Isoetarine 1 1 101 N Br2. CH30H CI bromine CI imidozole 2'.4'-dichloro- ocetophenone 2-bromo- 2',4'-dichloro- acetophenone NaBH4. CH30H I - sodium 2.6-dichloro- borohydride benzyl chloride 1-(2.4-dichloro- phenyl)-2-(1H- imidazol-1 -yl)- ethonol 1 -(2,4-dichloro- phenocyl)irnidozole (I) DOS 1 940 388 (Janssen; appl. 8.8.1969; USA-prior. 19.8.1968). US 3 717 655 (Janssen; 20.2.1973; prior. 19.8.1968,23.7.1969). US 3 839 574 (Janssen; 1.10.1974; prior. 19.8.1968, 23.7.1969, 19.7.1972). Godefroi, E.F. et al.: J. Med. Chem. (JMCMAR) 12,784 (1969). Forrnulation(s): cream 10 mglg (1 %); pessaries 100 mg,300 mg, 600 mg (as nitrate); spray 10 mglml Trade Name(s): D: Bi-Vaspit (Axhe)-comb. F: Fazol (Bellon; RhBne- Travocort (Schering)-comb. Travocort (Schering)-comb. Poulenc Rorer; 1979) Travogen (Schering) Travogen (Schering; 1979) GB: Travogyn (Schering) J: Adestan (Schering) I: Isogyn (Crosara) Isoetarine (Etyprenalinum; Isoetharine) ATC: R03AC07; R03CC06 Use: bronchodilator, sympathomimetic RN: 530-08-5 MF: C,,H2,N03 MW: 239.32 EINECS: 208-472-1 CN: 4-[l-hydroxy-2-[(l-methylethyl)amino]butyl]-1,2-benzenediol hydrochloride RN: 50-96-4 MF: C,,H2,N03. HCI MW: 275.78 LD,,: 57 mgkg (M, Lv.) H3C ,I isopropylamine T.4'-dibenzyloxy- butyrophenone 1102 1 Isoflupredone acetate Reference(s): DRP 638 650 (I. G. Farben; 1934). lsoetorine Formulation(s): amp. 1 mg, 2.4 mg, 5 mg, 5.1 mg; sol. for inhalation 0.125 %, 0.61 %, 1 % (as hydrochloride) Trade Name(s): D: Asthmalitan (Kettelhack- GB: Bronchilator (Sterling USA: Bronkometer (Sanofi)- Riker); wfm Res.); wfm comb. Numotac (Riker); wfm Bronkosol (Sanofi)-comb. Isoflupredone acetate ATC: H02AB Use: glucocorticoid RN: 338-98-7 MF: C2,H2$0, MW: 420.48 EINECS: 206-423-9 CN: (ll~)-21-(acetyloxy)-9-fluoro-11,17-dihydroxypregna-l,4-diene-3,20-dione isotlupredone RN: 338-95-4 MF: C2,H2,F0, MW: 378.44 EINECS: 206-422-3 Se02 (H3C)3C-OH, Roney-Ni - selenium dioxide tert-butonol fludrocortisone 21 -acetote (cf. fludrocortisone synthesis) Isoflupredone acetate DE 1 096 900 (American Cyanamid; appl. 1959; USA-prior. 1958). microbiological dehydrogenation with Corynebacterium simplex (A.T.C.C. 6946): US 2 837 464 (Schering Corp.; 1958; prior. 1955). alternative synthesis: DE 1 159 947 (Merck & Co.; appl. 1956; USA-prior. 1955). GB 826 364 (Merck & Co.; valid from 1956; USA-prior. 1955). Formulation(s): amp. 10 ml Trade Name(s): I: Altaflor (1ntes)-comb.; wfm Biorinil (Farmila)-comb.; wfm Cortifluoral (Schering); Dermaflogil (Nuovo Cons. wfm Sanit. Naz.)