formulations: injection form: EP 136 463 Bioresearch; appl.. gastric juice resistant form: EP 136 464 Bioresearch; appl... 20 ml with 300 mg meglumine salVml triiodobenzaic acid cf.
Trang 1Adiphenine A 41
4-toluenesulfonate sulfates:
US 3 954 726 (Bioresearch; 4.5.1976; I-prior 27.6.1973; 24.5.1974)
other sulfonates:
DOS 2530 898 (Bioresearch; appl 10.7.1975; I-prior 12.7.1974)
US 4057 686 (Bioresearch; 8.1 1.1977; I-prior 12.7.1974)
US 4 465 672 (Bioresearch; 14.8.1984; I-prior 24.8.1981)
EP 72 980 (Bioresearch; appl 12.8.1982; I-prior 24.8.1981)
EP 162 323 (Bioresearch; appl 25.4.1985; I-prior 16.5.1984)
EP 162 324 (Bioresearch; appl 25.4.1985; I-prior 16.5.1984)
other salts:
EP 73 376 (Bioresearch; appl 12.8.1982; I-prior 24.8.1981)
EP 74 555 (Bioresearch; appl 30.8.1982; I-prior 11.9.1981)
EP 108 817 (Kanegafuchi; appl 6.11.1982)
EP 141 462 (Tecofar; appl 19.10.1984; I-prior 26.10.1983)
formulations:
injection form:
EP 136 463 (Bioresearch; appl 1.8.1984; I-prior 24.8.1983)
gastric juice resistant form:
EP 136 464 (Bioresearch; appl 1.8.1984; I-prior 24.8.1983)
Formulation(s): amp 384 mg; tabl 384 mg (as bisulfate)
Trade Name(s):
I: Donamet (Knoll) Transmetil (Bioresearch)
Use: antispasmodic, anticholinergic RN: 64-95-9 MF: C,oH25N02 MW: 31 1.43 EINECS: 200-599-0
LD,,: 182 rnglkg (M, i.p.); 21.5 mglkg (M, i.v.); 600 mglkg (M, p.0.); 400 mglkg (M, s.c.);
27 mgkg (R, i.v.);
35 mgkg (dog, i.v.);
30 mgfkg (rabbit, i.v.)
CN: a-phenylbenzeneacetic acid 2-(diethy1amino)ethylester
hydrochIoride
RN: 50-42-0 MF: C2,H2,N02 HCI MW: 347.89 EINECS: 200-036-9
LD,,: 185 mglkg (M, i.p.); 500 mglkg (M, p.0.); 650 mglkg (M, LC.);
250 mglkg (R, i.p.); 17.3 mgkg (R, i.v.)
<CH, HO&N-CH3 _*
ethanol
Reference(s):
DE 626 539 (Ciba; 1934)
drg 20 mg, 25 mg; suppos 40 mg, 50 mg
Trang 242 A Adipiodone
Trade Name(s):
F: Spasmo-Cibalgine (Ciba)- I: Nisidina (De Angel+ USA: Trasentine (Ciba); wfm
Adipiodone
(Iodipamide)
ATC: V08AC04 Use: X-ray contrast medium
RN: 606-17-7 MF: C2,H,,IhN20, MW: 11 39.76 EINECS: 210-105-5
LD,,: 2440 m g k g (M, i.v.)
CN: 3,3'-[(I ,6-dioxo-1,6-hexanediyl)diimino]bis[2,4,6-triiodoben~0i~ acid]
disodium salt
RN: 2618-26-0 MF: C,,H,,I,N,Na,O, MW 1183.73 EINECS: 220-049-3
LD,,: 3400 m g k g (R, i.v.)
meglumine salt (1:2)
RN: 3521-84-4 MF: C2,H,,IhN20~ 2C7H,,N05 MW: 1530.19 EINECS: 222-534-5
LD,,: 3195 m g k g (M, i.v.);
5000 m g k g (R, i.v.); 1921 m g k g (R, parented);
1446 m g k g (rabbit, parenteral);
1200 m g k g (dog, i.v.)
