Nalorphine N 1391 monohydrochloride RN: 58895-64-0 MF: C2,H2,NOq. HCI MW: 375.90 (+)-base RN: 131378-67-1 MF: C2,H2,N03 MW: 339.44 (+)-monohydrochloride RN: 131712-55-5 MF: C2,H2,NO3. HC1 MW: 375.90 naltrexone (q. v.) Nolrnefene hydrochloride Reference(s): Hahn, F.E. et al.: J. Med. Chem. (JMCMAR) 18,259 (1975). syntltesis of nalmefene from naltrexone: US 7 421 900 (Nat. Inst. of Health; appl. 28.8.1990; USA-prior. 26.10.1989). US 4 322 426 (Du Pont de N.; appl. 30.3.1982; USA-prior. 28.4.1980). US 4 751 307 (Mallinckrodt, Inc.; appl. 27.2.1987; USA-prior. 17.1 .l98S). EP 140 367 (Key Pharm. Inc.; appl. 8.5.1985; USA-prior. 1.1 1.1983). use of nalmefene: US 4 880 813 (Baker Cummins Pharm.; appl. 14.1 1.1989; USA-prior. 22.7.1988). WO 8 910 125 (Baker Curnmins Pharm.; appl. 2.1 1.1989; USA-prior. 27.4.1988). WO 8 702 586 (Key Pharmaceuticals; appl. 7.5.1987; 29.1.1985). US 4 639 455 (Key Pharmaceuticals; appl. 27.1.1987; USA-prior. 2.1.1984). US 4 863 928 (Baker Cummins Pharm.; appl. 5.9.1989; USA-prior. 4.1.1989). US 4 877 791 (Baker Cummins Pharm.; appl. 31.10.1989; USA-prior. 1.1 1 .l988). US 4 923 875 (Baker Cummins Pharm.; appl. 8.5.1990; 10.7.1989). WO 9 218 126 (Baker Cummins Pharm.; appl. 29.10.1992; USA-prior. 10.4.1991). WO 9 11 8 605 (Finland; appl. 12.12.1991; USA-prior. 4.6.1990). formulariotl: US 4 51 1 570 (Key Pharmaceuticals; appl. 16.4.1985; 28.3.1983). cornbitzutiorz: WO 9 51 985 (Italy; appl. 30.1 1.1995; 1-prior. 24.5.1994). Formulation(s): amp. 100 pglml, 2 mg12 ml; syringe 2 mg12 rnl (as hydrochloride) Trade Name(s): USA: Revex (Ohmeda) Nalorphine ATC: V03AB02 Use: morphine antagonist RN: 62-67-9 MF: CI9II2,NO3 MW: 311.38 EINECS: 200-546-1 LD,,,: 127 mglkg (M, i.v.); 1 140 mgkg (M, p.0.); 226 mglkg (R, i.v.) CN: (5a,6a)-7,8-didehydro-4,5-epoxy-17-(2-propenyl)morphinan-3,6-diol 1392 N Naloxone hydrochloride RN: 57-29-4 MF: C,yH2,N03 . HCI MW: 347.84 EINECS: 200-321 -8 LD,,,: 63 mgkg (M, i.v.); 1 150 mgkg (R, p.0.); 120 mg/kg (dog, i.v.) hydrobromide RN: 1041-90-3 MF: C,,HzlN03. HBr MW: 392.29 EINECS: 213-868-2 LD,,,: 260 mg/kg (M, i.p.); 921 mg/kg (M, s.c.) HO cyanogenl bromide CH3 BrCN + H3C' '0' 'CH, morphine diarnorphine ;&:H2 1 Nalorphine Reference(s): US 2 364 833 (Merck & Co.; 1944; prior. 1941). US 2 89 1 954 (Merck & Co.; 1959; prior. 