Doxazosin D 71 1 1. sodium amide chlorapyrrolidine diphenyl- acetonitrile PBr3 I phosphorus(l1l) bromide US 3 192 230 (A. H. Robins; 29.6.1965; prior. 9.2.1961). Lunsford, C.D. et al.: J. Med. Chem. (JMCMAR) 7, 302 (1964) Formulation(s): amp. 20 mglml Trade Narne(s): D: Dopram (Brenner); wfm I: Doxapril (Carlo Erba); wfm J: Dopram (Kissei) F: Dopram (Martinet); wfm Doxapril (Farmalabor); USA: Dopram (Robins; as GB: Dopram (Anpharm) w fm hydrochloride) Doxazosin ATC: C02CA04 Use: a,-receptor antagonist, antihypertensive RN: 74191-85-8 MF: C2,H2,N,05 MW: 451.48 LD,,: > 1000 mglkg (M, R, p.0.) CN: 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-[(2,3-dihydro-l,4-benzodioxin-2-yl)carbonyl]piperazine hydrochloride RN: 70918-01-3 MF: C23H2sNsOs . HCl MW: 487.94 mesylate RN: 77883-43-3 MF: C2,HZ5N5O5 . CH,03S MW: 547.59 LD,,: 2935 mglkg (M, p.0.); >5 glkg (R, p.0.); >1 gkg (dog, p.0.) piperazine 1,4-benzodioxan-2- N-(1,4-benzodioxon-2- ylcarbonyl chloride ylcarbony1)piperazine (I) 3 712 D Doxefazepam 4-amino-2-chloro-6,7- dimethoxyquinozoline (cf. prozosine synthesis) Doxozosin DE 2 847 623 (Pfizer; appl. 2.1 1.1978; GB-prior. 5.1 1.1977). US 4 188 390 (Piizer; 12.2.1980; GB-prior. 5.1 1.1977). EP 848 001 (Alfa Chem.; appl. 17.10.1997; I-prior. 13.12.1996). WO 9 935 143 (Knoll; appl. 18.12.1998; D-prior. 6.1.1998) medical use for treatment of atherosclerosis: US 4 758 569 (Pfizer; 19.7.1988; appl. 26.8.1987). osmotic device: US 4 837 11 1 (Alza; 6.6.1989; appl. 21.3.1988). Formulation(s): tabl. 1 mg, 2 mg, 4 mg ~rade Name(s): D: Cardular (Pfizer; 1989 as I: Cardura (Roerig; 1989 as mesy late) mesylate) Diblocin (Astra; 1989 as Dedralen (Lifepharma; mesylate) 1989 as mesylate) J: GB: Cardura (Invicta; 1989 as USA: Cardura (Pfizer; 1990 as mesy late) mesylate) Normothen (Fisons Italchimici; 1989 as mesylate) Cardenalin (Pfizer) Doxefazepam ATC: N05CD12 Use: hypnotic RN: 40762- 15-0 MF: C1,H,,C1FN20, MW: 348.76 LD,,: 274 mglkg (M, i.p.); 1500 mglkg (M, p.0.); 586 mglkg (R, i.p.1; 1500 mgkg (M, p.0.) CN: 7-chloro-5-(2-fluorophenyl)-1,3-dihydro-3-hydroxy-l-(2-hydroxyethyl)-2H-1,4-benzodiazepin-2-one + H C 0 pyridine 3 ~NH~' O HCI b clg 31 H peracetic C~O~~H \ / acid 2-amino-5-chloro- glycine ethyl ester 2'-fluorobenzo- hydrochloride phenone (cl. flunitrozepom synthesis) + HOrvB' Z-bromo- ethanol I Doxefazepam I M-1.4-benzod~azep~n- 2-one )-oxide (I) Referencefs): Wagnone, G.F. et al.: Arzneim Forsch. (ARZNAD) 25,720 (1975). B'DOS 2 338 058 (Schiapparelli; appl. 26.7.1973; E-prior. 28.7.1972). 1 synthesis of 7-chloro- 1.3-dihydro-5-(2-fluoopheny1)-2 14benzodiazepin-one 4-oxide: ? SA 6 802 239 (Hoffmann-La Roche; US A-prior. 21.4.1967, 23.10.1967). 