500 mg Trade Nanles: D: Epsilon-Aminocapronsaure F: Hexalense Leurquin Resplamin Kyorin "Roche" Roche; wfm I: Caprolisin Malesci USA: Amicar Immunex Epsilon-Tachostypan J: Capusumine Ni
Trang 1Aminocaproic acid A 9 1
5-0x0-l0,ll-dihydro- 5-hydroxy- l 0 , l 1 - 5-chloro-l0,l 1 -dihydro-5H-
SH-dibenzo[o,d]cyclo- dihydro-5H-di- dibenzo[a,d]cyclohep(ene (I)
heptene benzo[a,d]cycloheptene
ethyl 7-aminoheptanoote I Amineptine I
Reference ( s ) :
DOS 2 01 1 806 (Science Union; appl 12.3.1970; GB-P 27.3.1969)
US 3 758 528 (Science Union; 11.9.1973; appl 13.3.1970)
US 3 821 249 (Science Union; 28.6.1974; prior 13.3.1970, 30.10.1972)
Fomularion(s): tabl 100 mg (as hydrochloride)
Trade Name(s):
F : Survector (Euthtrapic; 1: Maneon (Poli; 1983)
1978); wfm 1999 Survector (Stroder; 1983)
(Acide aminocaproique; Epsilcapramin) Use: antifibrinolytic, plasmin inhibitor RN: 60-32-2 MF: C6H,,N02 MW: 131.18 EINECS: 200-469-3
LD,,: 4900 m g k g (M, i.v.); 14.3 glkg (M, p.0.);
3300 m g k g (R, i.v.);
>7 glkg (dog, p.0.)
CN: 6-aminohexanoic acid
&-caproloctom I Aminocaproic acid
US 2 453 234 (American Enka Corp.; 1948; NL-prior 1946)
Formularion(s): inj flask 250 mglml; syrup 25 %; tabl 500 mg
Trade Nanle(s):
D: Epsilon-Aminocapronsaure F: Hexalense (Leurquin) Resplamin (Kyorin)
"Roche" (Roche); wfm I: Caprolisin (Malesci) USA: Amicar (Immunex) Epsilon-Tachostypan J: Capusumine (Nichiiko)
(Hormon-Chemie)-comb.; Hemotin (Hokuriku)
Trang 292 A Aminoglutethimide
Use: antineoplastic (aromatase inhibitor) RN: 125-84-8 MF: C,,H,,N,O, MW: 232.28 EINECS: 204-756-4
LD,,: 625 mglkg (M, i.p.)
CN: 3-(4-aminopheny1)-3-ethyl-2,6-piperidinedione
NO2 glutethimide 2-(4-nitropheny1)- Aminoglutethimide
2-phenyl-
butyronitrile
2-(4-nitropheny1)- butyronitrile
Reference(s):
US 2 848 455 (Ciba; 1958; CH-prior 1955)
racemate resolution:
Finch, N et al.: Experientia (EXPEAM) 31, 1002 (1975)
Formulation(s): tabl 250 mg
Trade Name(s):
D: Orimeten (Novartis F: Orimkthe (Novartis) USA: Cytadren (Novartis)
Rodazol (Novartis Pharma) I: Orimeten (Novartis)
Aminophenazone
(Amidophenazon; Amidopyrin; Aminopyrine)
ATC: N02BB03 Use: analgesic, antipyretic, anti- inflammatory
RN: 58-15-1 MF: C,,H,,N,O MW: 231.30 EINECS: 200-365-8
LDS,,: 78 mg/kg (M, i.v.); 350 mglkg (M, p.0.);
98 mglkg (R, i.v.); 285 mglkg (R, p.0.);
121 mglkg (dog, i.v.); 220 mglkg (dog, p.0.)
Trang 3Aminopromazine A 93
ascorbate
RN: 23635-43-0 MF: C,,H,,N,O C6H80, MW: 407.42
ethyl acetoacetate phenylhydrazine
4-amino-2,3-dimethyl- I Aminophenarone I
1 -phenyl-5-~3- pyrazolone
Referencefs):
DRP 193 632 (E Scheitlin; 1907)
Ehrhart, Ruschig I, 171
Formulation(s): suppos 200 mg, 500 mg; tabl 100 mg, 300 mg
Trade Name(s):
D: Compretten (Cascan); wfm Pyramidon (Hoechst); wfm numerous combination
Dimametten (Hormosan); I: Farmidone (Farmitalia) preparations
Aminopromazine
(Proquamezine)
Use: antispasmodic
RN: 58-37-7 MF: C,,H,,N,S MW: 327.50 EINECS: 200-378-9
CN: N,N,Ar,Ar-tetramethy1-3-(1OH-phenothiazin-lO-yl)-l,2-propanediamine
fumarate (2:l)
RN: 3688-62-8 MF: C1yHZSN3S 1/2C4H404 MW: 771.06 EINECS: 222-987-9
a:?O
3 fract crystallization
of the hydrochlorides
1 sodium amide
2 1,3-bis(dimethy1omino)-
2-chloropropane
Trang 49 4 A D-Aminosalicvlic acid
Reference(s):
GB 800 635 (Rh6ne-Poulenc; appl 1954)
DE 1 034 637 (RhGne-Poulenc; appl 1955; F-prior 1954)
Trade Name(s):
D: Lorusil (Bayer); wfm F: Lispamol (Specia); wfm
p-Aminosalicylic acid
(Aminosalylum; PAS)
ATC: J04AAOI Use: tuberculostatic RN: 65-49-6 MF: C7H7N03 MW: 153.14 EINECS: 200-613-5
LD,,: 3898 m g k g (M, i.v.); 4 glkg (M, p.0.)
