Ibuprofen lysinate 1 1041 GB: Brufen Retard (Knoll; J: 1969) Fenbid spansule (Goldshield) Motrin (Pharmacia & Upjohn) numerous generics I: Algofen (Blue Cross) Antagil (Janssen) Brufen (Boots Italia; 1972) Brufort (Lampugnani) Dolocyl (Novartis) Moment (Angelini) Nurofen (Boots Italia) generics Ibuprofen lysinate Andran (Takata) Anflagen (Ohta) Bluton (Morishita) Brufanic (Teiyo; 1976) Brufen (Kakenyaku) Buburone (Towa) Butylenin (Sanwa) Daiprophen (Daito) Donjust-B (Horita) Epinal (Mitsubishi Yuka) Epobron (Ono) Eputes (Kobayashi Kako) IB-100 (Hishiyama) Ibuprocin (Nisshin) Lamidon (Kowa) Landelun (Tsuruhara) Liptan (Kowa) Manypren (Zensei) Mynosedin (Toho Yakuhin) Napacetin (Toyama) Nobfelon (Toho) Nobfen (Toho) Nobgen (Kanebo) Roidenin (Showa) Sednafen (Taisho) generic USA: Motrin (McNeil) Vicoprofen (Knoll) generics ATC: MOI AE; M02AA Use: anti-inflammatory, analgesic RN: 57469-77-9 MF: C,3H1802~C6H14N202 MW: 352.48 EINECS: 260-751-7 LD,,: 299 mgkg (M, p.0.); 841 mg/kg (R, p.0.) CN: L-lysine mono[a-methyl-4-(2-methylpropyl)benzeneacetate] ibuprofen (9. v.) Ibuprofen lysinote u Reference(s): DOS 2 419 317 (Neopharmed; appl. 22.4.1974; I-prior. 22.3.1974). GB 1 497 044 (SPA Soc. Prodotti Antibiotici; appl. 6.3.1975; prior. 7.3.1974). Fomulation(s): eff. tab]. 342 mg; f. c. tabl. 250 mg, 500 mg; gel 10 %; s. r. tabl. 800 mg; suppos. 500 mg; vial (lyo.) 400 mg Trade Name(s): D: Imbun (Merckle); wfm I: Aciril (Delalande Isnardi) Arfen (Lisapharma) Ibuproxam ATC: MOlAE13; M02AA Use: anti-inflammatory RN: 53648-05-8 MF: C13H,,N02 MW: 221.30 EINECS: 258-683-8 LD,,: >2 g/kg (M, p.0.); >3 gkg (R, p.0.) CN: N-hydroxy-a-methyl-4-(2-methylpropyl)benzeneacetamide 1042 I Ibutilide fumarate - 1. C2H50H. H,SO, 2. H2N-OH 2. hydroxylamine H3C ibuprofen I Ibuproxam (4. v.) Reference(s): DOS 2 400 531 (Manetti Roberts; appl. 7.1.1974; I-prior. 8.1.1973, 5.7.1973). Formulation(s): ointment 5 9%; suppos. 600 mg; tabl. 300 mg Trade Name(s): I: Deflogon (Damor); wfm Ibudros (Manetti Roberts) Ibutilide fumarate (U-70226E) ATC: COIBDO5 Use: antiarrhythmic RN: 122647-32-9 MF: C20H36N,0,S . 1/2C4H404 MW: 885.24 LD,,,: 94.2 rnglkg (R, i. v.) CN: N-[4-[4-(ethylheptylamino)-l-hydroxybutyl]phenyl]methanesulfonamide (E)-2-butenedioate (2:l) (salt) base RN: 122647-3 1-8 MF: C,,,H,,N203S MW: 384.59 0 I1 H3C-S-CI 1) 0 methone- sulfonyl chloride aniline pyridine 10-15 'C ____, succinic anhydride OCC, OMF, PH 4-[(methylsulfonyl)omina]- ethylheptyl- y-oxobenzenebutanoic acid (I) omine N-ethyl-N-heptyl-y-oxo-4- [(methylsulfonyl)amino]benzene- butonomide (11) Idarubicin 1 1043 lbutilide furnorote Reference(s): EP 164 865 (Upjohn; appl. 1.5.1985; USA-prior. 