3 Td Namefs): I: Doxans (Schiapparelli Searle); wfm Doxepin ATC: N06AA12 Use: antidepressant, tranquilizer RN: 1668-19-5 MF: C,,H,,NO MW: 279.38 LD5,: 26 mgkg (M, i.v.); 135 mag (M, p.0.); 16 m&g (R, i.v.); 147 mglkg (R, p.0.) CN: 3-dibenz[b,e]oxepin- 1 1 (6H)-ylidene-N,N-dimethyl- 1 -propanamine hydrochloride RN: 1229-29-4 MF: C,,H2,N0 . HCl MW: 315.84 EINECS: 214-966-8 LD,: 15 mgkg (M, i.v.); 180 mgkg (M, p.0.); 13 mgkg (R, i.v.); 147 mag (R, p.0.); ethyl 2-bromo- phenol methylbenzoate (F,C-CO),O b trifluoroacetic 2-phenoxymethyl- anhydride benzoic acid (I) ethyl Z-phenoxy- methylbenzoate -N/CH3 CW I CH3 , 11 3-dimethylaminopropyl- magnesium chloride 11 -om-6,ll- dihydrodibenz- [b,e]oxepin 714 D Doxifluridine 7H3 FH3 HCI Reference(s): US 3 420 851 (Pfizer; 7.1.1969; appl. 19.12.1962; prior. 13.3.1962). DE 1 232 161 (Boehringer Mannh.; appl. 7.10.1961). Formulation(s): amp. 25 mg/2 ml; coloured tabl. 50 mg, 100 mg; drg. 5 mg, 10 mg, 20 mg; drops 10 mg/ml;f c. tabl. 25 mg, 50 mg, 75 mg, 100 mg Trade Name(s): D: Aponal (Boehringer F: Quitaxon (Boehringer . I: Sinequan (Pfizer); wfm Mannh./AWD) Mannh.; as hydrochloride) USA: Sinequan (Pfizer; as Maren (Krewel Sinequan (Pfizer; as hydrochloride) Meuselbach) hydrochloride) Zonalon (GenDerm) Sinquan (Pfizer) GB: Sinequan (Pfizer; as hydrochloride) Doxifluridine (5'-dFUR) ATC: LOlBB Use: antineoplastic, antimetabolite RN: 3094-09-5 MF: C9HIIPNZOS MW. 246.19 EINECS: 221-440-1 LD,,,: >2000 mg/kg (M, i.p.); >1 glkg (M, i.v.); ~5000 mgkg (M, p.0.); >2000 mglkg (R, i.p.); >I glkg (R, i.v.); 3390 mgkg (R, p.o.), 3471 mg/kg (Rm, pa); 3390 mg/kg (Rf, p.0.) CN: 5'-deoxy-5-fluorouridine H phosphonium iodide 0 0 x H3C CH, 5-fluoro- 2.2-dimethoxy- uridine (I) propane Doxofylline D 715 (c,H,-O),P+CH, I- nZ. ~d-c methyltriphenoxy- phosphonium iodide HO OH Referencefs): a,b DOS 2 756 653 (Hoffmann-La Roche; appl. 19.1 2.1977; USA-prior. 20.12.1976). US 4 071 680 (Hoffmann-La Roche; appl. 20.12.1976). Cook, A.F. et al.: J. Med. Chem. (JMCMAR) 22, 1330 (1979). additional synthesis: EP 21 231 (Hoffmann-La Roche; appl. 10.6.1980; CH-prior. 15.6.1979). Hrebabecky, H.; Beranek, J.: Collect. Czech. Chem. Commun. (CCCCAK) 43, 3268 (1978). Kiss, J, et al.: Helv. Chim. Acta (HCACAV) 65, 1522 (1982). Scott, J.W. et al.: J. Carbohydr., Nucleosides, Nucleotides (JCNNAF) 8, 171 (1981). Ajmera, S.; Danenberg, V.: J. Med. Chem. (JMCMAR) 25,999 (1982). Rosowsky, A. et al.: J. Med. Chem. (JMCMAR) 25, 1034 (1982). combination with purine nucleosides or. nucleotides: EP 189 755 (Hoffmann-La Roche; appl. 9.10.1985). Formulation(s): cps. 100 mg, 200 rng Trade Namefs): . J: Furtulon (Nippon Roche; 1987) Doxofylline (ABC-I 213) ATC: R03DA11 Use: antiasthmatic, bronchodilator RN: 69975-86-6 MF: CllHI4N1O4 MW: 266.26 EINECS: 274-239-6 LD,,: 216 mglkg (M, i.v.); 841 mgkg (M, p.0.); 445 mglkg (R, i.p.); 315 rnglkg (R, i.v.); 966 mglkg (R, p.0.) CN: 7-(1,3-dioxolan-2-ylmethy1)-3,7-dihydro- 1,3-dimethyl-1H-purine-2,6-dione 716 D Doxorubicin CH3 '3'3 theophylline 3-chloro-1.2- 7-(2,3-dihydroxy- dihydroxypropane pr0pyl)theophylline HO CH3 theophylline- ethylene Doxofylline 7-acetaldehyde (I) glycol Reference(s): DE 2 827 497 (ABC; appl. 22.6.1978; I-prior. 4.6.1978). US 4 187 308 (ABC; 5.2.1980; I-prior. 4.6.1978). Avico, U. eta].: Farmaco, Ed. Sci. (FRPSAX) 17,73 (1962). synthesis of theophylline-7-acetaldehyde: Maney, P.V.: .I. Am. Pharm. Assoc. (JPHAA3) 35,266 (1946). Toffoli, F. et al.: Farmaco, Ed. Sci. (FRPSAX) 11, 516 (1956). Formularion(s): amp. 100 mg11O ml; cps. 300 mg; sachet 200 mg; s. r. tabl. 300 mg; tabl. 400 mg Trade Namc(s): I: Ansimar (ABC; 1988) Doxorubicin (Adriamycin) ATC: LOlDBOl Use: antineoplastic, antibacterial RN: 23214-92-8 MF: C27H2,N0,1 MW: 543.53 EINECS: 245-495-6 LD,,,: 10 mglkg (M, i.v.); 570 mglkg (M, p.0.); 10.510 mglkg (R, i.v.); 2.4 mglkg (dog, i.v.) CN: (8S-cis)-l0-[(3-amino-2,3,6-trideoxy-a-L-lyxo-hexopyanosyl)oxy]-7,8,9,l0-tetrahydro-6,8,11- trihydroxy-8-(hydroxyacety1)- I-methoxy-5,12-naphthacenedione hydrochloride RN: 25316-40-9 MF: C2,H2,NO,, . HC1 MW: 579.99 EINECS: 246-818-3 LD,,,: 1245 @,/kg (M, i.v.); 698 mgkg (M, p.0.); 12510 pglkg (R, i.v.) I Doxycycline D 717 Doxorubicin L From culture of mutant F. 1. 106 of Streptomyces peucetius va,: caesius. Reference(s): DE 1 770 204 (Soc. Farmaceutici Italia; prior. 13.4.1968). US 3 590 028 (Soc. Farmaceutici Italia; 29.6.1971; appl. 18.4.1968; I-prior. 18.4.1967). GB 1 161 278 (Soc. Farmaceutici Italia; appl. 16.4.1968; I-prior. 18.4.1967). alternative syntheses: partial synthesis from daunorubicin: DOS 1 917 874 (Soc. Farrnaceutici Italia; appl. 8.4.1969; I-prior. 12.4.1968). partial synthesis from adriarnycinon: US 4 058 519 (Soc. Farmaceutici Italia; 15.1 1.1977; GB-prior. 22.3.1974). US 4 098 798 (Soc. Farmaceutici Italia; 4.7.1978; GB-prior. 22.3.1974). daunorubicin (from cultures of Streptomyces peucetius F. I. 1762): GB 1 003 383 (Soc. Farmaceutici Italia; appl. 11.11.1963; I-prior. 16.11.1962). doxombicin- 14-octanoate: DOS 2 260 438 (Soc. Farrnaceutici Italia; appl. 11.12.1972). US 3 803 124 (Soc. Farmaceutici Italia; 9.4.1974: I-prior. 12.4.1968,4.5.1971). stable liposome composition: WO 9 202 208 (Liposome Technology Inc.; appl. 2.8.1991; USA-prior. 