-comb.; wfm Isoflurane 1 1103 Fluoroinil (Farmila)-comb.; Menaderm simp. USA: Predef 2x (Upjohn); wfm wfm (Menarini); wfm Isoflurane ATC: NOIAB06 Use: inhalation anesthetic RN: 26675-46-7 MF: C,H,CIF,O MW: 184.49 EINECS: 247-897-7 LD,,: 5080 yL1kg (M, p.0.); 4770 yLlkg (R, p.0.) CN: 2-chloro-2-(difluoromethoxy)- 1,1,1-trifluoroethane 2,Z.Z-trifluoro- dimethyl ethanol sulfate HZF,. SbCI, 1- hydrogen fluoride. F~C-O antimony pentochloride DOS 1 814 962 (Air Reduction Comp.; appl. 16.12.1968; USA-prior. 15.1 2.1967, 22.5.1968). US 3 535 388 (Air Reduction Comp.; 20.10.1970; prior. 15.12.1967, 21.3.1969). US 3 535 425 (Air Reduction Comp.; 20.10.1970; prior. 15.1 2.1967, 18.12.1969). alternative synthesis: DOS 2 344 442 (Hoechst; appl. 4.9.1973). US 3 637 477 (Air Reduction Comp.; 25.1.1972; prior. 20.2.1970, 22.5.1968). Formulation(s): sol. for inhalation 100 ml Trade Narne(s): D: Forene (Abbott; 1984) J: Forane (Dainabot) USA: Forane (Ohmeda; 198 1 ) Isoflurophate - (Difluorophate) ATC: SO3 Use: parasympathomimetic, miotic RN: 55-91-4 MF: C,H,,FO,P MW: 184.15 EJNECS: 200-247-6 LD,: 3200 yg/kg (M, i.v.); 2 mglkg (M, p.0.); 5 mg/kg (R, p.o.1; 3430 yglkg (dog, i.v.) CN: phosphorofluoridic acid bis(1-methylethyl) ester isopropyl phosphorus alcohol trichloride diisopropyl phosphite 1 104 1 Isometheptene lsoflurophote Reference(s): US 2 409 039 (Monsanto; 1946; appl. 1944). Formulatiorz(s): eye drops 0.01 %; eye ointment 0.025 % Trade Name(s): F: Diflupyl (Labaz); wfm USA: Floropryl (Merck Sharp & J: D. F. P. Inj. (Sumitomo) Dohme); wfm Isometheptene ATC: A03AX10 Use: sympathetic antispasmodic for gut and urinary tract RN: 503-01-5 MF: CYH,,N MW: 141.26 EINECS: 207-959-6 LD,,,: 34 mgkg (M, i.v.); 134 mgkg (M, p.0.) CN: N,6-dimethyl-5-hepten-2-amine hydrochloride RN: 6168-86-1 MF: C,HlyN. HC1 MW: 177.72 EINECS: 228-21 1-5 LD,,,: 18 mglkg (M, i.v.); 26 mglkg (dog, i.v.) tartrate (1:l) RN: 5984-50-9 MF: C,H,,N . C,H,O, MW. 291.34 EINECS: 227-795-9 LD,,: 130 mglkg (R, i.p.) 2-methy!-6-0x0- methylomine 2-heptene Isometheptene Reference(s): US 1 972 450 (Knoll; 1934; D-prior. 1931). US 2 230 753 (E. Bilhuber; 1941; D-prior. 1937). US 2 230 754 (E. Bilhuber; 1941; D-prior. 