Stada; wfm F: Binoctal Houd6-comb.; wfm Carlytkne amobarbital Dedieu-comb.; wfm Methxane Ga1lier- comb.; wfrn Nardyl Vemin-comb.; wfrn Noctadiol Millot-Solac- comb.; wfrn Supponoctal Hou
Trang 1Amobarbital A 101
Amobarbital
(Amylobarhitone)
ATC: N05CA02 Use: hypnotic RN: 57-43-2 MF: C,,H,,N,O, MW: 226.28 EINECS: 200-330-7
LD,,: 345 mg/kg (M, p.0.);
250 mg/kg (R, p.0.);
58 m g k g (dog, i.v.)
CN: 5-ethyl-5-(3-methylbutyl)-2,4,6(1H,3H,5H)-pyrimidinetrione
monosodium salt
RN: 64-43-7 MF: C,,H,,N,NaO, MW: 248.26 EINECS: 200-584-9
LDs,: 505 m@g (M, p a ) ;
128 mg/kg (R, i.v.); 275 mglkg (R, p.0.);
75 m g k g (dog, i.v.); 99 m g k g (dog, p.0.)
0 C 0 , 3 I N O D C ~ H ,
'w.,-Br
diethyl malonote diethyl ethylrnalonate
diethyl e-ethyl-
a-isapentylmalonate (I)
Amobarbital
u
Reference(s):
GB 191 008 (E Layraud; 1922; F-prior 192 1)
US 1 856 792 (Eli Lilly; 1932; prior 1929)
Formulation(s): tabl 15 mg, 30 mg, 50 mg, I00 mg
Trade Name(s):
D: Ansudoral (Basothem)-
comb.; wfrn
Jalonac (Riihm Pharma)-
comb.; wfrn
Metrotonin (Temm1er)-
comb.; wfm
Stadadorm Tabl (Stada);
wfm
F: Binoctal (Houd6)-comb.;
wfm
Carlytkne amobarbital
(Dedieu)-comb.; wfm
Methxane (Ga1lier)- comb.; wfrn
Nardyl (Vemin)-comb.;
wfrn Noctadiol (Millot-Solac)- comb.; wfrn
Supponoctal (Houd6)- comb.; wfrn
Tensophoril (Syn1ab)- comb.; wfrn
ViscCralgine comprimCs (Riom)-comb.; wfrn
GR: Amytal(F1ynn) Sodium Amytal (Flynn) Tuinal (Flynn)-comb 1: Amobarb (Tariff
lntegrativo) J: Amytal (Yamanouchi) Isomytal (Nippon Shinyaku) USA: Amytal (Lilly) Amytal Sodium (Lilly) Tuinal (Lilly)
Trang 2102 A Amodiaquine
Use: antimalarial RN: 86-42-0 MF: C2,H,,C1N3O MW: 355.87 EINECS: 201-669-3
LD,,,: 550 mglkg (M, p.0.)
CN: 4-[(7-chloro-4-quinolinyl)amino]-2-[(diethylamino)methyl]phenol
dihydrochloride dihydrate
RN: 69-44-3 MF: C2,H22C1N30 2HC1 2H20 MW: 464.82 EINECS: 200-706-0
4.7-dichloro- 4-ominophenol
quinoline
(cf chloroquine
synthesis)
formaldehyde diethylomine
7-chloro-4-(4-hydroxy- phenylomino)quinoline (I)
Amodioquine
US 2 474 821 (Parke Davis; 1949; prior 1945)
Burckhalter, J.F et al.: J Am Chem Soc (JACSAT) 68, 1894 (1946)
Fonnulation(s): tabl 200 mg (as dihydrochloride dihydrate)
Trade Name(s):
F: Flavoquine (Roussel GB: Camoquin (Parke Davis);
USA: Camoquin (Parke Davis); wfm
Use: topical antimycotic RN: 78613-35-1 MF: C2,H,N0 MW: 317.52
CN: cis-(f)-4-[3-[4-(1,1-dimethylpropyl)phenyl]-2-methylpropyl]-2,6-dimethylmorpholine
hydrochloride
RN: 78613-38-4 MF: C,,H3SN0 HCl MW: 353.98
4-tert-omyl-a-methyl- cinnomoldehyde (I)
Trang 3Amosulalol A 103
H
rnorpholine
Reference(s):
DE 2 752 135 (Hoffmann-La Roche; appl 22.1 1.1976)
EP 24 334 (Hoffrnann-La Roche; appl 7.8.1980; CH-prior 17.8.1979, 29.5.1980)
