Diacerein D 621 synthesis of 1-methyl-7-methoxy-2-tetralone: Howele, EH.; Taylor, D.A.H.: J. Chem. Soc. (JCSOA9) 1958, 1248. pharmaceutical formulations: US 4 605 671 (American Home; 12.8.1986; appl. 23.7.1985; prior. 28.9.1984). WO 9 000 390 (American Home; appl. 19.6.1989; S-prior. 8.7.1988). EP 180 303 (American Home; appl. 27.8.1985; USA-prior. 28.9.1984, 23.7.1985). Formulation(s): vial and Tubex syringe 5 mg/2 ml, 10 mg/2 ml, 15 mg/2 ml Trade Name(s): USA: Dalgan (Wyeth-Ayerst; 1990) Diacerein ATC: MOIAX21 Use: anti-inflammatory RN: 13739-02-1 MF: CI,H,208 MW: 368.30 EINECS: 237-310-2 LD,o: 7500 mglkg (R, route unreported) CN: 4,5-bis(acetyloxy)-9,10-d~hydro-9,1O-dioxo-2-anthracenecarboxylic acid 1,8-dihydroxy-3- 1 ,a-dihydroxy-3- hydmxyrnethyl- onthroquinone- anthroquinone carboxylic acid (e.g. from borboloin) Diacerein DOS 2 71 1 493 (C. A. Friedmann; appl. 16.3.1977; SA-prior. 16.3.1976). Oesterle, O.A.: ~rih. Pharm. (Weinheim, Ger.) (ARPMAS) 241, 604 (1903). Robinson, R.; Simonsen, J.L.: J. Chem. Soc. (JCSOA9) 1909, 1085. Cahn, R.S.; Simonsen, J.L.: J. Chem. Soc. (JCSOA9) 1932, 2573. Formulation(sJ: cps. 50 mg Trade Name(& 1: Artrodar (Proter) Fisiodar (Gentili) Diazepam ATC: NOSBAO1 Use: tranquilizer, hypnotic RN: 439-14-5 MF: C,,H,,ClN,O MW: 284.75 EINECS: 207-122-5 CN: 7-chloro-1,3-dihydro-l-methyl-5-phenyl-2H-l,4-benzodiazepin-2-one 622 D Diazepam 2-amino-5- glycine ethyl ester 7-chlaro-2-0x0- chlorobenzo- hydrochloride (11) 5-phenyl-2,3-di- phenone (I) hydra-1 H-1.4- benzodiazepine NaOCH, dimethyl sulfate (111) p-toluenesulfonyl chloride (Tos-CI) benzophenone (N) H3C CI hexomethylenetetrarnine + cl<cl \ chloroocetyl chloride NaN02, HCI C I CI ethyl a-benzyl- ocetoacetate 4-chlorobenzene- diazonium chloride 7H3 7'43 In TO To NH3 %zH2 v 4 CI +CI\ / \ CH~ 07 - Cl - / \ CH3 / \ - - ethyl 5-chloro- ('a 3-phenylindole- Diazepam D 623 olonote oxide [Alternatively to the Japp-Klingemann reaction phenylpyruvic acid or ethyl phenylpyruvatc can be condensed with 4-chlorophenylhydrazine.] Referencefs): a,bUS 3 109 843 (Hoffmann-La Roche; 5.1 1.1963; appl. 21.6.1962; prior. 28.7.1961 ) US 3 136 815 (Hoffmann-La Roche, 9.6.1964; USA-prior. 10.12.1959). DE 1 136 709 (Hoffmann-La Roche; appl. 7.12.1960; USA-prior. 10.12.1959). DE 1 145 626 (Hoffmann-La Roche; appl. 7.12.1960; USA Prior. 10.12.1959). DE 1 290 143 (Hoifmann-La Roche; prior. 7.12.1960). US 3 371 085 (Roche; 27.2.1968; CH-prior. 2.10.1960). c DAS 2 016 084 (Hoffmann-La Roche; appl. 3.4.1970; CH-prior. 16.10.1969). DOS 2 233 482 (Hoffmann-La Roche; appl. 7.7.1972; GB-prior. 8.7.1971). d Yamamoto, H. et al.: Chem. Ber. (CHBEAM) 101,4245 (1968). US 3 632573 (Sumitomo; 4.1.1972; J-prior. 