Reference(s):
US 2 776 241 (Schering AG; 1957; D-prior 1952)
DE 936 928 (Schering AG; appl 1952)
DE 962 698 (Schering AG; appl 1952)
DE 962 699 (Schering AG; appl 1953)
DE 1 006 428 (Schering AG; appl 1955)
3-amino-2.4,6- odipoyl chloride
starting material:
Kretzer, H.: Ber Dtsch Chem Ges (BDCGAS) 30, 1944 (1897)
Adipiadone
Formulation(s): amp 20 ml with 300 mg meglumine salVml
triiodobenzaic
acid
(cf ocetrizaic
acid synthesis)
Trade Name(s):
D: Biligrafin (Schering); wfm Endografin (Schering Endografin (Schering- Endografin (Schering); Chemicals); wfm Nichidoku; as meglumine
F: Transbilix (Guerbet; as Endocistobil (Bracco); wfm USA: Cholografin (Squibb); wfm meglumine salt) J: Biligrafin (Schering- Cholografin Meglumin
Chemicals); wfrn
Trang 3Adrafinil A 43
Adrafinil
(CRL-40028)
ATC: N06BX17 Use: a-adrenergic agonist (for symptomatic treatment of vigilance and depresswe manifestations), antidepressant
RN: 63547-13-7 MF: C,,H,,NO,S MW: 289.36 EINECS: 264-303-1
LD,,,: >2048 mglkg (M, i.p.); 1950 m g k g (M, p.0.)
CN: 2-[(diphenylmethyl)sulfinyl]-N-hydroxyacetamide
thiourea chlaroacetic acid S-COOH
benzhydrol diphenyl-
rnethanethiol
(benzhydry1thia)-
acetic acid (I)
1 (H,CO),SO,, NaHCOJ
2 N H 2 0 H , NaOH
hydrogen $-COOH 1 dirnethyl sulfate
peroxide 2 2 hydroxylarnine
(benzhydrylsulfi- Adrafinil nyl)ocetic acid
1 CZH,OH, H2S0,
2 N H 2 0 H , KOH
I H z 0 2
2 hydroxylornine
hydrogen
0
peroxide
Reference(s):
DOS 2 642 51 1 (Lab Lafon; appl 22.9.1976; GB-prior 2.10.1975)
US 4 066 686 (Lab Lafon; 3.1.1978; GB-prior 2.10.1975)
US 4 098 824 (Lab Lafon; 4.7.1978; GB-prior 2.10.1975)
Trade Name(s):
F: Olmifon (Lafon; 1985)
Use: sympathomimetic, vasoconstrictor, hernostyptic
RN: 99-45-6 MF: C,H,,NO, MW: 181.19 EINECS: 202-756-9
LD,,: 275 mgfkg (M, i.v.)
CN: 1-(3,4-dihydroxypheny1)-2-(methy1amino)ethanone
hydrochloride
RN: 62-13-5 MF: C,H,,NO, HCI MW: 217.65 EINECS: 200-525-7
LD,,,: 902 mglkg (M, i.p.)
Trang 444 A Afloqualone
chloroocetic cotechol
acid
2-chloro-3'.4'- dihydroxy- ocetophenone (I)
I Adrenalone
H3C-NH,
I b
rnethylomine
Reference (s):
DRP 152 8 14 (Hoechst; 1903)
OH
Trade Name(s):
D: Stryphnasal (Sertiimer) F: Adrtnalone Tktracaine HCrnorrodine (Rocher)-
Guillon (Pharmascience)- comb.; wfrn comb.; wfm
Use: muscle relaxant RN: 56287-74-2 MF: C1,Hl4FN3O MW: 283.31
LDso: 397 mglkg (M, p.0.);
249 mglkg (R, p.0.)
hydrochloride
RN: 56287-75-3 MF: C,,H,,FN,O xHC1 MW: unspecified
SOCI,
5-nitroonthronilic
H 3 C N-(2-amino-5-nitro-
fluoroocetyl
Trang 5Ajmaline A 45
-
Reference(s):
DOS 2 449 11 3 (Tanabe; appl 15.10.1974; J-prior 15.10.1973)
US 3 966 73 1 (Tanabe; 29.6.1976; J-prior 15.10.1973)
Tani, J et al.: J Med Chem (JMCMAR) 22, 95 (1979)
Formulation(s): tabl 20 mg
Trade Name(s):
J: Aflospan (Kyowa) Arofuto (Tanabe; 1983)
Ajmaline
(Rauwolfine)
ATC: COlBAO5 Use:- antiarrhythmic RN: 4360-12-7 MF: C,oH26N202 MW: 326.44 EINECS: 224-439-4
LD,,: 75 m g k g (M, i.p.); 21 m g k g (M, i.v.); 255 mgkg (M, p.0.); 180 m g k g (M, s.c.);
94 m g k g (R, i.p.); 26 mglkg (R, i.v.); 360 m g k g (R, p.0.); 216 mglkg (R, s.c.)
CN: (l7RJl a)-ajmalan-l7,21-diol
monohydrochloride
RN: 4410-48-4 MF: C20H26N202 HC1 MW: 362.90 EINECS: 224-562-3
LDso: 105 mg/kg (M, i.p.); 26 m g k g (M, i.v.); 205 m g k g (M, p.0.);
86 m g k g (R, i.p.); 19.3 m g k g (R, i.v.); 290 m g k g (R, p.0.);
135 mg/kg (g p., p.0.)
I Ajrnoline
By extraction from the pulverized roots of Rauwolfia serpentina (L.) Beuth
Reference(s):
Siddiqui, S.; Siddiqui, R.H.: J Indian Chem Soc (JICSAH) 8, 667 (1931); 9, 539 (1932); 12, 37 (1935)
Formulation(s): amp 2 mg12 ml, 50 mg/2 ml, 10 mgIlO ml, 50 mg/lO ml
Trade Name(s):
D: Gilurytmal (Solvay F: Cardiorythmine (Servier); Ritmosedina (Inverni della
Tachmalin (ASTA Medica Dipaxan (1nnothCra)- J: Gilurytmal (Giulini-Tokyo
I: Aritmina (UCM)
Trang 64 6 A Alacepril
Alacepril
(DU-1219)
ATC: C09A Use: antihypertensive (ACE inhibitor), metabolizes partly to captopril RN: 74258-86-9 MF: C20H2hN20SS MW: 406.50
LD,,: >5 glkg (M, p.0.);
>5 glkg (R, p.0.)
CN: (S)-N-[l-[3-(acetylthio)-2-methyl-l-oxopropyl]-~-prolyl]-~-phenylalanine
1 THF N-methylmarpholine ~ O ~ , -15 C O C I
-
b 1
1 phenyl chloroformote
CH3 2 L-phenylalonine tert-butyl ester
1 -[(S)-3-ocetylthio- hydrochloride
2-methylpraponoyl]-
L-proline
(cf captopril synthesis)
Referencefs):
US 4 248 883 (Dainippon Pharmac Co.; 3.2.1981; J-prior 6.7.1978)
EP 7 477 (Dainippon Pharmac Co.; appl 3.7.1979; J-prior 6.7.1978)
pharrnmology:
Takeyama, K et al.: Arzneim.-Forsch (ARZNAD) 35, 15U2 (1985)
metabolistn:
Matsumoto, K et al.: Arzneim.-Forsch (ARZNAD) 36,40 (1986)
Formulation(s): tabl 12.5 mg, 25 mg
Trade Name(s):
J: Cetapril (Dainippon; 1988)
Use: non-essential proteinogenic amino acid (part of infusion solutions) RN: 56-41-7 MF: C3H7N02 MW: 89.09 EINECS: 200-273-8
CN: L-alanine
Trang 7Alatrofloxacin mesilate A 47
enzyrn rocernote resolution
1 with ominoocylose
H3C COOH
enzym rocernote resolution
NaOH with orninoocylose
L-Alonine
enzyrn decorboxylotion with L-osportote 8-decorboxylose, '
YH2 e.g in irnrnobil Pseudomonos docunhoe (IAM 1152)
HOOC+
COOH
L-osporoginic
acid
Reference(s):
review:
Ullmann's Encyclopedia of Industrial Chemistry, 5th Ed., Vol A2,69
Kaneko, T.; Izumi, Y.; Chibata, I.; Itoh, T.: Synthetic Production and Utilization of Amino Acids, Kodansha Ltd and John Wiley & Sons, Tokyo, New York, p 62 (1974)
c US 3 898 128 (Tanabe; 5.8.1975; J-prior 20.11.1972)
Yamamoto, K et a].: Biotechnol Bioeng (BIBIAU) 22, 2045 (1980)
Formulation(s): tabl 400 mg
Trade Name(s):
F: Theraplix (Abufene)
Alatrofloxacin mesilate
(CP 116517; CP 116517-27)
ATC: JOlMA Use: antibacterial, prodrug of trovafloxacin
RN: 146961-77-5 MF: C2,H2,F3N605 CH403S MW: 654.62
naphthyridin-2-yl]-3-azabicyclo[3.1 O]hex-6-yl]-L-alaninamide monomethanesulfonate
base
RN: 146961-76-4 MF: C2,H2,F3N,0, MW: 558.52
Trang 848 A Alclofenac
-
H,C-S03H
acetane/H20
11
rnethanesulfonic
acid
dihydroquinoline
(EEDP)
F
Alatrofloxacin rnesilate
US 5 164 402 (Pfizer; 17.1 1.1992; appl 4.2.1991; WO-prior 16.8.1989)
WO 9 700 268 (Pfizer; appl 27.3.1996; USA-prior 15.6.1995)
Formulation(s): vials 200 mgl40 ml, 300 mg160 ml(5 mg/ml) (as mesilate)
Trade Narne(s):
D: TROVAN (Pfizer); wfm GB: Turvel (Pfizer); wfm USA: Trovan (Pfizer); wfm F: Turvel (Pfizer); wfm I: Turvel (Pfizer); wfm
Use: analgesic, antipyretic, anti- inflammatory
RN: 22131-79-9 MF: CIIH,,C103 MW: 226.66 EINECS: 244-7954
LD,,: 508 mg/kg (M, i.p.); 1100mg/kg (M, p.0.);
465 mglkg (R, i.p.); 1050 mg/kg (R, po.)
CN: 3-chloro-4-(2-propeny1oxy)benzeneacetic acid
sodium salt
RN: 24049-1 8-1 MF: C,,H,,ClNaO, MW: 248.64
LD,,: 530 m g k g (R, i.p.); 1050 mg/kg (R, p.0.)
Trang 9Alclometasone dipropionate A 49
ollyl bromide (1) 2-chloraphenol 2-chlorophenyl ally1 ether (n)
HCI, A s 2 0 3 NoCN DMSO
I1 + HCHO -
sodium cyonide ' 111
CI
formolde- 4-ollyloxy-3-chloro-
CI
4-allyloxy-3-chloro-
benzyl cyanide (nI)
3-chloro-4-hydroxy-
benzoldehyde
benzyltrimethyl- ammonium hydroxide
formoldehyde
dimethyl mercoptol
S-oxide
Alclofenoc
4-allyloxy-3-chloro- benzoldehyde (IV)
1 -(2-methylsulfinyl-2-methyl-
thioviny1)-4-ollyloxy-3-
chlorobenzene
Reference(s):
a BE 704 368 (Madan; appl 27.9.1967)
BE 718 930 (Madan; appl 1.8.1968; prior 27.9.1967)
GB 1 174 535 (Madan; appl 28.8.1968; B-prior 27.9.1967, 1.8.1968)
b GB 1 504 828 (Sagami; appl 26.1 1.1976; J-prior 1.12.1975)
lysine salt:
DOS 2 71 1 964 (Biochcfarm; appl 18.3.1977)
Formulation(s): amp 833 mg; tabl 1 g, 500 mg
Trade Nanze(s):
D: Neoston (Beiersdorf); wfm I: Rentenac (Tosi); wfm J: Allopydin (Chugai)
GB: Prinalgin (Berk); wfm Zumaril (Sidus); wfm Epinal (Mitsubishi Yuka)
Use: topical steroidal anti-inflammatory (glucocorticoid)
RN: 66734- 13-2 MF: C2,H&1O7 MW 521 .O5 EINECS: 266-464-3
LD,,: 2506 mgkg (M, s.c.);
3593 mgkg (R, s.c.)
CN: (7a, 1 lb,l6a)-7-chloro-l l -hydroxy-16-methyl-l7,21-bis(l-oxopropoxy)pregna-l,4-diene-3,2O-dione
Trang 1050 A Alclometasone dipropionate
16a-methylprednisolone
21 -ocetote
(intermediate of
dexarnethasone
synthesis)
, HCI, dioxane,
0
room temp 24 h
b
2.3-dichloro-5.6-dicyano- benzoquinone (0012)
16a-methyl-21 -acetoxy-
1 lfl.17n-dihydroxypregna- 1,4,6-triene-3.20-diane (I)
triethyl orthopropionate
H ~ C / ~ ~ V C H , , pyridine
0 0
I V
propionic anhydride (V)
HCI, dioxane
VI -+
Alclometasone dipropiontlte
hue, H.-J.; Green, M.J.: J Med Chem (JMCMAR) 23,430 (1980)
US 4 124 707 (Schering Corp.; 7.1 1.1978; prior 12.12.1976,7.11.1977)
US 4 076 708 (Schering Curp.; 28.2.1978; prior 22.12.1976)
DOS 2 756 550 (Scherico; appl 19.12.1977; USA-prior 22.12.1976)
Formulation(s): cream and ointment 0.5 mgll g