Ioxaglic acid 1 1091 COOH COOH / ocid 3.6.9-triaxaundecane- 3-amino-2.4.6- Reference(s): DAS 2 405 652 (Schering AG; appl. 4.2.1974). lotroxic acid Formulafion(s); vial 10.5 g1100 ml, 11.4 g15O mi dioyl chloride (I) triiodobenzoic Trade Name(s): D: Biliscopin (Schering) F: Biliscopine (Schering); I: Chologram (Schering) wfm J: Biliscopin (Schering) Ioxaglic acid (Acide ioxaglique) ATC: VO8AB03 Use: X-ray contrast medium RN: 59017-64-0 MF: Cz4H2,1,N,0n MW: 1268.88 EINECS: 261-560-1 LD,,: >13.3 g/kg(M, i.v.); 13.3 glkg (R, i.v.); 13.3 glkg (R, p.0.); >10.7 glkg (dog, i.v.) CN: 3-[[[[3-(acetylmethylamino)-2,4,6-triiodo-S-[(methylamino)c~bonyl]benzoyl]amino]acetyl]an~ino]-5- [[(2-hydroxyethyl)amino]carbonyl]-2,4,6-triiodobenzoic acid monosodium salt RN: 67992-58-9 MF: CZ4H2,I,N,NaOn MW: 1290.87 EINECS: 268-060-2 meglumine salt RN: 59018-1 3-2 MF: C24H2,1,N,0n . C7HL7NOS MW: 1464.10 EINECS: 261-561-7 N-phthaloyl- 2.4.6-triiodo-3-(2- glycyl chloride hydroxyethylcorbamoyl)- 5-ominobenzoic acid (cf. ioxita!amic ocid synthesis) COOH COOH ,* O? Hr-NH~ N&~-N / N/LCN hydroline ' 0 OIH 0 0IH 2.4.6-triiodo-3-(2-hydroxy- ethylcorbornoyl)-5-amino- ocetarnidobenzoic ocid (11) 1092 I Ioxitalamic acid Reference(s): US 4 014 986 (Guerbet; 29.3.1977; appl. 20.5.1975; GB-prior. 31.7.1974). DE 2 523 567 (Guerbet; appl. 28.5.1975; GB-prior. 31.5.1974, 31.7.1974). US 4 055 188 (Guerbet; 25.1.1977; GB-prior. 31.5.1974). K C I N CH, OI' CH3 2.4.6-triiodo-J- rnethylcorbamoyl- Formulation(s): amp. 393 mgtml (as sodium salt) H Ioxaglic acid Trade Name(s): D: Hexabrix (Guerbet; 1979) I: Hexabrix (Byk Gulden) F: Hexabrix (Guerbet; 1980) J: Hexabrix (Eiken) 5-acetylmethylarnino- benzoyl chloride Ioxitalamic acid (Acide ioxitalamique) ATC: V08AA05 Use: X-ray contrast medium RN: 28179-44-4 MF: C,,HIII3N2O, MW: 643.94 EINECS: 248-887-5 CN: 3-(acetylamino)-5-[[(2-hydroxyethyl)amino]carbonyl]-2,4,6-triiodobenzoic acid HOOC' thionyl uN02 chloride - ethanolomine p~02 u " 2. HCI - 0 NalCI2. HCI b 0 I Ipratropium bromide 1 1093 ocetyl chloride DMF loxitolomic acid COOH OIH Reference(s): DOS 1 928 838 (Nyegaard; appl. 6.6.1969; GB-prior. 10.6.1968). Formulalion(s): amp. 397.2 mg, 660.3 mglml (as meglumine salt) Trade Name(s): D: Telebrix (Byk Gulden) TClkbrix (Guerbet)-comb. F: TCltbrix (Guerbet) I: Telebrix (Byk Gulden) Ipratropium bromide ATC: R01 AX03; R03BB01 Use: bronchodilator RN: 22254-24-6 MF: C,,H,&rNO, MW: 41 2.37 EINECS: 244-873-8 LD,,: 12.29 mglkg (M, i.v.); 1001 mglkg (M, p.0.); 15.7 mg/kg (R, i.v.); 1663 mglkg (R, p.0.); 1300 mglkg (dog, p.0.) CN: (endo,syn)-(f)-3-(3-hydroxy-1-oxo-2-phenylpropoxy)-8-methyl-8-(l-methylethyl)-8- azoniabicyclo[3.2. lloctane bromide N-isopropylnorotropine methyl bromide Reference(s): DE 1 670 177 (Boehringer Ing.; prior. 