CN: 4-amino-2-hydroxybenzoic acid
calcium salt (2:l)
RN: 133- 15-3 MF: C14H12CaN206 MW: 344.34 EINECS: 205-095-4
LD,,,: 6500 m g k g (M, p.0.)
monosodium salt
RN: 133- 10-8 MF: C,H,NNaO? MW: 175.12 EINECS: 205-091 -2
qoH + CO, KHC03 5- 10 atm
NH2
3-amino- carbon
phenol dioxide
Reference(s):
US 2 540 104 (Parke Davis; 195 1 ; prior 1949)
purijication:
US 2 844 625 (Miles, 1958; appl 1954)
NH2
p-Aminosalicylic ocid
Fo~-mulation(s): vial -1 3.49 g (as monosodium salt)
Trade Name(s):
D: Pas-Fatol N (Fatol) GB: Asacol (SmithKline
F: B-PAS (Salvoxyl-Wander); Beecham)
Salf-Pas (Salf; as sodium salt)
(Pharmacotechnie); wfm I: Eupasal sodico (Bieffe Sanpas Cal (Sankyo); wfm
Medital; as sodium salt) USA: Paser (Jacobus)
Use: antiarrhythmic RN: 1951-25-3 MF: C25H2912N03 MW: 645.32 EINECS: 217-772-1
LD,,,: 178mg/kg(M,i.v.);>4g/kg(M,p.o.)
Trang 5hydrochloride
RN: 19774-82-4 MF: C2,H2,I2NO, HCI MW: 681.78
0 0
hydrate benzofuron butyric anhydride 2-butyrylbenzofuran 2-butylbenzofuran (I)
I
C H 3
4-rnethoxy- 2-butyl-3-(4-methoxy- 2-butyl-3-(4-hydroxy-
benzoyl chloride benzoy1)-benzofuron benzoyl)-benzofuron (11)
2-butyI-3-(4-hydroxy-
3,5-diiado-benzayl)
benzofuron
(C"3
"a C t i - 0 t h ~ ~ ' ' ~ ~ 3
\ O H P-diethylornina-
ethyl chloride
I
Arniodarone
I
/ ' o -
I
Reference(s):
FR 1 339 389 (Labaz; appl 22.11.1962)
US 3 248 401 (Labaz; 26.4.1966; prior 24.1 1.1961)
2-butylbenzofuran:
Buu-Hoi', N.P et al.: J Chem Soc (JCSOA9) 1964, 173
Formulation(s): inj sol 150 mgl3ml; tabl 200 mg
Trade Name(s):
Tachydaron (ASTA Medica GB: Cordarone X (Sanofi USA:
Amiodar (Midy) Cordarone (Sigma-Tau) Cordarone (Wyeth-Ayerst;
as hydrochloride)
Use: respiratory stimulant, morphine antagonist, antidote (barbiturate poisonings)
RN: 490-55-1 MF: C9HyN,S MW: 191.26 EINECS: 207-713-8
LD,,,: 400 mglkg (M, p.0.)
CN: 5-phenyl-2,4-thiazolediamine
monohy drochloride
RN: 942-31-4 MF: C,HyN3S HC1 MW: 227.72 EINECS: 213-389-9
LD,,,: 372 mglkg (M, p.0.)
Trang 6thiourea a-bromo-
phenylocetonitrile
Reference(s):
Davis, W et al.: J Chem Soc (JSCOA9) 1955, 3491
Chase, B.H et al.: J Chem Soc (JSCOA9) 1955,4443
Formulation(s): inj flask 150 mg
Trade Narne(s):
N
H2N Arniphenozole
,
D: Daptazile 100 (Nicholas); Daptazile Injektion GB:
Daptazole (Nicholas); wfm
Use: antidepressant RN: 50-48-6 MF: C,,H,,N MW: 277.41 EINECS: 200-041-6
LD,,,: 16mgkg(M,i.v.); 140mg/kg(M,p.o.);
320 mgtkg (R, p.0.)
