy-~-~-ribo-hexopyranosyl- (l-t4)-2,6-dideoxy-~-~-ribo-hexopyranosyl)oxy]-14-hydroxycard-20(22)-enolide 644 D Digitoxin extraction Digitalis purpurea + OH AH purpureoglycoside A (I) enzymatic hydrolysis [Digilonidose] 1- Digitoxin from Digitalis lanato Reference(s): a DRP 646 930 (Sandoz; appl. 1933). US 2 449 673 (Wyeth; 1948; prior. 1944). US 2 557 916 (Wyeth; 1951; appl. 1948). US 2 615 884 (Wyeth; 1952; prior. 1948). HU 155 252 (Richter Gedeon; appl. 14.12.1966). b HU 156 753 (Richter Gedeon; appl. 7.1.1968). IN 62 497 (Council of Scientifique & Industrial Research; appl. 17.9.1958). alternative synrheses: Ullmanns Encykl. Tech. Chem., 3. Aufl., Vol. 8,229 DOS 2 006 9i6 (Deutsche Akademie der Wissenschaften; appl. 16.2.1970; DDR-prior. 15.8.1969). Formulation(s): amp. 0.1 mglml, 0.25 mglml; eye drops 0.02 mg/ml; lotion; tabl. 0.05 mg, 0.07 mg, 0.1 mg, 0.25 mg Digoxin D 645 Name(s): : Digicor (Henning) Digimed (Hormosan) Digimed (TrommsdorK) Digimerck (Merck) Digipural (Schaper & Briimmer) Digitoxin Didier (Hormosan) Digitoxin Hameln (Harneln) Digophton-Augentropfen (ankerpharm) Dirautheon (Robugen)- comb. Ditaven (Cascan)-comb. Ditaven Lot. (Cascan) GB: mono-glycocard (R.A.N.) Recorsan-Herzdragees I: (Recorsan) Tardigal (Beiersdorf) Targital (Beiersdori] generics J: F: Digitaline Nativelle (Procter & Gamble) USA: Ditavkne (Pharmad6veloppement)- comb. Nativelle Digitaline (Wilcox); wfm Digifar (Farmila)-comb. Digitalina (Procter & Gamble) Digitos (Formulario Naz.) Digitoxin (Shionogi) Digitoxin-Sandoz (Sankyo) Crystodigin (Lilly) Digoxin ATC: COlAAO5 Use: cardiac glycoside, cardiotonic RN: 20830-75-5 MF: C,,HMOI4 MW: 780.95 EINECS: 244-068-1 LD,: 7.670 mglkg (M, i.v.); 17.78 mglkg (M, p.0.); 25 mgkg (R, i.v.); 28.27 mglkg (R, p.0.) CN: (3~,5~,12~)-3-[(0-2,6-dideoxy-~-~-ribo-hexopyranosy1-(1~4)-0-2,6-dideox~-~-~-ribo-hexo~~ranos~l- (14)-2,6-dideoxy-~-~-ribo-hexopyranosyl)oxy]-12,14-dihydroxycard-20(22)-enolide @ from Digitalis lonata by extraction H KOH. DMF '3'3 a-acetyldigoxin Digaxin 646 D Dihydralazine Keference (s): a GB 337 091 (Wcllcome Found.; appl. 1929). Smith, S.: J. Chem. Soc. (JCSOA9) 1930, 508. IN 62 497 (Council of Scientific & Industrial Research; appl. 17.9.1958). HU 149 778 (Richter Gedeon; appl. 8.1 2.1959). HU 151 897 (Richter Gedeon; appl. 29.2.1964). HU 156 753 (Richter Gedeon; appl. 7.6.1968). DAS 2 225 039 (VEB Arzneimittelwerke Dresden; appl. 23.5.1972; DDR-prior. 