9.10.1967). variant with a-benzylcyanoacetic acid ester: US 4 069 230 (Surnitomo; 17.1.1978; J-prior. 4.6.1975, 9.6.1975). alternative syntheses: DAS 1 545 724 (Delmar Chemicals; appl. 14.1.1965; GB-prior. 14.1.1964). DAS 1 695 789 (Sumitomo; appl. 2.1 1.1967; J-prior. 2.1 1.1966, 16.1 1.1966, 6.9.1967). DAS 1 944 404 (Takeda; appl. 2.9.1969; J-prior. 3.9.1968). DOS 2 252 378 (Roche; appl. 25.10.1972; CH-prior. 18.1 1.1971 ). Sugasawa, T. et al.: J. Heterocycl. Chem. (JHTCAD) 16,445 (1979). purificalion: US 3 102 116 (Hoffmann-La Rochc; 27.8.1963; prior. 12.3.1962). DAS 1 906 262 (Sumitomo; appl. 7.2.1969; J-prior. 21.2.1968). Fomulofion(s): amp. (i.v. or i.m.) 10 mg/2 ml; tabl. 2 mg, 5 mg, 10 mg Dade Namefs): D: Faustan (ASTA Medica AWD) Lamra (Merckle) Stesolid (Dumex) Tranquase (Azuchemie) Valiquid (Roche; 1985) Valium (Roche; 1963) F: Novazam (Gtntvrier) Valium (Roche) GB: Diazemuls (Dumex) Stesolid (Dumex) Valclair (Sinclalr) Valium (Roche; 1963) I: Aliseum (Zoja) J: Ansiolin (Roussel) Eridan (SIT) Noan (Ravizza) Spasmeridan (UCB)-comb. Spasmomen (Menarini)- comb. USA: Tranquirit (RhGne-Poulenc Rorer) Valium (Roche; 1965) Valpinax (Crinos)-comb. Valtrax (Valeas)-comb. Vatran (Valeas) Cercine (Takeda) Horizon (Yamanouchi) Sedaril (Kodama) Scrcnamin (Toyo Jozo) Serenzin (Sumitomo; 1968) Sonacon (Chugai) Diastat (Athena) Dizac (Ohmeda) Valium (Roche Products; 1963) Valrelease (Roche) 624 D Diazoxide Diazoxide ATC: C02DAO1; V03AHO1 Use: antihypertensive, hyperglycemic RN: 364-98-7 MF: C,H7ClN,0,S MW: 230.68 EINECS: 206-668- 1 LDsn: 228 mg/kg (M, i.v.); 444 mglkg (M, p.0.); 980 mglkg (R, p.0.) CN: 7-chloro-3-methyl-2H-1,2,4-benzothiadiazine 1,l-dioxide 0 \'pH2 02H" "a \A + H,C-40 , _+ 0, CH3 NH2 '33 5-chloro-2- triethyl Diazoxide arninobenzene- orthoacetote sulfarnide Reference(s1: US 2 986 573 (Schering Corp.; 30.5.1961; prior. 18.1.1961). US 3 345 365 (Schering Corp.; 3.10.1967; prior. 19.9.1960, 18.1.196.1, 31.3.1964). Farmulation(s): amp. 300 mgl20 ml (i.v. inj.); cps. 25 mg, 100 mg Trade Name(s): D: Hypertonalum (Essex Proglicem (Schering- Proglicem (Schering- Pharma) Plough) Plough) Proglicem (Essex Pharma) GB: Eudemine (Fink) USA: Hyperstat (Schering) F: Hyperstat (Schering- I. Hyperstat (Schering- Proglycem (Baker Norton) Plough) Plough) Dibekacin ATC: JOIGR09; JOlKD Use: aminoglycoside antibiotic RN: 34493-98-6 MF: C18H3,N508 MW: 451.52 EINECS: 252-064-6 LD,,: 373-380 mgkg (M, i.p.); 61-68 mdkg (M, i.v.) CN: 0-3-amino-3-deoxy-a-~-g~ucopyranosy~-(l+6)-0-[2,6-diamino-~,3,4,6-tetradeoxy-a-~-erythro- hexopyranosyl-(I +4)]-2-deoxy-D-slreptamine sulfate RN: 58580-55-5 MF: C1RH37NSOll . xH2S04 MW: unspecified EINECS: 261-341-0 LD,,: 62.6 mgkg (M, i.v.); >6950 mgkg (M, p.0.); 140 mglkg (R, i.v.); 6950 mg/kg (R, p.0.) Dibekacin D 625 0 1. cI-R. H,cKcH,. K2c03 HO 2. H,C, ?,CH~ ns02H* 0 0 (1) . H,C 3. dr: -idin. 1 ethyl chloroFormate 2. 