Imidapril I 1051 Trade Name(s): D: Ilornedin (Schering; 1992) I: Endoprost (Schering) F: Ilornedine (Schering) Ilomedin (Schering) Imidapril (TA-6366) ATC: C09A Use: antihypertensive (ACE inhibitor) RN: 89371-37-9 MF: C,,,H2,N30, MW: 405.45 CN: [4S-[3[R*(R*)],4R*]]-3-[2-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]-I-oxopropyl]-l-methyl-2-oxo-4- imidazolidinecarboxylic acid munohydrochloride RN: 89396-94- 1 MF: C,,H,,N,O, . HC1 MW: 44 1.9 1 N COOH + (25)-2-[(IS)-1 -ethoxy- corbonyl-3-phenyl- propy~omino]propionic ocid benzyl (4s)-I-methyl- 2-0x0-imidorolidine- 4-cahaxylate DCC. THF. (2s)-2-[(lS)-1-ethoxy- corbonyl-3-phenylpropyl- omino]propianic ocid succinimido ester (1) KOC(CH,)~ TW. -40 OC ', 0 benzyl (45)-1-methyl-3-[(lS)- 2-[(1S)-1-ethoxycarbonyl-3-phenyl. prapylomino]propionyI]-2-0x0- imidozolidine-4-corboxyl~te (11) H Pd-C. ethanol u lmidopril 1052 1 Imipenem tert-butyl (4s)- 1 - (2R)-2-(p-toluene- methyl-2-oxoimi- sulfonyloxy)pro- dozolidine 4-corboxylote pionyl chloride tert-butyl (4s)-1- methyl-3-[(2R)-2- (p- toluenesulfonyloxy)- propionyl]-2-oxoimida- zolidine-4-carboxylate (nl) HCI, dioxane ethyl (2s)-2- amino-4-phenyl- butyrate Reference(s): a EP 95 163 (Tanabe Seiyaku; appl. 20.5.1983; J-prior. 24.5.1982). b EP 373 881 (Tanabe Seiyaku; appl. 12.12.1989; J-prior. 16.12.1988). formulation with increased stability: JP 06 100 447 (Tanabe Seiyaku; appl. 24.9.1992; J-prior. 24.9.1992). composition for treatment of kidney diseases: JP 272 849 (Tanabe Seiyaku; appl. 10.12.1987; J-prior. 12.12.1986). composition for treatment of heart failure: EP 274 230 (Tanabe Seiyaku; appl. 8.12.1987; J-prior. 9.12.1986). Formulation(s): tabl. 2.5 mg, 5 mg, 10 mg (as hydrochloride) Trade Narne(s): J: Novaroc (Nihon Schering) Tanatril (Tanabe Seiyaku) Imipenem (Imipemide) ATC: JOlDH51 Use: p-lactam antibiotic RN: 64221-86-9 MF: C,,HI,N,04S MW: 299.35 EINECS: 264-734-5 LD,,,: 1660 mgkg (M, i.v.); >5 glkg (M, p.0.); 1972 mglkg (R, i.v.); >5 glkg (R, p.0.) CN: [5R-[5a,6a(R*)]]-6-(1-hydroxyethyl)-3-[[2-[(iminomethyl)amino]ethyl]thio]-7-oxo-l- azabicyclo[3.2.O]hept-2-ene-2-carboxylic acid monohydrate RN: 7443 1-23-5 MF: C,,H,,N,04S . H20 MW: 317.37 Imipramine 1 1053 COOH HOWS + H3C\O~NH e HCI + pH 8.5 k H3C H NH2 Reference(s): Leanza, W.J. et al.: J. Med. Chem. (JMCMAR) 22, 1435 (1979). US 4 194 047 (Merck & Co.; 18.3.1980; prior. 21.11.1975). DOS 2 652 679 (Merck & Co.; appl. 19.1 1.1976; USA-prior. 21.1 1.1975). COOH B7\N H thienamycin methyl formimidate production of thienamycin (by fermentation of S. cattleya): US 3 950 357 (Merck & Co.; 13.4.1976; appl. 25.1 1.1974). DOS 2 552 638 (Merck & Co.; appl. 24.1 1.1975; USA-prior. 