CN: 3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-N,N-dimethyl-l-propanamine
hydrochloride
RN: 549-18-8 MF: Cz0H2,N HC1 MW: 313.87 EINECS: 208-964-6
LDSo: 21 m g k g (M, i.v.); 140 m g k g (M, p.0.);
14 m g k g (R, i.v.); 240 m g k g (R, p.0.);
>27 m g k g (dog, i.v.)
CH3 dibenzosuberone (I) 3-dimcthylominopropyl- 5-(3-dimethylominopropyl)-
magnesium chloride l 0 , l l -dihydro-5H-
I Amitriptyline
Trang 7Amitriptylinoxide A 97
I11
cyclopropyl-
magnesium
bromide
5-(3-bromopropylidene)-
10,l 1-dihydro-5H-
dibenzo[o.d]cycloheptene (IU)
C H 3
dimethylomine
Reference(s):
a GB 858 187 (Hoffmann- La Roche; appl 24.3.1959; CH-prior 3.4.1958)
DE 1 109 166 (Hoffmann-La Roche; appl 16.3.1959; CH-prior 3.4.1958)
BE 584 061 (Merck & Co.; appl 27.10.1959; USA-prior 31.10.1958)
BE 609 095 (Kefalas AIS; appl 12.10.1961; DK-prior 12.10.1960)
b Hoffsommer, R.D et al.: J Org Chem (JOCEAH) 27,4134 (1962)
alternative synthesis:
DAS 1 468 138 (Kefalas; appl 12.3.1963; GB-prior 23.3.1962,9.11.1962)
US 3 205 264 (Merck & Co.; 7.9.1965; appl 15.6.1962)
Formulation(s): amp 56.6 mg; f c tabl 10 mg, 25 mg, 50 mg; drg 11.32 mg, 28.3 mg; drops 40 mg/l ml;
inj 50 mg/2 ml; tabl 25 mg, 50 mg (as hydrochloride) Trade Name(s):
D: Amineurin (Neuro Hexal) I:
Limbatril (ICN)
Saroten (Bayer Vital)
F: Elavil (Merck Sharp &
Dohme-Chibret)
Laroxyl (Roche)
GB: Lentizol (Parke Davis)
Triptafen (Goldshield)-
comb
Tryptizol (Morson)
Adepril (Lepetit) Amilit-ifi (IFI) Amitript (Formulario Naz.) Diapatol (Teofarma)-comb
Laroxyl (Roche) Limbitryl (Roche)-comb
Sedans (Ganassini)-comb
Triptizol (Merck Sharp &
Dohme) combination preparations
J: Tryptanol (Merck-Banyu;
as hydrochloride) USA: Elavil (Zeneca; as hydrochloride) Etrafon (Schering) Limbitrol (Roche Products;
as hydrochloride) Triavil (Merck; as hydrochloride) generics
Use: antidepressant RN: 4317-14-0 MF: C,,H,,NO MW: 293.41
LD,,: 320 mg/kg (M, i.p.); 87 mglkg (M, i.v.); 330 mg/kg (M, p.0.);
120 m g k g (R, i.p.); 25 mg/kg (R, i.v.); 1800 mg/kg (R, p.0.);
330-460 mglkg (rabbit, p.0.);
330 mglkg (dog, p.0.)
CN: 3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-N,N-dimethyl-l-propanamine N-oxide
Trang 898 A Amixetrine
ornitriptyline I Arnitriptylinoxide
p H 3
+ HO-N,
5-(3- bromopropy1idene)- N,N-dimethyl-
10.1 1 -dihydro-5H- hydroxylamine
dibenzo[o.d]cycloheptene
(cf ornitriptyline synthesis)
Reference(s):
DE 1 243 180 (Dumex; appl 15.2.1964; GB-prior 20.2.1963)
FR-M 3 222 (Dumex; appl 20.2.1964; GB-prior 20.2.1963)
NL-appl 6 51 1 947 (Merck & Co., appl 14.9.1965; USA-prior 14.9 1964)
Fortnulation(s): tabl 30 mg, 6 0 mg, 90 mg, 120 mg
Trade Narne(s):
D: Equilibrin (Rh6ne-Poulenc
Rorer)
Use: anticholinergic, antidepressant, antispasmodic
RN: 24622-72-8 MF: C,,H,NO MW: 261.41
CN: 1-(2-(3-methy1butoxy)-2-phenylethyllpyrrolidine
hydrochloride
RN: 24622-52-4 MF: C,,H,,NO HCl MW: 297.87 EINECS: 246-365-1
-CH, tert-butyl - codCH3 pyrrolidine
hypobrornite Br
styrene isoomyl alcohol a-isoomyloxy-
phenethyl bromide
Reference(s):
DOS 1 81 1 767 (Mauvernay; appl 29.1 1.1968; F-prior 15.12.1967)
Amixetrine
Formulation(s): tabl 50 mg
Trade Name(s):
F: Somagest (Riom); wfm
Trang 9Amlexanox A 99
Amlexanox
(AA-673)
ATC: R03DXO I ; R06AX
Use: antiallergic, antiasthmatic
RN 68302-57-8 MF: CI,H,,N20, MW: 198.30
LD,: 2320 m g k g (M p.a ):
10 @g (R p.0.)