2,2-dimethoxypropane 3. benzoyl chloride NH2 HN-R H bekanamycin (4. 4 0 II + 3 methanesulfonyl chloride H3C- 1 Dibekacin 1. Nal, Zn. DMF 2. H,. Pt 3. CH,COOH, H20 4. BO(OH) 2 DE 2 135 191 (Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai; appl. 14.7.1971; J-prior. 29.7.1970, 1 1 S.1971). Umezawa, S. et al.: Bull. Chem. Soc. Jpn. (BCSJA8) 45, 3624 (1972). Umezawa, H. et al.: J. Antibiot. (JANTAJ) 24,485 (1971). alternative syntheses: DOS 2414 416 (Hoechst; appl. 26.3.1974). DOS 2 654 764 (Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai; appl. 3.12.1976; J-prior. 10.12.1975,9.12.1975). DOS 2 655 731 (Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai; appl. 9.12.1976; J-prior. 11.12.1975). DOS 2 756 057 (Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai; appl. 15.12.1977; J-prior. 16.12.1976). US 4 169 939 (Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai; 2.10.1979, J-prior. 16.12.1976). Migake, T. et al.: Carbohydr. Res. (CRBRAT) 49, 141 (1 976). Fomulrrtion(s)r amp. 50 rng/rnl, 75 mg/ 1.5 ml 626 D Dibenzepine Trade Name(s): D: Orbicin (Mack); wfrn I: Icacine (Bristol); wfrn J: Panirnycin (Meiji Seika F: Dtbtkacyl (Bellon; as Kappabi (Carlo Erba); wfrn Kaisha) sulfate) Dibenzepine ATC: N06AA08 Use: antidepressant RN: 4498-32-2 MF: C,,H,,N,O MW: 295.39 LD,,,: 22 mgkg (M, i.v.); 194 rngkg (M, p.0.); 22 mgkg (R, i.v.); 220 mag (R, p.0.) CN: 10-[2-(dimethylarnino)ethyl]-5,l0-dihydro-5-methyl-1lH-dibenzo[b,e][l,4]diazepin-ll-one monohydrochloride RN: 315-80-0 MF: C18H2,N30. HC1 MW: 331.85 EINECS: 206-255-6 LD,,,: 22 mglkg (M, i.v.); 174 mglkg (M, p.0.); 22 mgkg (R, i.v.); 220 mgkg (R, p.0.) CH3 I CH3 methyl N-methyl- anthranilate CH3 2. 2-(dimethylomino)- ethyl chloride 11 -om-5-methyl- 10.1 1 -dihydro-5H- dibenza[b.e][l.4]- diozepine Dibenzepine Referencefs): DE 1 263 774 (Wander; appl. 13.9.1960; CH-prior. 22.9.1959), US 3 41 9 547 (Wander; 3 171 2.1968; ~~-~rior. 22.9.1959). GB 961 106 (Wander; appl. 22.9.1960; CH-prior. 22.9.1959). FR 1 295 37 1 (Wander; appl. 20.9.1960; CH-prior. 22.9.1959). Hunziker, F. et al.: Arzneirn Forsch. (ARZNAD) 13, 324 (1963). Formulation(s): amp. 20 rnglrnl; drg. 40 mg, 80 mg; s. r. tabl. 240 mg; tabl. 80 mg Trade Name(s): D: Noveril (Novartis Pharrna); Noveril (Sandoz); wfrn J: Noveril (Morishita) wfm GB: Noveril (Wander); wfrn F: Ecatril (Sandoz); wfm I: Noveril (Sandoz) Dibrompropamidine D 627 Dibrompropamidine ATC: D08ACOl; SOlAX14 Use: chemotherapeutic RN: 496-00-4 MF: Cl7HIRBr2N4o2 MW: 470.17 CN: 4,4'-[1,3-propanediylbis(oxy)]bis[3-bromobenzenecarbox1midamide] dlisethionate (1:Z) RN: 614-87-9 MF: C17H,,Br2N402 . 