28.12.1966). lprotropium bromide US 3 505 337 (Boehringer Ing.; 7.4.1970; D-prior. 22.12.1967). inhalation spray, also in combination with mucolytica and/or sympathomimetic effective bronchodilators: US 3 681 500 (Boehringer Ing.; 1.8.1972; D-prior. 12.12.1969). Formulation(s): aerosol inhalation 20 ~glmetered inhalation, 40 pglmetered inhalation; inhalation sol. 250 ~g/ ml; inhalation cps. 20 pg, 40 pg; doses aerosol 0.25 mg, 0.4 mg; doses aerosol susp. 0.02 mg; sol. 0.02 mg, 0.25 mg/2 ml, 0.5 mg/2 ml Trade Name(s): D: Atrovent (Boehringer lng.; Bronchodual (Boehringer numerous combination 1975) Ing.)-comb. preparations Berodual (Boehringer Ing.; Combivent (Boehringer I: Atem (Chiesi) 1980)-comb. 1ng.)-comb. Breva (Valeas)-comb. Itrop (Boehringer Ing.) GB: Atrovent (Boehringer Ing.) Duovent (Boehringer 1ng.)- F: Atrovent (Roehringer Ing.) Duovent (Boehringer 1ng.)- comb. comb. Iprafen (Chiesi)-comb. 1094 1 Ipriflavone J: Atrovent (Tejim Phar.) USA: Atrovent (Boehringer Ing.; Combivent (Boehringer 1987) Ing.) Ipriflavone (FL-113; TC-80) ATC: MOSBXO1 Use: calcium regulator (for treatment of osteoporosis) RN: 35212-22-7 MF: C1,H,,O, MW: 280.32 LD,,,: >2.5 glkg (M, i.p.1; 3185 mg/kg (M, p.0.); >5 glkg (M, s.c.); >2.5 glkg (R, i.p.); 2.5 g/kg (R, p.0.); >5 glkg (R, s.c.) CN: 7-(1-methylethoxy)-3-phenyl-4H-l-benzopyran-4-one 2,4-dihydroxyphenyl isopropyl benzyl ketone bromide triethyl orthoformote 2-hydroxy-4-isopropoxy- phenyl benzyl ketone (I) Ipriflavone US 4 166 862 (Chinoin; 4.9.1979; appl. 25.5.1971; prior. 16.5.1974; H-prior. 27.5.1970). DE 2 125 245 (Chinoin; appl. 21.5.1971; H-prior. 27.5.1970). Szuk, G. et al.: Magy. Kem. Lapja (MGKLAL) 43,401, (1988) (CA 110,179494 d). synthesis of I: GB 1 374 925 (Chinoin; appl. 30.1 1.1972; H-prior. 2.12.1971). pharmaceutical formulations: JP 53 133 635 (Chinoin; appl. 20.4.1978; H-prior, 20.4.1978). EP 129 893 (Takeda; appl. 23.6.1984; J-prior. 28.6.1983). US 4 772 627 (Takeda; 20.9.1988; appl. 15.1.1987; J-prior. 8.6.1984, 23.6.1984, 28.6.1983). cyclodextrin clathrates: EP 214 647 (Chinoin; appl. 9.9.1986; J-prior. 10.9.1985). medical use for treatment of heart and lung diseases: JP 53 133 635 (Chinoin; appl. 20.4.1978; H-prior. 20.4.1977). medical use for treatment of climacteric disorders: EP 129 667 (Takeda; appl. 25.4.1984; J-prior. 26.4.1983). dental compositions: EP 349 535 (Reanal Finomvegyszergyar; appl. 29.1.1988; H-prior. 3.2.1987). Formulation(s): tabl. 200 mg Trade Name(s): I: Iprosten (Takeda; 1991) Osteofix (Chiesi; 199 1) J: Osten (Takeda; 1989) Iproniazid 1 1095 Iproniazid ATC: N06AF045 Use: tuberculostatic, psychoenergetic, antidepressant RN: 54-92-2 MF: C,H,,N,O MW: 179.22 EINECS: 200-218-8 LD,,,: 719 mglkg (M, i.v.); 681 mg/kg (M, p.0.); 365 mg/kg (R, p.0.); 95 mglkg (dog, p.0.) CN: 4-pyridinecarboxylic acid 2-(1-methylethy1)hydrazide phosphate RN: 305-33-9 MF: C,H,lN,O. H,PO, MW: 277.22 isoniozid acetone (4. v.) I lproniozid I Reference(s): US 2 685 585 (Hoffmann-La Roche; 1954; prior. 1% 1). Fomulation(s): tabl. 50 mg (as phosphate) Trade Name(s): F: Marsilid (Laphal) I: Ellepibina (LPB)-comb.; GB: Marsilid (Roche); wfm wfm Irbesartan (BMS-186295; SR-47436) ATC: C09CA04 Use: anlihypertensive, angiotensin 11 antagonist RN: 138402-1 1-6 MF: C,,H,,N,O MW: 428.54 CN: 2-butyl-3-[[2'-(I H-tetrazol-5-yl)[ 1,l '-biphenyl]-4-yllmethyll- 1,3-diazaspiro[4.4]non- I -en-4-one CH OH. H 0 + NciCN . + oNH2 3. KOH, NH,CI, CH30H, H20 t I CN 2. pentanoyl chloride cyclo- sodium pentonone cyonide l-arnino-l- cyclopentone- corbonitrile 1096 1 Irinotecan 2-butyl-1,3-diozo- 4'-(bromomethyl)- spiro[4.4]non-1 -en- biphenyl-2-corbo- 4-one (I) nitrile (cf. losartan synthesis) NoN3 or Bu SnN A sodium ozide. tributyltin ozide 4'-(2-butyl-4-0x0-1.3- lrbesortan diazospiro[4.4]non-1 -en- 3-y1methyl)biphenyl-2- corbonitrile (11) alternative synthesis of intermediote I: ethyl 1 -amino- ethyl pentan- 1 -cyclopentane- imidate corboxylate Reference(s): US 5 270 3 17 (Elf Sanofi; 14.1 2.1993; F-prior. 20.3.1990, 1.9.1990, 10.9.1991). Bernhart, C.A. et al.: J. Med. Chem. (JMCMAR) 36, 3371-3380 (1993). EP 454 51 1 (Sanofi; appl. 20.3.1991; F-prior. 20.3.1990, 8.8.1990). Formulation(s): tabl. 75 mg, 150 mg, 300 mg Trade Name(s): D: Aprovel (Sanofi Winthrop; KARVEZIDETM (BMS)- USA: Avapro (BMS)-comb. 1997) comb. Avalide (Sanofi COAPROVEL (Sanofi F: Aprovel (Bristol-Myers Synthelabo) Synthelabo; BMS)-comb. Squibb) Karvea (Bristol-Myers GB: Aprovel (Bristol-Myers Squibb) Squi bbISanofi) Irinotecan (CPT-11; DQ-2805; NSC-616348) ATC: LOlXX19 Use: antineoplastic, topoisomerase inhibitor RN: 97682-44-5 MF: C,,H,8N,0, MW: 586.69 CN: (S)-[l,4'-bipiperidinel- 1 '-carboxylic acid 4,11-diethyl-3,4,12,14-tetrahydro-4-hydroxy-3,14-dioxo-l H- pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl ester monohydrochloride RN: 100286-90-6 MF: C33H38N406. HCl MW: 623.15 monohydrochloride trihydrate RN: 136572-09-3 MF: C33H38N406. HCl . 3H20 MW: 677.20 LD,,: 132 mglkg (M, i.v.); 1045 mglkg (M, p.0.); 83.6 mglkg (R, i.v.); 867 mglkg (R, p.0.); 40 mgkg (dog, i.v.) racemate RN: 130144-33-1 MF: C33H38N406 MW: 586.69 7-ethyl-10-hydroxy- phosgene camptothecin 7-ethyl-1 0-(chlorocarbonyl- oxy)camptothecin (I) Reference(s): EP 137 145 (Yakult Honsha; appl. 14.7.1983; J-prior. 