I Nilutamide N 1441 f CH3 POCI, koo, + HNvCH3 - i kfc~3 N-CH3 1 oxychloride nicotinic diethylamine Nikethamide acid Reference(s): DRP 351 085 (Ciba; 1920). DRP 441 707 (Ciba; 1924). Fonnulation(s): drg. 50 mg in comb. (as calcium thiocyanate); powder 150 mg; sol. 250 mg/ml Trade Name(s): D: Felsol (Roland)-comb. GB: Coramine (Ciba); wfm J: Coramin (Ciba-Geigy- Zellaforte Plus (Eurim 1: Miocardina (Croce Takeda) Pharma)-comb. Bianca); wfm USA: Coramine (Ciba); wfm F: Coramine (Ciba); wfm Nilutamide ATC: G03H; L02BB02 (RU-23908) . Use: non-steroidal antiandrogen (for treatment of prostatic carcinoma) RN: 63612-50-0 MF: C,,H,,F,N,04 MW: 317.22 LD,,: 200 mg/kg (M, p.0.); 195 mg/kg (R, p.0.) CN: 5,5-dimethyl-3-[4-nitro-3-(trifluoromethyl)phenyl]-2,4-imidazolidinedione 3'-trifluoromethyl- ocetonilide NO2 2-amino-2- 1 -(3-trifluoromethyl- cyonopropane 4-nitrophenyl)-4.4- dimethyl-5-imino-Z- irnidazolidinone 3-lrifluoromethyl- 4-nitrophenyl isocyanaie (I) Nilutamide , . DOS 2 649 925 (Roussel-Uclaf; appl. 29.10.1976; F-prior. 29.1 0.1975). US 4 097 578 (Roussel-Uclaf; 28.6.1978; F-prior. 29.10.1975). synthesis of 3-trifluoromethyl-4-nitrophenyl isocyanate: Rouche, H.: Bull. CI. Sci., Acad. R. Belg. (BCSAAF) 13, 346 (1927). JP 6 725 067 (Japan Bureau of Ind. Techn.; appl. 15.3.1966). 1442 N Nilvadipine medical use for the treatment of hormone dependent cancer other than pmsraric cancer: WO 8 803 404 (Roussel-Uclaf; appl. 3.11 .l987; I-prior. 4.1 1.1986). Formulatinn(s): tabl. 50 mg Trade Name(s): F: Anandron (Cassenne) USA: Nilandron (Hoechst Marion Roussel) Nilvadipine (FR-34235; Niprodipine) ATC: C08CAlO Use: calcium antagonist, antihypertensive, antianginal RN: 75530-68-6 MF: C19HIYN306 MW: 385.38 LD,,,: 9150 pg/kg (M, i.v.); 1300 mg/kg (M, p.0.); 9650 pglkg (R, i.v.); 1560 mglkg (R, p.0.); 3850 pgkg (dog, i.v.); 510 mgikg (dog, p.0.) CN: 2-cyano-1 .4-dihydro-6-methyl-4-(3-nitrophenyl)-3,5-pyridinedi~arboxylic acid 3-methyl 5-(1- methylethyl) ester 3-nitro- isopropyl benzoldehyde acetoocetate methyl 3-amino- 4,4-dimethoxy- crotonote isopropyl 2-(3-nitro- benzy1idene)oceto- acetote (I) 0,CH3 HCI 5-isopropyl 3-methyl 2-(dimethoxymethyl)-6- methyl-4-(3-nitropheny1)- 1,4-dihydropyridine-3.5- dicarboxylote Reference(s): DE 2940 833 (Fujisawa; appl. 9.10.1979; GB-prior. 10.10.1978). US 4 338 322 (Fujisawa; 6.7.1982; GB-prior. 10.10.1978). US 4 525 478 (Fujisawa; 25.6.1985; GB-prior. 10.10.1978). Migamal, A. et al.: Chem. Pharm. Bull. (CPBTAL) 34,3071 (1986). H3C ! CHO NH OH. (CH3C0)20 '3c'f0~0.cH3 CH30 hydroxylarnine NO2 H H3C N CN H~~TH:T:~~ Nimesulide N 1443 medical use for treatment of arteriosclerosis: EP 185 283 (Fujisawa; appl. 7.12.1985; GB-prior. 10.12.1984). medical use for treatment of cerebral dysfunction: EP 253 173 (Fujisawa; appl. 26.6.1987; J-prior. 1.7.1986,29.6.1987). Formulation(s): s. r. cps. 8 mg, 16 mg Trade Name(s): D: Escor (Merck) Nivadil (Klinge) J: Nivadil (Fujisawa; 1989) Nimesulide ATC: MOlAX17 Use: anti-inflammatory RN: 51803-78-2 MF: C,,Hl,N,OSS MW: 308.31 EINECS: 257-431-4 LD,,: 392 mglkg (M, p.0.); 200 mgkg (R, p.0.) CN: N-(4-nitro-2-phenoxyphenyl)methanesulfonamide~ 2-bramo-1- potassium 2-nitrodiphenyl 2-aminodiphenyl nitrobenzene phenolote ether ether (I) I Nimesulide methanesulfonyl 2'-phenaxymethane- chloride (11) sulfonanilide acetyl chloride 0 H~~$~~~ 2-phenoxy-4- nitroaniline (111) Reference (s): US 3 840 597 (Riker; 8.10.1974; prior. 3.7.1972; 24.2.1971, 13.4.1970). DOS 2 333 643 (Riker; appl. 2.7.1973; USA-prior. 3.7.1972). synthesis of 2-phenoxy-4-nitroaniline: DOS 2 842 186 (BASF; appl. 28.9.1978). McCombie, H. et al.: J. Chem. Soc. (JCSOA9) 1931,529. 1444 N Nimetazepam synthesis of2-nitrodiphenyl ether: Suter, C.M.: J. Am. Chem. Soc. (JACSAT) 51, 2581 (1929). Lock, G.: Monatsh. Chem. (MOCMB7) 55, 167 (1930). Formulation(s): gran. 100 mg; suppos. 200 mg; tabl. 100 mg, 200 mg Trade Name(s): I: Algolide (Garant) Folid (CT) Nimesil (Lucofarmaco) Aulin (Boehringer Mannh.; Laider (Esseti) Remov (Piam) 1985) Mesid (Janssen-Cilag) generics Eudolene (Savio IBN) Mesulid (Novartis Farma; Fansidol (NCSN) 1985) Nimetazepam ATC: NOSCD Use: hypnotic, tranquilizer, anticonvulsant, skeletal muscle relaxant RN: 201 1-67-8 MF: C,,H,,N303 MW: 295.30 EINECS: 217-931-5 LD,,,: 750 mglkg (M, p.0.); 970 mglkg (R, p.0.) CN: 1,3-dihydro-l-methyl-7-nitro-5-phenyl-2H-1,4-benzodiazepin-2-one 1. HCI. NoNO, 2. ethyl o-benzyl- ocetoacetote ethyl phenylpyruvote 4-nitrophenylhydrozone (1) HCI or HZSO, KOH, H,O I O2N ethyl 5-nitro-3- phenylindol-2- corboxylate 1. SOC$ 7 NH. dimethyl sulfate 1 -methyl-5-nitro- 3-phenylindol-2- corboxylic acid Nimodipine N 1445 NaBH,, BF3 . 0(C2H& I11 - . O2N . 2-aminomethyl-1 - Nimetozepom methyl-5-nitro-3- phenylindole Rejerence(s): US 3 652 551 (Surnitomo; 28.3.1972; J-prior. 1.12.1967,9.12.1967, 14.12.1967, 15.12.1967,21.12.1967, 28.12.1967, 10.1.1968, 11.3.1968). DOS 1811 830 (Sumitorno; appl. 29.11.1968; J-prior. 1.12.1967,9.12.1967,14.12.1967,15.12.1967,21.12.1967, 28.12.1967, 10.1.1968, 11.3.1968). DOS 1 816 046 (Surnitomo; appl. 20.12.1968; J-prior. 25.12.1967,9.4.1968). DOS 1817761 (Sumitomo; appl. 29.11.1968; J-prior. 1.12.1967,9.12.1967, 14.12.1967, 15.12.1967,21.12.1967, 28.12.1967, 10.1.1968, 11.3.1968). DOS 1 817 794 (Sumitomo; appl. 20.12.1968; J-prior. 25.12.1967). Ihizurni, K. et al.: J. Org. Chem. (JOCEAH) 37,4111 (1972). indole precursor: US 3 770 767 (Sumitomo; 6.1 1.1973; J-prior. 28.12.1967). Formulation(s): tabl. 3 mg, 5 mg Trade Narne(s): J: Erirnin (Sumitomo) Nimodipine ATC: C08CA06 Use: calcium antagonist, cerebral RN: LD,": CN: vasodilator 66085-59-4 MF: C2,H26N207 MW: 418.45 EINECS: 266-127-0 26.2 mgkg (M, i.v.); 940 mg/kg (M, p.0.); 5 mag (R, i.v.); 2738 mgkg (R, p.0.); 4 mag (dog, i.v.); 1 gkg (dog, p.0.) 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-methoxyethyl 1-methylethyl ester diketene (1) isopropyl 3-omino- crotonote (11) 1446 N Nimorazole 2-methoxyethyl Nimodipine 2-(3-nitrobenzy1idene)- ocetoocetate (lU) Reference(s): DOS 2 117 571 (Bayer; appl. 10.4.1971). DE 2 117 573 (Bayer; prior. 10.4.1971). US 3 799 934 (Bayer; 26.3.1974; D-prior. 10.4.197 1). US 3 932 645 (Bayer; 13.1.1976; D-prior. 10.4.197 1). Meyer, H. et al.: Arzneim Forsch. (ARZNAD) 31,407 (1981); 33, 106 (1983). Formulation(s): cps. 30 mg; f. c. tabl. 30 mg; vial 10 mgI50 ml Trade Name(s): D: Nimotop (Rayer Vital; GB: Nimotop (Baycr; 1988) USA: Nimotop (Bayer) 1985) I: Nimotop (Bayer Italia) F: Nimotop (Bayer) Periplum (Italfarmaco) Nimorazole (Nitrimidazine) ATC: POIAB06 Use: chemotherapeutic (trichomonas), antiprotozoal RN: 6506-37-2 MF: C,H,,N,O, MW: 226.24 EINECS: 229-394-4 LD,,,: 1530 mgkg (M, p.0.); 1540 mgkg (R, p.o.) CN: 4-[2-(5-nitro- 1 H-imidazol- l -yl)ethyl]morpholine 2-morpholino- 4-nitro- ethyl chloride imidozole sodium salt Reference(s): US 3 399 193 (Carlo Erba; 27.8.1968; prior. 4.8.1965). US 3 458 528 (Merck & Co.; 29.7.1969; prior. 7.7.1965, 18.5.1966). US 3 646 027 (Merck & Co.; 29.2.1972; prior. 7.7.1965, 18.5.1966). Formulatiorz(s): tabl. 500 mg Trade Name(s): D: Esclama (Pharmacia & F: Naxogyn (Pharmacia & GB: Naxogin (Carlo Erba); wfm IJpjohn) Upjohn) Nulogyl (Bristol); wfm Nimustine N 1447 1: Naxogin (Erba) Sirledi (Cansyth) Sirledi (Inverni della Beffa) Nimustine (ACNU) ATC: LOIAD06 Use: antineoplastic RN: 42471-28-3 MF: C,Hl,C1N,02 MW: 272.70 EINECS: 255-838-1 CN: N-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-N-(2-chloroethyl)-N-nitrosourea 2-chloroethyl 4-ornino-5- isocyanate ominomethyl- 2-methylpyrimidine HCI. NONO* Reference(s): DOS 2 257 360 (Sankyo; appl. 20.1 1.1972; J-prior. 20.1 1.1971,4.12.1971,26.7.1972). US 4 003 901 (Sankyo; 18.1.1977; J-prior. 20.1 1.1971,4.12.1971, 26.7.1972). Formulation(s): vial 25 mg, 50 mg Trade Name(s): D: ACNU 50 (ASTA Medica J: Nidran (Sankyo) AWD) Nipradilol (Nipradolol) ATC: C07A; C04A Use: P-antagonist with vasodilating activity, antihypertensive, antianginal RN: 81486-22-8 MF: Cl,H2,N,0, MW: 326.35 LD,,: 68 mgkg (M, i.v.); 461 mglkg (M, p.0.); 144 mgkg (R, i.p.); 78 mglkg (R, i.v.); 1040 mgkg (R, p.0.); 850 mgtkg (R, s.c.); 20 mgkg (dog, i.v.1; >400 mglkg (dog, p.0.) CN: 3,4-dihydro-8-[2-hydroxy-3-[(l-methylethyl)amino]propoxy]-2H-l-benz.opyran-3-ol 3-nitrate NoOH CHO C N COOH 2-hydroxy-3- acrylo- rnethoxybenz- nitrile aldehyde V 1448 N Niridazole 0 CICOOC2H5, NoN3, H2S04 I. ethyl chloroformote OH 2. nitric ocid sodium azide 3.4-dihydro-8-(ethoxy- carbonyloxy)-ZH-1 -benzo- pyron-3-01 3-nitrote (II) 3. isopropylamine I I Niprodilol EP 42 299 (Kowa; appl. 16.6.1981; J-prior. 25.12.1980, 17.6.1980). US 4 394 382 (Kowa; 19.7.1983; appl. 9.6.1981; J-prior. 25.12.1980, 17.6.1980). Shiratsuchi, M. et al.: Chem. Pharm. Bull. (CPBTAL) 35, 632 (1987). separation of diastereomeric racemates: EP 154 51 1 (Kowa; appl. 27.2.1985; J-prior. 29.2.1984). US 4 727 085 (Kowa; 23.2.1988; appl. 28.8.1985; J-prior. 29.2.1984). synthesis of enantiomers: Shiratsuchi, M. et al.: Chem. Pharm. Bull. (CPBTAL), 33,2735 (1985); 35,3691 (1987). synthesis of 3,4-dihydro-2H- 1 -benzopyran-3,s-diol: JP 59 029 681 (Kowa; appl. 12.8.1982). Kawamura, K. et al.: Chem. Pharrn. Bull. (CPBTAL) 38,2088 (1990). Formulation(s): tabl. 3 mg, 6 mg Trade Name(s): J: Hypadil(Kowa;1988) Niridazole ATC: P02BX02 Use: chemotherapeutic (antischistosomal) RN: 61-57-4 MF: C6H6N40,S MW: 214.21 EINECS: 200-512-6 LD,,: 2500 mgkg (M, p.0.); 900 mg/kg (R, p.0.) CN: 1-(5-nitr0-2-thiazolyl)-2-imidazolidinone 2-amino- 2-omino-5- thiozole nitrothiozole r=\ ,4 N S two A NyS r I=( NO2 NS 2-chloroethyl- Y NH2 NH2 isocyonote Nisoldipine N 1449 Heference(s): Lambert, C.R. et al.: Experientia (EXPEAM) 20,452 (1964). GB 986 562 (Ciba; appl. 22.5.1963; CH-prior. 30.5.1962,23.4.1963). alternative syntheses: DAS 2 033 61 1 (Egyt; appl. 7.7.1970; H-prior. 7.7.1969). DAS 2 117 050 (Egyt; appl. 7.4.1971; H-prior. 16.4.1970). Formulation(s): tabl. 100 mg, 500 mg Trade Name(s): F: Ambilhar (Ciba); wfm Nisoldipine (Bay-K 5552) ATC: C02DE; C08CA07 Use: calcium antagonist, antihypertensive, antianginal RN: 63675-72-9 MF: C2,H,N2O6 MW: 388.42 EINECS: 264-407-7 LD,,: 360 pglkg (M, i.v.); 41 1 mglkg (M, p.0.); 384 mgkg (M, s.c.); 1120 pglkg (R, i.v.); 1257 mglkg (R, p.0.); 654 mgkg (R, s.c.); 2 mg/kg (dog, i.v.); 400 mgkg (dog, p.0.) CN: 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylic acid methyl 2-methylpropyl ester 2-nitro- isobutyl isobutyl 2-(2-nitro- benzoldehyde acetoacetate benzylidene)acetoacetate (I) methyl 3-amino- crotonate Nisoldipine Li Keference(s): DOS 2 549 568 (Bayer; appl. 5.11.1975). US 4 154 839 (Bayer; 15.5.1979; appl. 8.5.1978; D-prior. 5.1 1.1975). additional synthesis: ES 539 113 (Ind. y Comercial Quimica; appl. 27.12.1984). ES 549 302 (Mora Ruedas; appl. 26.1 1.1985). ES 546 423 (Inke; appl. 31.7.1985). ES 546 784 (Sune Coma; appl. 9.9.1985). CS 243 591 (P. Cupka et al.; appl. 25.1.1985). medical use for treatment of alcoholism: DOS 3 806 277 (Tropon; appl. 27.2.1988). medical use for inhibition of opioid tolerance: JP 61 260 025 (Miles; appl. 12.5.1986; USA-prior. 13.5.1985). 1450 N Nitrazepam medical use as saluretic: DOS 3 212 736 (Bayer; appl. 6.4.1982). medical use as antiarteriosclerotic: DOS 3 222 367 (Bayer; appl. 15.6.1982). Formulation(s): f. c. tabl. 5 mg, 10 rng, 20 rng, 30 mg, 40 rng Trade lYame(s); D: Baymycard (Bayer Vital1 I: Syscor (Bayer Italia) J: Baymycard (Bayer; 1990) Zeneca; 1990) Zadipina (SrnithKline USA: Sular (Zeneca) GB: Syscor MR (Bayer) Beecharn) Nitrazepam ATC: N05CD02 Use: hypnotic, anticonvulsant RN: mo: CN: (3 146-22-5 MF: C,,H,,N,O, MW: 281.27 EINECS: 205-665-2 130 mglkg (M, i.v.); 550 mglkg (M, p.0.); 825 mglkg (R, p.0.) 1,3-dihydr0-7-nitro-5-phenyl-2H-1,4-benzodiazepin-2-one 0 pyridine + H,c-o'i HCI d NH2 2-amino- glycine ethyl 2-0x0-5-phenyl- benzophenone ester hydrochloride (I) 2.3-dihydro-1 H- HNO,. H2S0, 11 b 2-chloro-5- nitrobenzo- 02N$-f. , Nitrozepam p-toluene- sulfomide sodium salt . 4247 1-2 8-3 MF: C,Hl,C1N,02 MW: 272.70 EINECS: 25 5-8 3 8-1 CN: N-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-N-(2-chloroethyl)-N-nitrosourea 2-chloroethyl 4-ornino- 5- isocyanate ominomethyl- 2-methylpyrimidine. 5,5-dimethyl- 3-[ 4-nitro- 3-( trifluoromethyl)phenyl ]-2 ,4-imidazolidinedione 3'-trifluoromethyl- ocetonilide NO2 2-amino- 2- 1 -( 3-trifluoromethyl- cyonopropane 4-nitrophenyl )-4 . 4- dimethyl-5-imino-Z-. 2-cyano-1 .4-dihydro-6-methyl- 4-( 3-nitrophenyl )-3 ,5-pyridinedi~arboxylic acid 3-methyl 5-( 1- methylethyl) ester 3-nitro- isopropyl benzoldehyde acetoocetate methyl 3-amino- 4,4-dimethoxy- crotonote