1937). Formulation(s): amp. 100 mg (as hydrochloride); drops 100 mg, 50 mg; tabl. (as tartrate) Trade Namefs): D: Neopyrin (Nordmark)- GB: Midrid (Shire)-comb. USA: Duradrin (Duramed; as comb.; wfm I: Octinum (Knoll); wfm mucate)-comb. Neosal (Nordmark)-comb.; J: Cesal (Dainippon)-comb. Midrin (Camrick; as wfm mucate) Isoniazid 1 1105 Isoniazid ATC: J04ACOI Use: tuberculostatic RN: 54-85-3 MF: C,H,N,O MW: 137.14 EINECS: 200-214-6 LD,,: 149 mglkg (M, i.v.); 133 mgkg (M, p.0.); 365 mgkg (R, i.v.); 1250 mg/kg (R, p.0.); 50 mgkg (dog, p.0.) CN: 4-pyridinecarboxylic acid hydrazide HZN-NHZ b hydrazine H ethyl isonicotinate lsoniozid u Reference(s): Meyer, H.; Mally, J.: Monatsh. Chem. (MOCMB7) 33, 393 (1912). US 2 596 069 (Roche; 1952; appl. 1952). US 2 830 994 (Distillers; 15.4.1958; GB-prior. 29.6.1955). DE 1 116 667 (BASF; appl. 3.7.1956). combination with protionamide and dapsone: DAS 2 340 515 (Saarstickstoff-Fatol; appl. 10.8.1973). Formulation(s): amp. 100 mg15 ml, 250 mg/5 ml; tabl. 50 mg, 100 mg, 200 mg, 300 mg Trade Name(s): D: Isoprodian (Fato1)-comb. Isozid (Fatol) Myambutol (Leder1e)- comb. Tebesium (Hefa Pharma) F: Dexambutol-INH (LIArguenon)-comb. Rifater (Marion Merrel1)- comb. Rifinah (Marion Merrel1)- comb. Rimifon (Roche) GB: Rifater (Hoechst)-comb. Rifinah (Hoechst)-comb. Rimactazid (Novartis)- comb. Rimifon (Roche); wfm I: Emozide B6 (Piam)-comb. Etanicozid (Piam)-comb. Etibi (Zoja)-comb. Miazide (Cyanamid)-comb. Nicazide (In) Nicizina (Pharmacia & Upjohn) Nicozid (Piam) Rifanicozid (Piam)-comb. Rifinah (Lepetit)-comb. combination preparations J: Anteben (Dainippon) Diazid (Nippon Shinyaku) Hycozid (Takeda) Hydra (Otsuka) Iscotin (Daiichi) Niazid (Sankyo) Niplen (Tanabe) Sumifon (Sumitomo) Tuberon (Shionogi) USA: Nydrazid (Apothecon) Rifamate (Hoechst Marion Roussel) Rifater (Hoechst Marion Roussel) generic Isoprenaline (Isoproterenol) ATC: COlCA02; R03AB02; R03CBOI Use: bronchodilator, dermatic RN: 7683-59-2 MF: C, ,H,,NO, MW: 21 1.26 EINECS: 23 1-687-7 LD,,: 83 mgkg (M, i.v.); 450 mgkg (M, p.0.); 57 mgkg (R, i.v.); 355 mg/kg (R, p.0.); 50 mgkg (dog, i.v.); 600 mglkg (dog, p.0.) CN: 4-[l-hydroxy-2-[(l-methylethyl)amino]ethyl]-l,2-benzenediol 1 106 1 Isopropamide iodide bitartrate (1:l) RN: 59-60-9 MF: C,,H,,NO, . C,H,O, MW: 361.35 EINECS: 200-437-9 hydrochloride RN: 51-30-9 MF: C,,H,,NO, . HCI MW: 247.72 EINECS: 200-089-8 LD,,, 77 mglkg (M. i.v.); 1260 mglkg (M, p.0.); 26.9 mglkg (R, i.v.); 2221 mglkg (R, p.0.); 50 mglkg (dog, i.v.); 600 mgkg (dog, p.0.) sulfate (21) RN. 299-95-6 MF: C,,H,,N03 . 112H2S04 MW: 520.60 EINECS: 206-085-2 LD,,,: 188 mglkg (M, i.v.); >3 glkg (M, p.0.); 96 mglkg (R, i.v.); 2230 mg/kg (R, p.0.); 50 mglkg (dog, i.v.); 600 mglkg (dog, p.0.) 2-chloro-3'.4'-di- isopropylarnine hydroxyacctophenone lsoprcnoline I Reference(s): US 2 308 232 (Boehringer Ing.; 1943; D-prior. 