Pharmaceutical Substances Syntheses, Patents, Applications - Part 8 potx

Alprazolam
A
71
1.
POCI,
2.
H
H
C"~*CH
n;
1.
phosphorus oxychloride
2.
dipropylornine
H3C-N7,-
CH3
Reference(s):
EP
50 563 (Synthelabo; appl. 15.10.1981
;
F-prior. 22.10.1980).
US
4 382 938 (Synthelabo; 10.5.1983; F-prior. 22.10.1980).
US
4460 592 (Synthelabo; 17.7.1984; F-prior. 22.10.1980).
Formulation(s):
tabl. 50
mg
Trade
Name(s):
F:

Anaxyl (SynthClabo; 1991);
wfm
Alprazolam
ATC: N05BA12
Use:
tranquilizer
RN: 28981-97-7
MF:
C,,H,,C1N4
MW:
308.77
EINECS:
249-349-2
LD,,:
770
mgkg
(M,
p.0.);
1220
mglkg
(R,
p.0.)
CN: 8-chloro-
1
-methyl-6-phenyl-4H-[1,2,4]triazolo[4,3-a][
1,4]benzodiazepine
hydrazine hydrote tricthyi orthoocetote
7-chloro-1 -methyl-5.
phenyl[l.2.4]tn'ozolo-
[4,3-alquinoiine

(I)
H3C'7s~\
No104,
Ru02
ocetone.
H20
2.PBr3,
CHCI,
I
sodium periodole'
CI
1.
formaldehyde
'
CI
ruthenium dioxide
2.
phosphorus(ll1)
bromide
NH,.
THF,
CH30H
I1
Alprozoiarn
1
72
A
Alprenolol
benzoyl 2-omino-5-chloro
chloride benzophenone

'4'10
+
phosphorus(V)
sulfide
pyridine
+
111
ethyl glycinote hydrochloride
CH3-CO-NH-NH2
,
butanol
-
acetohydrazide
2-0x0-2.3-dihydro-lH-
2-thioxo-2,3-dihydro- 7-chloro-5-phenyl-3H-
1.4-benzodiazepine
(111)
1
H-
1
-4-benzodiazepine l,4-benzadiozepine
.
(IV)
25OoC
N
b
Alprazolom
Reference(s):
US 3 987 052 (Upjohn; 19.10.1976; appl. 29.10.1969; USA-prior. 17.3.1969).
US 3 980 789 (Upjohn; 14.9.1976; appl. 19.6.1972; USA-prior. 29.3.1971).

DE 1 955 349 (Takeda; D-prior. 4.1 1.1969).
GB 1 298 364 (Upjohn; GB-prior. 27.10.1969).
a
DOS
2
203 782 (Upjohn; appl. 27.1.1972; USA-prior. 9.2.1971).
US 3 709 898 (Upjohn; 9.1.1973; prior. 9.2.1971).
US 3 781 289
(Upjohn; 25.12.1973; prior. 1 1.5.1972).
b
DOS 2 012 190 (Upjohn; appl. 14.3.1970; USA-prior. 17.3.1969).
Formulation(s): tabl. 0.25 mg, 0.5
mg,
1 mg, 1
g
Trade Name(s):
D: Cassadan O,25/0,5/l (ASTA
F:
Medica AWD) GB
:
Tafil0,5/1,0 Tabletten
(Pharmacia
&
Upjohn;
I:
1984)
Xanax (Pharmacia
&
Upjohn)
Alprenolol

Xanax (Upjohn; 1984) Xanax (Upjohn; 1985)
Xanax (Pharmacia
&
J:
Constan (Takeda; 1984)
Upjohn; 1983) Solanax (Upjohn-
Frontal (UCM) Sumitomo; 1984)
Mialin (Biomedica USA: Xanax (Pharmacia
&
Foscama) Upjohn; 1981)
Valeans (Valeas)
ATC: C07AAO1
Use: beta blocking agent
RN: 13655-52-2 MF: C,,H,,NO, MW: 249.35 EINECS: 237-140-9
LD,,,: 20 mgkg (M,
i.v.)
CN:
l-[(l-methylethyl)amino]-3-[2-(2-propenyl)phenoxy]-2-propanol
Altizide
A
73
hydrochloride
RN:
13707-88-5 MF: C15H2,N02. HCI MW: 285.82 EINECS: 237-244-4
LDso:
29 mglkg (M, i.v.); 184 mgkg (M, p.0.);
17 mgkg
(R,
i.v.); 590 mglkg
(R,

