Alcuronium chloride A Trade Name(s): D: Delonal (Essex Pharma; GB: Modrasone (Dominion; J: Almeta (Shionogi) 1985) 1986) USA: Aclovate (Glaxo Wellcome; \ F: Aclosone (Schering- I: Legederm (Schering- 1986) Plough) Plough; 1988) Alcuronium chloride ATC: M03AAOl Use: muscle relaxant RN: 15180-03-7 MF: C44H50CIZN402 MW: 737.82 EINECS: 239-229-8 LD,,: 610 pglkg (M, i.p.); 240 pglkg (M, i.v.); 38500 pglkg (M, p.0.); 610 pglkg (M, s.c.); 270 pgkg (R, i.p.); 27600 pglkg (R, p.0.); 280 pglkg (R, s.c.) CN: [iR-(la,3aS*,lOa,l la~,12a,14aS*,19aa,20ba,21a,22a~,23E,26]-2,3,11,1 la,13,14,22,22a-octahydro- 23,26-bis(2-hydroxyethylidene)-l , 12-di-2-propenyl-1OH,19aH,20bH,21H-1,21: 10,12-diethano- dipyrrolo[3,2-~3',2'-f1[1,5]diazocino[3,2,1-jk:7,6,5-j'k']dicarbazolium dichloride iodide Wieland-Gumlich aldehyde (degradation product of strychnine) IRA-400 (CI form) A N(b)-ollyl-heminortoxi- ferine iodide (1) diollylnortoxiferin diiodide (11) Alcuronium chloride 52 A Aldosterone Reference(s): US 3 080 373 (Roche; 5.3.1963; F-prior. 29.8.1960). Karrer, P. et al.: Angew. Chem. (ANCEAD) 70, 644 (1958). Formulation(s): amp. 5 ml, 10 ml(1 mg/ml); inj. sol. 10 mg/2 ml Trade Name(s): D: Alloferin Amp. (Roche) GB: Alloferin (Roche); wfm USA: Alloferin (Roche); wfm F: Allofkrine (Roche); wfm J: Dialferin (Roche) Aldosterone ATC: Use: RN: 52-39-1 MF: C2,H2,0, MW: 360.45 EINECS: 200-139-9 CN: (1 1 p)- 11,21-dihydroxy-3,20-dioxopregn-4-en-18-a1 & nH3 -I, nitrosyl pyridine, & Me H 'cH3 H H chloride H H 0 / 0 / 21 -0-ocetyl-1 1-0-nitrosyl- corticosterone (I) H02AAO1 mineralocorticoid bosic soponificotion - 21 -0-ocetyloldosterone (II) Reference(s): Aldosterone Barton, D.H.R.; Beaton, J.M.: J. Am. Chem. Soc. (JACSAT), 82, 2641 (1960). starting material: The Merck Index, 25 13 (Rahway 1976). alternative syntheses: US 3 002 972 (Ciba; 3.10.1961; appl. 28.1 1.1958; CH-prior. 5.12.1957). US 3 014 029 (Ciba; 19.12.1961; appl. 16.6.1959; CH-prior. 18.6.1958). US 3 049 539 (Wisconsin Alumni Res. Found.; 14.8.1962; appl. 29.7.1957). Wettstein, A. et al.: Helv. Chim. Acta (HCACAV) 44, 502 (1961). Reichstein, T. et a].: Helv. Chim. Acta (HCACAV) 38, 1432 (1957). review: Fieser, L.F.; Fieser, M.: Steroide p. 766 ff, Verlag Chemie, Weinheim 1961. Alendronate sodium A 53 total synthesis: Johnson, P.S. et al.: J. Am. Chem. Soc. (JACSAT) 80,2585 (1958). Blickenstaff, R.T.; Ghosh, A.C.; Wolf, G.C.: Total Synthesis of Steroids (Organic Chemistry Vol. 30) p. 187 ff, Academic Press, New York, London 1974. Formulation(s): tabl. 500 mg, 750 mg Trade Name(s): D: Aldocorten (Ciba); wfm USA: Aldocortin (Burroughs GB: Aldocorten (Ciba); wfm Wellcome); wfm I: Sinsurrene Forte (Parke Electrocortin (Ciba-Geigy); Davis)-comb. wfm Alendronate sodium ATC: M05BA04 Use: treatment of osteoporosis RN: 121268-17-5 MF: C,H,,NNaO,P,. 