1939). DRP 723 278 (Roehringer Ing.; appl. 1939). racemate resolution with (+)-tartaric acid: US 2 715 141 (Delmar Chemicals; 1955; appl. 1952). Fornzulation(s): aerosol 0.1 mglpush; amp. 0.2 mg, 2 mg (as hydrochloride); sol. for inhalation 0.25 %, 0.5 % (as sulfate); tabl. 10 mg, 15 mg, 20 mg Trade Narrre(s): D: lngelan (Roehringer Ing.) J: Asthpul Sol. (Nippon Kattwilon (Kattwiga) Shoji) I;: lsuprel (Abbott) Isomeny 1 (Kaken) generic Medihaler-Iso (Dainippon) USA: GB: Saventrine (Pharmax) Protemal (Nikken) I: Aleudrin (Fher); wfm Proternol (Nikken) generics Sedansol "Iso" (Nippon Zoki) Sooner (Kaken) Isuprel (Sanofi; as hydrochloride) Medihaler-Iso (3M; as sulfate) Isopropamide iodide ATC: A03AR09 IJse: anticholinergic, antispasmodic RN: 71-81-8 MF: C23H,,IN,0 MW: 480.43 EINECS: 200-766-8 LD,,,: 12.779 &/kg (M, i.v.); 1600 mgkg (M, p.0.) CN: y-(aminocarbonyl)-N-methyl-N,N-bis(l-methylethyl)-y-phenylbenzenepropanaminium iodide Isosorbide dinitrate 1 1 107 H C CH3 = Y '.HC N 3 y -cl CH3 b 1. sodium ornide 2. 2-diisopropylarnino- diphenyl- ethyl chloride acetonitrile (1) methyl iodide Reference(s): GB 772 921 (Janssen; appl. 1955: NL-prior. 1954). DE 1 003 744 (Janssen; appl. 1955; NL-prior. 1954). Janssen, P. et al.: Arch. Int. Pharmacodyn. Ther. (AIPTAK) CIII, 82 (1955). US 2 823 233 (Bristol; 1958; appl. 1954). Formulation(s): inj. sol. 3 mg12 ml; tabl. 5 mg Trade Narne(s): Ornatos (Rohm Pharma)- comb.; wfrn Priamide-Eupharma (Janssen); wfrn Stelabid (Rohm Pharma)- comb.; wfrn Enuretine vit. E isoprapamide (Le Marchand)-comb.; wfrn Priamide (Delalande); wfrn GB: Stelabid (S.K.F.)-comb.; wfrn Tyrimide (Smith Kline & French); wfrn I: Fluvaleas (Valeas)-comb. Iodosan (SmithKline Beecham)-comb. Valtrax (Valeas) combination preparations J: Marygin M (Sumitomo) USA: Combid (Smith Kline & French); wfrn Darbid (Smith Kline & French); wfrn Ornade (Srnilh Kline & French); wfrn Prochlor-lso (Schein); wfrn Pro-Iso (Zenith); wfrn Isosorbide dinitrate ATC: D03AX08 Use: coronary vasodilator RN: 87-33-2 MF: C,H,N20, MW, 236.14 EINECS: 201-740-9 LD,,: >40 mglkg (M, i.v.); 1050 mglkg (M, p.0.); >40 mglkg (R, i.v.); 747 mglkg (R, p.0.) CN: 1,4:3,6-dianhydro-D-glucitol dinitrate D-sorbitol isosarbide I lsosorbide dinitrote ( 1108 1 Isosorbide mononitrate Referencefs): Goldberg, L.: Acta Physiol. Scand. (APSCAX) 15, 173 (1948). Krantz, J.C. et a].: J. Pharmacol. Exp. Ther. (JPETAB) 67, 187 (1939). aqueous solutions,for parenteral application: DAS 2 623 800 (Sanol Schwarz-Monheim; appl. 28.5.1976). I;ormulation(s): r. r. cps. 20 mg, 40 mg, 60 mg, 80 mg, 100 mg; tabl. 2.5 mg, 5 mg, 10 