p.0.);
18 mgkg (dog, i.v.); 383 mgkg (dog, p.0.)
2-allylphenol epichlorohydrin
1
-(2-ollylphenoxy)-
2.3-epoxypropone
(I)
Reference(s):
US 3 466 376 (AB Hassle; 9.9.1969; prior. 18.1.1966, 17.6.1966).
Brandstrom, A.: Acta Pharm. Suec. (APSXAS) 1966,303.
isopropylornine
2-allylphenol
by
rearrangement of
ally1 phenyl ether:
DOS 2 746 002 (Firestone; appl. 13.10.1977; USA-prior. 18.10.1976).
Alprenolol
Formulation(s):
cps. I0 mg, 20 mg, 40 mg, 50
mg;
lyo. for inf. 42.6 mg; tabl. 200 mg
Trade Name(s):
D:
Aptin-Duriles (Astra)
J:
Apllobal (Fujisawa; as
hydrochloride)
Altizide
(Althiazide)
ATC: C03EAO 1

;
C03EA04
Use: diuretic, antihypertensive
RN: 5588-16-9 MF: C,,H14C1N304S3
MW:
383.90 EINECS: 226-994-8
CN:
6-chloro-3,4-dihydro-3-[(2-propenylthio)methy1]-2H-
1,2,4-benzothiadiazine-7-sulfonamide
1,
l-dioxide
6-amino-4-chloro- chloroocetaldehyde
benzene-1.3-disulfamide
o,\
/p
I
+
%A
CH, NoOH
1
H2N-02saiNH
CI
Lsa'CHq
ally1 rnercapton
I
H
I
I
Altizide
I

74
A
Altretamine
Reference(s):
GB 902 658 (Pfizer; appl. 10.1.1961; USA-prior. 27.9.1960).
Formulation(s):
cps. 0.25 mg, 0.5 mg; drops
1
mg; sol. 0.1 mglml; tabl. 0.25 mg, 0.5 mg, 1 mg, 2 mg
Trade Name(s):
F: Aldactazine (Momanto)- Prinactizide (Dakota).
I:
Aldatense (SPA)-comb.;
comb.
comb. wfm
Practazin (Cardel)-comb.
Spiroctazine (Boehringer USA: Aldactazide
(Searle)-
Mannh.)-comb. comb.; wfm
Altretamine
(Hexamethylmelamine)
ATC: LOlXXO3
Use: antineoplastic
RN: 645-05-6 MF: C,H,,N, MW: 210.29 EINECS: 211-428-4
LD,,: 350 mglkg (R, p.0.)
CN:
N,N,N,N,N',N'-hexamethyl-1,3,5-triazine-2,4,6-triamine
hydrochloride
RN: 15468-34-5 MF: C,Hl,N,
,

xHC1 MW: unspecified
LD,,: 100 mglkg (M, i.v.)
melamine formaldehyde
hexamethylolmelamine
hexamethyl ether
(I)
H3c/O\
f
O'cH,
0 N N,N 0
H3c'
-
\[;
Y
-
'
Hz,
Raney-Ni
CH3
.
NyN
I
Altretamine
7~3 y3
N N N,
C
CH3
N yN
CI N CI
N N N,

YY
+
11
,
NaOH
YH3
-
H~C/
Y
Y
CH3
,
NyN NH N yN
C
I
H,C/
CI
cyonuric dimethyl-
2-chlaro-4.6-bis-
chloride
omine
(11)
(dimethylomino)-
1.3.5-triazine
Altretamine
rn
a
DE 1 240 870 (Cassella; appl. 17.1 1.1965).
b
Gunduz, T.: Commun. Fac. Sci. Univ. Ankara, Ser. B: Chim. (CAKBA9) 1569 (1968).

Cumber, A.J.; Ross, W.C.J.: Chem Biol. Interact. (CBINA8) 17, 349 (1977).
Alufibrate
A
75
synthesis of
hexamethylolmelamine hexamethyl ether:
Gams, A. et al.: Helv. Chim. Acta (HCACAV)
24,
302 (1941).
US 3 322 762 (Pittsburgh Plate Glass; 30.5.1967; prior. 27.2.1962; 8.4.1964).
Formulafion(s):
cps. 50 mg, 100 mg
Trade Name(s):
D:
Hexamethylmelamin
F:
Hexastat (Roger Bellon);
I:
Hexastat (RhGne-Poulenc
(RhGne-Poulenc); wfm wfm Rorer)
GB:
Hexalen (Speywood) USA: Hexalen (US. Bioscience)
Alufibrate
(Aluminium clofibrate)
ATC: COIAB03
Use: cholesterol depressant
RN: 2481 8-79-9 MF: C,,H,,AlCl,O, MW: 471.27
EINECS:
246-477-0
CN:

bis[2-(4-chlorophenoxy-~O)-2-methylpropanoato-~O]hydroxyaluminum
Reference(s):
GB
860 303 (ICI; appl. 20.6.1958).
clofibric acid aluminum
Fortnulation(s):
tabl. 500 mg
Alufibrate
Trade Name(s):
D:
Atherolipin (Schwarz); F: Athtrolip (Millot-Solac);
wfm wfm
(cf. clafibrate ethylate
synthesis)
Aluminum nicotinate
ATC: CIOAD04
Use: antihyperlipidemic, vasodilator
(peripheral)
RN: 1976-28-9
MF:
C,,H,,AlN,O, MW: 393.29 EINECS: 217-832-7
CN: 3-pyridinecarboxylic acid aluminum salt
Reference(s):
US 2 970 082 (Walker Labs.; 3 1 .I. 1961; appl. 7.10.1958).
nicotinic acid aluminum
I
hydroxide
Aluminum nicatinate
76
A

Alverine
Formulation(s):
tabl. 125 mg
Trade Name(s):
USA: Nicalex (Merrell-National);
wfm
Alverine
(Dipropyline; Fenpropamine)
ATC: A03AX08
Use: antispasmodic
RN: 150-59-4
MF: CmH,N MW: 281.44 EINECS: 205-763-5
CN:
N-ethyl-N-(3-phenylpropy1)benzenepropanamine
citrate
(1:l)
RN: 5560-59-8 MF: C2,H2,N
.
C6H807 MW: 473.57 EINECS: 226-929-3
3-phenylpropyl ethyl-
chloride ornine
(1)
rYT
CH3
Alverine
WCH0
Hz,
Pt-BoS04
+
1

cinnornoldehyde
Refl.rence(s):
a
Kulz,
E
et al.: Ber. Dtsch. Chem. Ges. (BDCGAS) 72,2161 (1939)
b
Stuhmer, W.; Elbrachter, E A.: Arch. Pharm. Ber. Dtsch. Pharm. Ges. (APBDAJ) 287, 139 (1954).
Formulation(s):
inj. sol. 40 mgl2 ml; suppos. 80 mg; tabl. 40 mg
Trade Name(s):
D: Spasmocol (Norgine)- Schoum comprimCs Spasmonal (Norgine; as
comb.; wfm (Pharmysikne)-comb. citrate)
F: Hepatoum (Hepatourn)- SpasmavCrine (ThCraplix) I: Profenil (Ipti); wfm
comb.
SpasmavCrine suppos. Spasmaverine (Roger
MCttospasmyl (Mayoly- (ThCrap1ix)-comb.
Bellon); wfm
Spind1er)-comb.
GB: Alvercol (Norgine; as USA: Spacolin (Philips Roxane);
citrate)-comb. wfm
Amantadine
ATC: JOSAC;NO4BBOl
Use: antiparkinsonian, antiviral
RN: 768-94-5 MF: C,,H,,N MW: 151.25 EINECS: 212-201-2
LDso: 700 mglkg (M, p.0.);
900 mglkg (R, p.0.)
CN: tricyclo[3.3.1. 13-7]decan-l -amine
Ambazone
A