8.8.1990). Formulation(s): vial (lyo.) 10 mg, 20 mg, 50 rng, 150 rng (as hydrochloride) Trade Name(s): D: Adriblastin (Pharmacia & GB: Caelyx (Schering-Plough; USA: Adriamycin (Pharmacia & Upjohn; 1972) as hydrochloride) Upjohn; 1974) Adrimedac (rnedac) I: Adriblastina (Farrnitalia; Doxil (Sequus) Caelyx (Essex Pharrna) 1971) Rubex (Bristol-Myers Ribodoxo (ribosepharrn) J: Adriacin (Kyowa Hakko; Squibb) F: Adriblastine (Pharmacia & 1975) Upjohn; 1974) Doxycy cline ATC: JOlAA02 Use: antibiotic RN: 564-25-0 MF: Cz2H2,Nz0, MW: 444.44 EINECS: 209-27 1- 1 LD,: 241 mgkg (M, i.v.); 1870 rnglkg (M, p.0.); 228 mgkg (R, i.v.); >2 glkg (R, p.0.); >lo0 mglkg (dog, i.v.); >SO0 mglkg (dog, p.0.) CN: [4S-(4a,4aa,5a,Saa,6a,l2aa) J-4-(dimethylamino)- l,4,4a,S,Sa,6,ll, 12a-octahydro-3.5,10,12,12a- pentahy droxy-6-methyl- I, 1 l -dioxo-2-naphthacenecarboxarnide 718 D Doxycycline monohydrochloride RN: 10592- 13-9 MF: C2,H2,N20, . HCI MW: 480.90 EINECS: 234-198-7 LD,,,: 290 mglkg (M, i.v.); 1890 mg/kg (M, p.0.); 137 mglkg (R, i.v.); 1700 mglkg (R, p.0.); >500 mglkg (dog, p.0.) monohydrate RN: 17086-28- 1 MF: C22H24N20x . H,O MW: 462.46 hyclate RN: 24390-14-5 MF: CZ2Hz4N2O8 . 1/2C2H60. HCI . 1/2H20 MW: 1025.89 oxytetracycline (I) I Doxycycline Na~S204 radicol addn. II NH2 -b thiophenol rnethacycline H2, Roney-Ni OH Reference(s): a US 3 019 260 (American Cyanamid; 30.1.1962; prior. 13.5.1959). DE 1 082 905 (American Cyanamid; appl. 3.11.1958; USA-prior. 5.1 1.1957). b US 3 200 149 (Pfizer; 10.8.1965; prior. 23.5.1960). DAS 1 793 556 (Pfizcr; appl. 19.5.1961; USA-prior. 23.5.1960). DE 1 298 522 (Pfizer; appl. 23.5.1961 ; USA-prior. 23.5.1960). Blackwood, R.K. et al.: J. Am. Chem. Soc. (JACSAT) 85,3943 (1963). bmreospecific hydrogenation of rnetacycl~ne with d~aceto(tr~phenylphosph~ne)rhod~um(II) complex to { doxycycline: ;DAS 2 554 524 (Pfizer; appl. 4.1 2.1975, USA-prior. 28.1.1975). k Formulation(s): tabl. 50 mg, 100 mg, 200 mg i 1 kde Name($): i- g D: Azudoxat (Azuchemie) t Clinofug (Wolff) Mespafin 100 (Merckle) a' Mucotectan (Boehringer Iw.1 Neodox (Rosen Pharma) i 1 Sigadoxin (Kytta-Siegfried) Supracyclin 1001200 i (Griinenthal) V~bramycin N (Pfizer) t r" Vibravenos (Pfizer) i F: Doxycline Plantier (ASTA ii Medica) I Doxygram (Pharma 2000) I Doxylets (Galephar) c G~anudoxy (Pierre Fabre) : Monocline (Doms-Adrian) Spanor (Blothempie) Tolexine (Biorga) J: Vibramy cine (Pfizer) Vibraveineuse (Pfizer) GB: Doxatet (Cox); wfm Doxy lar (Lagap); wfm USA: Nordox (Norton); wfm Vibramycin Acne Pack (Trinity)-comb. I: Bassado (Ppli) Doxina (Ipfi) Farmodoxi (Lifepharma) Gram-Val (Polifarma) Miraclin (Farmacologico Milanese) Monodoxin (Crosara) Ribociclina (Puropharma)- comb. Unacil (Firma) I lydramycin (Sankyo) Liomycin (Daiichi) Roximycin (Kyorin) Vibramycin (Taito Pfizer) Doryx (Warner Chilcott Professional Products; as hydrate) Monodox (Oclassen; as monohydrate) Vibramycin (Pfizer; as calcium salt) Vibramycin (Pfizer; as hydrate) Vibramycin (Pfizer; as monohydrate) Dox ylamine ATC: ~06.4~09 Use: antihistaminic RN: 469-2 1-6 MF: CI,HZ2N2O MW: 270.38 EINECS: 207-414-2 LD,: 62 mgkg (M, i.v.); 470 mglkg (M, p.0.) CN: N,N-dimethyl-2-[I-phenyl-1-(2-pyridinyl)etho~y]ethanamine succinate (1:l) . RN: 562-10-7 MF: C17H2,N20. C4H604 MW: 388.46 EINECS: 209-228-7 LD,,: 62 mgkg (M, i.v.); 470 mgkg (M, p 0.) I. NaNHZ 2. FH3 pJ,p CI-~& b OH 1 sodium omide H3C 2. 