4.5.1984). Hester, J.B. et al.: J. Med. Chem. (JMCMAR) 34 (I), 308 (1991). controlled-release formulation: WO 9 421 237 (Univ. Michigan; appl. 15.3.1994; USA-prior. 15.3.1993). Formulation(s): vial 1 mg/ml Trade Name(s): USA: Corvert (Pharmacia & Upjohn) Idarubicin ATC: LOlDR06 Use: antineoplastic, anthracycline RN: 58957-92-9 MF: C2,Hl7NO, MW: 497.50 LD,,,: 3 mgkg (M, i.p.); 4 mgkg (M, i.v.); 16 mg/kg (M, p.0.) CN: (7S-cis)-9-acetyl-7-[(3-amino-2,3,6-trideoxy ~-lyxo-hexopyranosyl)oxy]-7,8,9,IO-tetrahydro-6,9,11- trihydroxy-5,12-naphthacenedione OH 0 AICI, 'c0* -1 , Tos-OH aluminurn ethylene glycol OH OH O O\cHX ctloride OH OH 0 OH dounomycinone 4-0-dernethyl- dounornycinone 4-0-dernethyldouno- mycinone 19-ethylene acetol (I) 4-0-dernethyl-4-0-(p- toluenesulfonyl)dauno- rnycinone 19-ethylene acetal (11) 1044 1 Idarubicin 4-methoxy- benzylomine acid 4-demethoxy-4-(4-methoxy- benzylomino)daunomycinone 19-ethylene ocetol 1. F3CCOOH. NaN02 HO 2. H,P02 _____, 2. hypophosphorous OH OH 0 NH2 acid OH OH 0 fermentation with S. peucetius corneus, S. coeruleus. S. coeruleorubidos IV b 1. HgO. HgBr2. molecular sieve 0.5 nm 4-demethoxy- dounamycinone (N) NH2 ldorubicin lyxo-hexopyronosyl chloride Reference(s): a US 4 471 052 (Adria; 9.1 1.1984; appl. 18.1.1982). b DOS 2 525 633 (Soc. Farmaceutici; appl. 6.9.1975; GB-prior. 16.12.1974). US 4 046 878 (Soc. Farmaceutici; 9.6.1977; appl. 22.5.1975; GB-prior. 6.12.1974). alternative synthesis: Arcamone, F. et al.: Experientia (EXPEAM) 34, 1255 (1978). synthesis of 4-demethoxydaunomycinone: EP 328 399 (Farmitalia; appl. 2.10.1989; GB-prior. 2.12.1988). lyophilisate: GB 2 165 75 1 (Farmitalia; appl. 22.10.1984). Formulation(s): cps. 5 mg, 10 mg, 25 mg; vial 5 mg, 10 mg (as hydrochloride) Idebenone 1 1045 Trade Name(s): D: Zavedos (Pharmacia & GB: Zavedos (Pharmacia & J: ldamycin (Pharmacia & Upjohn) Upjohn) Upjohn; as hydrochloride) F: Zavedos (Pharmacia SA; as I: Zavedos (Pharmacia & USA: Idamycin (Pharmacia & hydrochloride) Upjohn) Upjohn; as hydrochloride) Idebenone ATC: COlEB; N06BX13; N07X (CV-26 19) Use: senile dementia therapeutic, coenzyme Q10 derivative, nootropic RN: 58186-27-9 MF: C,,H,,O, MW: 338.44 LD,: >I0 g/kg (M, p.0.); 10 &/kg (R, p.o.1 CN: 2-(10-hydroxydecyl)-5,6-dimethoxy-3-methyl-2,5-cyclohexadiene-l,4-dione 3.4.5-trirnethoxy- ethyl 9-chloroforrnyl- toluene nonanoote 9-(2-hydrory-3.4-dirnelhoxy- 6-methylbenzoyl)nononoic ocid (I) OH Zn-Hg. HCI I -, H,c/' K,[(SO&NOI COOH -b 11 zinc omalgom H3C10 potassium nitrosodisulfate 1 ldebenone 0 1. C,H,OH. HCI 2. LiAlH COOH 4 , 0 Reference(s): DOS 2 519 730 (Takeda; appl. 2.5.1975; J-prior. 2.5.1974). JP 51 128 932 (Takeda; appl. 10.1 1.1976). JP 59 039 855 (Takeda; appl. 27.8.1982). US 4 139 545 (Takeda; 13.2.1979; J-prior. 2.5.1974). US 4 271 083 (Takeda; 2.6.1981; J-prior. 2.5.1974). US 4525 361 (Takeda; 13.2.1979; appl. 3.4.1975; J-prior. 2.5.1974). 0 H,C/O OH 0 medical use for the therapy of ischemic disease: EP 31 727 (Takeda; appl. 29.12.1980; J-prior. 30.12.1979). DOS 3 049 039 (Takeda; appl. 24.12.1980; J-prior. 30.1 2.1979). medical use for treatment of allergic disease: EP 38 674 (Takeda; appl. 15.4.1981; J-prior. 21.4.1980). medical use for treatment ofjibrosis: DOS 3 31 1 922 (Takeda; appl. 31.3.1983; J-prior. 6.4.1982). Okamoto, K. et al.: Chem. Pharm. Bull. (CPBTAL) 33,3745; 3756 (1985). Goto, G. et al.: Chem. Pharm. Bull. (CPBTAL) 33,4422 (1985). 1046 1 Idoxuridine alternative synthesis: EP 21 841 (Takeda; appl. 27.6.1980; J-prior. 28.6.1979). EP 58 057 (Takeda; appl. 4.2.1982; J-prior. 9.2.1981). Ebrmulation(s): drg. 30 rng, 45 mg; tabl. 30 mg Trade Name(s): I: Daruma (Cyanamid) Mnesis (Takeda) J: Avan (Takeda; 1987) Idoxuridine ATC: D06BBOl; J05AB02; SO1 ADO1 Use: chemotherapeutic (Herpes simplex) RN: 54-42-2 MF: C,H, ,IN20s MW: 354.10 EINECS: 200-207-8 LD,,,: 1 glkg (M, i.p.); 4 glkg (R, i.p.) CN: 2'-deoxy-5-iodouridine 5-iodo- uracil 1 -acetyl-5 iodouracil acetate 5-iodo-mono- mercuriurocil (I) Tos-0 3.5-di-O-tosyl-2- deoxyribofuronosyl chloride (11) I ldoxuridine I Idoxuridine / Ifenprodil I 1047 Reference(s): Chang, P.K.; Welch, A.D.: J. Med. Chem. (JMCMAR) 6,428 (1963). FR 1 336 866 (Roussel-Uclaf; appl. 27.7.1962). GB 1 024 156 (Roussel-Uclaf; appl. 24.7.1963; F-prior. 27.7.1962). Formulation(s): eye drops 0.1 %; ointment 0.2 %, 0.5 %; sol. 5 %, 10 %, 40 % Trade Name(s): D: ldugalen (Phannagalen) Iduridin (Ferring) J: I.D.U. (Sumitorno) Ophtal (Winzer) I: Iducher (Farmigea) USA: Dendrid (Alcon); wfm Virunguent (Hermal) Iducol (SIF1)-comb. Herplex (Allergan); wfm Zostrum (Galderma) Iduridin (Geymonat) Stoxil (Smith Kline & F: Iduviran (Chauvin) Idustatin (Delalande French); wfm GB: Herpid (Yamanouchi) 1snardi)-comb. Ifenprodil ATC: C04AX28 Use: cerebral and peripheral vasodilator RN: 23210-56-2 MF: C21H2,N02 MW: 325.45 EINECS: 245-491-4 LDS,: 320 mglkg (M, p.0.) CN: a-(4-hydroxyphenyl)-~methyl-4-(phenylmeyl)-l-piperidineethanol tartrate (2:l) RN: 23210-58-4 MF: C2,H2,NO2 1/2C,H606 MW: 800.99 BINECS: 245-493-5 benzyl 4'-hydroxy- 4'-benzyloxy- chloride propiophenone propiophenone Na CO , +#m =+ 8"" 4-benzyl- (11) piperidine I lfenprodil I Referencets): DAS 1 695 772 (Lab. Robert et Carribre; appl. 7.9.1967; F-prior. 27.9.1966). FR 5 733 M (Lab. Rohert et Carribre; appl. 27.9.1966). US 3 509 164 (Lab. Robert et Carribre; 28.4.1970; F-prior. 27.9.1966). Formulation(s): amp. 5 mgl2 ml; tabl. 20 mg (as tartrate) Trude Name(s): F: Vadilex (Synthtlabo; 1972) J: Cerocral (Funai; 1979) Ifosfarnide ATC: LOIAA06 Use: antineoplastic RN: 3778-73-2 MF: C,H,,CI,N,O,P MW: 26 1 .O9 EINECS: 223-237-3 LDS,; 338 mg/kg (M, i.v.); 1005 mglkg (M, p.0.); 190 mglkg (R, i.v.); 143 mglkg (R, p.0.) CN: N,3-bis(2-chloroethyI)tetrahydro-WI-1,3,2-oxazaphosphorin-2-amine 2-oxide P0C13 0 H2N~CI .HCI N(C~H5)~ OH 0HCI , 0. 11 p-CI N(C2H5)3 , 2-chloroethylornine hydrochloride N-(2-chloroethy1)- lfosfornide 3-hydroxypropylomine hydrochloride (cf. trofosfomide synthesis) Reference(s): DAS 1 645 921 (ASTA-Werke; appl. 1 1.7.1966). Formulation(s): vial 200 mg, 500 mg, I g, 2 g (dry powder) Trade Nameis): D: Holoxan (ASTA Medica GB: Mitoxana (ASTA Medica) USA: Ifex (Bristol-Myers AWD) I: Holoxan (ASTA Medica) Squibb) F: Holoxan (ASTA Medica) J: Ifomide (Shionogl) Iloprost (Ciloprost; E- 1030; SH-401; ZK-36374) ATC: BOlAC11 Use: vasodilator, platelet aggregation inhibitor RN: 78919-13-8 MF: C2,H,204 MW: 360.49 CN: 5-[Hexahydro-5-hydroxy-4-(3-hydroxy-4-methyl-l-octen-6-ynyl)-2(1H)-pentalenylidene]pentanoic acid (4R) RN: 74843-30-4 MF: C,,H3,04 MW: 360.49 (4s) RN: 74843-14-4 MF: C,,H,,O, MW: 360.49 trometamol salt RN: 73873-87-7 MF: C2,H43N07 MW: 481.63 Iloprost I 1049 (-)-Corey loctone derivative (cf. dinoprost) 1. ~i/hO4~3 , THF 0 2. Tos-OH. toluene 3. K,CO,. CH3OH 1. lithium ethyl ocetote cro, (n) I.(() , toluene H~,,O WEl - N(C2H5)3 3. NaBH,. CH30H 3. CH3COOH, H20, THF I + 0 H @ * In 1. Collin's oxidation 1. DABCO 2. 