25.11.1974). lmipenem combination with cilastatin: EP 48 301 (Merck & Co.; appl. 24.9.1980). hydrochloride Formulation(s): amp. 250 mg, 500 mg; vial 200 mg, 500 mg Trade Name(s): D: Zienam (MSD; 1985)- I: Imipem (Neopharmed)- all combination comb. with cilastatin comb. preparations with cilastatin F: Tiham (Merck Sharp & Tenacid (Sigma-Tau)- J: Tienam (Banyu; 1987)- Dohme-Chibret)-comb. comb. comb. with cilastatin GB: Primaxin IV (Merck Sharp Tienam (MSQ)-comb. sodium & Dohme) USA: Primaxin (Merck; 1985) Imipramine ATC: N06AA02 Use: antidepressant RN: 50-49-7 MF: C,,H2,N2 MW: 280.42 EINECS: 200-042-1 LD,,,: 21 mglkg(M, i.v.); 188 mglkg (M,p.o.); 9300 pglkg (R, i.v.); 250 mglkg (R, p.0.) CN: 10,11-dihydro-N,N-dimethyl-5H-dibenz[b~azepine-5-propanamine monohydrochloride RN: 113-52-0 MF: C,,H,,N,. HC1 MW: 316.88 EINECS: 204-030-7 LD,,: 27 mgkg (M, i.v.); 275 mglkg (M, p.0.); 18 mgkg (R, i.v.); 305 mglkg (R, p.0.) 2. CI N/CH3 I C"3 b 1. sodium amide 2. 3-dimethylamino- propyl chlaride 10,ll -dihydro-5H- dibenz[b,f]azepine Reference(s): US 2 554 736 (Geigy; 1951; CH-prior. 1949). DE 829 167 (Geigy; appl. 1950; CH-prior. 1949). 1054 I Imiquimod Formulntion(s): amp. 25 mg12 ml; cps. 75 mg, 100 mg, 125 mg, 150 mg; drg. 10 mg, 25 mg, 50 mg (as hydrochloride) Trade Narne(s): D: Imipramin (neuraxpharm; as hydrochloride) Pryleugan (ASTA Medica AWD; as hydrochloride) Tofranil (Novartis Pharma; as hydrochloride) F: Tofranil (Navartis; as hydrochloride) GB: Torrani1 (Novartis; as hydrochloride) I: Imipra C (Formulario Naz.) Tofranil (Novartis) combination preparations J: Depress (Toho) USA: Efuranol (Taito Pfizer) Feinalmin (Sanko) Imidol (Yoshitomi) Imilanyle (Takata) Meripramin (Kanebo Nakataki) Tohanil (Novartis) Tofranil (Novartis; as pamoate) generic Imiquimod ATC: D06BB10 Use: immunornodulator, interferon alfa inducer, antiviral RN: 9901 1-02-6 MF: C,,H,,N, MW: 240.31 CN: 1 -(2-Methylpropy1)- 1 H-imidazo[4,5-c]quinolin-4-amine hydrochloride RN: 9901 1-78-6 MF: C,,HI,N4 . HCI MW: 276.77 0 1. NoNJ, CHJCOOH 2. oq NoOH CH3 1. sodium ozide onthronilic ocetic anhydride 2-methyl-4- acid 0x0-3,) -benz- o~ozine 2-(5-methyl- iodoethone ethyl 2-(5-methyl- 1H-tetrozol-1 -yl)- 1H-tetrozol-1 -yl-)- benzoic ocid (I) benzoate 1. HNO, p: 4-nitrotetrozolo[l,5-a]- quinolin-5-yl trifluoro- ocetote (111) NH2 isobutylomine (N) diethoxymethyl ocetate triphenyl- phosphine 1. aq. HCI. CH3OH 2. aq. NoOH W - 6-(2-rnethylpropy1)-6H- irnidozo[4.5-c]tetrozolo- [1,5-alquinoline (VI) &N ____, N N 1,2-dichloro- benzene H3c~cH3 &N N NH, lmiquirnod 4-hydroxy-3- nitroquinoline (VIII) 4-chloro-3- nitroquinoline 1056 1 Imiquimod H,C CH, Y HZ. Pt-C. toluene d 1 -(2-methylpropy1)- 1 H-imidozo[4.5-c]- quinoline 5-oxide (X11) 1. H3C20407 (XI), 125OC CH3 2. CH3COOH, HZOZ 1. triethyl orthoformate 2. ocetic ocid, hydrogen peroxide (XI POCI3. DMF, 2O0C ___* lmiquimod 1. SOCl,, CHZCIZ, DMF (cot.) HNO,. 