77
hydrochloride
RN: 665-66-7 MF: C,,H,,N. HCI MW: 187.71 EINECS: 21 1-560-2
LD,,,: 95 mgkg (M, i.v.); 700 mglkg (M, p.0.);
90 mgkg
(R,
i.v.); 800 mglkg
(R,
p.0.);
37 mgkg (dog, i.v.)
sulfate
(2:l)
RN: 31377-23-8
MF:
CI,H17N. 112H2S04 MW: 400.58 EINECS: 250-604-5
-
acetonitrite
k-4
adamantone
1
-bromo-
adamontone
1
-acetylarnino- Amontodine
adornontane
Reference(s):
Stetter, H. et al.: Chern. Ber. (CHBEAM)
93,
226 (1960).
US

3
310469
(Du
Pont; 21.3.1967; prior. 28.8.1961, 15.4.1963,22.10.1963).
synthesis front
adamantane, HCN
and
H2S04:
US 3 152 180 (Studiengesellschaft Kohle; 6.1 0.1964, D-prior. 25.8.1960).
combination with
rnolindone
(antidepressant):
US 4 148 896 (Du Pont; 10.4.1979; appl. 22.2.1978).
Formulalion(s):
f.
c. tabl. 100 mg, 150 mg; cps. 100 mg; amp. 200 mgl500 ml (as sulfate); syrup 50 mg15 ml
Trade Name(s):
D: Amantadin (ratiopharm) GB: Symmetrel (Geigy; as
J:
Symmetrel (Fujisawa-
PK-Merz (Merz
&
Co.) hydrochloride) Novartis)
F:
Mantadix (Du Pont) I: Mantadan (Boehringer USA: Symmetrel (Endo)
Ing.)
Ambaaone
ATC: R02AAO1
Use: antiseptic, disinfectant (oral and
pharyngeal chemotherapeutic),

antineoplas tic
RN:
539-21-9 MF: C,H,,N,S MW: 237.29 EINECS: 208-713-0
LDSi 1 glkg
(M,
p.0.);
750 mgtkg (R, p.0.)
CN:
2-[4-[(aminoiminomethyl)hydrazono]-2.5-cyclohexadien-1-ylidene]hydrazinecarbothioamide
monohydrate
RN:
6011-12-7 MF: CnHlIN7S~H20 MW: 255.31
78
A
Ambenonium chloride
aminaguanidine p-benzo- p-benzoquinone
quinone arnidinohydrazane
Reference(s):
DE 965 723 (Bayer; appl. 1953).
Formulntion(s):
tabl. 10 mg, I00 mg
Trade Narne(s):
D: Iversal (Bayer); wfm GB: Iversal (Bayer); wfm
F:
Iversal (Bayer); wfm I: Primar (Bayer); wfm
Ambazone
L
Ambenonium chloride
ATC: N07AA3O
Use: cholinesterase inhibitor

RN: 1 15-79-7
MF:
C2,H42C14N,02
MW:
608.48 EINECS: 204-107-5
LD,,,: 1510 gkg
(M,
i.v.); 145 mglkg
(M,
p.0.);
2720 g/kg (R, i.v.); 18.5 mgkg (R, p.0.)
CN: N, N'-[(I ,2-dioxo-
l,2-ethanediyl)bis(imino-2,1-ethanediyl)]bis[2-chloro-N,N-
diethylbenzenemethanaminium]
dichloride
hydroxide
RN: 470-78-0
MF:
C2,H,C12N404
MW:
571.59
N,N-diethyl- diethyl oxalate
.
N,N'-bis(2-diethylaminoethyl)-
ethylenediomine oxamide
(I)
Reference(s):
DE 1 024 517 (Sterling Drug; appl. 1954; USA-prior. 1953).
US 3 096 373 (Sterling Drug; 2.7.1963; appl. 1956).
Phillips, A.P.:

