sodium cyano- @ from 1-N-ethyl-a-deoxy-D-streptomin by fermentation with Micmmonospora inyoensis 1550F-1G References: DOS 2 462 485 Scherico; appl... CN: 4-pyridinecarboxylic acid 2-
Trang 1Nevirapine N 1421
1 H2S0,, pH 5
2 H,C CHO
3 NaBH CN
2 acetaldehyde
3 sodium cyano-
@ from 1-N-ethyl-a-deoxy-D-streptomin by fermentation with Micmmonospora inyoensis 1550F-1G
Reference(s):
DOS 2 462 485 (Scherico; appl 1.8.1974; USA-prior 6.8.1973, 19.3.1974)
DOS 2 437 160 (Scherico; appl 1.8.1974; USA-prior 6.8.1973, 19.3.1974) - (also further methods)
US 4 002 742 (Scherico; 11.1.1977; prior 19.3.1974)
Formulation(s): amp 15 mgl1.5 ml, 50 mg /ml, 100 mglml, 150 mglml, 200 mg/2 ml (as sulfate)
Trade Name(s):
D: Certomycin (Essex GB: Netillin (Schering-Plough; J: Netilyn (Sankyo; 1985)
F: Netromicine (Schering- I: Nettacin (Schering-Plough; USA: Netromycin (Schering;
Zetamicin (Menarini; 1982)
Nevirapine
(BI-RG-587)
ATC: JOSAGO1 Use: antiviral, anti-AIDS therapeutic, reverse transcriptase inhibitor RN: 129618-40-2 MF: C,,H,,N,O MW: 266.30
CN: 11 -cyclopropyl-5,l l-dihydro-4-methyl-6H-dipyrido[3,2-b:2',3'-e][l,4]diazepin-6-one
A
Trang 21422 h Nevirapine
2-chloro-
nicotinoyl
chloride (11)
2-chloro-N-(2- chloro-4-methyl- 3-pyridinyl)-3-pyri- dinecorboxornide
N-(2-chloro-4-methyl- Neviropine
3-pyridy1)-2-cyclpro-
pylornino-3-pyridine-
corboxarnide (IV)
y 3
2-rnethoxy- pyridine (V)
2 HCI EtOAc
rnethoxy-4- rnethylpyridine
rnethoxy-4-methyl- 3-pyridiny1)-3- pyridinecorbox- arnide (VI)
Neviropine
rr U , I
2 HCI
N C
C H 3
N C
cyono- ethyl
ocetornide ocetoocetote
2.6-dichloro-4- methyl-3-pyridine-
Trang 3Nialamide N 14-23
2,6-dichloro-4- methyl-3-pyridine- carboxamide
3-amino-2,6- dichloro-4- methylpyridine
Nevirapine
0
2,6-dichloro-3-
(2-chloronicotinoyl-
amino)-4-methyl-
pyridine (VIII)
Referencefs):
review:
Pedersen, O.S.; Pedersen, E.B.: Synthesis (SYNTBF) ,(4), 479, (2000)
a EP 429 987 (Boehringer Ing.; USA-prior 19.10.1990)
b US 5 532 358 (Boehringer Ing.; 2.7.1996; USA-prior 12.10.1994)
c EP 482 481 (Boehringer Ing.; appl 16.10.1991; USA-prior 19.10.1990)
process for IV avoiding excess of cyclopropylamine:
DE 4403 31 1 (Boehringer Ing.; D-prior 3.2.1994)
combination with HIV-protease inhibitors:
WO 9 600 068 (Merck & Co.; appl 23.6.1995; USA-prior 27.6.1994)
osmotic dosage forms:
US 5 358 721 (Alza Corp.; appl 4.12.1992; USA-prior 4.12.1994)
Formulation(s): tabl 200 mg
Trade Name(s):
D: Viramune (Boehringer GB: Viramune (Boehringer USA: Viramune (Roxane; 1998) Ingel h.; 1998) Ingelh.; 1998)
Use: psychoanaleptic, antidepressant RN: 51-12-7 MF: C,,H,8N,02 MW: 298.35 EINECS: 200-079-3
LD,,,: 120 mgtkg (M, i.v.); 590 m a g (M, p.0.);
1700 m a g (R, p.0.)
CN: 4-pyridinecarboxylic acid 2-[3-0x0-3-[(phenylmethyl)amino]propyl]hydrazide
Trang 41424 N Niaprazine
Referencefs):
US 2 894 972 (Pfizer; 14.7.1959; prior 31.12.1958)
US 3 040 061 (Pfizer; 19.6.1962; prior 27.4.1959, 1.6.1961)
Formulation(s): cps 25 mg, 100 mg
Trade Name(s):
F: Niamide (Pfizer); wfm GB: Niamid (Pfizer); wfm J: Niamid (Taito Pfizcr)
Use: antiallergic, bronchodilator, sedative RN: 27367-90-4 MF: CzOHz5FN40 MW: 356.45 EINECS: 248-431-5
LD,: 145 mglkg (M, i.v.); 890 mglkg (M, p.0.)
CN: N-[3-[4-(4-fluoropheny1)- 1-piperazinyll- 1-methylpropyll-3-pyridinecarbpxamide
I -(4-fluorophenyl)-
piperozine dihydrochloride
hydroxylomine
DF
hydrochloride
N'OH
nicotinoyl
chloride
DF
0 CH,
DOS 1 957 371 (Mauvernay; appl 14.1 1.1969; F-prior 14.1 1.1968)
US 3 712 893 (Mauvernay; 23.1.1973; F-prior 14.1 1.1968)
Formulation(s): syrup 0.3 gI100 ml
Trang 5Trade Name(s):
F: Nopron (SynthClabo) I: Nopron (Sanofi Winthrop)
Use: calcium antagonist RN: 55985-32-5 MF: C2,HZyN3O6 MW: 479.53 EINECS: 259-932-3
LD,,: 9.7 mglkg (M, i.v.); 480 mglkg (M, p.0.);
320 mglkg (R, p.0.)
CN: 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid methyl 2-
[methyl(phenylmethyl)amino]ethyl ester
monohydrochloride
RN: 54527-84-3 MF: Cz6HzyN30, HC1 MW: 515.99 EINECS: 259-198-4
LD,,: 19.9 mglkg (M, i.v.); 322 m g k g (M, p.0.);
15.5 mglkg (R, i.v.); 184 mglkg (R, p.0.);
5 mglkg (dog, i.v.)
methyl 3-nitro-
3-amino- benzaldehyde
crotonate
2-(methylbenvlamino)- ethyl ocetoocetate
Nicordipine
US 3 985 758 (Yamanouchi; 12.10.1976; J-prior 20.2.1973)
DOS 2 407 115 (Yamanouchi; appl 15.2.1974; J-prior 20.2.1973, 3.3.1973, 20.4.1973, 11.5.1973, 17.5.1 973, 24.7.1973,29.11.1973)
Iwanami, M et al.: Chem Pharm Bull (CPBTAL) 27, 1426 (1979)
(alternative syntheses are described)
synthesis of enantiomers:
Shibanuma, T et al.: Chem Pharm Bull (CPBTAL) 28,2809 (1980)
Formulation(s): cps 20 mg, 30 mg; s r cps 30 mg, 45 mg, 60 mg (as hydrochloride)
Trade Name(s):
D: Antagonil (Novartis
Pharma)
F: Loxen (Novartis; 1986)
GB: Cardene (Yamanouchi;
1986)
I: Bionicard (Bioindustria)
Cardioten (OFF)
Cardip (Francia Farm.)
Cardipinen (Farmaceutica Pr.)
Lisanirc (Lisapharma) Neucor (CT) Nicapress (Benedetti) Nicardal (Italfarmaco) Nicarpin (Sancarlo) Nimicor (Formenti)
Niven (Pulitzer) Perdipina (Novartis Farma) Ranvil (Gentili)
Vasodin (Teofarma) Vasonorm (NCSN) J: Nicodel (Mitsui; 1981) Perdipine (Yamanouchi; 1981)
Trang 61426 N Nicergoline
U S A : C a r d e n e ( R o c h e ; W y e t h -
A y e r s t )
U s e : v a s o d i l a t o r RN: 2 7 8 4 8 - 8 4 - 6 MF: C,H,,BrN,O, MW: 4 8 4 3 9 E I N E C S : 2 4 8 - 6 9 4 - 6
LD,,,: 46 mglkg (M, i.v.); 6 3 3 mglkg (M, p.0.);
42 mgkg (R, i.v.); 1 1 9 3 mglkg (R, p.0.);
20 mglkg (dog, i.v.); 790 mglkg (dog, p.0.)
CN: (8P)-10-methoxy-l,6-dimethylergoline-8-methanol 5-bromo-3-pyridinecarboxylate (ester)
tartrate
RN: 3 2 2 2 2 - 7 5 - 6 MF: C,H,,BrN303 xC4H,0, MW: u n s p e c i f i e d E I N E C S : 2 5 0 - 9 6 4 - 3
methyl-lumilysergote
pyridine
H & N H + r y y L ,
0/""
N -
lumilysergol 5-bromonico- lumilysergol 10-methyl
10-methyl ether (I) tinoyl chloride ether 8-0-(5-bromo-
nicotinote) (11)
methyl
I Nicergoline iodide
KNH,
u + H3C-I potossium ,
omide
- + H3C-OH -b I III
N -
CH3
H3C\
N N -
I H CH3
lysergol
[by extraction from
Kolodono seeds
(Colonyction-lpomoeo
(Choisy) Hollier f
Trang 7Niceritrol h' 1427
Nicergoline
CH3
1 -methyl- 1 Oa-meth- 5-bromonicotinic
oxylumilysergol (111) acid
Reference (s):
US 3 879 554 (Soc Farmaceutici Italia; 22.4.1975; I-prior 20.3.1970)
a US 3 228 943 (Soc Farmaceutici Italia; 11.1.1966; I-prior 11.6.1962)
DOS 2 022 926 (Soc Farmaceutici Italia; appl 11.5.1970; I-prior 13.5.1969)
DOS 2 112 273 (Soc Farmaceutici Italia; appl 15.3.1 971; I-prior 20.3.1970)
Arcari, G et al.: Experientia (EXPEAM) 28, 819 (1972)
Bemardi, L.: Arzneim.-Forsch (ARZNAD) 29 (11), 1204 (1979)
alternative method for esterification with 5-bromonicotinic acid (imidazolide method):
DOS 2 752 533 (LEK; appl 24.1 1.1977; YU-prior 22.12.1976)
GB 1 557 506 (LEK; appl 6.12.1977; YU-prior 22.12.1976)
b a) isolation of lysergol from kaladana seeds:
Abou-Chaar, C.I.; Digenis, G.A.: Nature (London) (NATUAS) 212,6 I8 (1966)
DOS 2 240 266 (Simes; appl 16.8.1972; B-prior 17.8.1971: 14.1.1972)
DOS 2 834 703 (Simes; appl 8.8.1978; CH-prior 12.8.1977)
b b) method:
GB 2 018 245 (E Corvi Mora; appl 4.4.1979; I-prior 5.4.1978)
Formulation(s): cps 5 mg, 10 mg, 15 mg, 30 mg; f c tabl 5 mg, 10 mg, 20 mg, 30 mg; drg 5 mg, 10 mg;
tabl 10 mg, 20 mg; vial 4 mgl4 rnl (as tartrate)
Trade Name(s):
D: Circo-Maren (Krewel F: Sermion (Specia; 1975) Sermion (Pharmacia &
ergobel (Hormosan) Ergolin (Boniscontro & J: Sermion (Farmitalia-
Nicerium (Neuro Hexal) Nicer (1st Chim Inter.)
Sermion (Pharmacia & Sermidrina (Farmita1ia)-
Use: cholesterol depressant, antiarteriosclerotic RN: 5868-05-3 MF: C2,H24N,0, MW: 556.53 EINECS: 227-519-7
CN: 3-pyridinecarboxylic acid 2,2-bis[[(3-pyridinylcarbonyl)oxy]methyl]-1,3-propanediyl ester
Trang 81428 N Niclosamide
Referencefs):
GB 1 022 880 (Bofors; appl 18.1 1.1964; S-prior 13.10.1964)
Formulation(sJ: tabl 500 mg
Trade Name(s):
1: Perycit (Tosi); wfm J: Perycit (Sanwa Kagaku)
Use: anthelmintic RN: 50-65-7 MF: C,,H,Cl,N20, MW: 327.12 EINECS: 200-056-8
LDs,]: 7500 pglkg (M, i.v.); 1 g/kg (M, p.0.);
2500 m g k g (R, p.0.)
CI
phosphorus(lll) chloride 5-chlorosoli- 2-chloro-4-
Niclosornide
Reference(s):
US 3 079 297 (Bayer; 26.2.1963; prior 26.9.1956, 21.10.1959; 31.5.1960)
new formulations:
GB 1 527 638 (Bayer; appl 14.12.1976; D-prior 20.12.1975)
Formulation(sJ: tabl 500 mg
Trade Name(sJ:
D: Yomesan (Bayer Vital) GB: Yomesan (Bayer) USA: Niclocide (Miles Pharm.);
F TrCdCmine (Roger Bellon) I: Yomesan (Bayer Italia) wfm
Use: antiarteriosclerotic, hyperlipidemic RN: 10571-59-2 MF: Cl6H1,C1NO2 MW: 289.76 EINECS: -234-156-8
LD,,,: 2.27 g k g (M, i.p.)
CN: 3-pyridinecarboxylic acid 1-(4-chloropheny1)-2-methylpropyl ester
benzaldehyde magnesium 2-methyl-1 -propon01
Trang 9Nicofuranose N 1429
Referencefs):
FR-M 3 454 ( ~ t a b l Kuhlmann; appl 10.4.1964)
US 3 367 939 ( ~ t a b l Kuhlmann; 6.2.1968; F-prior 10.4.1964)
Formularion(s): cps 250 mg
Trade Name(s):
F: Lipidium-Sedaph I: Lipidium (Rorer)
(Sedaph)-comb.; wfm
Nicofuranose
(Tetranicotinoylfructose)
ATC: ClOAD03 Use: vasodilator
RN: 15351-13-0 MF: C30H,4N40,0 MW: 600.54 EINECS: 239-385-7
CN: (3-D-fructofuranose 1,3,4,6-tetra-3-pyridinecarboxylate
I CHC13, pyridini, Qcl '
0
iHOfloH 4 3 E HOW^ 1 nicotinoyl chloride hydrochloride
Nicofuronose
Reference (s):
CH 366 523 (Eprova; appl 1958)
Formulation(s); drg 250 mg
Trade Name(s):
D: Bradilan (Mundipharma); GB: Bradilan (Napp); wfm
wfm
Trang 101430 N Nicorandil
Nicorandil
RN: 65141-46-0 MF: C,HloN,O, MW: 166.18
LDSo: 626 mglkg (M, p.0.);
502 mg/kg (R, i.v.); 1220 mgkg (R, p.0.);
62.5 mglkg (dog, p.0.)
ATC: COIDX16 Use: coronary vasodilator
nicotinic
acid
methyl
nicotinate
Nicorondil
Reference(s):
Masayoshi, S.: Yakugaku Zasshi (YKKZAJ) 80, 1706 (1960)
DE 2 7 14 713 (Chugai; prior 1.4.1977)
n~edical use:
US 4 200 640 (Chugai; 29.4.1980; J-prior 2.4.1976)
JP-appl 58/85 819 (Chugai; appl 17.11.1981)
transdermal application system:
JP-appl 59/10 513 (Nitto; appl 12.7.1982)
Formulation(s): tabl 2.5 mg, 5 mg, 10 mg, 20 mg
Trade Nnme(s):
F : Adancor (Lipha SantC) GB: Ikorel (RhGne-Poulenc J: Perisalol (Mitsubishi;
Sigmart (Chugai; 1984)
Nicotafuryl
(Thurfyl nicotinate)
ATC: M01 Use: antirheumatic (extern), rubefacient RN: 70-19-9 MF: CllH13N03 MW: 207.23 EINECS: 200-727-5
CN: 3-pyridinecarboxylic acid (tetrahydro-2-furany1)methyl ester