1951). Formulation(s): amp. 1 mg, 5 mg, 10 mg (as hydrobromide) Trade Name(s): D: Lethidrone (Wellcome); GB: Lethidrone (Burroughs USA: Nalline (Merck Sharp & wfm Wellcome); wfm Dohme); wfm F: Nalorphine Serb I: Norfin (Lusofarmaco); wfm (L'Arguenon) Naloxone ATC: V03AB15 Use: narcotic antagonist RN: 465-65-6 MF: ClyHz1NO4 MW: 327.38 EINECS: 207-365-7 LD,,,: 260 mglkg (M, s.c.) CN: (5a)-4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)morphinan-6-one hydrochloride RN: 357-08-4 MF: Cl,Hz,N04 . HCl MW: 363.84 EINECS: 206-61 1-0 LD,,,: 90 mgkg (M, i.v.); >1 glkg (M, p.0.); 107 mglkg (R, i.v.); >I glkg (R, p.0.) Naltrexone N 1393 H3c/0@N 0 b HBr H:o&N A H 2. cyanogen OH \cH3 OH\ 0 0 CH~ bromide oxymorphone HO BreCH, HCI NoHCOJ b ollyl bromide 14-hydroxydihydro- norrnorphinone Noloxone US 3 254 088 (M. J. Lewenstein; 31.5.1966; appl. 14.3.1961). DE 1 183 508 (M. J. Lewenstein; appl. 7.3.1962; USAlprior. 14.3.1961). GB 929 287 (Sankyo; appl. 9.3.1962; J-prior. 14.3.1961). Formulation(s): amp. 0.04 mg/2 ml, 0.4 mglml; cps. 4 mg in comb. with tilidine (as hydrochloride); tabl. 0.5 mg in comb. with pentazocine.HC1 (as hydrochloride); vial 0.4 mglml, 1 mglml, 10 mglml Trade Name(s): D: Findol (Mundipharma)- comb. with tilidine Gruntin (Griinentha1)- comb. with tilidine Narcanti (Du Pont Pharma) Tilador (Hexa1)-comb. with tilidine Tilidin (Isis Puren; Heumann; Stada; BASF; ratiopharm; Sax)-comb. Valomerck (Merck)-comb. with tilidine Valoron (Godecke)-comb. with tilidine F: Nalone (Serb) Narcan (Du Pont) GB: Narcan (Du Pont; as hydrochloride) I: Narcan (Crinos) Narcan neonatal (Crinos) generics J: Naloxone Hydrochloride (Sankyo) USA: Narcan (Endo; as hydrochloride) Talwin Nx (Sanofi) generics and combination preparations Naltrexone ATC: V03AB30 Use: narcotic antagonist RN: 16590-41-3 MF: C2,H2,NO4 MW: 341.41 EINECS: 240-649-9 LD,,: 551 mg/kg (M, s.c.) CN: (5a)-17-(cyclopropylmethyl)-4,5-epoxy-3,14-dihydroxymo~hinan-6-one hydrochloride RN: 16676-29-2 MF: C20H23N04 . HCl MW: 377.87 EINECS: 240-723-0 LD,,: 1100 mgkg (M, p.0.); 1450 mgkg (R, p.0.) 1394 N Nandrolone DMF, 70 'C, 1 week + Br& * oxymorphone (1) cyclopropyl- (cf. noloxone methyl synthesis) bromide ethylene glycol 1. LiAIH, 2. NH4CI 3. HCI cyclopropane- corbonyl chloride Reference(s): DAS I 795 707 (Endo; appl. 19.12.1966; USA-prior. 19.1.1966). FX-M 6 358 (Endo; appl. 24.2.1967). US 3 332 950 (Endo; 25.7.1967; prior. 