2-(dimethylomino)- 2-acetyl- phenylmagnesiurn 1 -phenyl- 1 - ethyl chloride pyridine bromide (2-pyridyl)- ethanol Reference(s): Sperber, N. et al.: J. Am. Chem. Soc. (JACSAT) 71,887 (1949). Fomulation(s): eff. tabl. 25 mg; tabl. 25 mg (as succinatc) Trade Name(s): D: Gittalun (Boehringer Ing.) Mereprine (Cassella-med) Sedaplus (Rosen Pharma) Hewedomir forte (Hevert) Praedisup (Chephasaar)- Wick Formel 44 S (Wick Hoggar N (Stada) comb. Pharma)-comb. 720 D Drofenine ! F: Donormyl (0berlin)-comb. Nethaprin expect (Merrell Vicks Medinait (Procter & MCrCpnne (Marion Dow)-comb.; wfm Gamble)-comb. Merrell) Syndol (Merrell Dow)- USA: Unisom Nighttime Sleep GB: Nethaprin Dospan (Merrell comb.; wfm Aid (Pfizer; as succinate) Dow)-comb.; wfm 1: Doxised (Corvi) Drofenine (Hexahydroadiphenine) ATC: A03DA49 Use: antispasmodic RN: 1679-76-1 MF: C2,H3,N02 MW: 317.47 LD,,,: 37 mglkg (R, i.v.) CN: a-cyclohexylbenzeneacetic acid 2-(diethy1amino)ethyl ester hydrochloride RN: 548-66-3 MF: C2,H3,N02 . HCI MW: 353.93 EINECS: 208-954-1 LD,,: 47 mgkg (M, i.v.); 3700 mg/kg (M, pa.) Referencefs): CH 219 301 (Ciba; appl. 1938). odiphenine (q. v.) Formulation(s): drg. 20 mg, 25 mg (comb. with 220 mg propyphenazone) Drofenine Trade Name(s): D: Spasmo-Cibalgidcomp. F: Spasrno-Cibalgine (Ciba)- I: (Novartis Pharma) comb.; wfm Dronabinol (6-9-THC) ATC: A04A Use: anti-emetic, active ingredient of marijuana RN: 1972-08-3 MF: C2,H,,02 MW: 314.47 LD,,: 168 mgkg (M, i.p.); 42 mgkg (M, i.v.); 482 mg/kg (M, p.0.); 373 mgkg (R, i.p.); 29 mg/kg (R, i.v.); 666 mgkg (R, p.0.) CN: (6aR-t~ans)-6a,7,8,10a-tetrahydro-6,6,9-trimethy1-3-pentyl-6H-dibenzo[b,~pyran-l-o1 H3C ,;OH s+L BF,~O(C,H& or ZnCI, / boron trifluoride etherote H,C-+CH, H0 CH3 OH H3cccH3 H3C CH, (I S-cis)- olivetol (I) Dronobinol p-menth-2- ene-1.8-diol . (8S-cis)-l 0-[ (3-amino-2,3,6-trideoxy-a-L-lyxo-hexopyanosyl)oxy ]-7 ,8,9,l0-tetrahydro-6,8,1 1- trihydroxy- 8-( hydroxyacety1 )- I-methoxy-5,12-naphthacenedione hydrochloride RN: 2531 6-4 0-9 MF: C2,H2,NO,, . HC1. CN: 7-( 1,3-dioxolan-2-ylmethy1 )-3 ,7-dihydro- 1,3-dimethyl-1H-purine-2,6-dione 716 D Doxorubicin CH3 '3'3 theophylline 3-chloro-1. 2- 7-( 2,3-dihydroxy- dihydroxypropane pr0pyl)theophylline. a,-receptor antagonist, antihypertensive RN: 7419 1-8 5-8 MF: C2,H2,N,05 MW: 451.48 LD,,: > 1000 mglkg (M, R, p.0.) CN: 1-( 4-amino-6,7-dimethoxy-2-quinazolinyl )-4 -[ (2,3-dihydro-l,4-benzodioxin-2-yl)carbonyl]piperazine