2. N. CH2CIz. N(C,H,), H,C"COOH , M propionic 1. thionyl chloride acid 2. isobutylomine 4-hydroxy- quinoline Hz. Pt-C, MgSO, 1. HCOOH. A ethyl ocetote 2. H,C-CO-0-OH, CH,COOH . x , w 1. formic acid 2. peroxyocetic acid H,C CH, Y benzoyl isocyonote 1. HN03, CH3COOH, 40°C 2. F,C-SO,-0-SO, CF3 . CH2C12, N(C2H5), 0 2. trifluoromethonesulfonic anhydride 4-hydroxy-Z(1H)- quinolinone (XN) Imiquimod 1 1057 En: 0 or XI XVll sodium borohydride, nickel chloride B~ or triethyl orthoformote Hz. Pd-C. CzH50H _____, Imiquimod - - 2. POCI3, pyridine or toluene, 50°C xnr 2.4-dichloro-3- nitraquinoline (XVIII) 2-chloro-N4-(2-methyI- propyl)-3,4-quinoline- diomine (XK) NH,, CH,OH. 150°C. XI, BO°C skeel bomb , XIII . 1. POCI3, DMF 2. IV, N(%C5)3 H2, Pt-C. toluene Vlll b IX x 1058 1 Imolamine 1. XI, 185T 1. POCIS. OMF, 10°C 2. CHSCOOH. H202 2. NH3. CH30H. 145OC 1-xu- 1. triethyl orthoformate 2. hydrogen peroxide Rejkrence(s): a WO 9 748 704 (Minnesota Mining and Manufacturing Company; appl. 22.10.1996; USA-prior. 21.6.1996). b EP 145 340 (Riker Lab.; appl. 16.11 .l984; USA-prior. 18.11.1983). c WO 9 215 581 (Minnesota Mining and Manufacturing Company; appl. 13.2.1992; USA-prior. 1.3.1991). d WO 9 417 043 (Minnesota Mining and Manufacturing Company; appl. 25.1 .l994; USA-prior. 29.1.1993). e US 4 988 815 (Riker Lab.; 29.1.1991; USA-prior. 26.10.1989). f US 4 689 338 (Riker Lab.; 25.8.1987; USA-prior. 18.1 1.1983). Formulation(s): cream 5% Trade Name(s): D: Aldara (3M Medica Lab.; GB: Aldara (3M Health Care) USA: Aldara (3M Pharm.; 1997) 1998) I: Zarta (3M Medica) Imolamine ATC: COlDX09 Use: coronary vasodilator, antianginal RN: 3 18-23-0 MF: C,,H,,N,O MW: 260.34 EINECS: 206-267- 1 CN: N,N-diethyl-5-imino-3-phenyl- 1,2,4-oxadiazol-4(5H)-ethanamine monohydrochloride RN: 15823-89-9 MF: C,,H,N,O . HCI MW: 296.80 EINECS: 239-920-4 LD,,: 25 mgkg (M, i.v.); 475 mglkg (M, p.0.); 650 mglkg (R, p.0.) w \=/ hydroxyl- - cyonomide - - benzaldehyde omine 1.2.4-oxodiazole (1) ethyl chloride \ Reference(s): FR 2 023 M (J. Marcel, D. Aron-Samuel, J J. Sterne; appl. 10.10.1962; GB-prior. 