antirnycotic nail varnish:
EP 389 778 (Hoffmann-La Roche; appl 15.2.1990; CH-prior 9.1 1.1989, 24.2.1989)
Formulation(s): cream 0.25 %, sol 5 %
Trade Name(s):
D: Loccryl (Roche) GB: Loceryl (Roche; 1992 as J: Pekiron (Kyorin)
Amosulalol
(YM-W538)
ATC: CO2CB Use: a- and P-adrenoceptor blocker, antihypertensive
RN: 85320-68-9 MF: Cl,H,N,05S MW: 380.47
CN: (+)-5-[1-hydroxy-2-[[2-(2-methoxyphenoxy)ethyl]amino]ethyl]-2-methylbe~enesulfonamide
monohy drochloride
RN: 70958-86-0 MF: Cl,H,N,05S HCI MW: 416.93
Guoiacol 1,2-dibromo-
(2-rnethoxy- ethane
phenol)
3-amino-4-methyl-
acetaphenone
5-acetyl-2-methyl- benzenesulfanornide
5-[[N-[2-(2-rnethoxyphenoxy)ethyl]-
benzylarnino]ocetyl]-2-methyl-
Trang 4104 A Amoxapine
H, Pd-C
0
Reference(s):
DOS 2 843 016 (Yamanouchi; appl 3.10.1978; J-prior 12.10.1977,26.10.1977,23.12.1977,21.6.1978)
GB 2 006 772 (Yamanouchi; appl 12.10.1978; J-prior 12.10.1976, 26.10.1977, 23.12.1977, 21.6.1978)
synthesis of I:
Augstein, 1 et al.: J Med Chem (JMCMAR) 8, 365 (1965)
synthesis of 11:
EP 162 404 (Seitetsu Kagaku; appl 14.5.1985; J-prior 15.5.1984, 18.9.1984, 3.4.1985)
synthesis of 14~-amosulalol:
Arima, H.; Tamazawa, K.: J Labelled Compd Radiopham (JLCRD4) 20,803 (1983)
Formulation(s): tabl 10 mg
Trade Name(s):
J: Lowgan (Yamanouchi;
1988 as hydrochloride)
Use: antidepressant RN: 14028-44-5 MF: C,,H&lN,O MW: 313.79 EINECS: 237-867-1
LD,,: 122 mglkg (M, i.p.); 112 m g k g (M, p.0.)
CN: 2-chloro-l l-(l-piperaztnyl)dibenzo[b,fl[l ,410xazepine
-
2 H, Pd-C
_,
phenaxy)anilins
1 -ethoxycarbanyl
piperazine
1 Amoxapine
Trang 5Amoxicillin A 105
Referencefs):
US 3 681 357 (American Cyanamide; 16.5.1972; prior 20.5.1966)
US 3 444 169 (American Cyanamide; 13.5.1969; prior 17.1.1966)
GB 1 177 956 (American Cyanamide; prior 23.12.1966)
GB 1 192 812 (American Cyanamide; USA-prior 20.5.1966)
DE 1 645 954 (American Cyanamide; appl 17.1 l967; USA-prior 17.1.1966)
GB 1 157 957 (American Cyanamide; prior 15.9.1965)
US 3 663 696 (American Cyanamide; 16.5.1972; prior 28.2.1964, 20.5.1966,22.7.1970)
Schmutz, J et al.: Helv Chim Acta (HCACAV) 50,245 (1967)
Schmutz, J et al.: Chim Ther (CHTPBA) 2,424 (1967)
preparation of 2-(4-ch1orophenoxy)aniline:
DE 216 642 (Bayer; 1908)
Wassrnundt, F.W.; Pedemonte, R.P.: J Org Chern (JOCEAH) 60 (16), 4991 (1995)
Formulation(s): sol 5 %; sol 5 %; tabl 25 mg, 50 mg, 100 mg, 150 mg
Trade Namefs):
F: DCfanyl (Wyeth-Lederle) 1: Amoxan (Lederle; 1981) USA: Asendin (Lederle Labs.;
Amoxicillin
(Amoxycillin)
ATC: JOlCA04 Use: a'ntibiotic
RN: 26787-78-0 MF: C16H,,N305S MW: 365.41 EINECS: 248-003-8
LD,,: >25 g k g (M, p.0.);
>15 g k g (R, p.0.)