3H20 MW: 325.12 LD,,: >4 glkg (dog, p. 0.) CN: (4-Amino-1-hydroxybutylidene)bis[phosphonic acid] monosodium salt trihydrate acid RN: 66376-36-1 MF: C,H,,NO,P, MW: 249.10 anhydrous monosodium salt RN: 1293 18-43-0 MF: C4HI2NNaO,P2 MW: 271.08 y-ominobutyric acid 1. 140°C. 50 psi. 20h. 0 379; HCI Alendronote sodium I Reference(s): WO 9 506 052 (Merck & Co.; USA-prior. 25.8.1993). WO 9 533 756 (Merck & Co.; appl. 2.6.1995; USA-prior. 6.6.1994). US 5 510 517 (Merck & Co.; 2.3.1995; USA-prior. 25.8.1993). DE 3 016 289 (Henkel KG; D-prior. 28.4.1980). BE896 453 (1st. Gentili s. p. a.; appl. 14.4.1983; I-prior. 15.4.1982, 16.2.1983). BE903 513 (1st. Ccntili s. p. a.; appl. 25.10.1985; I-prior. 29.10.1984). EP 494 844 (1st. Gentili s. p. a.; appl. 2.1.1992; I-prior. 8.1.1991). US 4 621 077 (1st. Gentili s. p. a,; 8.6.1984; I-prior. 15.4.1982). US 5 019 651 (Merck & Co.; 27.12.1991; USA-prior. 20.6.1990). US 4 922 007 (Merck & Co.; 1.5.1990; USA-prior. 9.6.1989). alternative process for the production of alendronate: WO 9 834 940 (Apotcx Inc.; CA-prior. 11.2.1997). Formulation(s): amp. 5 mg, 10 mg; tabl. 5 mg, 10 mg, 40 mg (as sodium salt) 54 A Alfacalcidol Trade Name(s): D: Fosamax (Merck Sharp & Alendros (Gentili) 'Teiroc (Teijin) Dohme) Dronal (Sigmatau) USA: Fosamax (Merck Sharp &. GB: Fosamax (Merck Sharp & Fosamax (Merck Sharp & Dohme; 1993) Dohme) Dohme) I: Adronat (Neopharmed) J: Onclast (Banyu) Alfacalcidol ATC: AI ICCO~ (la-Hydroxycholecalciferol; la-Hydroxy-vitamin D,) Use: vitamin D-derivative RN: 41294-56-8 MF: C,,H,O, MW: 400.65 EINECS: 255-297-1 LD,,: 440 g/kg (M, p.0.); 340 g/kg (R, p.0.) CN: (la,3~,5Z,7E)-9,10-secocholesta-5,7,10(19)-triene-l,3-diol CH3 KOC(CH,), potassium tert-butylote 0 3-0x0-1.4.6-cholestatriene 3-0x0-1.5.7-cholestotriene (I) NoBH., sodium borohydride 3-chloroper- benzoic acid lithium aluminum la-hydroxyprovitomin 4 (U1) Alfadolone acetate A 55 Alfocolcidoi Reference(s): US 3 929 770 (Wisconsin Alumni Res.; 30.12. 1975; J-prior. 3.12.1973). alternative syntheses: Holick, M.F. et al.: Science (Washington, D.C.) (SCIEAS) 180, 190 (1973). Barton, D.H.R. et al.: J. Am. Chem. Soc. (JACSAT) 95,2748 (1973) Fiirst, A. et al.: Helv. Chim. Acta (HCACAV) 56, 1708 (1973). US 3 966 777 (Yeda Res. & Devel.; 29.6.1976; IL-prior. 22.10.1974). DOS 2 259 661 (Wisconsin Alumni Res.; appl. 1.12.1972; USA-prior. 2.12.1971). BE 877 356 (Wisconsin Alumni Res.; appl. 28.6.1979; USA-prior. 15.1.1979, 21.5.1979). GB 1 553 321 (Merck & Co.; valid from 30.6.1977; USA-prior. 1.7.1976). . DOS 2 923 953 (Upjohn; appl. 13.6.1979; USA-prior. 19.6.1978). total synthesis: Harrison, R.G. et al.: Tetrahedron Lett. (TELEAY) 1973, 3649. synthesis of intermediates: US 4 046 760 (Merck & Co., 6.9.1977; prior. 1.7.1976). pharmaceutical formulation: JP-appl. 78 136 512 (Chugai; appl. 28.4.1977). US 4 164 569 (Chugai; 14.8.1979; J-prior. 