12.6.1962, 11.7.1961). Formulation(s): inj. sol. 50 mg/5 ml; tabl. 30 mg Trade Name(s): D: Irrigor (Karlspharma); wfm I: Irrigor (Lipha); wfm F: Irrigor (Aron); wfm Irrigor Aron (Spemsa); wfm Improsulfan ATC: LO1 Use: antineoplastic RN: 13425-98-4 MF: CRH19N0,S2 MW: 289.37 CN: 3,3'-iminobis[l -propanoil dimethanesulfonatc (ester) R R I1 II HOr\/'RwOH + H3C-S-0-S-CH, oceto- 0 0 nitrile Reference(s): Sakurai, J.; El-Merzabani, M.M.: Chem. Pharm. Bull. (CPBTAL) 12, 954 (1964). bis(3-hydroxypropy1)- rnethonesulfonic sulfonic acid salts: DOS 2 059 377 (Yoshitomi; appl. 2.12.1970; J-prior. 2.12.1969, 12.8.1970). GB 1 272 497 (Yoshitomi; appl. 25.12.1970; J-prior. 2.12.1969, 12.8.1970). lrnprosulfon Formulation(s): tabl. 10 mg ornine anhydride Trade Name(s): J: Protecton (Yoshitomi; as tosylate) Incadronic acid 'use: bone resorption inhibitor, antiarthritic agent RN: 124351-85-5 MF: CRH,,N0,P2 MW: 287.19 CN: [(Cycloheptylarnino)methylene]bis[phosphonic acid] disodium salt monohydrate RN: 183808-97-1 MF: CxH,,NNa20,P2 . H20 MW: 349.17 disodium salt RN: 138330-18-4 MF: C8HI,NNa,0,P2 MW: 33 1 .I5 CH3 cycloheptyl- triethyl diethyl phosphite mine orthaformate 1060 1 Indalpine conc. HCI ___* tetroethyl (cyclo- heptylamino)methylene- bis(phosphanate) (I) Reference(s): EP 325 482 (Yamanouchi Pharm. Co.; appl. 20.1.1989; J-prior. 20.1.1988) Takeuchi, M.; Sakamoto, S.; Yoshida, M.; Abe, T.; Isomura, Y.: Chem. Pharm. Bull. (CPBTAL) 41 (4), 688 (1 993) oral pharmaceutical compositions: EP 550 385 (Ciba-Geigy A. G.; appl. 11.12.1992; CH-prior. 19.12.199 1) pharmaceutical compositions: EP 693 285 (Eli Lilly & Co.; appl. 20.7.1995; USA-prior. 22.7.1994) Formulation(s): amp. 10 mg Trade Name(s): J: Bisphonal (Yamanouchi; 1997) Indalpine ATC: N06B Use: antidepressant, selective serotonin- uptake inhibitor RN: 63758-79-2 MF: C,,H2,N2 MW: 228.34 EINECS: 264-445-4 CN: 3-[2-(4-pipendiny1)ethyll-1 H-indole monohydrochloride RN: 63845-42-1 MF: C,,HzONz . HC1 MW: 264.80 LD,,,: 60 mgkg (M, i.v.); 600 mgkg (M, p.0.) 4-piperidine- benzyl 0' N-benzyloxycarbonyl- acetic acid chloroformate 4-piperidineacetic acid 1. CH3-MgI 2. HCI 1. methyl- cr::H magnesium iodide 3-indolyl 4-piperidylmethyl ketone (II) . 1 - (2R )-2 -( p-toluene- methyl-2-oxoimi- sulfonyloxy)pro- dozolidine 4-corboxylote pionyl chloride tert-butyl (4s )-1 - methyl- 3-[ (2R )-2 - (p- toluenesulfonyloxy )- propionyl ]-2 -oxoimida- zolidine-4-carboxylate. anhydride 2-methyl- 4- acid 0x 0-3 ,) -benz- o~ozine 2-( 5-methyl- iodoethone ethyl 2-( 5-methyl- 1H-tetrozol-1 -yl )- 1H-tetrozol-1 -yl- )- benzoic ocid (I) benzoate 1. HNO, p: 4-nitrotetrozolo[l,5-a ]-. (45 )-1 -methyl- 3-[ (lS )- 2-[ (1S )-1 -ethoxycarbonyl-3-phenyl. prapylomino]propionyI ]-2 -0 x 0- imidozolidine-4-corboxyl~te (11) H Pd-C. ethanol u lmidopril 1052 1 Imipenem tert-butyl (4s)-