CN: [2S-[2a,5a,6~(S*)]]-6-[[amino(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-4-thia-l- azabicyclo[3.2.0]heptane-2-carboxylic acid
sodium D(-)-a-(4-hydroxy- ethyl chloroformote
arnino)acetote
(DANE solt; cf
ampicillin, method
HO
~ o ' o n c H 3
COOH 1 (CH,),sicl N(C2H5)3
H"O-CH,
chlorosilone
D-a-(4-hydroxyphenyl)-a-(2- 6-amino-
methoxycarbonyl-1 -methyl- penicillonic acid (11)
etheny1amino)acetic acid
anhydride with monoethyl
carbonate (I)
Trang 6106 A Arnoxicillin
Arnoxicillin
trirnethyl-
chlorosilane
6-orninopenicillanic acid trirnethylsilyl ester (111)
D(-)-2-(4-hydraxypheny1)-
glycyl chloride hydrachlaride
arnoxicillin trirnethylsilyl ester (IV)
Reference(s):
"racemic arnoxicillin":
US 3 674 776 (Beecham; 4.7.1972; prior 23.8.1968)
GB 1 241 844 (Beecham; appl 18.8.1969; prior 23.8.1968)
DE 1 942 693 (Beecham; appl 18.8.1969; GB-prior 23.8.1968)
GB 978 178 (Beecham; appl 2.11.1962; valid from 25.10.1963)
US 3 192 198 (Beecham; 29.6.1965; GB-prior 2.11.1962)
amoxicillin:
Long, A.A.W et al.: J Chem Soc C (JSOOAX) 1971,1920
US 3 674 776 (Beecham; 4.7.1972; appl 18.8.1969; GB-prior 23.8.1968) DOS 1 942 693 (Beecham; appl 21.8.1969; GB-prior 23.8.1968)
GB 1 241 844 (Beecham; appl 23.8.1968; valid from 20.8.1969)
a US 4 128 547 (Gist-Brocades; 5.12.1978; NL-prior 6.9.1977)
GB 1 339 605 (Beecham; appl 1.4.1971; valid from 28.3.1972)
preparation of "DANE salt":
DE 2 400 489 (Upjohn Co.; appl 5.1.1974; USA-prior 12.1.1973)
US 3 904 606 (Upjohn Co.; prior 12.1.1973)
Dane, E et al.: Angew Chem (ANCEAD) 76,342 (1964)
Dane, E et al.: Chem Ber (CHBEAM) 98,789 (1965)
b DAS 2 61 1 286 (Bristol-Myers; appl 17.3.1976; USA-prior 17.3.1975) preparation of D(-)-2-(4-hydroxypheny1)glycyl chloride hydrochloride:
CA 1 024 507 (Bristol Myers Co.; appl 16.1.1974; USA-prior 18.1.1973)
Trang 7Amoxicillin A 107 alternative syntheses:
US 4 053 360 (Bristol-Myers; 11.10.1977; GB-prior 5.6.1974, 19.3.1975)
DOS 2 454 841 (Archifar; appl 19.1 1.1974; I-prior 17.5.1974)
DOS 2 755 903 (Dobfar; appl 15.12.1977; I-prior 16.12.1976)
GB 1 535 291 (Bristol-Myers; appl 5.3.1976; USA-prior 17.3.1975)
US 4 098 796 (Novo; 4.7.1978; appl 7.6.1976)
BE 867 414 (Antibioticos S.A.; appl 24.5.1978; E-prior 4.6.1977)
microbiologic acylation of 6-APA with methyl D-a-(4-hydroxypheny1)-glycinate hydrochloride by means of
Aphanocladium aranearum (ATCC 20453):
US 4 073 687 (Shionogi; 14.2.1978; J-prior 14.5.1975)
sodium salt:
GB 1 543 317 (Beecham; valid from 4.8.1976; prior 27.9.1975)
DOS 2 729 112 (Beecham; appl 28.6.1977; GB-prior 7.7.1976)
trihydrate:
DAS 2 61 1 286 (Bristol-Myers; appl 17.3.1976; USA-prior 17.3.1975)