CN 2-amino-7-( I-methylethyl)-5-0x0-SH-[I ~henzopyrano[2,3-b]pyr1dine-3-carhc~xyl~c a c ~ d
2-hydroxy-5-isopropyl- dimelhyl- 6-isopropy-4-0x0-
acetophenone formornide 4H-1 -benzopyran-3-
corboxaldehyde (I)
n
hydroxylomine CN morpholinc dimethyl- CHO
CH3 * formornnde C H 3 0
6-ixopropyl-4-oro- 2-amino-6-isopropyl- 4H- I - benropyron- 4-0x0-4H- 1-bentopyron- 3-corbonitrila 3-carboxoldehyde (D)
1 pipcridinc
Refcrerrrr(s):
DOS 2 809 720 (Takeda: appl 7.3.1978; J-prior 8.3.1977,20.12.1977)
US 4 143 042 (Takeda; 6.3.1979; J-prior 8.3.1977, 20.12.1977)
CIS 4 255 576 (Takcda; 10.3.1981; J-prior 8.3.1977, 10.12.1977)
US 4 299 963 (Takcda; 10.1 1.1981; J-prior 8.3.1977 10.12.1977)
Nohara, A ct al.: J Mcd Chcrn (JMCMAR) 28.559 (1985)
s y d i e s i s of6-isopropyl-4H- 1 -benxopyran-3-carbonitri1e:
H3C aNH2 C O O H
US 3 896 1 14 (Takeda Chemical Ind.; appl 22.7.1975; J-prior 12.4.1972, 14.4.1072)
DE 2 3 17 898 (Takeda Chemical Ind.; appl 25.10.1973; J-prior 12.4.1972)
Funn~rlr~rion{s): cream 5 %o; tabl 100 mp
Trade N(~me(a ):
J: Solfa (Takeda: 1989) USA: Aphthasol (Block Drug
Company)
Use: calcium antagon~st antianginal
antlhypcrtensivc RN: 88150-42-9 MF: C,H,,C1N20, MW: 408.88
CN: 2-i(2-aniinoethoxy )methyl]-4-i2-c21lorophenyl)- 1,4-di hydro-6-methyl-3.5-pyridinedicarboxylic acid 3-
ethyl 5-methyl ester
Trang 10100 A Amlodipine
rnaleate (1:l)
RN: 88150-47-4 MF: C20H,5ClN20, C4H404 MW: 524.95
ethyl 4-chloro-
ocetooctote
CHO
2-chlora-
benzaldehyde
methyl 3-omino- crotonate
ethyl 4-(2-ozidoethoxy) ocetoocetote (1)
3-ethyl 5-methyl 2-[(2-ozido- ethoxy)methyl]-4-(2-chloropheny1)- 1.4-dihydro-6-methyl-3.5- pyridinedicarbaxylote (U)
Arnlodipine
Reference(s):
EP 89 167 (Pfizer; appl 8.3.1983; GB-prior 11.3.1982)
EP 599 220 (Lek; appl 19.11.1993; SI-prior 26.1 1.1992)
CA 2 188 071 (Apotex; appl 17.10.1996; NZ-prior 1.1 1 l995)
besylate salt:
EP 244 944 (Pfizer; appl 31.3.1987; GB-prior 4.4.1986)
racemate resolution:
EP 331 315 (Pfizer; appl 16.2.1989; GB-prior 27.2.1988)
Arrowsmith, J.E et al.: J Med Chem (JMCMAR) 29, 1696 (1986)
combination with ACE-inhibitors:
WO 9 628 185 (Pfizer; appl 26.2.1996; USA-prior 16.3.1 995)
Formulation(s): cps 5 mg, 15 mg, 20 mg; tabl 2.5 mg, 5 mg, 10 mg
Trade Name(s):
D: Norvasc (Mack, Illert; I: Antacal (Errekappa J: Amlodin (Sumitomo)
F: Amlor (Pfizer) Monopina (Bioindustria; USA: Lotrel (Novartis)
Norvasc (Pfizer; 1990)