8.4.1977) use as anti-inflammatory: FX 2 389 377 (J. Brohult, appl. 6.5.1977). Formulation(s): amp. 0.001 mg, 0.002 mg; cps. 0.001 mg, 0.0025 mg, 1 mg; inj. 2 yglml Trade Name(s): D: Bondiol (Gry) One Alpha (Leo) Diseon (Smith Kline & Eins Alpha (Leo) I: Dediol (Rhhe-Poulenc French) - F: Un-Alfa (Leo) Rorer) J: Alfarol (Chugai) GB: Alfa D (Berk) Alfadolone acetate (Alphadolone acetate) ATC: NOlA Use: anesthetic (intravenous) RN: 23930-37-2 MF: C23H3405 MW: 390.52 EINECS: 245-942-5 LD5,,: >30 mglkg (rabbit, i.v.) CN: (3a,5a)-21-(acetyloxy)-3-hydroxypregnane-11,20-dione alfadolone RN: 14107-37-0 MF: C2,H320, MW: 348.48 EINECS: 237-961-2 LD,,,: 59 mgkg (M, i.v.) 56 A Alfaxalone - ride etherote alfaxalone (I) lead tetraacetate (4. v.) Alfodolane ocetote Br 0 Br2.HBr. CH,OH I H3C4&, acetone bromine patossium acetate Reference(s): DE 2 030 402 (Glaxo; appl. 19.6.1970; GB-prior. 20.6.1969; 11.6.1970). ZA 703 861 (Glaxo; appl. 8.6.1970; GB-prior. 20.6.1969) (alternative synthesis). Browne, P.A.; Kirk, D.N.: J. Chem. Soc. (JCSOA9) 1969, 1653. Formulalion(s): amp. 0.5 mglml Trade Name(s): D: Aurantex (Glaxo)-comb.; GB: Althesin (G1axo)-comb.; wfm wfm F: Alfatesine (G1axo)-comb.; I: Althesin (G1axo)-comb.; wfm wfm Alfaxalone (Alphaxalone) ATC: NOlAXO5 Use: anesthetic (intravenous) RN: 23930-19-0 MF: C2,H3,0, MW: 332.48 LDso: 430 mdkg (M, i.p.); 36.9 mglkg (M, i.v.); 880 mgikg (M, p.0.); 5220 mglkg (M, s.c.); 1 16 mdkg (R, i.p.); 19.4 mglkg (R, i.v.); 297 mglkg (R, p.0.); >2200 mgkg (R, s.c.); 9.36 mgkg (rabbit, i.v.) CN: (3o?,5a)-3-hydroxypregnane-l1,20-dione acetate RN: 51267-69-7 MF: C23H3404 MW: 374.52 Rhizopus nigricans progesterone 11 u-hydroxypragesterone Alfaxalone A 57 Cr03. HOAc I la-hydroxy-5a-pregnone- 3,20-dione (I) pregnone (U) H2lrCI6, P(OCH3)3. (CH&HOH (Henbest reduction) u b hexochloro- trimethyl iridic phosphite acid Alfoxalone 1 1 -oxotigogenin (from hecogenin) 1. TOSCI , pyridine 2. 0 H~C~ OK , DMF v - 1. HZ. Pd-C 2. NoOH ___* 11 -20-dioxo-3p-hydroxy- 5a-pregnane (V) Alfaxolone ocetote 1 a Browne, P.A.; Kirk, D.N.: J. Chem. Soc. C (JSOOAX) 1969, 1653. b Naaata. W. et al.: Helv. Chim. Acta (HCACAV) 42. 1399 (1959). 5 8 A Alfentanil medical use: DE 2 030 402 (Glaxo; appl. 19.6.1970; GB-prior. 20.6.1969, 11.6.1970). Formulation(s): amp. 5 ml, 10 ml, 0.3 % Trade Natne(s): J: Alphadione (Shin Nihon Jitsugyo) Alfentanil ATC: NOlAH02 Use: analgesic, short-time anesthetic (for basal narcosis) RN: 71195-58-9 MF: C2,H32N,03 MW: 416.53 CN: N-[1-[2-(4-ethyl-4,5-dihydro-5-oxo-1H-tetrazol-l-yl)ethyl]-4-(methoxymethyl)-4-pipe~dinyl]-N- phenylpropanamide monohydrochloride RN: 69049-06-5 MF: C21H32N,03 . HCl MW: 452.99 EINECS: 273-846-3 monohydrochloride monohydrate RN: 70879-28-6 MF: C2,H32N,0, . HC1. H20 MW: 471.00 ethyl sodium isocyanate azide chloroethone (1) p H0vCH3 . HCI 0 + ON, + HCN A 11 0 I -benzyl-4- aniline hydrogen piperidane cyanide propionic anhydride Alfuzosin A 59 Alfentonil L Reference(s): GB 1 598 872 (Janssen; appl. 3.5.1978; USA-prior. 5.5.1977). DOS 2 819 873 (Janssen; appl. 5.5.1978; USA-prior. 5.5.1977, 13.3.1978). 17s 4 167 574 (Janssen; 11.9.1979; appl. 25.10.1978; prior. 13.3.1978). Forrnulution(s): amp. 500 pglml; inj. sol. I mgl2 ml, 5 mg/lO ml; intensive care inj. 5 mgtml Trade Nutne(s): D: Rapifen (Janssen-Cilag; GB: Rapifen (Janssen-Cilag; 1983) 1983) F: Rapifen (Janssen-Cilag) USA: Alfenta (Janssen; 1987) Alfuzosin ATC: C02CA; G04CBOl Use: antihypertensive, a,-antagonist, treatment 6f benign prostatic hypertrophy RN: 81403-80-7 MF: C,,HnN504 MW 389.46 CN: (+)-N-[3-[(4-amino-6,7-dimethoxy-2-quinazalinyl)methylamino]propyl]tetrahydro-2-furancarboxamide monohydrochloride RN: 81403-68-1 MF: C19H27N504. HCI MW 425.92 3. NH, OHCaO-CH~ *No3 , OHC~~'~~: , , . I12N~-~~3 0-CH, O2N 02N 0-CH~ perrnongonate 3,4-dirnethoxybenz- aldehyde (veratroldehyde) 0 0 Fe, CH,COOH b H2N%-"3 I. won urea + HNW-CHJ HzN 0-CH3 OAN / 0-CH3 H 2-amino-4.5-di- rnethoxybenzomide 60 A Algestone acetophenide CI POCI, II NW-C'~ ClhN 0-CH, 4-amino-2-chloro- 6,7-dimethoxy- quinazoline (111) triethylarnine 0 0 ' "i ~COOH + - @oAo-cH3 CH~ bnr 3-(methylomino)- tetrohydrofuran- ethyl 2-corboxylic acid chloroformote proponenitrile N-tetrahydrofuroyl- ethylomine (N) hydrofuroyl-trime- thylenediomine (V) Reference(s): US 4 315 007 (Synthelabo; 9.2.1982; F-prior. 6.2.1978, 29.12.1978). DE 290 445 (Synthelabo; appl. 16.8.1979; F-prior. 6.2.1978,29.12.1978). Manoury, P.M. et al.: J. Med. Chem. (JMCMAR) 29, 19 (1986). isoomyl alcohol v + 111 synthesis of 6,7-dimethoxyquinazoline-2,4-dione: Althuis, T.H.; Hess, H.J.: J. Med. Chem. (JMCMAR) 20, 146 (1977). Nb-CH3 d#Mr*N 0-CHI C"3 Alfuzosin Formulation(s): tabl. 2.5 mg (as hydrochloride) Trade Name(s): D: Urion (Byk Gulden) Xatral (SynthClabo; 1989) Xatral (Synthelabo) Uroxatral (Synthelabo) GB: Xatral (Lorex) F: Urion (Zambon) I: Mittoval (Schering) Algestone acetophenide ATC: DlOAX; G03DA (Alfasone acetophenide; Alphasone acetophenide) Use: antiacne, progestogen RN: 24356-94-3 MF: C2,H3,04 MW: 448.60 EINECS: 246-195-8 CN: [16a(R)]-16,17-[(l-phenylethylidene)bis(oxy)]pregn-4-ene-3,2O-dione dgestone RN: 595-77-7 MF: C2,H3,0, MW: 346.47 EINECS: 209-869-2 . 7119 5-5 8-9 MF: C2,H32N,03 MW: 4 16. 53 CN: N-[ 1-[ 2-( 4-ethyl-4,5-dihydro-5-oxo-1H-tetrazol-l-yl)ethyl ]-4 -( methoxymethyl )-4 -pipe~dinyl]-N- phenylpropanamide monohydrochloride RN: 69 04 9-0 6- 5 MF:. 2435 6- 9 4-3 MF: C2,H3,04 MW: 448 .60 EINECS: 24 6- 1 9 5-8 CN: [16a(R) ]-1 6, 1 7-[ (l-phenylethylidene)bis(oxy)]pregn-4-ene-3,2O-dione dgestone RN: 59 5-7 7-7 MF: C2,H3,0, MW: 3 46. 47 EINECS: 20 9-8 6 9-2 . la~,12a,14aS*,19aa,20ba,21a,22a~,23E, 26 ]-2 ,3,11,1 la,13,14,22,22a-octahydro- 23, 2 6- bis(2-hydroxyethylidene)-l , 12-di-2-propenyl-1OH,19aH,20bH,21H-1,21: 10,12-diethano- dipyrrolo[3, 2-~ 3',2'-f1[1,5]diazocino[3,2,1-jk:7 ,6, 5-j'k']dicarbazolium