1 -5-diazobicyclo- 2. benzoyl chloride [4.3.0]non-5-ene (DEN) 1.10s-OH \ CH3 v HO HO OHC O (_+)-dimethyl 3-methyl- ' 2-0x0-5-heptynyl- (no ethylene phosphonote (N) glycol 1 NoBH,, CH30H 2 K2COJ, CH,OH 3 CH3COOH. H20, THF , Tos-OH - 4 dihydropyron H3C-CEC 1. NaH. DMSO. chromatographic separation 2 CH3COOH, H20, THF YI + 2. acetic ocid 4-corboxybutylidene- lloprost triphenylphosphorane sodium solt (VII) 1050 1 Iloprost preporotion of 4 corboxybutylidenetriphenylphosphorone sodium solt 2. DMSO. NOH B,-COOH b VII 1. triphenylphosphine 5-bromopentonoic acid preporotion of (?)-dimethyl 3-methyl-2-0x0-5-heptynylphosphanote 1-brorno-2-butyne diethyl rnethylmolonote CH3 LiCI. DMSO. A H3C\ CH BuLi, DMSO vII1 b c'C,,$b,~~3 N 0 Reference(s): DE 2 845 770 (Schering AG; D-prior. 19.10.1978) DE 3 839 155 (Schering AG; D-prior. 17.1 1.1988) Skuballa, W.; Vorbrueggen, H.: Angew. Chem. (ANCEAD) 93 (12), 1080 (1981) preparation of 4-carboxybutylidenetriphenylphosphorane sodium salt: Martinelli, M.J.: J. Org. Chem. (JOCEAH) 55 (17), 5065 (1990). Johnson, F.P. et al.: J. Am. Chern. Soc. (JACSAT) 104 (a), 2190 (1982). Niwa, H. et al.: Tetrahedron (TETRAB) 50 (25), 7385 (1994). preparation of (+)-dimethyl 3-methyl-2-0x0-5-heptynylphosphonate: DE 2 729 960 (Schering AG; prior. 30.6.1977). footnote [6] in: Skuballa, W.; Vorbrueggen, H.: Angew. Chem. (ANCEAD) 93 (12), 1080 (1981). (a- or (a-selective Wittig reactions in the synthesis of carbacyclins: Westermann, J.; Harre, M.; Hickisch, K.: Tetrahedron Lett. (TELEAY) 33 (52), 8055 (1992). alternative synthesis of cis-bicyclo/3.3.0]oc~ylidene derivative: EP 153 822 (Sagami Chemical Research Center; J-prior. 10.2.1984). Sodeoka, M.; Ogawa, Y.; Kirio, Y.; Shibasaki, M.: Chem. Pharm. Bull. (CPBTAL) 39 (2), 309 (1991) Formulation(s): amp. 50 pg10.5 mi, 100 pg/l ml (as trometamol salt) . 2-( 10-hydroxydecyl )-5 ,6-dimethoxy-3-methyl-2,5-cyclohexadiene-l,4-dione 3.4.5-trirnethoxy- ethyl 9-chloroforrnyl- toluene nonanoote 9-( 2-hydrory-3.4-dirnelhoxy- 6-methylbenzoyl)nononoic ocid (I) OH Zn-Hg 4-0 -dernethyldouno- mycinone 19-ethylene acetol (I) 4-0 -dernethyl- 4-0 -( p- toluenesulfonyl)dauno- rnycinone 19-ethylene acetal (11) 1044 1 Idarubicin 4-methoxy- benzylomine acid 4-demethoxy- 4-( 4-methoxy-. E- 1030; SH-401; ZK-36374) ATC: BOlAC11 Use: vasodilator, platelet aggregation inhibitor RN: 7891 9-1 3-8 MF: C2,H,204 MW: 360.49 CN: 5-[ Hexahydro-5-hydroxy- 4-( 3-hydroxy-4-methyl-l-octen-6-ynyl )-2 (1H)-pentalenylidene]pentanoic