mg, 20 mg, 30 mg, 40 mg Trade Name(s): D: Corovliss (Boehringer Mannh.) Dignonitrat (Sankyo) Duranitrat (durachemie) isoket (Schwarz) Iso Mack (Mack, Illert.) Isostenase (Aiuchemie) May cor (Godecke; Parke Davis) Nitrosorbon (Pohl) TD spray Iso Mack (Mack) generic and numerous combination preparations F: Isocard (Bouchara) Langoran (Marion Merrell) Risordan (Specia) GB: Cedocard retard (Phannacia & Upjohn) Isocard (Eastern) Isoket retard (Schwarz) Isordil (Monmouth) Sorbichew (Zeneca) Sorbid SA (Zeneca) Sorbitrate (Zeneca) 1: Carvasin (Wyeth) Diniket (Schwarz) Nitrosorbide (Lusofarmaco) Stenodilate (Schwarz)- comb. J: Cardis (Iwaki) Carvanil (Banyu) Diretan (Ono) Nitroret (Hishiyama) USA: Dilatrate-SR (Schwarz) Isordil (Wyeth-Ayerst) Sorbitrate (Zeneca) generic Isosorbide mononitrate (Isosorbide 5-nitrate) ATC: COlDA14 Use: . coronary vasodilator RN: 16051-77-7 MF: C6H9N06 MW: 191.14 EINECS: 240-197-2 LD,,: 1820 mglkg (M, i.v.); 1771 mgkg (M, p.0.); 1750 mglkg (R, i.v.); 2010 mglkg (R, p.0.) CN: 1,4:3,6-dianhydro-D-glucitol 5-nitrate HO H 1. HN03. Ac20, AcOH 2. NaOH. pH 7.0 0 H isosorbide (I) Isosorbide (cf. isosorbide mononitrate dinitrate synthesis) 0 CH3 pyridine, CH2CI2 AcOH. AC~O. HNO~ + 3KK + 0 0 isosarbide (olong with Isosorbide mononitrate 1 1109 isosorbide 2-acetate 5-nitrate (11) Reference(s): a US 3 886 186 (American Home; 27.5.1975; prior. 29.4.1971, 30.8.1973). EP 143 507 (Toshin Chemical; appl. 13.7.1984; J-prior. 25.1 1.1983). DOS 2 221 080 (American Home Products; appl. 28.4.1972; USA-prior. 29.4.1971). b DOS 2 751 934 (American Home Products; appl. 21.1 1 .l977; USA-prior. 24.2.1977). US 4 065 488 (American Home Products; 27.12.1977; appl. 24.2.1977). EP 45 076 (Boehringer Mannh.; appl. 25.7.1981 ; D-prior. 30.7.1980). DOS 3 028 873 (Boehringer Mannh.; appl. 30.7.1980). US 4 431 829 (Boehringer Mannh.; 14.2.1984; D-prior. 30.7.1980). similar methods (via 2-acyloxy derivative): DE 2 903 927 (Sanol-Schwarz; appl. 2.2.1979). EP 64 194 (Cassella; appl. 16.4.1982; D-prior. 5.5.198 1). EP 57 847 (H. Mack Nachf.; appl. 26.1.1982; D-prior. 29.1.1981). DOS 3 102 947 (H. Mack Nachf.; appl. 29.1.1981). EP 67 964 (H. Mack Nachf.; appl. 18.5.1982; D-prior. 22.6.1981). DOS 3 124 410 (H. Mack Nachf.; appl. 22.6.1981). US 4417 065 (H. Mack Nachf.; 22.1 1.1983; D-prior. 22.6.1981). preparation from isosorbide dinitrate: EP 59 664 (SNPE; appl. 25.2.1982; F-prior. 