Dexchlorpheniramine D 61 1 rocemotc resolution w~th 0-phenylsuccinlc acid I CH3 (f)-bmmphenirornine (q. v.) Reference (s): US 3 030 371 (L. A. Walter; 17.4.1962; appl. 1958). US 3 061 517 (Schering Corp.; 30.10.1962; prior. 16.2.1962). Formulation(s): tabl. 2 mg Trade Name(s): USA: Disobrom (Geneva) Dexchlorpheniramine ATC: R06AB02 Use: antihistaminic RN: 25523-97-1 MF: C,,H19C1N2 MW: 274.80 EINECS: 247-073-7 CN: (S)-y-(4-chlorophenyI)-N,N-dimethyl-2-pyridinepropanamine maleate (1:l) RN: 2438-32-6 MF: CI,H,,ClN2. C4H404 MW: 390.87 EINECS: 219-450-6 LD,: 28 mg/kg (M, i.v.); 189 mglkg (M, p.0.); 267 mglkg (R, p.0.) chlorphenarnine (q. v.) Dexchlorpheniramine GB 834 984 (Scherico; appl. 4.7.1958; USA-prior. 4.3.1958). US 3 030 371 (L. H. Walter; 17.4.1962; appl. 4.3.1958). US 3 061 517 (Schering Corp.; 30.10.1962; prior. 16.2.1962). Formulation(s): drg. 6 mg; tabl. 2 mg Trade Name(s): D: Celestamine (Essex)-comb. Polaramine (Schering- Polaronil (B yk Essex) Plough; as maleate) F: Celestamine (Schering- I: Polaramin (Schering- Plough; as meleate) Plough) J: Polaramine (Schering- Shionogi) USA: Baylarmine (Bay); wfm 612 D Dexfenfluramine Dexchlor Repeat Action Poladex (T.D.); wfm Polaramine (Schering); (Schein); wfm wfm 1 1 I i 1 ! Dexfenfluramine ATC: A08AA04 Use: antiobesity, S-enantiomer of fenfluramine RN: 3239-44-9 MF: C,,H,,F,N MW: 231.26 LD,,: 1 15 mg/kg (R, p.0.) CN: (S)-N-ethyl-a-methyl-3-(trifluoromethyl)benzeneethanamine hydrochloride RN: 3239-45-0 MF: CI,H,,F3N . HCI MW: 267.72 EINECS: 221-806-0 1. racemate resolution with: Ga,CO% fenfluramine (rocemote) H3C CH3 I. crystallization C H 2. NaOH HOOC~lI.&,,,C~oH Dexfenfluramine DE 1 293 774 (Sience-Union et Cie., Soc. Franq. de Recherche MCdicale; appl. 22.6.1965; USA-prior. 27.7.1964). GB 1 078 186 (Sience-Union et Cie., Soc. Franq. de Recherche MCdicale; appl. 16.6.1965; USA-prior. 27.7.1964). medical use as antidepressant: EP 2 531 146 (R. J. Wurtman et al.; USA-prior. 16.6.1987). medical use for intermittent carbohydrate craving: EP 53 175 (J. R.Wurtman et al.; appl. 15.6.1981; USA-prior. 16.6.1980). Formulation(s): cps. 15 mg Trade Name(s): D: Isomeride (as GB: Adifax (Servier; 1990 as Isomeride (Servier; 1990 as hydrochloride); wfm hydrochloride); wfm hydrochloride) F: Isomeride (Ardix; as I: Glypolix (Servier; as USA: Redux (Wyeth-Ayerst) hydrochloride); wfm hydrochloride) Dexketoprofen trometamol D 61 3 i Dexketoprofen trometamol ((S)-(+)-Ketoprofen; LM- 1 158 as acid) ATC: MOlAE17 Use: analgesic, anti-inflammatory RN: 156604-79-4 MF: C16H1403 . C4HllN03 MW: 375.42 CN: (S)-3-benzoyl-a-methylbenzeneacetic acid compd. with 2-amino-2-(hydroxymethy1)-1,3-propanediol (1:l) dexketoprofen RN: 22161-81-5 MF: CI6Hl4O3 MW: 254.29 1 C2H50H, H+ 2. enzymatic hydrolysis of (S)-ester with esterose from ophiostoma or ceratocystls b (i)-ketoprofen (q. v.) (S)-ketoprofen (I) Dexketoprofen trometomol Reference(s): WO 9 41 1 332 (Lab. Menarini; appl. 9.1 1.1993; E-prior. 