300 mg as sulfate Trade Names: 1999 Abciximab 7E3; C7E3; C7E3 Fab; C7E3-Fabq2 ATC: BOlAC13 Use: platelet antiaggregation inhibitor, antianginal, GPIIbIIIIa-receptor antagonist RN: 1436
Trang 1Abacavir A 1
Abacavir
(1 592U89)
ATC: J05AF06
Use: antiviral, anti HIV, reverse transcriptase inhibitor
I
succinate
RN: 168146-84-7 MF: Cl,HluN,O C,H,O M W : 356.43
sulfate
pyrirnidinedione
2-amino-6-
chloro-4(3H)-
pyrimidinone (I)
Z-acetylomino-6- chlora-5-nitro-4(3H) pyrimidinone
A A
H,C N N' CI
Z-cyclopentene-
1 -methanol (N)
I
ocetic ocid diethoxymethyl
VII
Trang 22 A Abacavir
cyclopropyi-
amine (VIII)
@ synthesis of (IS-cis)-4-amino-2-cyclopentene-1 -methanol (N)
pentadiene sulfonyl isocyanate
p-lactamase, pH 7 ,
enzymatic, stereoselective hydrolysis
cis-4-amino-2- cyclopentene- 1 -
corboxylic acid
4-pentenoic pivalic anhydride
P(C6Hl l),
I
Ph-CHZRu-C12
I
P(C& 113
5(R)-(hydroxy-
cyclopenten-
Trang 3Abacavir A 3
methyl chloroformate
2-ornino-6- chloropurine (cf fomciclovir)
2-arnino-4.6-
dichloropyrimidine
4-chlorobenzene- diazonium chloride
TEA, DMAP, CH2C12
(m
NOH, THF, DMSO
Pd(PPhJ4
V I I tetrokis(tripheny1-
phosphine)pollodium
TEA , 1-butonal
H2N
(f)-cis-4-[(2-amino-4-
c h l o r 0 - 6 - ~ ~ r i m i d i n y l ) - amino]-2-cyclopentene-
1 -methanol (XIV)
1 Ac-ONa CHSCOOH
2 Zn CH3COOH C,H,OH
1 POCI,
2 stereoselective enzyrnotic hydrolysis
!
with alkaline phosphatase
Trang 44 A Abciximab
VIll
Abacavir
2-omino-6- 2-amino-6- phosphine)palladium
chloropurine (cyclopropyl-
amino)purine
Reference(s):
a EP 434 450 (Wellcome Found.; 26.6.1991; appl 21.12.1990; USA-prior 22.12.1989)
Crimmins, M.T et al.: J Org Chem (JOCEAH) 61 4192 (1996)
aa EP 424 064 (Enzymatix; appl 24.4.1991 ; GB-prior 16.10.1 989)
b Olivo, H.F et al.: J Chem Soc., Perkin Trans 1 (JCPRB4) 1998,391
c US 5 034 394 (Welcome Found.; 23.7.1991; appl 22.12.1989; GB-prior 27.6.1988)
d WO 9 924 431 (Glaxo; appl 12.1 1.1998; WO-prior 12.1 1.1997)
alternative syntheses:
EP 878 548 (Lonza; appl 13.5.1998; CH-prior 13.5.1997)
condensation of pyrimidines with cyclopentylamine IV:
Vince, R.; Hua, M.: J Med Chem (JMCMAR) 33 (I), 17 (1990)
EP 349 242 (Wellcome Found.; appl 26.6.1989; GB-prior 27.6.1988)
EP 366 385 (Wellcome Found.; appl 23.10.1989; GB-prior 24.10.1988)
Grumam, A et al.: Tetrahedron Lett (TELEAY) 36 (42), 7767 (1995)
JP 1 022 853 (Asahi Glass Co.; appl 17.7.1987)
alternative preparation of 4-amino-2-cyclopentene-1-methanol:
EP 926 131 (Lonza; appl 24.1 1.1998; CH-prior 27.1 1.1997)
WO 9 745 529 (Lonza; appl 30.5.1997; CH-prior 30.5.1996)
abacavir succinate as antiviral agent:
WO 9 606 844 (Wellcome; 7.3.1996; appl 25.8.1995; GB-prior 26.8.1994)
synergistic combinations for treatment of HIV infection:
WO 9 630 025 (Wellcome; 3.10.1996; appl 28.3.1996; GB-prior 30.3.1995)
Formulation(s): oral sol 20 mglml; tabl 300 mg (as sulfate)
Trade Name(s):
1999)
Abciximab
(7E3; C7E3; C7E3 Fab; C7E3-F(abq)2)
ATC: BOlAC13 Use: platelet antiaggregation inhibitor, antianginal, GPIIbIIIIa-receptor antagonist
RN: 143653-53-6 MF: unspecified MW: unspecified
CN: immunoglobulin G (human-mouse monoclonal c7E3 clone p7E3VHhCy4 Fab fragment antihuman glycoprotein IIb/lIIa receptor), disulfide with human-mouse monoclonal c7E3 clone p7E3VKhCK light chain
Reference (s):
Gold, H.K et al.: Circulation Suppl (CISUAQ) 80(4) (1989), Abst 1063
Trang 5Acamprosate calcium A 5
Fornlulation(s): vial 10 mgI5 ml
Trade Name(s):
D: ReoPro (Lilly) GB: Reopro (Lilly)
F: ReoPro (Lilly) USA: ReoPro (Lilly)
Use: alcohol detcrrcnt RN: 77337-73-6 MF: C,,H,,CaN,O,S, MW: 400.49 EINECS: 278-665-3
LD,,,: >10 glkg (M, p.0.)
CN: 3-(acety1amino)-1 -propanesulfonic acid calcium salt (2: 1)
free acid
RN: 77337-76-9 MF: C,H, ,NO,S MW: 18 1.21 EINECS: 278-667-4
3-amino-1
proponol
3-ominopropone-
1 -sulfonic acid
Reference(s):
DE 3 019 350 (Lab Meram; appl 21.5.1980; F-prior 23.5.1979)
synthesis of 3-aminopropane-l -sulfonic acid:
3P 46 002 012 (Kowa; appl 19.1.1971)
Fujii, A et al.: J Med Chem ( J M C M A R ) ' ~ ~ , 502 (1975)
WO 8 400 958 (Mitsui; appl 15.3.1984; J-prior 7.9.1982, 19.7.1983, 8.9.1982)
Forrnulation(s): tab] 333 mg
Trade Name(s):
Acarbose
(Bay-g-542 1)
ATC: AlOBFOl Use: antidiabetic, a-glucosidase inhibitor, hypoglycemic
RN: 56180-94-0 MF: C2sH43NOlx MW: 645.61 EINECS: 260-030-7
LD,,,: >500.000 SIElkg (M, i.v.); >1000.000 SIWkg (M, p.0.);
478.000 SIEIkg (R, i.v.); >1000.000 SIEIkg (R, p.0.)
65.000 SIE = l g (SIE = saccharase inhibitory units)
a-D-glucopyranosyl(1 -+4)-O-a-D-glucopyranosy~-(~+4)-D-g~ucose
Trang 66 A Acebutolol
Fermentation of Actinoplanes SE501110
Reference fs):
US 4 062 950 (Bayer; 13.12.1977; D-prior 22.9.1973)
DOS 2 347 782 (Bayer; appl 21.9.1973)
Schmidt, D.D et al.: Naturwissenschaften (NATWAY) 64,535 (1977)
total synthesis:
Ogawa, S.; Shibata, Y.: Chem Commun (CCOMA8) 1988,605
review:
Tschesche, H in Arzneimittel, Fortschritte 1972-1985 (Ed A Kleemann, E Lindner, J Engel), p 87, VCH Verlagsgesellschaft, Weinheim 1987
Trade Name($):
D: Glucobay (Bayer; 1990) GB: Glucobay (Bayer) USA: Precose (Bayer) F: Glucor (Bayer) J: Glucobay (Bayer)
Use: P-adrenergi'c receptor blocker RN: 37517-30-9 MF: C,,H2,N204 MW: 336.43 EINECS: 253-539-0
LD,,: 7'5.2 mglkg (M, i.v.);
4 m g k g (dog, i.v.)
CN: (~)-N-[3-acetyl-4-[2-hydroxy-3-~(1-methylethyl)amino]propoxy]phenyl]butanamide
(R)-base
RN: 68107-81-3 MF: C,,H2,N204 MW: 336.43
(S)-base
RN: 68107-82-4 MF: C,,H2,N204 MW: 336.43
(RS)-monohydrochloride
RN: 3438 1-68-5 MF: C,,H2,N204 HC1 MW: 372.89 EINECS: 251-980-3
LD,,: 185 mglkg (M, i.p.); 53 mglkg (M, i.v.); 4050 mglkg (M, p.0.); 291 m a g (M, s.c.);
222 mglkg (R, i.p.); 103 m a g (R, i.v.); 6620 mgkg (R, p.0.); 1310 mglkg (R, s.c.);
41 m g k g (rabbit, i.v.); 296 m a g (rabbit, p.0.)
0 0
chloride
Trang 7Acecarbromal A 7
Reference(s):
G B 1 247 384 (May & Baker; appl 22.12.1967)
DAS 1 815 808 (May & Baker; appl 19.12.1968; GB-prior 22.12.1967, 14.5.1968, 2.8.1968)
US 3 726 919 (May &Baker; appl 19.12.1968; GB-prior 22.12.1967, 14.5.1968, 2.8.1968)
US 3 857 952 (May & Baker; appl 3.8.1972)
preparation of 4-bu tyramidophenol:
Kuhn; Koehler; Koehler: Hoppe-Seyler's Z Physiol Chem (HSZPAZ) 247, 197,216 (1937)
Verma, K.K.; Tyagi, P.: Anal Chem (ANCHAM) 56 (12), 2157 (1984)
US 2 824 838 (Esso Research & Eng Co.; 25.2.1958; appl 13.1.1955)
Formulation(s): amp 25 mg; tabl 200 mg, 400 mg (as hydrochloride)
Trade Narne(s):
F: Sectral (Specia; 1976) Prent (Bayropharm; 1981)
GB: Secadrex (RhBne-Poulenc Sectral (RhBne-Poulenc
Acecarbromal
(Acetylcarbromal; Acetcarbromal)
Use: sedative, hypnotic RN: 77-66-7 MF: C,H,,BrN,O, MW: 279.13 EINECS: 201-047- 1
LD,,: 1600 mgkg (M, p.0.)
CN: N-[(acetylamino)carbony I]-2-bromo-2-ethylbutanamide
Reference(s):
DRP 225 710 (Bayer; 1910)
( q v.1
Trang 8alternative syntheses:
DRP 286 760 (Bayer; 1913)
DRP 327 129 (Bayer; 1917)
Trade Nameis):
D: Abasin (Bayer); wfm USA: Carbased (Mallard); wfm
Afrodor (Farco-Pharma) Sedamyl (Riker); wfm
Use: antiglaucoma, miotic RN: 827-61-2 MF: C,H,,N02 MW: 169.22 EINECS: 212-574-1
LDso: 78 m g k g (M, i.p.); 36 m g k g (M, i.v.); 165 m g k g (M, p.0.); 102 mglkg (M, s.c.);
45 m g k g (R, i.v.); 225 m g k g (R, LC.)
CN: 1-azabicyclo[2.2.2]octan-3-01 acetate (ester)
hydrochloride
RN: 6109-70-2 MF: C,H15N02 HCl MW: 205.69 EINECS: 228-071-5
LD,,,: 27mgkg(M,i.v.); 165mgkg(M,p.o.);
45 m g k g (R, i.v.)
salicylate (1:l)
RN: 6821-59-6 MF: C,H,,N02 C,H,O, MW: 307.35
LD,,,: 113 m g k g (M, LC.)
3-hydroxy- acetic anhydride
quinuclidine
(cf clidinium
bromide synthesis)
Reference(s):
US 2 648 667 (Roche; 1953; prior 195 1)
Grob, C.A et al.: Helv Chim Acta (HCACAV) 40, 2170 (1957)
Trade Narne(s):
D: Glaucotat (Chibret) Glaucostat (Merck Sharp &
F: Glaucadrine (Merck Sharp Dohme-Chibret)
& Dohme-Chibret)-comb 1: Glaunorm (Farmigea)
Use: non-steroidal anti-inflammatory, analgesic, antipyretic, prostaglandin synthesis inhibitor
RN: 89796-99-6 MF: C,,H,,CI2NO4 MW: 354.19
LD,,: 121 mglkg (M, p.0.)
CN: 2-[(2,6-dichlorophenyl)amino]benzeneacetic acid carboxymethyl ester
Trang 9Acediasulfone A 9
0
3 Hz Pd-C
+
CI 2 benzyl brornoocetote
diclofenoc
(4 v.)
0 COOH
C I
Reference(s):
EP 119 932 (Prodes; appl 19.3.1984; E-prior 21.3.1983)
US 4 548 952 (Prodes; 22.10.1985; appl 15.3.1984; E-prior 21.3.1983)
alternative synthesis:
ES 2 020 146 (Prodesfarma; appl 29.5.1990)
Formulation(s): cream 1.5 %; vial 150 mg; tabl 100 mg
Trade Name(s):
GB: Preservex (Bristol-Myers
Squibb; 1992)
Use: antibacterial, cytotoxic agent RN: 80-03-5 MF: C,,H,,N,O,S MW: 306.34 EINECS: 201-243-7
CN: N-[4-[(4-aminophenyl)sulfonyl]phenyl]glycine
monosodium salt
RN: 127-60-6 MF: C,,H,,N2Na04S MW: 328.32 EINECS: 204-852-6
Reference(s):
CH 254 803 (Cilag; appl 1946)
CH 278 482 (Cilag; appl 1949)
US 2 589 21 1 (Parke Davis; 1952; appl 1948)
US 2 454 835 (Parke Davis; 1948; prior 1943)
US 2 751 382 (Cilag; 1956; D-prior 6.7.1953)
dapsone chloroocetic
Trade Name(s):
D: Ciloprin (Cilag-Chemie)-
comb.; wfm
Acediasulfone
Trang 1010 A Acefylline
Use: cardiotonic, diuretic, antispasmodic, bronchodilator
RN: 652-37-9 MF: CyH1,N404 MW: 238.20 EINECS: 21 1-490-2
LD,,,: 1180mgkg(M,i.p.);2733mg/kg(M,p.o.)
CN: 1,2,3,6-tetrahydro-1,3-dimethyl-2,6-dioxo-7H-purine-7-acetic acid
I
CH3
theophylline chloroacetic
ocid
Acepifylline
RN: 18833-13-1 MF: C,UloN40,~ xC4HloN, MW: unspecified EINECS: 242-614-3
CN: 1,2,3,6-tetrahydro-l,3-dimethyl-2,6-dioxo-7H-purine-7-acetic acid compd with piperazine
Acefylline heptaminol
piperazine
RN: 59989-20-7 MF: C,H,oNd03 C,HIyNO MW: 367.45 EINECS: 262-012-4
CN: ' 1,2,3,6-tetrahydro-l,3-dimethyl-2,6-dioxo-7H-purine-7-acetic acid compd with 6-amino-2-methyl-2-
Acepifylline
heptaminol (1 : 1)
Rc$erence(s):
Blaisse, J.: Bull Soc Chim Fr (BSCFAS) 1949,769
hepiorninol (q v.)
Fortnulation(s): amp 500 mg/200 ml; drg 250 mg; suppos 500 mg; tabl 250 mg (acepifylline); drg 250 mg;
inj 0.5 g; suppos 0.5-1 g
-
CH3 Acefylline heptominal
Trade Nameis):
D: Etaphydel (Delalande; as F: Sureptil (SynthClabo; as GB: Etophylate (Delalande; as acepifylline); wfm acefylline-heptamino1)- acepifylline); wfm
1snardi)-comb