24.1.1972) Ullmanns Encykl. Tech. Chem., 3. Aufl., Vol. 8, 231. b DD 70 088 (C. Lindig, K. Repke; appl. 1.1 1.1963). alternative synthesis: DD 134 644 (VEB Arzneimittelwerke Dresden; appl. 6.10.1977). Formulatiorz(s): amp. 0.1 mglml, 0.25 mglml, 0.2 mg/ml, 0.5 mg12 ml; cps. 0.1 mg, 0.2 mg; drops; tabl. 0.125 mg, 0.25 mg Trade Namefs): D: Digacin (Beiersdorf-Lilly) GB: Lanoxin (Glaxo Wellcome) J: Digosin (Chugai) Dilanacin (ASTA Medica I: Digomal (Malesci) Digosin Erixir (Chugai) AW D) Digos (Biologici Italia) Digoxin (Yamanouchi) Lanicor (Boehringer Digoss (Formulario Naz.; Lanoxin (Wellcome- Mannh.) Sifra) Tanabe) Lenoxln (Glaxo Wellcome) . D~gossina (Scfrn) USA: Lanoxicaps (Glaxo Novod~gal Amp. Eudigox (Astra-Simes) Wellcome) (Beiersdorf) Lanicor (Roehringer Lanox~n (Glaxo Wellcome) F: Dlgox~ne Nativelle (Procter Mannh ) generic & Gamble) Lanoxin (Wellcome) Dihydralazine (Dihydrallazine) ATC: C02DBOI Use: antihypertensive RN: 484-23-1 MF: C,H,,,N, MW: 190.21 ElNECS: 207-605-0 LD5,,: 300 mgkg (M, i.v.) CN: 2,3-dihydro-l ,4-phthalazinedione dihydrazone sulfate (1:l) RN: 7327-87-9 MF: C8HI,,N,. H,SO, MW: 288.29 EINECS: 230-808-0 LD,,,: 400 mglkg (M, p.0.); 400 mglkg (R, p.0.) Dihydrocodeine D 647 CN t CS, CN hydrazine hydrate phtholo- carbon nltrils disulfide (teference(s): DE 845 200 (Cassella; appl. 1951). DE 847 748 (Ciba; appl. 1949; CH-prior. 1947). Fomulation(s): tabl. 25 mg, 50 mg (as sulfatc) Tmde Name(s): D: Adelphan-Esidrix (Novartis Obsilazin (Isis Pharma)- Pharma)-comb? comb. Depressan (OPW) Triniton (Apogepha) ~ii~zin (Henning Berlin) 'lk-Torrat (Boehringer Nepresol (Novartis Mannh.)-comb. Pharma)-comb. F; NCpressol (Novartls; as hydrogen sulfate) Dihydralazine Trasipressol (Novartis; as hydrogen sulfate)-comb. I: Adelfan (Novartis)-comb. Ipogen (Gcnti1i)-comb. Nepresol (Novartis) Dihydrocodeine (Drocode) ATC: N02AA08 Use: antitussive, analgesic RN: 125-28-0 MF: C,,H,,NO, MW: 301.39 EINECS: 204-732-3 LD,,: 80 mgkg (M, i.v.) CN: (5a,6a)-4,5-epoxy-3-methoxy-17-mcthylmorphinan-6-ol hydrogen tartrate (1:l) RN: 5965-13-9 MF: C,RH,3N03 . C4H606 MW: 451.47 EINECS: 227-747-7 LD,o: 359 mg/kg (R, p.0.) codeine Dihydracodeine L Reference(s): Ehrhart, Ruschig I, 11 8. Stein, A.: Pharmazie (PHARAT) 10, 180 (1955). Formulation(s): cps. 20 mg; sol. 10 mg/g; s. r. tabl. 60 mg, 90 mg, 120 mg; syrup 12.1 mgl5 ml; tabl. 10 mg (as hydrogen tartrate) Tmde Name(s): D: Antibex forte (Lappe)- Antitussivum (Ysatfabrik)- Makatussin (Roland)- - - comb. comb. comb. DHC (Mundipharma) Paracodin (Knoll) 648 D Dihydroergocristine Remedacen (RhBne- Remedeme (Napp)-comb. USA: DHC plus (Purdue Poulcnc Rorer) 1: Alla Paracodina (Knoll)- Frcderick; as bitartrate) Tiamon (Tcmm1er)-comb. comb. Synalgos-DC (Wyeth- F: Dicodin (ASTA Mcdica; as Paracodina (Knoll) Ayersl; as bitartrate) tartrate) Sciroppo Knoll paracodina GB: DF- 1 18 forte (Napp) (Knoll)-comb. DHC Contiums (Napp) Tavolette (Knoll) Dihydroergocristine ATC: C04AE04 Usc: adrenolytic, sympatholytic RN: 17479-19-5 MF: C3SH4,N,0S MW: 61 1.74 EINECS: 241-493-4 CN: (5'a,lOa)-9,I0-dihydro-l2'-hydroxy-2'-(l-methylethyl)-5'-(phenylmethyl)crgotaman-3',6',l8-tnone monomesylate RN: 24730-10-7 MF: C3sf14,NSOs - CH403S MW: 707.85 EINECS: 246-434-6 LD5,,: 70 mgkg (M, i.v.); >2500 mglkg (M, p.0.); 91 mglkg (R, i.v.); 2643 mglkg (R, p.0.); >50 mglkg (dog, i.v.); >I250 mglkg (dog, p.0.) constituent of dihydroergotoxine (q. v.) ergocrisiine Referencers): Stoll, A.; Hofmann, A,: Helv. Chim. Acta (fICACAV) 26, 2070 (1943). Dihydroergocristine combination with pentoxifylline: BE 865 891 (Roussel-Uclaf; appl. 11.4.1978; F-prior. 12.4.1977). Fnrmulation(s): amp. 0.3 mglml; sol. 1 mglml; tabl. 1.5 mg (as mesylate) Trade Name(s): D: Bellaserp (Atmos)-comb.; Panthesin-Hydergin Decril (Damor) wfm (Sandoz)-comb.; wfm Defluina (Teofarma) Briserin (Sandoz)-comb.; Rexiluven (Sandoz)-comb.; Diertina (Poli) wfm wfm Difluid (Bioprogress) Card-Hydergin (Sandoz)- comb.; wfrn Decme (Spitzner); wfrn Decme (Zy ma); wfm Defluina (Natrapharm)- comb.; wfrn Enirant Tropflosung (Dcsitin); wfm Nehydrin (TAD); wfrn Sinedyston (Steiner); wfm Ergo (Foletto) Vertebran N (Rentschler); Ergotina (1st. Chim. Inter.) wfm Gral (Boniscontro & Wallerox (Sandoz); wfm Gazzone) F: Cervilanc (Cassenne)- Sandoven (Sandoz)-comb. comb. Unergol (Poli) IskCdyl (Pierre Fabre; as mesy1ate)-comb. I: Brinerdina (Sandoz)-comb. Dihydroergotamine D 649 * Dihydroergotamine ATC: N02CAOI Use: sympatholytic, antimigraine agent RN: 511-12-6 MF: C,,H,,N505 MW: 583.69 EINECS: 208-123-3 LDN: 1 18 mgkg (M, i.v.) CN: (5'a,10a)-9,10-dihydro-l2'-hydroxy-2'-methyl-5'-(phenylmethyl)ergotaman-3',6',18-trione monomesylate RN: 6190-39-2 MF: C33H37N50s. CH403S MW: 679.80 EINECS: 228-235-6 LD,,: >2 gkg (M, p.0.); >2 gkg (R, p.4 tartrate (2:l) RN: 5989-77-5 MF: C3,H3,N5Oy l/2C4H606 MW: 131 7.46 EINECS: 227-8 16-1 LD,: 118 mgkg (M, i.v.); 110 mgkg (R, i.v.) ergotarnine Dihydroergotarnine Stoll, A,; Hoffmann, A.: Helv. Chim. Acta (HCACAV) 26,2070 (1943). DE 883 153 (Sandoz; appl. 1941; CH-prior. 1940). naral formulation: DOS 2 802 113 (Sandoz; appl. 19.1.1978). Formulation(s): amp. 1 mg, 2 mg; s. r. cps. 2.5 mg; 5.0 mg; tabl. 1 mg, 2.5 mg (as mesylate) Trade Name(s): D: Agit (Sanofi Winthrop) Agit (Sanofi Winthrop)- comb. Angionorm (Faimasan) clavigrenin (Hormosan) DET-MS (Rentschler) DHE-Puren (Isis Puren) Dihydergot-fortelretard (Novartis Pharma) Dihydergot-plus (Novartis Pharma)-comb. Dihytamin (ASTA Medica AWD) Effortil (Boehringer 1ng.)- comb. Embolex (Novartis Pharma)-comb. Ergo-Lonarid (Boehringer 1ng.)-comb. Ergomimet (Klinge) Ergont (Desitin) ergotam (ct-Arzneimittel) Optalidon (Novartis Pharma) Tonopres-forte (Boehringer Ing.) Venelbin (Hoechst)-comb. Verladyn (Verla) F: Ikaran (Pierre Fabre; as mesylate) SCglor (Sanofi Winthrop; as mesylate) Tamik (EG Labo; as mesylate) GB: Dihydergot (Sandoz); wfm I: Diidergot (Sandoz) Ikaran (Formenti) Seglor (Synthelabo) J: Dihydergot (Sandoz- Sankyo) USA: DHE 45 (Novartis) 650 D Dihydroergotoxine Dihydroergotoxine ATC: CO~AE (Dihydroergocornine Dihydro-a-ergocryptine) Use: sympatholytic, cognition adjuvant RN: 11032-41-0 MF: unspecified MW: unspecified LD,,: 71 mgkg (M, s.c.) CN: dihydroergotoxine mesy late RN: 8067-24- 1 MF: unspecified MW: unspecified "ergotoxine" (ergocornine + ergacristine + ergocryptine A 1:l:l) "Dihydroergotoxine' Reference(s): Stoll, A.; Hofmann, A,: Helv. Chim. Acta (HCACAV) 26, 2070 (1943). DE 883 153 (Sandoz; appl. 1941; CH-prior. 1940). nasal formulation: DOS 2 802 113 (Sandoz; appl. 19.1.1978). Formulation(s): amp. 0.3 mglml, 1.5 mgI5 ml; sol. 1 mglml, 2 mglml; tabl. 2 mg Trade Nume(s): D: Circanol (3M Medica) Dacoren (Nattermann) DCCK (Rentschler) Defluina (Nattermann) Enirant (gepepharm) Ergodesit (Desitin) ergoplus (Hormosan) ergotux (ct-Arzneimittel) Hydergid-forte (Novartis Pharma) Hydro-Cebral-ratiopharm (ratiopharm) Nehydrin (TAD) Orphol (Opfermann) Sponsin (Farmasan) F: Capergyl (ThCrica) Ergodose (Murat; as mesylate) Hydergine (Novartis; as mesylate) Optamine (ThCraplix) PCrtnan (Sanofi Winthrop) GB: Hydergine (Novartis) I: Coristin (San Carlo) Hydergina (Sandoz) Ischelium (Polifarma) Ischelium Papaverina (Po1ifarma)-comb. with papaverine hydrochloride Progeril (Midy) Progeril Papaverina (Midy)-comb, with papaverine Trelidat (Coop. Farm.) Visergil (Sandoz)-comb. J: Hydergine (Sandoz- Sankyo) USA: Circanol (Riker); wfm Deapril (Mead Johnson); wfm Hydergine (Sandoz); wfrn Hydro-Ergoloid (Schein); wfm Hydro-Ergot (Interstate); wfrn . 7 1-6 3-6 MF: C4,HMOI3 MW: 764.95 EINECS: 20 0-7 6 0-5 LD,,: 0.18 mglkg (cat, p.0.) CN: (3~,5~ )-3 -[ ( 0-2 ,6-dideoxy-~-ribo-hexopyranosy-(l+4 )-0 -2 ,6-dideoxy- ~-~ -ribo-hexopyranosyl- (l-t4 )-2 ,6-dideoxy- ~-~ -ribo-hexopyranosyl)oxy ]-1 4-hydroxycard-20(22)-enolide. (3~,5~,12~ )-3 -[ ( 0-2 ,6-dideoxy- ~-~ -ribo-hexopyranosy 1-( 1~4 )-0 -2 ,6-dideox ~-~ -~ -ribo-hexo~~ranos~l- (14 )-2 ,6-dideoxy- ~-~ -ribo-hexopyranosyl)oxy ]-1 2,14-dihydroxycard-20(22)-enolide @ from Digitalis lonata. 24 1-4 9 3-4 CN: (5'a,lOa )-9 ,I0-dihydro-l2'-hydroxy-2&apos ;-( l-methylethyl )-5 &apos ;-( phenylmethyl)crgotaman-3',6',l8-tnone monomesylate RN: 2473 0-1 0-7 MF: C3sf14,NSOs - CH403S