Trade Narnes: D: Athmakhell Steigerwald; wfrn Bilicordan Repha; wfm Broncaid RhGne-Poulenc Pharma; wfm Cardiopax Wider; wfm Coronar-Homocent Fides; wfrn Coropar Redel; wfm Farctil Gewo;
Trang 1Trade Narne(s):
D: Athmakhell (Steigerwald);
wfrn
Bilicordan (Repha); wfm
Broncaid (RhGne-Poulenc
Pharma); wfm
Cardiopax (Wider); wfm
Coronar-Homocent (Fides);
wfrn
Coropar (Redel); wfm
Farctil (Gewo); wfm F:
Hyperidyst 11 (Vogel &
losimitan (Wider); wfm Keldrin (Thiemann); wfrn Puraeton E (Dolorgiet);
wfm Solamin (Ardeypharm);
wfm
Khelline Promethazine Berthier (Labaz); wfrn Kellina (UCB); wfrn Nefrolitin (Geymonat)- comb.; wfrn
Vasokellina papaverina (Ange1ini)-comb.; wfm
Trang 21132 L Labetalol
Use: antihypertensive (a- and P-receptor blocker)
RN: 36894-69-6 MF: C,,H2,N203 MW: 328.41 EINECS: 253-258-3
LD,,,: 97.5 m g k g (M, i.v.); 660 mglkg (M, p.0.);
>SO mglkg (R, i.v.); >2 g k g (R, p.0.)
CN: 2-hydroxy-5-[l-hydroxy-2-[(1-methyl-3-phenylpropyl)amino]ethyl]benzaide
hydrochloride
RN: 32780-64-6 MF: C,yH24N20, HCl MW: 364.87 EINECS: 251-21 1-1
LD,,,: 47 mglkg (M, i.v.); 1.45 glkg (M, p.0.);
53 m g k g (R, i.v.); 2.1 14 g k g (R, p.0.);
>1.5 glkg (dog, p.0.)
N-benzyl-1- 5-brornoacetyl-
methyl-3-phenyl- solicylamide (I)
propylarnine
Hz, Pd-Pt-C
dibenzyl-
ornine
Reference(s):
US 4 012 444 (Allen & Hanburys;.15.3.1977; prior 29.6.1970)
US 4 066 755 (Allen & Hanburys; 3.1.1978; GB-prior 30.1 1.1973)
DOS 2 032 642 (Allen & Hanburys; appl 1.7.1970; GB-prior 8.7.1969)
DAS 1 643 224 (Allen & Hanburys; appl 22.9.1967; GB-prior 23.9.1966,21.4.1967)
US 3 705 233 (Allen & Hanburys; 5.12.1972; GB-prior 23.9.1966)
Formulation(s): amp 5 mglml, 50 mg, 100 mg; tabl 50 mg, 100 mg, 200 mg, 300 mg, 400 mg (as
hydrochloride)
Trang 3Trade Name(s):
D: Trandate (Glaxo; 1978); Diurolab (Lebenls)-comb J: Trandate (Shim Nihon
F: Trandate (Novartis; 1980) Lolum (Lifepharma) USA: Normodyne (Schering- GB: Trandate (Evans; 1977) Pressalolo (Locatelli) Plough; 1984)
Amipres (Salus Research) Wellcome)-comb
Biotens (Kemyos)-comb
(Lacipil; GR-43659X; GX-1048; SN-305) Use: once-daily calcium antagonist,
antihypertensive RN: 103890-78-4 MF: C,,H,,NO, MW: 455.55
LD,,: 3150 m g k g (M, p.0.);
880 mglkg (R, p.0.)
CN: (6-4-[2-[3-(1,l -dimethylethoxy)-3-oxo- I-propenyl]phenyl]- 1,4-dihydro-2,6-dimethyl-3,s-
pyridinedicarboxylic acid diethyl ester
phthal-
aldehyde
(9
CHO
1 CH2CI, O°C
2 chromatography CHO +
triphenylphosphoranylidene- acetic acid 1 , l -dimethylethyl ester
(E)-3-(2-formylphenyl)- 2-propenoic acid 1.1 -dimethylethyl ester (1)
H C 0 toluene,
ethyl 3-arnino-
crotonate (11)
2-formyl- ethyl aceto-
Lacidipine
Trang 41134 L Lactulose
N.N-dimethyllormomide
di-tert-butyl ocetal
1 C2H50H
2 HCI
CH3 + 11 . b
0 CH,
2 HCI
8 H 3 $ ~ ~ 3 + 11 +
/
Reference(s):
a DE 3 529 997 (Glaxo; appl 22.8.1985; I-prior 22.8.1984; 5.7.1985)
US 4 801 599 (Glaxo; 31.1.1989; appl 20.8.1985; I-prior 22.8.1984,5.7.1985)
US 5 01 1 848 (Glaxo; 30.4.1990; appl 23.1.1989; prior 20.8.1985; I-prior 22.8.1984, 5.7.1985)
b EP 370 974 (Glaxo; appl 21.11.1989; I-prior 21.1 1.1989)
c EP 534 520 (Merck + Co.; appl 5.9.1992; USA-prior 13.9.1991,28.7.1992)
lacidipine for treating arteriosclerosis:
EP 499 920 (Glaxo; appl 8.2.1992; I-prior 13.2.1991)
long-acting formulation for dihydropyridines:
EP 301 133 (Syntex; appl 21.12.1987; USA-prior 26.7.1987)
prolonged-release oral pharmaceuticals:
EP 557 244 (Siegfried Pharma; appl 3.2.1993; CH-prior 17.2.1993)
process for preparation of solid dispersions:
W O 9 508 987 (KRKA Tovarna; appl 26.9.1994; SI-prior 28.9.1993)
Formulation(s): tabl 2 mg, 4 mg
Trade Name(s):
D: Motens (Boehringer Ing.) I: Apanil (Fidia) Viapres (Zambon; 199 1) F: Caldine (Boehringer Ing.) Lacipil (Glaxo Wellcome)
GB: Motens (Boehringer Ing.) Lacirex (Guidotti; 199 1)
Lactulose
(Laktulose)
ATC: A06ADI 1 Use: laxative RN: 46 18- 18-2 MF: C,2H22011 MW: 342.30 EINECS: 225-027-7
CN: 4-0-P-D-galactopyranosyl-D-fructose
CHO
alkaline isornerizotion
_d
Trang 5Lactylphenetidin L 1 135
Reference(s):
Montgomery, E.M.; Hudson, C.S.: J Am Chem Soc (JACSAT) 52,2101 (1930)
use of alkali aluminate:
US 3 546 206 (Kraftco; 8.12.1970; prior 20.9.1967)
US 3 850 905 (Kraftco; 26.1 1.1974; prior 30.12.1972)
use of borax and NaOH:
JP 7 700 091 (Morinaga Milk Ind.; appl 13.4.1971)
use of MgO, MgCO,:
ES 397 810 (Jalup Jaures; appl 26.11.1971)
use of alkali tetraborate:
US 3 505 309 (Research Corp.; 7.4.1970; prior 25.9.1967)
use qf alkali metal hydroxide or ammonia:
DOS 2 038 230 (Hayashibora; appl 3 1.7.1970; J-prior 3 1.7.1969, 2.8.1969)
lactulose syrup:
DOS 2 224 680 (Morinaga Milk Ind.; appl 19.5.1972; J-prior 22.5.1971),
lactulose powder:
DAS 1 189 839 (N.V Tervalon; appl 20.4.1961; N-prior 22.4.1960)
DOS 2 153 106 (Morinaga Milk Ind.; appl 25.10.1971; J-prior 31.5.1971)
BE 843 777 (Morinaga Milk Ind.; appl 5.7.1976; J-prior 4.7.1975, 8.7.1975)
DOS 2 038 230 (Hayashibara; appl 31.7.1970; J-prior 31.7.1969,2.8.1969)
crystalline lactulose:
US 5 003 061 (SIRAC; 26.3.1991; I-prior 1.12.1987)
AT 327 224 (Laevosan; appl 12.10.1973; valid from 15.4.1975)
Osten, B.J.: Recl Trav Chim Pays-Bas (RTCPA3) 86,673 (1967)
CS 161 498 (M Tadra et al.; appl 24.5.1973)
Formulationis): gran 3 g, 5 g, 6 g, 10 g; syrup 3.33 g, 50 %, 66.7 %
Trade Namefs):
D: Bifiteral (Solvay
Arzneimi ttel)
Eugalac (Topfer)
Lactofalk (Falk)
Lactuflor (MIP Pharma)
Lacvilac S (Fresenius-
Praxis)
generic
F: Duphalac (Solvay Pharma)
Lactylphenetidin
(Lactophenin)
Fitaxal (Phygihe) Melaxose (Boehringer 1ng.)-comb
Transulose (Schwarz)- comb
GB: Duphalac (Solvay) Lactugal (Galen)
1: Diacolon (Piam) Duphalac (UCM)
Epalfen (Zambon) Lactoger (Ripari-Gero) Lacvolac (Boehringer Mannh.)
Lassifar (Lafare) Normase (Molteni) Osmolac (Savio IBN) USA: Duphalac (Solvay) lxxose (ECR)
ATC: N02B Use: analgesic, antipyretic, antirheumatic RN: 539-08-2 MF: CI,H,,NO, MW: 209.25 EINECS: 208-708-3
CN: N-(4-ethoxypheny1)-2-hydroxypropanamide
Trang 61136 L Lamivudine
Reference(s):
DRP 70 250 (Chem Fabr formerly Goldenberg Geromont; 1892)
Formulation(s): tabl 200 mg
Trade Name(s):
D: Octadon (Thiemann)- Quadronal (ASTA)-comb.;
Lamivudine
(3 TC; BCH-790; GR- 109714X; (-)sddc)
ATC: J05AF05 Use: antiviral, reverse transcriptase inhibitor
RN: 134678-17-4 MF: CmH,lN303S MW: 229.26
CN: (2R-cis)-4-amino-l-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-2(1H)-pyrimidinone
(2s-cis)-form
RN: 134680-32-3 MF: CmH,lN303S MW: 229.26
racemate
RN: 136891-12-8 MF: CmH,,N303S MW: 229.26
benzoyloxy- rnercoptoocet-
acetaldehyde (I) aldehyde di-
methyl ocetol
N H 2
N H 2
1 hexornethyldisilozone
2 trirnethylsilyl triflote or SnCI, cl0
H
arnberlite, cytidine dearninose
CH,OH (enontinspecific hydrolysis)
BCH 189 (roc.) (V) I Lornivvdine
Trang 7Lamivudine L 1137
trimethyl phosphate
1 5'-nucleotidose from Crotolus otrox
2 bocteriol olkoline phosphotose
1 Lewis acid
H 3 C b o
(+)-mereapto-
lactic acid (W)
I-Si(CH3)3
iodide (X)
@
OHC-COOH +
glyoxylic
acid
1 separation
2 deprotection
1 Lewis acid 1 resolution
2 VIIl CH, 2 H3C-OH , SOCI2
reduction
_,
Trang 81138 L Lamivudine
thioglycolic 2-(tert-butyldiphenyl-
acid silyloxyrnethyl)-5-0x0-
oxy- 1,J-oxothiolane (XII)
1 c i e C I , SnCI4
2 N+[(cH~)~-cH~]~ F-, THF
trans-5-hydroxy-1.3- trirnethyl
oxathiolane-2- orthoformats
2.6-lutidine, 1 H3cn1 DMF
Reference(s):
a,bEP 382 526 (IAF Biochem Int.; appl 16.8.1990; USA-prior 8.2.1989)
WO 9 117 159 (IAF Biochem Int.; appl 14.1 1.1991; GB-prior 2.5.1990) Bcach, I.W et al.: J Org Chem (JOCEAH) 57 (8), 2217 (1992)
(synthesis via L-gulosc see also WO 9 210 496)
c Humber, D.-C et al.: Tetrahedron Lett (TELEAY) 33 (32), 4625 (1992)
d Drugs Future (DRFUD4) 18 (41,319-323 (1993)
e WO 9 l l l 186 (Emory Univ.; appl 31 I 1991; USA-prior 1.2.1990)
US 5 210 085 (Emory Univ.; 22.2.1991; USA-prior 1.2.1990)
f WO 9 429 301 (Biochem Pharma Inc.; appl 7.6.1994; GB-prior 7.6.1993)
process that avoids Lewis acids:
WO 9 529 174 (Glaxo; appl 21.4.1995; GB-prior 23.4.1994)
Trang 9Lamotrigine L 1139
crystalline new form:
EP 517 145 (Glaxo; appl 2.6.1992; GB-prior 3.6.1991)
use for treating and preventing hepatitis B infection:
EP 494 119 (P Bellean; IAF Biochem Int.; Biochem Pharma Inc.; appl 3.1.1992; GB-prior 3.1.1991)
composition for HIV infections:
EP 513 917 (Glaxo; appl 11.5.1992; GB-prior 16.5.1991)
WO 9 504 525 (Andrulis Pharm.; appl 3.8.1994; USA-prior 4.8.1993)
combination with zidovudine and loviride:
WO 9 601 110 (Janssen Pharm.; appl 23.6.1995; EP-prior 1.7.1994)
Formulation(s): f c tabl 100 mg; oral sol 10 mglml; sol 1 %; tabl 150 mg
Trade Name(s):
Wellcome)-comb with Wellcome)-comb with J: Epivir (Nippon Wellcome)
Epivir (Glaxo Wellcome) Epivir (Glaxo Wellcome) Wellcome)-comb with Zeffix (Glaxo Wellcome) Zeffix (Glaxo Wellcome) Zidovudine
F: Epivir (Glaxo Wellcome) I: Combivir (Glaxo Epivir (Glaxo Wellcome)
Wellcome)-comb with 3TC (Glaxo Wellcome) Zidovudine
Lamotrigine
(B W-430C)
ATC: N03AX09 Use: anticonvulsant, glutamate inhibitor
RN: 84057-84-1 MF: C,H,Cl,N5 MW: 256.10 EINECS: 281-901-8
LD,,: 245 mg/kg (M, p.0.);
205 mg/kg (R, p.0.)
CN: 6-(2,3-dichloropheny1)-1,2,4-triazine-3,5-diamine
1 SOCI*
Q, + C O 2 -2% c, 2 CuCN , KI
potossiurn iodide 2,3-dichloro- carbon 2.3-dichloro- 2.3-dichlorobe,nzoyl
1 -iodobenzene dioxide benzoic ocid cyanide (1)
1 H N 0 3
H 2 KOH CH,OH
orninoguanidine
Reference(s):
US 4 560 687 (Wellcome; 24.12.1985; appl 5.3.1984; prior 15.9.1981, 29.5.1980; GB-prior 1.6.1979)
US 4 602 017 (Wellcome; 22.7.1986; appl 27.2.1984; prior 15.9.1981,29.5.1980; GB-prior 1.6.1979)
EP 21 121 (Wellcome; appl 30.5.1980; GB-prior 1.6.1979)
US 5 912 345 (Glaxo Wellcome; 15.6.1999; appl 29.12.1995; GB-prior 30.12.1994)
Formulation(s): tabl 5 mg, 25 mg, 50 mg, 100 mg, 200 mg
Trang 101140 L Lanatoside C
~ -~~ - - - - - -
Trade N a m e ( ~ ) :
Lanatoside C
(Lanatoside)
Use: cardiac glycoside
CN: (3~,5~,12~)-3-[(0-~-~-glucopyranos~l-(1+4)-0-3-0-acety1-2,6-dideoxy-~-d-ribo-hexopyranosy1-
(1 44)-0-2,6-dideoxy-P-D-ribo-hexopyranosyl-1 +4)-2,6-dideoxy-~-~-ribo-hexopyranosyl)oxy]-l2,14-
dih ydroxycard-20(22)-enolide
deslanoside
NH4CI CH3COOC2H5
Digitalis lonota b - 'Lonota-Reintannoid' (1)
partition between
Pb(OH)Z H,O CH,OH CHCI, and CH,0H/H20
(gross glycoside)
separation from lanatoside A ond B
lanotoside C ( I ) + n t s i e A ( I ) + a n a t s i B ( ) i ]
I Lonotoside C