J.
Am. Chem. Soc. (JACSAT) 73,5822 (1951).
2-chlorabenzyl
Ambenoniurn chloride
chloride
Ambroxol
A
79
oxamide intermediate:
US
2 438 200 (Du Pont; 1948; appl. 1946).
Formulation(s):
cps. 10 mg; tabl. 10 mg
Trade Name(s):
D: Mytelase Tabletten GB: Mytelase (Winthrop); wfm
J:
Mytelase (Winthrop-
(Winthrop); wfm
I:
Mytelase (Winthrop); wfm Nippon Shoji)
F:
Mytelase (Sanofi Winthrop) USA: Mytelase (Winthrop); wfm
Ambroxol
ATC: RO5CB
Use: expectorant
RN:
18683-91-5 MF: C,,H,,Br,N,O MW: 378.1 1 EINECS: 242-500-3
LDS,,: 138 mglkg (M, i.v.); 2720 mglkg (M, p.0.);
13.4 g/kg (R, p.0.)
CN:

trans-4-[[(2-amino-3,5-dibromophenyl)methyl]amino]cyclohexanol
poracetamol trans-4-met- trans-4-omina-
(q.
v.1
omidocyclohexona~ cyclohexanol
(I)
OH
NaBH4
or
HCOOH
OHC
Br
NHZ NH2
NH2
2-amino-3.5- trans-4-(2-amino-3,5-
dibromobenzoldehyde
dibromobenzylidenamina)-
Ambroxol
I
cyclohexanol
.
Reference(s):
GB
1 178 034 (Boehnnger Ingelh.; appl. 10.5.1967; D-prior. 10.5.1966).
US
3 536 713 (Boehringer Ingelh.; 27.10.1970; appl. 10.5.1967; S-prior. 10.5.1966).
DE
1 593 579 (Thomae; appl. 10.5.1966).
DOS 2 218 647 (Thomae; appl. 18.4.1972).
DOS 2 223 193 (Thomae; appl. 12.5.1972).

Keck, J.: Justus Liebigs Ann. Chem. (JLACBF)
707,
107 (1967).
Formulation(s):
amp. 15 mg; cps. 75 mg; drops 7.5 mg, 30 mg;
eff.
tabl. 30 mg, 60 mg; f.
c.
tabl. 30 mg,
60 mg; inhalation sol. 7,5 mg; inj. 1000 mg; syrup 15 mg, 30 mg; tabl. 30 mg, 60 mg
(as hydrochloride)
Trade Namefs):
D:
Ambril (Glaxo Wcllcome) frenopect (Hefa Pharma) Mucosolvan (Boehringer
Bronchopront (Mack,
Lindoxyl (Lindopharm) Ing.; 1979)
Illert.)
Mucoclear (Mundipharma) Mucotablin-Tropfen
duramucal (durachemie)
Mucophlogat (Azuchemie) (Sanorania)
80
A
Ambuside
-

Mucotectan (Boehringer Fluibron (Chiesi)
Secretil (Caber)
1ng.)-comb.
Fluixol (Ripari-Gero) Surfacatal (Boehringer
stas-Hustenloser (Stada) LisopuIm (Esseti)

Ing.)
I: Amobronc (1st. Chim. Muciclar (Piam) Tauxolo (SIT)
Inter.)
Mucobron (OFF) Viscomucil (ABC-Torino)
Atus (Metapharma) Mucosolvan (Boehringer J: Mucosolvan (Teijin; 1984)
Broxol (Pulitzer)
Ing.; 1982)
Ambuside
ATC: C02L
Use: diuretic, antihypertensive
RN: 3754-19-6 MF: C,,H,,CIN,0,S2 MW: 393.87 EINECS: 223-158-4
CN:
4-chloro-6-[(3-hydroxy-2-butenylidene)amino]-N'-2-propenyl-l,3-benzenedisulfonamide
6-amino-4-chloro- diethyl corbonate 6-chioro-3,4-dihydro-J-oxo-
benzene-
1
,J-disulfonornide
2H-1.2.4-benzothiadiozine-
(cf.
chlorothiozide synthesis) 7-sulfonarnide S,S-dioxide
(I)
ocetoocetoldehyde
1
Ambuside
dirnethyl ocetol
Reference(s):
US 3 188 329 (Colgate-Palmolive; 8.6.1965; appl. 10.4.1962).
intermediates:
Close, W.J. et al.: J. Am. Chem. Soc. (JACSAT)
82,

1 132 (1960).
Trade Name(s):
F: Hydrion (Robert et
Carrikre); wfm