23.3.1963, lSS.1963,6.12.1966). Formulation(s): tabl. 50 mg (as hydrochloride) Trade Name(s): D: Nemexin (Du Pont Pharma) GB: Nalorex (Du Pont) Narcoral (Crinos) F: Nalorex (Du Pont) I: Antaxone (Zambon Italia) USA: ReVia (Du Pont) Revia (Du Pont) Nalorex (Du Pont Pharma) Nandrolone ATC: A14ABO1; SOlXAll Use: anabolic RN: 434-22-0 MF: C,*H2,02 MW: 274.40 EINECS: 207-101-0 CN: (17P)-l7-hydroxyestr-4-en-3-one Nandrolone decanoate N 1395 estradiol dirnethyl sulfate (9. v.) Li. NH, I b '0 I Nandralone Reference(s): US 2 698 855 (Organics; 1955; prior. 1953). US 2 774 777 (Syntex; 1956; prior. 1952). Wilds, A.L.; Nelson, N.A.: J. Am. Chem. Soc. (JACSAT) 75,5366 (1953). Djerassi, C. et al.: J. Am. Chem. Soc. (JACSAT) 76,4092 (1954). Formularion(s): eye drops 10 mglml (as monosodium sulfate) ' Trade Name(s): D: Keratyl (Chauvin I: Dynabolon (Crinos); wfm USA: Nortestonate (Upjohn); ankerpharm) J: Andol (Tokyo Tanabe; as wfm F: Keratyl (Chauvin) cyclohexylpropionate) Nandrolone decanoate ATC: A14ABO1 Use: anabolic RN: 360-70-3 MF: C,,H,03 MW: 428.66 EINECS: 206-639-3 LD,,,: >566 mg/kg (M, i.p.) CN: (l7P)- 17-[(I -oxodecyl)oxy]estr-4-en-3-one pyridine d Reference(s): US 2 998 423 (Organon; 29.8.1961; appl. 2.2.1959; NL-prior. 25.2.1958). 0 &A(cH2)8-cH3 H H H H 0 A nandralane decanoyl chloride Formulation(s): amp 25 mglml, 50 mg/ml Nandrolone decanoate Trade Name(s): D: Deca-Durabolin (Organon) F: Deca-Durabolin (Organon); I: Deca-Durabolin (Organon Keratyl (Chauvin wfm Italia) ankerpharm) GB: Deca-Durabolin (Organon) (9. v.) 1396 N Nandrolone hexyloxyphenylpropionate J: Deca-Durabolin (Organon- USA: Deca-Durabolin (Organon) Sankyo) Nandrolone hexyloxyphenylpropionate ATC: ~14~~01 Use: anabolic RN: 52279-57-9 MF: C,,H4,04 MW: 506.73 EINECS: 257-810-4 CN: (17~)-17-[3-[4-(hexyloxy)phenyl]-l-oxopropoxy]estr-4-en-3-one nondrolone 3-(4-hexyloxypheny1)- (4. v.) propionyl chloride I Nondrolone hexyloxyphenylpropionote (I) Reference(s): US 2 904 562 (Leo; 15.9.1959; appl. 20.1.1958). Formulmtion(s): amp. 50 mg; susp. 50 mgl2 ml Trade Name(s): D: Anadur (Bastian-Werk); F: Anador (Logeais); wfm w fm Nandrolone phenylpropionate ATC: ~14~~01 (Nandrolone phenpropionate) Use: anabolic RN: 62-90-8 MF: C,H3403 MW: 406.57 EINECS: 200-551-9 LD,,,: >l g/kg (M, i.p.); 595 mg/kg (R, i.p.) CN: (17~)-17-(1-oxo-3-phenylpropoxy)estr-4-en-3-one nondrolone 3-phenylpropionic Nondrolone phenylpropionote (4. v.1 anhydride Nandrolone undecylate N 1397 Reference(s): GB 826 028 (Organon; appl. 1956; NL-prior. 1955). US 2 868 809 (Upjohn; 1959; prior. 