10.1 1.1992). WO 9 420 449 (DompC Farmac.; appl. 7.3.1994; I-prior. 9.3.1993). enantio-selective synthesis of (+)-(S)-2-(3-benzoy1phenyl)propionic acid: Fadel, A.: Synlett. (SYNLES) 1,48 (1992). stereoselective hydrolysis of ketoprofene esters using esterase: US 5 912 164 (~ab. Menark; app1.~9.5. 1997; GB-prior. 3.3.1993; 3.3.1994; USA-prior. 3 1.8.1995; 5.9.1995). WO 9 420 633 (Lab. Menarini; appl. 9.5.1997; GB-prior. 3.3.1993; 3.3.1994; USA-prior. 3 1.8.1995; 5.9.1995). WO 9 304 189 (Lab. Menarini; appl. 19.8.1992; GB-prior. 22.8.1991). Hernaiz, M.J.: J. Mol. Catal. A: Chem. (JMCCF2) 96 (3), 317 (1995). Garcia, M.: Biotechnol. Lett. (BILED3) 19 (lo), 999 (1997). WO 9 015 146 (RhBne-Poulenc; appl. 1.6.1990; USA-prior. 5.6.1989). Formulation(s): ' tabl. 12.5 mg, 25 mg Trade Name(s): D: Enantyum (Lab. Menarini; 1998) Dexpanthenol (Pantothenyl alcohol; Panthenol) ATC: A1 lHA30; D03AX03; SOlXA12 Use: growth factor, wound remedy RN: 81-13-0 MF: C9Hl,N0, MW: 205.25 EINECS: 201-327-3 LDS& 7 glkg (M, i.v.); 15 glkg (M, p.0.) CN: (R)-2,4-dihydroxy-N-(3-hydroxypropyl)-3,3-dimethylbutanamide 614 D Dexrazoxane 3-amino-1 - propanol Dexpanthenal butonolide Reference(s): US 2 4 13 077 (Roche; 1946; CH-prior. 1942). use as aerusol: DAS 2 531 260 (Desitin-Werke; appl. 12.7.1975). Fornlulation(s): amp. 500 mg; emulsion 50 mg; eye and nasal ointment 50 mg; inj. sol. 500 mgl2 ml; nasal spray 50 mg; ointment 5 %, 50 mg; sol. 50 mg; tabl. 100 mg Trade Name(sj: D: Bepanthen Roche (Roche) Corveregel (Mann) Cutemol (Medopharm) Dexpanthenol Heumann (Heumann) Marolderm (Dermapharm) Pan-Ophthal (Winzer) Panthenol Drobena (Drobena) Pelina (MIP Pharma) Ucee (Merck Produkte) Urupan (Merckle) generics F: Alvityl (Solvay Pharma)- comb. BCcozyme injkctable (Roche)-comb. Bepanthene (Roche) Cernevit (Clintec Nutrition C1inique)-comb. Hydrosol polyvitamini (Roche)-comb. 1: Bcpanten (Roche) Pantenolo(Formulario Naz.) J: Pantene (Shionogi) Pant01 (Toa Eiyo- Yamanouchi) USA: Ilopan (Savage) - Ilopan-Choline (Savage) Dexrazoxane (ICRF- 187) ATC: V03AB; V03AF02 Use: antineoplastic, protectant of anthracycline induced cardiotoxicity, (+)-enantiomer of razoxane (q. v.) RN: 24584-09-6 MF: CllHl6N4O4 MW: 268.27 CN: (S)-4,4'-(l-methyl-1,2-ethanediyl)bis[2,6-piperazinedione] (S)-1.2-propane- paraform diomine aldehyde Dexrazoxane I (S)-N,N,N'.NC-tetrakis- (cyonornethy1)-1,2- proponediomine (I) Reference(s): EP 330 381 (Erbamont; appl. 17.2.1989; USA-prior. 17.2.1988) [ alternative synthesis: EP 2 845 594 (Monsanto; appl. 22.3.1988; USA-prior. 23.3.1987). i DE 1910 283 (National Research Development Corp.; appl. 28.2.1969; USA-pnor. 2.7.1968). GB 1 234 935 (National Research Development Corp.; appl. 3.7.1967). Fonnulation(s): lyo. for inf. 500 mg Trade Name(s): I: Cardioxane (Eurocetus) IJSA: Zinecard (Pharmac~a & Eucardion (DompC Biotec) Upjohn) Dextromethorphan (D-Methorphan) ATC: R05DA09 IJse: antitussive, analgesic RN: 125-71-3 MF: C18H2sN0 MW: 271.40 EINECS: 204-752-2 LD,,: 210 mglkg (M, p.0.); 16.286 mg/kg (R, i.v.); 116 mglkg (R, p.0.) CN: (9a,13a,14a)-3-methoxy-17-methylmorphinan hydrobromide RN: 125-69-9 MF: C,,H2,N0. HBr MW: 352.32 EINECS: 204-750-1 LD,,: 34 mgkg (M, i.v.); 165 mgkg (M, p.0.); 350 mgkg (R, p.0.) hydrobromide monohydrate RN: 6700-34-1 MF: C,,H,,NO . HBr . H,O MW: 370.33 (_+)-3-hydroxy-N- phenyltrimethyl- rnethylrnorphinan ornrnonium chloride (cf. levorphanol synthesis) 1. D-tartaric acid 2. resolution Dextromethorphon (2)-3-rnethoxy-N- rnethylmorphinon (I) Reference(s): US 2 676 177 (Roche; 1954; CH-prior. 1949). Schnider, 0.; Grussner, A,: Helv. Chim. Acta (HCACAV) 34,221 1 (1951) medical use as analgesic: US 4 316 888 (Nelson Research; 23.2.1982; appl. 15.4.1980). US 4 446 140 (Nclson Research; 1.5.1984; prior. 10.12.1981, 29.3.1982). nasal use as antitussive: US 4 454 140 (Roche; 12.6.1984; appl. 7.9.1982). Formulation(s): syrup 5 mg, 6.65 m Trade Natne(s): Dextromoramide Arpha (Fournier Pharma) NeoTussan (Novartis) Robitussin plus (Scheurich)-comb. tuss (Rentschler) Wick (Wick Pharma) Nodex (Brothier; as hydrobromide) Nortussine (Norgine; as hydrobromide)-comb. Tuxium (Galephar; as hydrobromic':) Actifed Compound (Wellcome)-comb.; wfm Actifed Compound Linctus (Wellcome)-comb.; wfm Benafed (Parke Davis)- comb.; wfm Cosylan (Parke Davis); w fm Lotussin (Searle); wfm S yrtussar (Amour); wfm Actifed (Wellcome)-comb. Aricodil (Ma1esci)-comb. Balsatux (Edmond)-comb. Bechilar (Montefarmaco) Benadryl Complex (Parke Davis)-comb. Broncal (SmithKline Beecham)-comb. Bronchenolo Tosse (Midy) Broncobeta (Beta)-comb. Broncodex (Pastor Farina)- comb. Canfodion (Gentili) DextroB Afo (Afom) Euci (Fa1qui)-comb. Fluprim (Roche) Ingro (Farmacologico Milanese)-comb. Iodozan (SmithKline Beecham)-comb. Neoborocillina (Schiapparel1i)-comb. Ozopulmin (Geymonat)- comb. Resyl (Zyma)-comb. Rornilar (Roche)-comb. Sanabronchiol (Kalda) Sedotus Valda (Valda) Torfan (AbbottJ-comb. Valatux (Farmacologico Milanese) Vicks Medinait (Procler & Gamble)-comb. J: Coughcon (Kyowa Yakuhin-Santen) Dextophan (Hishi yama) Hihustan-M (Maruko) Medicon (Shionogi) Methorcon (Kyowa Yakuhin) Oricolon (Dojin) Radeophan (Tokyo Tanabe) Testamin (Toy ama) USA: Anatuss (Merz; as hydrobromidc) Benylm (Warner-Lambelt; as hydrobrom~de) Bromfed-DM (Muro; as hy drobromide) Codimal (Schwarz; as hydrobromide) Diabe-Tuss DM (Paddock; as hydrobromide) Dimetane-DX (Robins; as hydrobrornide) Donatussin (Laser; as hydrobromide) Duratuss DM (UCB; as hydrobromide) Fenesin DM (Dura; as hydrobromide) Muco-Fen (Wakefield; as hydrobrom~de) Poly-Histine DM (Sanofi; as hydrobromide) Safe Tussin (Krarner; as hy drobrornidc) S yn-Rx DM (Medeva; as hydrobromide) Tussar DM (Rhane- Poulenc Rorer; as hydrobromide)-comb, Tussi-Organidin (Wallace; as hydrobromide) Tylenol (McNeil; as hydrobromide) generics Dextromoramide ATC: NO2ACOl Use: analgesic RN: 357-56-2 MF: C2sH3ZN202 MW: 392.54 EINECS: 206-613-1 LD,,: 21 rngkg (M, i.v.); 168 mglkg (M, p.0.); 13 mglkg (R, i.v.); 71.8 mg/kg (R, p.0.) CN: (S)-l-[3-methyl-4-(4-morpholinyl)-1-oxo-2,2-diphenylbutyl]pyrrolidine bitartrate (1:l) RN: 2922-44-3 MF: C25H3zNz02. C4H606 MW: 542.63 EINECS: 220-870-7 LD,,,: 71.8 mgikg (R, p.0.) 1. NoNH, H o$$ + 6 % 2. CI ENp -+ 0 -1 1. sodium omide 6 2. 4-(2-chloropropyl)- rnorpholine diphenylacetyl pyrrolidine diphenylacetic chloride pyrrolidide Dextropropoxyphene D 6 17 racernate resolution with D-tartaric acid . (f)-moromide (I) Dextromoromide BE 544 757 (Janssen; appl. 5.2.1957; NL-prior. 9.2.1956). DE 1 117 126 (Janssen; appl. 5.12.1956; NL-prior. 9.2.1956). GB 822 055 (Janssen; appl. 23.10.1956; NL-prior. 9.2.1956). Formulation(s): suppos. 13.8 mg; tabl. 6.9 mg, 13.8 mg (as bitartrate) hie Name(s): D: Jetrium (Hek); wfm GR: Palfium (B.M. Pharm) F: Palfium (Delalande) I: Narcolo (Lusofarmaco) Dextropropoxyphene ATC: NO~ACO~ (Dextropropoxiphene; a-D-Propoxyphene; Propoxyphene) Use: RN: 469-62-5 MF: C2,H2,N02 MW: 339.48 EINECS: 207-420-5 IDw; 25 mgkg (M, i.v.); 140 mgkg (M, p.0.); 135 mglkg (R, p.0.) 3-4: [S-(R*,S*)]-a-[2-(dimethylamino)-l-methylethyl]-a-phenylbenzeneethanol propanoate (ester) ~ydmchloride W: 1639-60-7 MF: C2,H2,N02. HCI MW: 375.94 EINECS: 216-683-5 Ds: 28 mglkg (M, i.v.); 282 mgkg (M, p.0.); 15 mglkg (R, i.v.); 230 mglkg (R, p.0.) 29 mg!kg (dog, i.v.); 100 mglkg (dog, p.0.) lnpsylate (1:l) monohydrate W: 26570-10-5 MF: C2,H2,N02. C,,H,O,S . H20 MW: 565.73 ,D,: 973 mglkg (M, p.o.1; 485 mglkg (R, p.0.); 990 mglkg (Rf, p.0.) form- dimethyl- aldehyde arnine p-dimethylomino- isobutyrophenone (1) 6 1 R D Dcxtropropoxyphene benzylmagnesium a-(f)-4-dimethylomino- 1.2- chloride (11) diphenyl-3-methyl-2-butanol (111) (75%. crystallizes) along with 15% of the diastereo- meric fl form, which is better soluble ond remains in solution 1. resolution by fractional crystallization of the salts with D-comphorsulfonic acid I resolution by fractional crystallization of the salts with (-)-dibenzoyltartaric acid in acetone I b I Dextropropoxyphene I (-)-8-dimethylomino- isobutyrophenone (V) IV, pyridina V + 11 * H 0 Referencefs): US 2 728 779 (Lilly; 1955; prior. 1952). Pohland, A,; Sullivan, H.R.: J. Am. Chern. Soc. (JACSAT) 75,4458 (1953); 77,3400 (1955). Pohland, A. et a].: J. Org. Chcm. (JOCEAH) 28,2483 (1963). Formulation(s): cps. 150 mg (hydrochloride; s. r. formulation); cps. 65 mg (hydrochloride); tabl. 100 mg (napsylate); susp. 50 mg15 ml (napsylate) Trade Narne(s): D: Develin retard (Godecke) Di-Antalvic (Hoechst GB: Cosalgesic (Lox)-comb. F: Antalvic (Hoechst Houdt; Houdt; as hydrochloride)- Distalgesic (Dista)-comb. as hydrochloride) comb. Doloxene (Lilly) Propofan (Marion Merrel1)- Doloxene Co. (Li1ly)-comt comb. I: Liberen (~isa~harma) Dextrothyroxine D 619 t I combination preparations Darvon-N (Lilly; as USA: Darvocet-N (Lilly; as napsy late) napsylate) Propacet (Teva; as Darvon (Lilly; as napsylate) hydrochloride) Wygesic (Wyeth-Ayerst; as hydrochloride) numerous combination preparations Dextrothyroxine (D-Thyroxine) ATC: ClOAXOl Use: cholesterol depressant, antihyperlipidemic RN: 51-49-0 MF: C1sHll14N04 MW: 776.87 EINECS: 200-102-7 CN: 0-(4-hydroxy-3,5-dilodophenyl)-3,5-diiodo-~-tyrosine sodium salt RN: 137-53-1 MF: C,,H,,J4NNa04 MW: 798.85 EINECS: 205-301-2 CHO 4-methoxyphenol CHO nzsns- 4-hydroxy- Ifochloride 3-iodo-5-nitro- benzoldehyde 0 0 0 CHO N-ocetylglycine ti c '0 'N NoO-CH3 CH30H H3c, a:& O'CH H 2 *H3C\ , Roney-Ni 0 N CH3 H H (W methyl m-acetarnido-3.5-diiodo-4- (4-methoxyphenoxy)cinnamote HCOOH rocemote resolution with brucine in isoproponol v HO N H DL-N-formyl-3.5- diiodothyronine 7 620 D Dezocine D(-)-N-formyl-3,5- D(-)-3,5-diiodothyronine diiodothyronine (V) Reference(s): Nahm, H.; Siedel, W.: Chem. Ber. (CHBEAM) 96, 1 (1963). DE 1 067 826 (Hoechst; appl. 24.12.1955). DE 1 077 673 (Hoechst; appl. 19.8.1958). Formulation(s): tabl. 2 mg Trade Name(s): D: Dynothel (Henning Berlin) Nadrothyron-D (Nadrol) Eulipos (Boehringer F: Biotirmone (Solac); wfm Mannh.) DCbCtrol (Choay); wfm I Dextrothyroxine I USA: Choloxin (Flint); wfm Dezocine (Wy- 16225) ATC: N02AX03 Use: central acting analgesic, mixed opioid agonist antagonist related to pentazocine RN: 53648-55-8 MF: CI,H2,N0 MW: 245.37 LD,,,: 129 mgkg (M, i.m.); 313 mglkg (M, p.0.); 270 mag (R, i.m.); 232 mgkg (R, p.0.) CN: [5R-(5a,l la,13S*)]-13-amino-5,6,7,8,9,10,11,12-octahydro-5-methyl-5,Il-methanobenzocyclodecen-3- 01 NaH perbenzoic 1.5-dibromo- pentone 1 -2-dihydro-6- Ocid 1 -methyl-7- 1-(5-brornopenty1)- methoxy-4- methoxy- 1 -methyl-7-methoxy- methylnaphthalene 2-tetralone 2-tetralone (I) 1. H2. Roney-Ni 2. separation of isomeric I 5a-methyl-3-rnethoxy- 5,6,7,8,9,10,11a,12- octahydro-5.1 1 -methono- benzacyclodecen- 13-one oxirne 1. NOH hydrochlorides 2. NH20H 2. hydraxyl- ornine H Reference (s): BE 776 173 (American Home; appl. 2.12.1971; USA-prior. 4.12.1970). DE 2 159 324 (American Home; appl. 30.11.1971; USA-prior. 3.12.1970). Freed, M.E. et al.: J. Med. Chem. (JMCMAR) 19,560 (1976); 16, 595 (1973). H . la,13S*) ]-1 3-amino-5,6,7,8,9,10,11,12-octahydro-5-methyl-5,Il-methanobenzocyclodecen- 3- 01 NaH perbenzoic 1.5-dibromo- pentone 1 -2 -dihydro- 6- Ocid 1 -methyl- 7- 1-( 5-brornopenty1 )- methoxy- 4- methoxy- 1 -methyl-7-methoxy- methylnaphthalene. 20 0-1 0 2-7 CN: 0-( 4-hydroxy-3,5-dilodophenyl )-3 ,5-diiodo-~-tyrosine sodium salt RN: 13 7-5 3-1 MF: C,,H,,J4NNa04 MW: 798.85 EINECS: 20 5-3 0 1-2 CHO 4-methoxyphenol CHO nzsns- 4-hydroxy-. m-acetarnido-3.5-diiodo- 4- (4-methoxyphenoxy)cinnamote HCOOH rocemote resolution with brucine in isoproponol v HO N H DL-N-formyl-3. 5- diiodothyronine 7 620 D Dezocine D (-) -N-formyl-3,5-