DOS 2 732 528 (Bristol-Myers; appl 19.7.1977; GB-prior 20.7.1976)
water soluble salts with arginine or lysine:
GB I 504 767 (Beecham; valid from 23.8.1976; prior 2.7.1975,30.9.1975; 3.1 1.1975)
GB 1 539 510 (Beecham; valid from 23.8.1976; prior 23.8.1975,30.9.1975, 3.1 1.1975)
"amorphous" amoxicillin:
DAS 2 112 634 (Beecham; appl 16.3.1971; GB-prior 16.3.1970)
,fomulation,for injection solutions:
GB 1 532 993 (Beecham; appl 7.3.1975; valid from 9.2.1976)
0-acetylamoxicillin:
US 4 053 360 (Bristol-Myers; 11.10.1977; GB-prior 5.6.1974, 19.3.1975)
Fomulation(s): syrup 500 mg/5 ml, 2.5 %, 5 %, 10 %; tabl 500 mg, 750 mg, 1 g
Trade Name(s):
D: Amagesan (Pharbita)
Amoxi-Diolan (Engelhard)
Amoxillat (Azupharma)
Amoxypen (Grunenthal)
Augmentan (SmithKline
Beecham; 1982)-comb
Clamoxyl (SmithKline
Beecham; 1974)
dura AX (durachemie)
Flanamox (Wolff)
Sigamopen (Kytta-
Siegfried)
F: Agram (Inava)
Amodex (Bouchara)
Amophar (Dakota)
Amoxine (Negma)
Augmentin (SmithKline
Beecham; 1984)-comb
Bactox (Innotech
International)
Bristamox (Bristol-Myers
Squibb)
Ciblor (1nava)-comb
Clamoxyl (SmithKline Beecham; 1974)
- Flemoxine (Yamanouchi Pharma)
Gramidil (EG Labo) Hiconcil (Bristol-Myers Squibb)
Zamocilline (Zambon) GB: Amoran (Eastern) Amoxil (Bencard; 1972) Augmentin (SmithKline Beecham; 1984)-comb
Galenamox (Galen) I: Alfamox (Alfa Wassermann) Am-73 (Medici) Amoflux (Lampugnani) Amox (Salus Research) Amoxina (Magis) Amoxipen (Metapharma) Cabermox (Caber) Ibiamox (IBI; as trihydrate) Isimoxin (ISI)
Mopen (Firma)
Pamocil (Farma Uno) Simoxil (Herdel) Sintopen (Mitim) Velamox (SmithKline Beecham)
Zimox (Carlo Erba) generics and numerous combination preparations J: Amolin (Takeda) Clamoxyl (SmithKline Beecham; 1975) Delacillin (Sankyo) Efpenix (Toyo Jozo) Hiconcil (Bristol) Himinomax (Kaken) Pacetocin (Kyowa) Sawacillin (Fujisawa) Widecillin (Meiji) generics
USA: Amoxil (SmithKline Beecham; 1974) Wymox (Wyeth-Ayerst; 1978)
Trang 8108 A Amphetaminil
(Amfetaminil)
RN: 17590-01- 1 MF: C17H,,N2 M W : 250.35 EINECS: 241-560-8
LDS,,: 182 mgkg (M, p.0.);
37.6 mgkg (R, p.0.)
CN: cr-[(l-methy1-2-phenylethyl)amino]benzeneacetonitrile
phenylpropane cyanide
Reference(s):
AT 223 606 (Dr H Voigt; appl 25.4.1961; valid from 15.3.1962)
Klosa, J.: J Prakt Chem (JPCEAO) 20,275 (1963)
Formulation(s): amp 20 mg, 60 mg
Trade Name(s):
D: AN 1 (Voigt); wfm Ton-0, (Voigt)-comb.; wfm Vit-0, (Voigt)-comb.; wfm
Use: fungicidal antibiotic RN: 1397-89-3 MF: C,,H7,NO17 MW: 924.09 EINECS: 215-742-2
LD,,: 1200 pg/kg (M, i.v.); >8 gkg (M, p.0.);
1600 pgkg (R, i.v.); >5 g/kg (R, p.0.);
6 mg/kg (dog, i.v.)
CN: [lR-
(lR*,3S*,5R*,6R*,9R*,l lR*, 15S*,16R*,17R*,I 8S*,l9E,21E,23E,25E,27E929E,3 1 E,33R*,35S*,36R*,37
S*)]-33-[(3-amino-3,6-dideoxy-~-~-mannopyranosyl)oxy]-l,3,5,6,9,11,17,37-octahydroxy-15,16,18- trimethyl-13-oxo-14,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,23,25,27,29,3 1-heptaene-36-carboxylic
acid
Trang 9Ampicillin A 109
Fementatively from Streptomyces nodosus
Reference(s):
U S 2 908 61 1 (Olin Mathieson; 1959; prior 1954)
Formulation(s): caramels 10 mg; cream 30 mg/g; ointment 30 mg/l g; powder 50 mg; susp 100 mg, 500 mg;
tabl 10 mg, 100 mg; liposome-encapsulated amphotericin B in a complex with dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol, vials 20 ml
Trade Name(s):
D: AmBisome (NeXstar;
1999)
Ampho-Moronal (Bristol-
Myers Squibb)
Amphotericin B zur
Infusion (Bristol-Myers
Squibb)
Mysteclin (Bristol-Myers
Squibb)-comb
F: Amphocycline (Bristol-
Myers Squibb)-comb
Fungizone (Squibb) USA:
GB: Abelcet (Liposome Co.) Ambisone (NeXstar) Amphicol (Zeneca) Fungilin r (Squibb) Fungizone (Squibb) I: Fungilin (Mead Johnson) Fungizone (Bristol-Myers Squibb)
J: Fungizone (Bristol-Myers Squibb-Sankyo)
Abelect Injection (Liposome Co.) Amphotec for Injection (Sequus)
Fungizone (Bristol-Myers Squibb, Oncology/
Immunology)
Use: antibiotic RN: 69-53-4 MF: C16HlyN304S MW: 349.41 EINECS: 200-709-7
LD,,: 4600mgkg (M, i.v.); >5 g/kg (M, p.0.);
6200 mgkg (R, i.v.)
CN: [2S-[2a,5a,6~(S*)]]-6-[(aminophenylacetyl)amino]-3,3-dimethyl-7-oxo-4-thia-1-
azabicyclo[3.2.0]heptane-2-carboxylic acid
trihydrate
RN: 7177-48-2 MF: C,,HIyN30,S 3H20 MW: 403.46
LD,,: 15.2 g k g (M, p.0.);
10 gfkg (R, p.o.1
monosodium salt
RN: 69-52-3 MF: Cl,H,,N3Na04S MW: 37 1.39 EINECS: 200-708- 1
LD,,: >5314 mg/kg (M,R, p.0.)
monopotassium salt
RN: 23277-71-6 MF: C,,H1,KN3O4S MW: 387.50 EINECS: 245-550-4
_,
K
carbonate (11)
Trang 10I1 +
H-N 0
-T I
penicillanic acid (UI)
Cbo-am~icillin sodium salt (IV)
D(-)-a-phenylglycine
chloride hydrochloride
D(-)-phenylglycine methyl N-(2-methoxycorbonyl-1 -methyl-
sodium salt ocetoocetate etheny1)-D(-)-phenylglycine sodium salt (V)
1 1 , pyridine
2.111, NaHC03
Reference(s):
a GB 893 049 (Beecham; appl 6.10.1958, 12.5.1959)
GB 902 703 (Beecham; valid from 19.5.1961; prior 25.8.1960)
US 2 985 648 (Beecham; 23.5.1961; GB-prior 6.10.1958)
DAS 1 139 844 (Beecham; appl 6.10.1959; GB-prior 6.10.1958, 12.5.1960)
DE 1 156 078 (Beecham; appl 29.5.1961; GB-prior 25.8.1960)
b US 3 140 282 (Bristol-Myers; 7.7.1964; appl 5.3.1962)
c GB 991 586 (Beecham; appl 28.2.1963, 3.12.1963; valid from 13.2.1964)
alternati~~e syntheses:
DE 1 168 910 (Beecham; appl 3.7.1962; GB-prior 21.7.1961)
US 3 144 445 (American Home; 11.8.1964; appl 26.12.1962)
DAS 1 445 506 (Bristol-Myers; appl 24.10.1963; USA-prior 29.10.1962)
DAS 1 545 534 (Astra; appl 4.3.1965; S-prior 6.3.1964)
DAS 2 029 195 (Yamanouchi; appl 13.6.1970; J-prior 16.6.1969)
DAS 1 800 698 (American Home Products; appl 2.10.1968; USA-prior 2.10.1967) DOS 2 755 903 (Dobfar; appl 15.12.1977; I-prior 16.12.1976)