2C2H,04S MW: 722.43 EINECS: 210-399-5 OH + Br-Br - NC CN 1,3-dibrorno- (1) propane NH N H Dibrornpropomidine GB 598 91 1 (May & Baker; appl. 1945). nulation(s): eye drops 0.1 %; eyc ointment 0.15 % B: Brolene (May & Baker) Golden Eye Ointment Phenergan (May & Baker; Bmlidine (May & Baker) (Typharm) as isethionate)-comb. Otamidyl (May &Baker) ATC: D07AA Use: topical glucocorticoid RN: 7008-26-6 MF: C2,H2&l2o4 MW: 413.34 EINECS: 230-283-8 CN: (1 1 P)-9,ll-dichloro-17,21 -dihydroxypregna-l,4-d1ene-3,20-dionc acetate !i RN: 79-61-8 MF: C2,H2,Cl,05 MW: 455.38 EINECS: 201-213-3 f 0 H,C-SO2-CI, pyridine, DMF 628 D Dichlorophen dichlorisone acetate Dichlorisone Reference(s): US 2 894 963 (Schering Corp.; 1959; prior. 1958). Robinson, C.H. et a].: J. Am. Chem. Soc. (JACSAT) 81,2191 (1959). Formulation(s): cream 0.25 % Trade Name(s): I: Astroderm (Lagap); wfrn J: Diloderm Cream (Schering-Shionogi) Neo-Diloderm Cream (Schering-Shionogi)-coml Dichlorophen ATC: P02DX Use: antifungal, antiseptic, anthelmintic RN: 97-23-4 MF: Cl3H,,,C1,0, MW: 269.13 EINECS: 202-567-1 LDso: 1 glkg (M, p.0.); 17 mglkg (R, i.v.); 1506 mglkg (R, p.0.); 2 glkg (dog, p.o.1 CN: 2,2'-methylenebis(4-chlorophenol) 4-chloro- form- phenol oldehyde Dichlorophen I Reference(s): DRP 530 219 (I. G. Farben; appl. 1927). GB 1 208 325 (BDH; appl. 22.4.1968; valid from 15.4.1969). US 2 334 408 (B.T. Bush; 1943; appl. 1941). DAS 2 551 498 (Bayer; appl. 17.1 1.1975). Formulation(s): cream 10 mg; powder 50 mg; sol. 10 mg; spray 10 mg Trade Name(s): D: Fissan Brustwarzensalbe Ovis FuRbad/Spray GB: Anthiphen (May & Baker); (Fink)-comb.; wfm (Warner); wfm wfm Onychofissan (Fink)- Wespuril (Spitzner)-comb.; comb.; wfm wfm Ovis Fliissigkeithalbe F: Plath-Lyse (GCntvrier); (Warner)-comb.; wfm wfm Diclofenac D 629 Diclofenac ATC: M01AB05; M02AA15; S01BC03 Use: anti-inflammatory, antirheumatic RN: 15307-86-5 MF: C,,HI1CI2NO2 MW: 296.15 EINECS: 239-348-5 LD,: 170 mglkg (M, p.0.); 62.5 mgkg (R, p.0.) , CN: 2-[(2,6-dichlorophenyl)amino]benzeneacetic acid osodium salt : 15307-79-6 MF: C,,HloC12NNa0, MW: 318.14 EINECS: 239-346-4 ,: 116 mgkg (M, i.v.); 390 mgkg (M, p.0.); 117 mgkg (R, i.v.); 150 mg/kg (R, p.0.) -chlom- 2.6-dichloro- 2-(2,6-dichloro- bnzoic aniline anilino)benzoic acid (I) 2,6-dichloro- diphenylomine 690 (Geigy; 26.1.1971; CH-prior. 8.4.1965, 25.2.1966, 30.3.1966,20.12.1967). 3 639 (Ciba-Geigy; appl. 7.4.1966; CH-prior. 8.4.1965). DAS 1793 592 (Ciba-Geigy; appl. 7.4.1966; CH-prior. 8.4.1965). 3 652 762 (Ciba-Geigy; 28.3.1972; prior. 9.12.1968, 29.9.1969, 14.4.1970). 3 778 470(Geigy; 11.12.1973; appl. 2.10.1970; prior. 4.4.1966). 492 679 (Geigy; appl. 30.3.1966). 630 D Diclofenamide alternative syntltesis: DOS 2 613 838 (Ikcda Mohando; appl. 3 1.3.1976; J-prior. 3 1.3.1 975) Formulation(s): amp. 75 mg; cps. and drg. 25 mg, 50 mg, 100 mg, 140 mg; eye drops 1 mg, 0.3 mg, 5 mgI5 ml; gel 1 1.6 mg, 1 %; inj. sol. 75 mg/3 ml; suppos. 12.5 mg, 25 mg, 50 mg, 100 rng; tabl. 25 mg, 50 mg, 75 mg Trade Name(s): D: Allvoran (TAD) arthrex (BASF Generics) Benfofen (Sanofi Winthrop) Delphimix (Cy anamid) Delphinac (Lederle) Diclac (Hcxal) dido (ct-Arzneimittel) Diclofenbeta (betapharm) Diclo KD (Kade) Diclophlogont (Azupharma) Diclo-Phlogont (Azuchemie) Diclo-Puren (Isis Puren) Diclo-rectal (Beiersdorf) Diclo-saar (Chephasaar) F: Diclo-Spondyril (Dorsch) Diclo-Tablinen (Beiersdorf- Dolgit-Diclo (Dolorgict) 1: Dolobasan (Sagitta) Duravolten (durachemie) Effekton (Brenner-Efekd Law) Jenafenac (Jenapharm) Lexobene (Merckle) Monoflam (Lichtenstein) J: Myogit (Pfleger) Rehumavincin (Owege) Rcwodina (ASTA Medica AW D) Sigafenac (Kytta-Siegfried) Toryxil (Baer) Voltaren (Novartis Pharma; 1976) Flector (Gtntvrier) Voltartne (Novartis; 1976) USA: Xenid (Biogaltnique) Tablinen) GB: Voltarol (Novartis; 1979) Diclo-Wolff (Wolff) numerous generics Dicloreum (Alfa Wassermann) Flogofenac (Ecobi) ~orgenac (Zoja) Novapirina (Zyma) Voltaren (Ciba-Geigy; 1975) Adefuronic (Taiyo) Dichronic (San-a) Docell (Nippon Kayaku) Irinatolon (Tatumi) Neriodin (Teikoku) Nifleriel (Mohan) Sofarin (Nippon Chemiphar) Tsudohmin (Toho) Voltaren (Fujisawa; 1974) Voltaren (Novartis; as sodium salt) Diclofenamide (Dichlorphenamide) ATC: SOIEC02 Use: carboanhydrase inh~bitor (against glaucon~a) RN: 120-97-8 MF: C6H6C12N204S2 MW: 305.16 EINECS: 204-440-6 LDso: 643 mglkg (M, i.v.); 1710 mgkg (M, p.0.) CN: 4,5-dichloro- l,3-benzenedisulfonamide 2-chloro- phenol Reference(s1: US 2 835 702 (Merck & Co.; 20.5.1958; prior. 2.5.1956). Diclofenarnide Formulation(s): tabl. 50 mg Trade Name(sJ: . 43 9-1 4-5 MF: C,,H,,ClN,O MW: 284.75 EINECS: 20 7-1 2 2-5 CN: 7-chloro-1,3-dihydro-l-methyl-5-phenyl-2H-l,4-benzodiazepin-2-one 622 D Diazepam 2-amino- 5- glycine ethyl ester 7-chlaro- 2-0 x 0-. 3449 3-9 8-6 MF: C18H3,N508 MW: 451.52 EINECS: 25 2-0 6 4-6 LD,,: 37 3-3 80 mgkg (M, i.p.); 6 1-6 8 mdkg (M, i.v.) CN: 0-3 -amino-3-deoxy-a-~-g~ucopyranosy ~-( l+6 )-0 -[ 2,6-diamino-~,3,4,6-tetradeoxy-a-~-erythro-. unreported) CN: 4,5-bis(acetyloxy )-9 ,10-d~hydro-9,1O-dioxo-2-anthracenecarboxylic acid 1,8-dihydroxy- 3- 1 ,a-dihydroxy- 3- hydmxyrnethyl- onthroquinone- anthroquinone carboxylic acid (e.g.