14.7.1983). Henegar, K.E. et al.: J. Org. Chem. (JOCEAH) 62,6588 (1997). 4-piperidino- slow release formulation: JP 07 277 981 (Daiichi Pharm.; appl. 12.4.1994; J-prior. 12.4.1994). Irinotecan synergistic combinations: JP 04 208 224 (Daiichi Pharm.; appl. 30.1 1.1990; J-prior. 30.11.1990). WO 9 309 782 (SmithKline Beecham; appl. 13.1 1.1992; USA-prior. 15.1 1.1991). WO 9 410 995 (RhBne-Poulenc Rorer; appl. 10.11.1992; F-prior. 10.11.1992). piperidine Formulation(s): vial 40 mgl2 ml, 100 mgl 5 ml (as hydrochloride) Trade Name(s): F: Campto (RhBne-Poulenc J: Campto (Yakult Housha; as USA: Camptosar (Pharmacia & Rorer; as hydrochloride) hydrochloride) Upjohn) GB: Campto (RhBne-Poulenc Topotecin (Daiichi Rorer; as hydrochloride) Seiyaku; as hydrochloride) Isepamicin (Sch-21420) ATC: JOlGB11;JOlKD Use: aminoglycoside antibiotic (against urinary and respiratory tract infections) RN: 58152-03-7 MF: CZZH43NSOIZ MW: 569.61 EINECS: 261-143-4 LD,,: 5000 mglkg (M, i.p.); 330 mgkg (M, i.v.) CN: (S)-O-6-amino-6-deoxy-a-~-glucopyranosyl-(1+4)-0-[3-deoxy-4-C-methyl-3-(methylamino)-~-~- arabinopyranosyl-(l+6)]-N1-(3-amino-2-hydroxy- 1-oxopropy1)-2-deoxy-D-streptamine 1098 1 Isepamicin sulfate RN: 67814-76-0 MF: C22H4DN5012. H2S04 MW: 667.69 LD,,,: 2088 mgkg (R, i.m.); 1591 mgkg (R, i.p.); 476 mg/kg (R, i.v.); 3392 mg/kg (R, s.c.) disulfate RN: 68000-78-2 MF: C22H43N50,2 . 2H2S04 MW: 765.77 LD,,,: 234 mglkg (M, i.v.); >5 glkg (M, p.0.); 476 rng/kg (R, i.v.); >5 glkg (R, p.0.); 720 rnglkg (dog, i.v.) pyridine 0 H2S0, + 0 00 0 -+ NH2 gentarnicin B sulfate HN-CH, succinirnide HN-CH, N' -[(S)-3-benzyloxycarbonylamino- lseparnicin 2-hydroxypropionyl]betarnicin (I) Reference(s): DOS 2 502 296 (Scherico; appl. 21.1.1975; USA-prior. 19.3.1974). US 4 029 882 (Schering Corp.; 14.6.1977; appl. 19.3.1974). alternative synthesis: EP 405 820 (Schering Corp.; appl. 19.6.1990; USA-prior. 21.6.1989). US 4 136 254 (Scherico; 23.1.1979; appl. 18.5.1978; prior. 17.6.1976). US 4 230 847 (Schering Corp.; 28.1.1980; appl. 26.12.1979; prior. 18.5.1978, 17.6.1976). US 4 337 335 (Schering Corp.; 29.6.1982; appl. 26.12.1979; prior. 18.5.1978, 17.6.1976). EP 430 234 (Kanegafuchi; appl. 29.1 1.1990; J-prior. 29.1 1.1989). stable ampoule formulation: JP 1 268 698 (Toyo Jozo; appl. 20.4.1988). Formularion(s): amp. 250 mg, 500 mg Trade Name(s): F: ls6palline (Schering- J: Exacin (Toyo Jozo; 1988) Plough) lsepacin (Essex; 1988) Isoaminile 1 1099 Isoaminile ATC: R05DB04 Use: antitussive RN: 77-51-0 MF: C16H2,N2 MW: 244.38 EINECS: 201-033-5 LD,: 55 mgkg (M, i.v.); 48.4 mgkg (dog, i.v.) CN: a-[2-~dimethylamino)propyl]-a-(l-methylethyl)benzeneacetonitrile citrate (1:l) RN: 28416-66-2 MF: C,,H,N2 . C,H,O, MW: 436.51 EINECS: 249-01 1-4 cyclamate (1:l) RN: 10075-36-2 MF: C16H24N2 . C6H13N03S MW: 423.62 EINECS: 233-207-1 LD,,,: 57 mgkg (M, i.v.); 298 mglkg (M, p.0.); 270 mglkg (R, p.0.); 84 mglkg (dog, i.v.) b 1. sodium amide 2. isopropyl chloride 3-methyl-2- 2. Z-dimethylomino- cyanide phenyl- propyl chloride butyranitrile I lsoaminile Re.ference(s): GB 765 510 (Kali-Chemie; appl. 1955; D-prior. 1954). DE 960 462 (Kali-Chemie; appl. 1954). DE 964 499 (Kali-Chemie; appl. 1954). US 2 934 557 (Kali-Chemie; 1960; D-prior. 1957). Krause, D.: Arzneim Forsch. (ARZNAD) 8,553 (1958). cycloheqlsulfamic acid salt: US 3 074 996 (Abbott; 22.1.1963; appl. 18.4.1960). Fonnulation(s): drg., tabl. 40 mg (as citrate); drops 50 mg; sol. 50 mgl15 ml (as cyclamate) Trade Name(s): D: Peracon (Kali-Chemie); GB: Dimyril (Fisons); wfm Sedotosse (Panthox & wfm I: Peracon Kali-Chemie (Sir); Burck); wfm F: Mucalan (Delagrange); wfm J: Peracan (Toyo) wfm Isocarboxazid ATC: N06AFOl Use: MAO-inhibitor, antidepressant RN: 59-63-2 MF: C12H,3N302 MW: 23 1.26 EINECS: 200-438-4 LD,,,: 193 mglkg (M, p.0.); 280 mglkg (R, p.0.); >40 mglkg (dog, p.0.) CN: 5-methyl-3-isoxazolecarboxylic acid 2-(phenylmethy1)hydrazide 1100 1 Isoconazole H3c%-ci3 H0/-CH3 . H2S04 HN03 , H3c'$34 , COOH H3CqorCH3 0 0 2,5-hexonedione 5-methyl- isoxozole-3- corboxylic ocid OHC ethyl 5-methyl- isoxozole-3- carboxylote (I) H2N-NH2 . H20 H3cqz\ hydrozine hydrate O NH, "";\ 0 (11) I lsocorbaxozid I LiAIH4 ___, lithium olonote H2N\ I + Isocorboxozid 0 benzylhydrozine Keference(s): US 2 908 688 (Hoffmann-La Roche; 13.10.1959;-~rior. 15.4.1958). F.brmulation(s): tabl. 10 mg Trude Nume(s): F: Marplan (Roche); wfm I: Marplan (Roche); wfm US GB: Marplan (Roche); wfm J: Enerzer (Takeda) Marplan (Roche); w Isoconazole ATC: DO1 ACOS; GOlAF07 Use: antifungal, antibacterial RN: 27523-40-6 MF: C,nH,4C14N20 MW: 416.14 EINECS: 248-508-3 LD,,,: 189 mglkg (M, i.p.) CN: 1-[2-(2,4-dichlorophenyl)-2-[(2,6-dichlorophenyl)methoxy]ethyl]-lH-imidazole mononitrate RN: 24168-96-5 MF: CIRH,,Cl4N2O~ HN03 MW: 479.15 EINECS: 246-051-4 LDsl,: 2 glkg (M, p.0.); 5600 mgkg (R, p.0.) . (M, i.v.) CN: (S)-O-6-amino-6-deoxy-a-~-glucopyranosyl-(1+4 )-0 -[ 3-deoxy-4-C-methyl- 3-( methylamino )-~ - ~- arabinopyranosyl-(l+6)]-N 1-( 3-amino-2-hydroxy- 1-oxopropy1 )-2 -deoxy-D-streptamine 1098. chloride cyclo- sodium pentonone cyonide l-arnino-l- cyclopentone- corbonitrile 1096 1 Irinotecan 2-butyl-1,3-diozo- 4&apos ;-( bromomethyl )- spiro[4.4]non-1 -en- biphenyl-2-corbo- 4-one (I). 1300 mglkg (dog, p.0.) CN: (endo,syn )-( f )-3 -( 3-hydroxy-1-oxo-2-phenylpropoxy )-8 -methyl- 8-( l-methylethyl )-8 - azoniabicyclo[3.2. lloctane bromide N-isopropylnorotropine methyl bromide Reference(s):