27.2.1981). formulations: DOS 3 325 652 (Dr. Rentschler; appl. 15.7.1983). Formulation(s): s. r. cps. 40 mg, 60 mg; tabl. 20 mg, 40 mg Trade Name(s): D: Coleb (AstraIPromed) Corangin (Novartis Pharma) elantan (Synthelabo) IS 5 mono-ratiopharm (ratiopharm) Ismo (Boehringer Mannh.) Monit-Puren (Isis Puren) Monoclair (Hennig) Mono Mack (Mack, Illert.) Monostenase (Azupharma) Olicard (Solvay Arzneimittel) numerous generics F: Monicor L.P. (Pierre Fabre) GB: Elantan (Schwarz) Imdur (Astra) isib XL (Ashbourne) Ismo retard (Boehringer Mannh.) MCR 50 (Pharmacia & Upjohn) Monit (Lorex) Mono-Cedocard (Pharmacia & Upjohn) Monomax (Trinity) I: Duronitrin (Astra) Elan (Schwarz) Ismo (Boehringer Mannh.) Ismo Diffutab (Boehringer Mannh.) Monocinque (Lusofarmaco) Monoket (Chiesi) Nitralfa (Malesci) Orasorbil (Rottapharm) dinitrate: Nltrosorbide (Lusofarmaco) Stenodilate (Schwarz)- comb. J: Itocol (Toa Eiyo- Yamanouchi) USA: Imdur (Key Pharm.) Ismo (Wyeth- Ayerst) Monoket (Schwarz) 11 10 1 Isothipendyl Isothipendyl ATC: D04AA22; R06AD09 Use: antiallergic, antihistaminic RN: 482-15-5 MF: CI6HIyN3S MW: 285.42 EINECS: 207-578-5 LD,,: 222 mglkg (M, p.0.) CN: N,N,~-trimethyl-lOH-pyrido[3,2-b][l,4]benzothiazine-lO-ethanamine monohydrochloride RN: 1225-60-1 MF: C16HlyN3S . HC1 MW: 321.88 EINECS: 214-957-9 LD,,: 28 mglkg (M, i.v.); 222 mglkg (M, p.0.); 1220 mglkg (R, p.0.) Reference(s): DE 1 001 684 (Degussa; appl. 1954). US 2 974 139 (Degussa; 7.3.1961; D-prior. 2.10.1954). Formulation(s): drg. 12 mg; gel 0.75 % (as hydrochloride) Trade Name(s): D: Andantol-fortel-Gelee GB: Nilergex (ICI); wfm J: Aczen NS (Kanebo) (Homburg); wfm I: Calmogel (RhGne-Poulenc Andantol (Sumitomo) F: SCdermyl (RPR Cooper) Rorer) Isotretinoin ATC: D10AD04; DIOBAOI Use: keratolytic, acne therapeutic RN: 4759-48-2 MF: C2,H2,02 MW: 300.44 EINECS: 225-296-0 LD,,,: 3389 mglkg (M, p.0.); >4 glkg (R, p.0.) CN: 13-cis-retinoic acid sodium salt RN: 13497-05-7 MF: C2,H2,Na02 MW: 322.42 potassium salt RN: 22232-80-0 MF: Ca,HZ7KO2 MW: 338.53 vinyl-8-ionol triphenyl- (cf. retinal synthesis phosphine ond tretinoin synthesis) . glucocorticoid RN: 33 8-9 8-7 MF: C2,H2$0, MW: 420.48 EINECS: 20 6-4 2 3-9 CN: (ll~ )-2 1-( acetyloxy )-9 -fluoro-11,17-dihydroxypregna-l,4-diene-3,20-dione isotlupredone RN: 33 8-9 5-4 MF: C2,H2,F0, MW:. 2'.4'-dichloro- ocetophenone 2-bromo- 2',4'-dichloro- acetophenone NaBH4. CH30H I - sodium 2.6-dichloro- borohydride benzyl chloride 1-( 2.4-dichloro- phenyl )-2 -( 1H- imidazol-1. sympathomimetic RN: 53 0-0 8-5 MF: C,,H2,N03 MW: 239.32 EINECS: 20 8-4 7 2-1 CN: 4-[ l-hydroxy- 2-[ (l-methylethyl)amino]butyl ]-1 ,2-benzenediol hydrochloride RN: 5 0-9 6-4 MF: C,,H2,N03. HCI MW: