Pharmaceutical Substances Syntheses, Patents, Applications - Part 146 pot

Nitrefazole N 1451 HCI 11 + 02N4 '. -1 / 2-amino-5- nitrobenzo- phenone Reference(s): US 3 109 843 (Hoffmann-La Roche; 5.1 1.1963; appl. 21.6.1962; prior. 28.7.1961,4.12.1961). US 3 116 203 (Hoffman-La Roche; 31.12.1963; prior. 14.3.1962). US 3 123 529 (Hoffman-La Roche; 3.3.1964; prior. 9.3.1962). DE 1 136 709 (Hoffman-La Roche; appl. 7.12.1960; USA-prior. 10.12.1959, 27.6.1960). DE 1 145 626 (Hoffman-La Roche; appl. 7.12.1960; USA-prior. 10.12.1959, 15.1.1960, 26.4.1960, 27.6.1960). Sternbach, L.H. et a].: J. Med. Chem. (JMCMAR) 6, 261 (1963). DAS 1 8 11 785 (Delmar Chemicals; appl. 29.1 1.1968; CDN-prior. 29.11.1967). condensation of 2-aminobenzophenone with glycine and POC13/nitrobenzene and following nitration with KN0,I H2S04: DOS 2 252 378 (Roche; appl. 25.10.1972; CH-prior. 18.1 1.1971). Formulation(s): drops 0.5 g1100 g; tabl. 5 mg, 10 mg Trade Name(s): D: Dormalon (Pharma Novanoxl-forte (Pfleger) generics Wernigerode) Radedorm (ASTA Medica 1: Mogadon (Roche) Dormo-Puren (Isis Puren) AWD) J: Benzalm (Shionogi) Eatan N (Desitin) F: Mogadon (Roche) Nelbon (Sankyo) Imeson (Desitin) Rohypnol (Roche) USA: Mogadon (Roche); wfnl Mogadan Roche (Roche) GB: Mogadon (Roche) Nitrefazole ATC: V03AA Use: alcohol deterrent RN: 21721-92-6 MF: CloH,N404 MW: 248.20 EINECS: 244-542-8 LD,,,: 5.501 glkg (M, p.0.); 4.813 glkg (R, p.0.); >6.4 glkg (dog, p.0.) CN: 2-methyl-4-nitro- L(4-nitropheny1)- 1 H-imidazole 2-methyl-4-nitro- 1 -fluoro-4- ( Nitrefozole imidozol nitrobenzene sodium salt I Reference(s): DE 1 620 043 (Merck AG; appl. 15.10.1966). DOS 2 145 65 1 (Merck AG; appl. 13.9.197 1). 1452 N Nitrendipine medical use: DOS 2 645 709 (Merck AG; appl. 9.10.1976). Formulation(s): cps. 0.2 g Trade Narne(s): D: Altimol (Merck); wfm Nitrendipine ATC: C08CA08 Use: calcium antagonist, antihypertensive RN: 39562-70-4 MF: CI,H2,N,O, MW: 360.37 EINECS: 254-513-1 LD,,: 34.5 mglkg (M, i.v.); 2540 mglkg (M, p.0.); 12.6 mglkg (R, i.v.); 15.37 gkg (R, p.0.); >2.5 mgkg (dog, i.v.); >lo0 mglkg (dog, p.0.) CN: 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pydinicarboxylic acid ethyl methyl ester ethyl acetoacetote 3-nitro- ethyl 3-nitro- benzoldehyde benzylideneaceto- acetate (I) methyl acetoacetote methyl 3- aminocrotonate (U) I Nitrendipine I Keference(s): US 3 799 934 (Bayer; 26.3.1974; appl. 7.4.1972; D-prior. 10.4.1971). US 3 932 645 (Bayer; 13.1.1976; D-prior. 10.4.1971). DOS 2 1 17 57 1 (Bayer; appl. 10.4.1971). Meyer, H. et al.: Arzneim Forsch. (ARZNAD) 31,407 (1981). Ebrmulation(s): sol. 5 mglml; tabl. 10 mg, 20 mg Nitrofural N 1453 Trade Name(s): D: Bayotensin (Bayer Vital; I: Baypress (Bayer Italia) J: Baylotensin (Bayer- 1985) Deiten (ABC Farmaceutici) Yoshitomi) numerous generics Nitrofural (Nitrofurazone) ATC: B05CA03; D08AF01; D09AA03; POlCC02; SO1 AX04; S02AA02 Use: antiseptic, topical antibacterial RN: 59-87-0 MF: C,H,N404 MW: 198.14 EINECS: 200-443-1 LD,,: 249 mgikg (M, p.0.); 590 mg/kg (R, p.0.) CN: 2-[(5-nitro-2-furanyl)methylene]hydrazinecarboxamide 5-nitrofurfurol semicarbozide hydrochloride I Nitrofural I Reference(s): US 2 416 234 (Eaton Labs.; 1947; prior. 1945). US 2 927 110 (Norwich Pharmacal; 1.3.1960; appl. 23.1.1958). Formulation(s): cream 0.2 g1100 g; ointment 0.2 g1100 g; sol. 0.2 gllOO g Trade Name(s): D: Furacin (Procter & I: Furanvit (SIF1)-comb. J: Monafuracin (Dainippon) Gamble) Furotricina (Biomedica USA: Furacin (Eaton); wfm GB: Furacin (Eaton); wfm Foscama)-comb. Nitrofurantoin ATC: G04AC01 Use: chemotherapeutic (urinary tract infections) RN: 67-20-9 MF: C,H,N40, MW: 238.16 EINECS: 200-646-5 LD,,: 360 mgikg (M, p.0.); 604 mg/kg (R, p.0.) CN: 1-[[(5-nitro-2-furanyl)methylene]amino]-2,4-imidazolidinedione hydrazine chloroacetic 2-hydrazinoacetic (hydrate) acid ocid (I) 0 I + KOCN , H2N\N"XH2 HN a 'N NH LOOH '4 0 patassium semicarbozidoacetic 1 -aminohydantoin (11) cyonote acid ! 1454 N Nitroxoline I Nitrofurontoin Reference(s): US 2 610 181 (Eaton Labs.; 1950; prior. 1950). US 2 779 786 (Norwich; 29.1.1957; prior. 17.4.1953). US 2 898 335 (Norwich; 4.8.1959; prior. 28.2.1958). US 2 927 110 (Norwich; 1.3.1960; prior. 23.1.1958). special pharmaceutical formulations: US 3 401 221 (Norwich Pharmacal; 10.9.1968; prior. 25.8.1964). US 4 122 157 (Richardson-Merrell; 24.10.1978; appl. 4.3.1977). sustained release.fortnulation: DOS 2 749 745 (Chem. Fabrik von Heyden; appl. 7.1 1.1977; F-prior. 15.9.1977). Formulation(s): cps. 25 mg, 50 mg, 100 mg, 150 mg; drg. 20 mg, 100 mg; s:r. cps. 100 mg; susp. 25 mg15 ml; tabl. 50 mg Trade Name(s): D: Cystit (Bristol-Myers Squibb) Furadantidretard (Procter & Gamble) Uro-Tablinen (Sanorania) numerous generics and combination preparations F: Furadantine (Lipha SantC) FuradoTne (Lipha SantC) Microdoi'ne (Gomenol) GB: Furadantin (Procter & Gamble) Macrobid (Procter & Gamble) Macrodantin (Procter & Gamble) I: Cistofuran (Crosara) Furadantin (Formenti) Furedan (Scharper) Furil (OFF) Nitrofurin (IFI) J: Furadantin (Yamanouchi) Parfuran (Parke Davis) Trantoin (McKesson) Uretoin (Azusa-Tokyo Tanabe) USA: Furadantin (Dura) Macrodantin (Procter & Gamble) Nitroxoline ATC: G04AG06 Use: urinary antiseptic, antifungal RN: 4008-48-4 MF: C9H6N203 MW: 190.16 EINECS: 223-662-4 LD,,,: 8300 pglkg (M, i.v.); 104 mgkg (M, p.0.); 510 mglkg (R, p.0.) CN: 5-nitro-8-quinolinol 0 H & @ HN03 , @ NO oxyquinoline 8-hydroxy- Nitroxoline (9. v.) 5-nitroso- quinoline Nizatidine N 1455 Reference(s): Kostanecki, St. v.: Ber. Dtsch. Chem. Ges. (BDCGAS) 24, 150 (1891). Petrow, V.; Sturgeon, B.: J. Chem. Soc. (JCSOA9) 1954, 570. Formulation(s): cps. 50 mg, 80 mg, 150 mg, 250 mg; susp. 1 % Trade Name(s): D: Nitroxolin (Cephasaar) I: Urocoli (Roussel- F: Nibiol (DCbat) Maestretti); wfm Nizatidine ATC: A02BA04 Use: ulcer therapeutic, H,-receptor antagonist RN: 76963-41-2 MF: CIZHZIN502S2 MW: 33 1.47 LD,,: 265 mglkg (M, i.v.); 1685 mglkg (M, p.0.); 301 mglkg (R, i.v.); 1680 mg/kg (R, p.0.); 175 mgkg (dog, i.v.); SO0 mg/kg (dog, p.0.) CN: N-[2-[[[2-[(dimethylamino)methyl]-4-thiazolyl]methyl]thio]ethyl]-N'-methyl-2-nitro-1,1-ethenediamine B r H3cVo$0 + SyfH3 + H3cVo - I n NH,CH3 0 CH3 lithium triethyi- borohydride ethyl brorno- dimethylamino- ethyl 2-(dimethylomino- pyruvote thioocetornide methyl)-4-thiozole- corboxylote cysteornine 2-(dimethylominornethy1)- 4-(2-ominoethy1thiomethyl)- thiozole (11) I1 + 02~.&.S/CH3 1 -(rnethylthio)-2-nitro- Nizotidine N-methylethylenornine (cf. ronitidine synthesis) Reference(s): EP 49 618 (Lilly; appl. 2.10.1981; USA-prior. 2.10.1980). US 4 375 547 (Lilly; 1.3.1983; prior. 2.10.1980). DE 3 171 819 (Lilly; appl. 14.4.1982; USA-prior. 2.10.1980). US 4 382 090 (Lilly; 3.5.1983; prior. 2.10.1980). preparation of ethyl 2-(dimethylaminomethyl)-4-thiazolecarboxyate from ethyl bromopymvate and dimethylaminothioacetamide: Trumm, K.A. et al.: Arzneim Forsch. (ARZNAD) 35 (3), 573 (1985). alternative synthesis: GB 2 134 521 (Lilly; appl. 6.2.1984; USA-prior. 7.2.1983). F 1456 N Nizofenone Formulation(s): amp. 100 mg, 150 mg, 300 mg; cps. 150 mg, 300 mg Trade Narne(s): D: Gastrax (Asche; 1989) F: Nizaxid (Norgine Phanna) Nizax (Lilly; 1988) Gastrax mite (Asche; 1989) GB: Axid (Lilly; 1987) Zanizal (Italfarmaco; 1988) Nizax (Lilly; 1989) Zinga (Ashbourne) I: Acinon (Zeria; Lilly; 1990) Nizax mite (Lilly; 1989) I: Cronizat (Farmitalia; 1988) USA: Axid (Lilly) Nizofenone (Y-9 1 79) ATC: N06BX10 Use: antianoxic, nootropic RN: 54533-85-6 MF: C2,H2,C1N403 MW: 412.88 CN: (2-chlorophenyl)[2-[2-[(diethyla1nino)methyl]-1H-imidazol-l-yl]-5-nitrophenyllmethanone fumarate (1:l) RN: 54533-86-7 MF: C2,H2,C1N4O3. C4H404 MW: 528.95 LD,,,: 70 mglkg (M, i.v.); 495 mglkg (Mm, p.0.); 504 mglkg (Mf, p.0.); 270 mglkg (M, s.c.); 65 mgkg (R, i.v.); 171 1 mg/kg (Rm, p.0.); 1580 mglkg (Rf, p.0.); 1830 mgkg (R, LC.) 7. HCI. NoNOz 2. CUCI NO2 NO2 2-ornino-5-nitro- 22'-dichloro-5-nitro- 2'-chlorobenzo- benzophenone (I) phenone rCH3 NOH H 2-(diethylamino- Nizofenone me1hyl)imidazole Reference(s): US 3 915 981 (Yoshitomi; 28.10.1975; J-prior. 16.3.1973,20.3.1973). DE 2 403 416 (Yoshitomi; appl. 24.1.1974; J-prior. 24.1.1973, 16.3.1973, 20.3.1973, 14.5.1973, 16.6.1973, 7.7.1973). Formulation(s): amp. 5 mg12 ml Trade Narne(s): J: Ekonal (Yoshitomi; 1989) Nomegestrol acetate N 1457 Nomegestrol acetate ATC: G03DB04 Use: synthetic progestogen for treatment of gynecological disturbances RN: 58652-20-3 MF: C2&O4 MW: 370.49 EINECS: 261-379-8 LD,,: >2 gkg (M, p.0.); >2 gkg (R, p.0.) CN: 17-(acetyloxy)-6-methyl-19-norpregna-4,6-diene-3,20-dione nomegestrol RN: 58691-88-6 MF: C21H2R03 MW: 328.45 1. HC(OC,H,), & H3 t: :FAH , pyridine , & H3 1. triethyl H H 0 H3C\0 \ \ orthoformate 3-rnethoxy-17-ocetoxy-19-nor- 3.5-pregnadien-20-one (I) CHO 6-forrnyl-3-rnethoxy-17- acetoxy-19-nor-3.5- pregnodien-20-one (11) 1. NoBH4 2. HCI 3. H2. Pd-C, NoOAc u - CH3 Nomegestral acetate DOS 2 522 533 (J. M. Gastaud; 21.5.1975; GB-prior. 21.5.1974). alternative synthesis: EP 157 842 (ThCramex; appl. 4.10.1984; F-prior. 4.10.1983). medical use for i.m. treatment of luteal dejciency: US4 544 555 (J. M. Gastaud; 1.10.1985; appl. 27.9.1982; prior. 28.4.1980, 13.5.1975). Formulation(s): tabl. 5 mg Trade Name(s): F: Lutenyl (Theramex; 1985) I: Lutenyl (Schering) I 1458 N Nomifensine Nomifensine ATC: N06AX04 Use: antidepressant RN: 24526-64-5 MF: ClhH1& MW: 238.33 LD,,,: 260 mg/kg (M, p.0.) CN: 1,2,3,4-tetrahydro-2-11~e~hy1-4-phenyl-8-isoquinolinamine maleate (1:l) RN: 32795-47-4 MF: C,,H,,N, , C4H404 MW: 354.41 EINECS: 251-223-7 LD,,,: 68 mglkg (M, i.v.); 300 mglkg (M, p.0.); 66 mglkg (R, i.v.); 430 mglkg (R, p.0.) N-methyl-2-nitro- 2-bromoocelo benrylomine phenone Hz. Roney-Ni I + NH2 2 @N\ CH3 Nomifensine I N-methyl-N-(2-nitrobenzy1)- phenocylornine (1) NoBH, b sodium boronote XH Qd, NH2 CH3 2-nitrobenzyl chloride Hz. Roney-Ni , H~S04 , I11 Referencefs): DE 1 670 694 (Hoechst; appl. 5.5.1966). DAS 1 795 830 (Hoechst; appl. 12.8.1966). US 3 577 424 (Hoechst; 4.5.1971; D-prior. 5.5.1966, 12.8.1966, 15.4.1967). GB 1 164 192 (Hoechst; appl. 5.5.1967; D-prior. 5.5.1966, 12.8.1966, 14.4.1967). Hoffmann, J. et al.: Arzneim Forsch. (ARZNAD) 21, 1045 A (1971). Formulation(s): cps. 25 mg, 50 mg (as hydrogen maleate) Trade Name(s): D: Alival (Hoechst); wfm GB: Merital25 (Hoechst); wfm I: Psicronizer (Albert-Farma); F: Alival (Hoechst); wfm wfm RN: 26027-38-3 MF: [C,H40]xC,,Hz40 MW: unspecified CN: a-(4-nonylpheny1)-61-hydroxypoly(oxy- 1,2-ethanediyl) ATC: G02BB Use: spermatocide Reference(s): US 2 3 13 477 (GAF; 1940). 4-nonylphenol ethylene Formulation(s): foam 12.5 %; suppos. 0.075 g; vaginal gel 2 g1100 g Nonoxinol 9 Trade Name(s): D: Ortho-Creme (Janssen- Double Check (Family Staycept (Syntex) Cilag) Planning Sales) I: Florigien (Schering)-comb. Patentex Oral (Patentex) Gynol I1 (Janssen-Cilag) Koromex (Sanico) F: Patentex (Lab. C.C.D.) Ortho-Creme (Janssen- USA: Ramses (Schmid Prod.); Semicid (ThCraplix) Cilag) wfm GB: Delfen (Janssen-Cilag) Ortho-Forms (Janssen- Semicid (Whitehall); wfm Cilag) oxide Norboletone (Norbolethone) ATC: A14AB Use: anabolic RN: 1235-15-0 MF: Cz,H,zOz MW: 316.49 LD,,,: >SO10 mglkg (M, p.0.) CN: (17a)-(f)-13-ethyl-17-hydroxy-18,19-dinorpregn-4-en-3-one 6 1460 N Nordazepam Norboletone L Reference(s): GB 1 041 280 (G. A. Hughes, H. Smith; valid from 8.10.1962; prior. l9.lO.l96l), total synthesis and synthesis of enantiomers: GB 1 096 761 (Roussel-Uclaf; valid from 17.12.1964; F-prior. 20.2.1964, 14.1.1964, 17.12.1963); US 3 959 322 (H. Smith; 25.5.1976; prior. 15.1.1964,4.10.1962, 16.5.1962, 15.5.1962, 12.9.1961, 24.2.1961, 23.9.1960). US 3 850 91 1 (G. A. Hughes, H. Smith; 26.11.1974; GB-prior. 22.9.1960). US 3 519 714(G. A. Hughes; H. Smith; 7.7.1970; prior. 15.3.1966, 16.5.1962, 15.5.1962,4.10.1962, 12.9.1961, 24.2.1961, 23.9.1960). Smith, H. et al.: J. Chem. Soc. (JCSOA9) 1964,4472. Trade Name(s): USA: Genabol (Wyeth); wfm Nordazepam (Nordiazepam) ATC: N05BA16 IJse: anxioly tic, benzodiazepine RN: 1088-1 1-5 MF: C,,H11C1N20 MW: 270.72 EINECS: 214-123-4 LDs,]: >400 mgtkg (M, i.p.); 670 mgkg (M, p.0.); >5200 mgtkg (R, p.0.) CN: 7-chloro- 1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one 2-amino-5- chlorooceiyl 2-chlorooceiomido- chlorobenzo- chloride 5-chlorobenzo- phenone phenone DE 1 136 709 (Hoffmann-La Roche; appl. 1960). Sternbach, L.H.; Reeder, E.: J. Org. Chem. (JOCEAH) 26,4936 (1961). Bell, S.C. et al.: J. Org. Chem. (JOCEAH) 27, 562 (1962). Fonnulation(s): drops 5 mgtg; tabl. 7.5 mg, 10 mg, 15 mg Trade Name(s): D: Tranxilium N (Sanofi F: Nordaz (Bouchara) Winthrop) I: Madar Notte (Ravizza) . 5865 2-2 0-3 MF: C2&O4 MW: 370.49 EINECS: 26 1-3 7 9-8 LD,,: >2 gkg (M, p.0.); >2 gkg (R, p.0.) CN: 1 7-( acetyloxy )-6 -methyl-19-norpregna-4,6-diene-3,20-dione nomegestrol RN: 5869 1-8 8-6 . CN: N-[ 2-[ [[ 2-[ (dimethylamino)methyl ]-4 -thiazolyl]methyl]thio]ethyl]-N'-methyl-2-nitro-1,1-ethenediamine B r H3cVo$0 + SyfH3 + H3cVo - I n NH,CH3 0 CH3 lithium triethyi- borohydride. p.0.) CN: 1,4-dihydro-2,6-dimethyl- 4-( 3-nitrophenyl )-3 ,5-pydinicarboxylic acid ethyl methyl ester ethyl acetoacetote 3-nitro- ethyl 3-nitro- benzoldehyde benzylideneaceto- acetate (I)