1953). Fortnulation(s): amp. 25 mg Trade Name(s): D: Docabolin (Nourypharma)- comb.; wfrn Durabolin (Organon); wfrn Hepa-Obaton (Nourypharma)-comb.; wfrn F: Durabolin (Organon); wfrn GB: Durabolin (Organon); wfrn I: Anticatabolin (Falorni); wfrn Anticatabolin (Nativelle); wfrn Durabolin (Ravasini); wfrn Norandrol (Panther-Osfa Chemie); wfrn Norbalin (Bieffe); wfrn Sintabolin (AFI); wfrn Stenabolin (AFI); wfrn Strabolene (Isola-Ibi); wfrn Superbolin (Labin; wfrn J: Durabolin (Organon- Sankyo) USA: Durabolin (Organon); wfrn Nandrolin (Tutag); wfrn generics; wfrn Nandrolone undecylate (Nandrolone undecanoate) .ATC: A14ABO1 Use: anabolic RN: 862-89-5 MF: C2,H,,0, MW: 442.68 EINECS: 212-729-3 CN: (17P)-17-[(1-oxoundecyl)oxy]estr-4-en-3-one Reference(s): BE 659 440 (N. Gueritee; appl. 9.2.1965; GB-prior. 21.2.1964). nandrolone undeconoyl chloride use as anabolic in combination with estradiol esters: FR-M 3 424 (N. Gueritee; appl. 27.1.1964). Nandralone undecylate alternative synthesis and combination with mineral corticoids: DOS 2 638 507 (Akzo; appl. 26.8.1976; NL-prior. 27.8.1975). (9. v.1 use in combination with vitamin E: FR-M 7 284 (J. M. Gastand; appl. 7.3.1968). Formulation(s): inj. sol. 80.5 mgll ml Trade Name(s): F: Dynabolon (Thtramex); Trophoboltne (Th6ramex)- I: Dynabolon (Fournier wfm comb.; wfm Pierrel) 1398 N Naphazoline Naphazoline ATC: R01AA08; ROlAB02; SOlGAOl Use: vasoconstrictor, rhinological therapeutic RN: 835-31-4 MF: CI4HL4N2 MW: 210.28 EINECS: 212-641-5 LD,,,: 170 mglkg (M, i.v.); 270 mg/kg (M, p.0.) CN: 4,5-dihydro-2-(l-naphthalenylmethyl)-1H-imidazole monohydrochloride RN: 550-99-2 MF: C14H14N2. HCI MW: 246.74 EINECS: 208-989-2 mononitrate RN: 5144-52-5 MF: C,4H,,N2 .HNO, MW: 273.29 EINECS: 225-915-4 LD,,: 13.2 mglkg (M, i.v.); 265 mglkg (M, p.0.); 1260 mgkg (R, p.0.) HCI ethylene- NC HN O HC' diamine 04% (1 -naphthyl)- Naphazoline acetonitrile Reference(s): US 2 161 938 (Ciba; 1939; D-prior. 1934). Formdation(s): eye drops 0.3 mglml, 1 mg/ml; nasal spray Trade Name(s): D: Antistin-Privin (CIBA Vision)-comb. Piniol (Spitzner; as hydrochloride) Privin (Novartis Pharma; as nitrate) Proculin (Chauvin ankerpharm) Rhinex (Pharma Wernigerode) Vistalbalon (Pharm- Allergan) numerous generics and combination preparations F: Collyres bleus Laiter (Leurquin)-comb. DCrinox (ThCrabel Lucien pharma)-comb. Frazoline (Bouchara)- comb. Soframycyne (Rowel)- comb. Xylocai'ne naphthazoline (Astra)-comb. GB: Antistin-Privinc (Ciba)- comb.; wfm Murine (Abbott); wfm Nomaze (Fisons); wfm Vasocon A (Cooper Vision)-comb.; wfm Vasocon A (Knox)-comb.; wfrn I: Citroftalmina (SIF1)-comb. Collirio Alfa (Bracco) Deltarinalo (Hoechst Marion Rousse1)-comb. Desamin Same (Savoma) Imidazyl (Recordati) Imizol (Farmigea) Naftazolina (Bruschettini) Pupilla (Alfa Wassermann) Rinazina (Maggioni) Rinazina Senza Sulfamlde (Maggioni) Virginiana Gocce Verdi (Kelemata) numerous combination preparations J: Pnvina (Ciba-Geigy- Takeda; as nitrate) USA: Naphcon (Alcon; as hydrochloride) Naproxen N 1399 Naproxen ATC: G02CC02; MOlAE02; M02AA 12 Use: anti-inflammatory, antirheumatic, analgesic RN: 22204-53-1 MF: C,,H,,O, MW: 230.26 EINECS: 244-838-7 LD,,,: 435 mglkg (M, i.v.); 360 mglkg (M, p.0.); 248 mglkg (R, p.o.1; >I dkg (dog, p.0.) CN: (S)-6-methoxy-a-methyl-2-naphthaleneacetic acid sodium salt RN: 26159-34-2 MF: CI4H,,NaO, MW: 252.25 @ Originol process: n AICI, H C + oluminu) 1 \o '0 morpholiner 'I1 2-methoxy- ocetyl chloride 2-acetyl-6-meth- sulfur naphthalene (1) chloride oxynaphtholene (11) 6-methoxy-2-naphthyl- acetic acid hydride methyl 6-methoxy- methyl methyl DL-2-(6-methaxy- 2-nophthylocetote (N) iodide 1 -nophthyl)prapionote (V) DL-2-(6-methoxy-2- nophthyl)propionic ocid (VI) Noproxen racemote resolution with cinchonidine V1 b @ First large-scole manufacturing process of Syntex: FH3 H C '0 POOH 1400 N Naproxen 1. Mg, THF 2. ZnCI2, THF 0 NOOH , , Br 4. NOOH VII + CI-CHI , - VI '-0 3. ethyl 2-bromo- propionote 2-bromo-&methyl- oxynaphtholene (VI11) rocemote resolution with cinchonidine VI -, @ Second large-scale manufacturing process of Syntex: resolution with N-olkyl-D-glucomine . (mode by reductive ominotion of D-glucose) @ Asymmetric hydrogenotion: I. CO, . electrolysis ocid catalyst 2. H~O+ COOH A I1 2-(6-methoxy-2- nophthyl)ocrylic acid (K) @ Zombon process: propionyl chloride 2-methoxy-6- propionylnaphtholene (X) OH 0 ocid cotolyst X f ,,0#~,~~3 , H3C 0 OH (R,R)-dimethyl tartrate (a 1. Br2 11 2. NoOH m:~~ H30+, 90-100 'c XI ___, . Xll (1,2-aryl shift with complete inversion) . oxynaphtholene (11) 6-methoxy-2-naphthyl- acetic acid hydride methyl 6-methoxy- methyl methyl DL- 2-( 6-methaxy- 2-nophthylocetote (N) iodide 1 -nophthyl)prapionote (V) DL- 2-( 6-methoxy- 2- nophthyl)propionic. antagonist RN: 46 5-6 5-6 MF: ClyHz1NO4 MW: 327.38 EINECS: 20 7-3 6 5-7 LD,,,: 260 mglkg (M, s.c.) CN: (5a )-4 ,5-epoxy-3,14-dihydroxy-1 7-( 2-propenyl)morphinan-6-one hydrochloride RN: 35 7-0 8-4 MF: Cl,Hz,N04. RN: 1659 0-4 1-3 MF: C2,H2,NO4 MW: 341.41 EINECS: 24 0-6 4 9-9 LD,,: 551 mg/kg (M, s.c.) CN: (5a )-1 7-( cyclopropylmethyl )-4 ,5-epoxy-3,14-dihydroxymo~hinan-6-one hydrochloride RN: 1667 6-2 9-2 MF: