Pharmaceutical Substances Syntheses, Patents, Applications - Part 7 docx

Alibendol
A
6
1
16-dehydroprogesterone 16u, 17a-dihydroxy-
progesterone
(I)
I
,
acetophenone
1
Algestone acetophenide
I
Reference(s):
DE
1 125 423 (Oh Mathieson; appl. 1959; USA-prior. 1958).
Fried,
J.
et al.: Chem. Ind. (London) (CHINAG) 1961,465.
alternative synthesis;
US 3 008 958 (Olin Mathieson; 1961; prior. 1961).
synthesis of intermediates:
US 2 727 909 (Searle; 1955; prior. 1954).
US 3 165 541 (Olin Mathieson; 12.1.1965; prior. 20.5.1963).
Cooley,
G.
eta].:
J.
Chem. Soc. (JCSOA9) 1955,4373.
Inhoffen, H.H. et al.: Chem. Ber. (CHBEAM)
87,593

(1954).
Hydorn, A.E. et al.: Steroids (STEDAM) 3,493 (1964).
injection solution:
US 3
164
520 (Olin Mathieson; 5.1.1965; prior. 29.10.1962).
medical
me
as
contraceptive:
GB
1
060 632 (Oh Mathieson; appl. 16.8.1963; USA-prior. ll.ll.1962).
Formulation(s):
cream 2
%
Trade Name(s):
I: Neolutin Depos. (Medici)
Alibendol
ATC: ClOA; A03
Use: antispasmodic, choleretic,
cholekinetic
RN: 26750-81-2
MF:
C,,H,,NO,
MW:
251.28 EINECS: 247-960-9
LD,:
>3000 mglkg (M, p.0.); >2000 mgkg (M, s.c.)
CN:

2-hydroxy-N-(2-hydroxyethyl)-3-methoxy-5-(2-propenyl)benzamide
2-hydroxy
-3-
methoxy-
benzaldehyde
-
ethyl P-hydroxy-
3-methoxybenzoate
62
A
Alimemazine
0
0-CH,
/,,&h3
+
H2NmOH
*
H,C'
ethyl 5-ollyl-2- ethonolamine Alibendol
hydroxy-3-methoxy-
benzoate
(I)
Reference(s):
DE 1 768 615 (Roussel-Uclaf; appl. 1968; F-prior. 1967).
Clemence, F. et al.: Chim. Ther. (CHTPBA)
5,
188 (1970).
Formulation(s):
tabl. 100 mg
Trade Name(s):

F: Cebera (Irex)
Alimemazine
(Trimeprazine)
ATC: R06ADO1
Use: antihistaminic, psychosedative
RN: 84-96-8 MF: C,,H,,N,S MW: 298.45 EINECS: 201-577-3
LD,,: 33 mgkg (M, i.v.); 300 mglkg (M, p.0.);
35 mgkg (R, i.v.); 210 mglkg (R, p.0.)
CN:
N,N,P-trimethyl-lOH-phenothiazine-10-propanamine
tartrate
(2:l)
RN: 4330-99-8 MF: C,,H2,N2S. 1/2C4H606 MW: 746.99 EINECS: 224-368-9
LD,,: 33 mgkg (M, i.v.); 300 mglkg
(M,
p.0.);
35 mgkg (R, i.v.); 210 mglkg (R, p.0.)
H
CH CH,
+
clA'.CH3
sodium
omide
Reference(s):
US 2 837 518 (RhGne-Poulenc; 1958; F-prior. 1954).
DE
1
034 639 (RhGne-Poulenc; appl. 1955; GB-prior. 1954 and 1955).
phenothiozine 3-dimethylomino-
Formulation(s):

drops 40 mg; tabl. 2.5 mg, 5 mg (as tartrate)
Alimemozine
Trade Name(s):
D: Repeltin (Bayer) GB: Vallergan (RhGne-Poulenc
F: Theralhne (Evans Medical) Rorer; as tartrate)
ThCralene Pectoral (Evans
I:
in comb. with prednisolone
Medical)-comb.
J:
Alimezine (Daiichi)
2-methylpropyl chloride
Alizapride
A
63
Alizapride
ATC: A03FA05; A04AD
Use: antl-emetic, neuroleptic
RN:
59338-93-1
MF:
C,,H,,N,O, MW: 315.38 EINECS: 261-710-6
LDw: 92.7 mglkg (M, i.v.)
CN:
6-mcthoxy-N-[[I-(2-propenyl)-2-pyrrolidinyl]methyl]-1H-benzotriazole-5-carboxamide
I:
FH3
HODC
I1
H3C'

II
H3C
0
0
p-amino- dimethyl methyl 4-amino-
salicylic acid sulfoie 2-methoxybenzoote
(9.
v.1
NONO*,
HCI
sodium
0
nitrite aminomethyl-
methyl 4.5-diomino- methyl 6-mthox- p~rra1idi.e
I
Uizopride
1
.
2-methoxybenzoate
(I)
benzotriozale-5-
corboxylote
Reference(s):
DE
2
500 919 (Delagrange; appl. 11.1.1975).
US
4 039 672 (Delagrange; 2.8.1977; D-priol.
1
1.1.1975).

synthesis
of
methyl
4-amino-2-methoxybenzoate:
DOS
1966 212 (Yamanouchi; appl. 29.12.1969; J-prior. 2.12.1968, 9.12.1968,4.4.1969).
Formulation(s):
amp. 50 mg/2 ml; drinking
amp.
360 mg; suppos. 50 mg; tabl. 50 mg
Trade Name(s):
D:
Vergentan (Synthelabo)
I:
Limican (Synthelabo)
F:
Plitican (S ynthelabo) Nausilen (Baldacci)
Allantoin
ATC:
Use:
RN:
97-59-6 MF: C4H,N403
MW:
158.12 EINECS: 202-592-8
CN:
(2,5-dioxo-4-imidazolidiny1)urea
D03; DO5
wound remedy, antipsoriatic,
adstringent, web stimulant,
keratolytic, antacid

RN:
13
17-25-5 MF: C4H,A1,CIN40,
MW:
3
14.55 EINECS: 215-262-3
LD,,,:
28
gkg
(MA
p.o.1
CN:
chloro[(2,5-dioxo-4-imidazolidinyl)uretato]tetrahydroxyaluminum
64
A
Aldioxa
Aldioxa
RN: 5579-81 -7 MF: C4H,A1N,0s MW: 218.1 1 EINECS: 226-964-4
LD,,: >8 glkg (M, p.0.)
CN:
[(2,.5-dioxo-4-imidazolidinyl)ureato]dihydroxyaluminum
urea glyoxylic
acid
Alcloxo
I
I
Aldioxo
Reference(s):
DOS 1 939 924 (BASF; appl. 6.8.1969).
from glyoxal viu "in

situr'-glyoxylic acid:
DOS 2 7 14 938 (Akad. d. Wiss. der DDR; appl. 2.4.1977; DDR-prior. 29 10.1976).
from
chloral hydrate
via "in
situV-glyoxylic acid:
DOS 2 717 698 (Akad. d. Wiss. der DDR; appl. 21.4.1977; DDR-prior. 29.10.1976).
by oxidation of uric acid with
PbO,
or
H202
or
potassium permanganate:
Org. Synth. (ORSYAT) 13 1 (1933).
by oxidation of
glycoluril
widz
H20,:
Biltz, H.; Schiemann, G.: J. Prakt. Chem. (JPCEAO) 113,92 (1926).
US 2 802 01 1 (Carbogen Corp.; 19.57; appl. 19.56).
by
condensation of glyoxylic acid esters or glyoxylic acid acetul esters with
urea:
US 2 1.58 098 (Merck
&
Co.; 1939; appl. 1937).
Formulation(s):
cream 0.2
%;
ointment 2

%;
powder 0.5
%;
tabl. 100 mg
Trade Name(s):
D: more than 70 combination
preparations
allantoin
Brand- und Wundgel (Eu
Rho Arznei)-comb.
Contractubex Gel (Merz
&
Co.)-comb.
Ellsurex (Ga1derma)-comb.
Essaven (Nattermann)-
comb.
HAEMO-Exhirud (Sanofi
Winthrop)-comb.
Hydro Cordes (Block Drug
Company;
Ichthyo1)-comb.
Lipo Cordes (Block Drug
Company)-comb.
Psoralon (Herma1)-comb.
Psoriasis-Salbe M
(Balneopharm)
Ulcurilen (Spitzner)-comb
alcloxa
Ansudor (Basotherm)-
comb.

aldioxa
Ansudor (Basotherm)-
comb.
Dexa-Mederma Akne
(Merz
&
Co.)-comb.
GB:
Elmedal (Thiemann)-comb.
Mederima (Merz
&
Co.)-
comb.
ZeaSorb Puder (Stiefe1)-
comb.
alcloxa
Ulfon (Lafon)-comb.
aldioxa
Ulfon (Lafon)-comb.
allantoin
Actinac (Hoechst)-comb.
with chloramphenicol and
hydrocortisone
Allobarbital
A
65
Alphosyl (Stafford-Miller)-
comb.
Aphosyl HC (Stafford-
Miller)-comb. with

hydrocortisone
Dermalex (Sanofi
Winthrop)-comb. with
squalene and
hexachlorophane
1:
allantoin
Alphosyle (Po1i)-comb.
Antiacne Samil (Sami1)-
comb.
Apsor pomata (ID1
Farrnaceutici)-comb.
J:
aldioxa
Aldioxa (Isei)
Chlokale (Sawai)
USA:
allantoin
Alphosyl (Reed
&
Camrick)-comb.; wfrn
Bahnex (Maxsi1)-comb.;
wfrn
Cervex
(Medics)-comb.;
wfrn
Cutemol Creme
(Summers); wfrn
Herpecin-L (Campbell)
comb.; wfm

Sufamal (Milex)-comb.;
wfm
Vagilia (Lemmon)-comb.;
wfrn
Allobarbital
(Allobarbitone)
ATC: N05CA21
Use: hypnotic, sedative
RN: 52-43-7 MF: CIOHl,N,O,
MW:
208.22 EINECS: 200-140-4
LD,,: 21 8 mglkg (M, i.v.)
CN:
5,5-di-2-propenyl-2,4,6(1H,3H,SH)-pyrimidinetrione
ally1 bramide borbituric
1
Allobarbital
1
acid
Reference(s):
DRP 268 158 (Ciba; appl. 1911).
DRP 526 854 (Hoffmann-La Roche; appl. 1930).
Formulation(s):
tabl. 30
mg,
100 mg, 300 mg
Trade Name(s):
D: Toximer (Merck1e)-comb.;
F:
Spasmo-Cibalgine (Ciba)- I: Allobarb (Tariff.

wfm comb.; wfm
Integrative)
USA: Diadol (Durst); wfrn
Allopurinol
ATC: M04AAO1
Use: uricosuric agent
RN: 315-30-0
MF:
C,H,N,O MW: 136.1 1 EINECS: 206-250-9
L&: >l glkg (M, p.0.)
CN:
1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one
66 .
A
Allopurinol
ethyl cyanoacetate triethy ortho- ethyl ethoxymethylene-
forrnate cyonoacetaie
(I)
ethyl 5-amino-
pyrazole-4-carboxylate
H2N-NH2
H2N-CHO
I
hydrazine
'
b
forrnornide
0
Allopurinol
u

H
0
cyanoaceiarnide forrnamidine
hydrochloride
3-amino-2-cyano-
acrylarnide
(11)
H,N-NH2
H,N-CHO
11
hydrozine formamide
0
Reference(s):
a
US 2 868 803 (Ciba; 13.1.1959; CH-prior. 10.2.1956).
US 3 624 205 (Burroughs Wellcome; 30.1 1.197 1; USA-prior. 25.4.1967).
b
DAS 1 720 024 (Wellcome Found; appl: 12.7.1967; GB-prior. 14.7.1966).
similar process:
DAS
1
904 894 (Wellcome Found; appl. 3 1.1.1969; GB-prior. 2.2.1968).
US 4 146 713 (Burroughs Wellcome; 27.3.1979; GB-prior. 2.2.1968).
alrernative syntheses:
US 3 474 098 (Burroughs Wellcome; 21.10.1969; prior. 29.3.1956).
DAS 2 224 382 (Henning Berlin; appl. 18.5.1972).
DE
1
118
221 (Wellcomc Found; appl. 4.8.1956; GB-prior. 10.8.1955).

DAS
1
814 082 (Wellcome Found; appl. 11.12.1968).
DAS 1 950 075 (Henning Berlin; appl. 3.10.1969).
DOS 2 018 345 (Delmar Chemicals; appl. 16.4.1970; GB-prior. 17.4.1969).
cornbirzation with
benzbromarone:
GB 1 493 237 (Henning Berlin; appl. 11.5.1976; D-prior. 10.12.1975)
Formulation(s):
tahl. 100 mg, 200 mg, 300 mg
Trade Nu~ne(s):
D:
~110-300-Tablinen (ct- Allomaron (Nattermann).
Arzneimittel) comb.
Allo-Puren 1001-300 (Isis
Puren)
~leminol (gepepharm)
Allylestrenol
A
67
Cellidrin (Henning)
dura A1 300 (durachemie)
Foligan (Henning Berlin)
Remid 1001-300 (TAD)
Suspend01 (Merckle)
Uribenz 300 (R.A.N.)
Uripurinol 1001300
(Azupharma)
Urosin (Boehringer
Mannh.)

Zyloric (Glaxo Wellcome;
1966)
combination preparations
F: Zy loric (Glaxo Wellcome;
1968)
GB: Zyloric (Glaxo Wellcome;
J:
1966) USA:
1: Allopuri (Formulario Naz.)
Allurit (RBS Pharma)
Allurit (Rh8ne-Poulenc
Rorer)
Uricemil (KT)
Uricodue (IF[)-comb.
Zyloric (Wellcome; 1969)
Zyloric (Tanabe; 1969)
Zyloprim (Glaxo
Wellcome; 1966)
Allylestrenol
(Allyloestrenol)
ATC: G03DCOI
Use: progestogen
RN: 432-60-0 MF: C,,H,,O MW: 300.49 EINECS: 207-082-9
LD,,: >640 mglkg (M, p.0.)
CN:
(17P)-17-(2-propenyl)estr-4-en-17-ol
nandrolone
ethane-
(q.v.)
1,2-dithial

EirtJ9+,CH2
A
allylmagnesium
bromide
17P-hydroxy-
4-estrene
(I)
17-0x0-4-
estrene
/
Allylestrenol
Referencefs):
GB 841 41
1
(Organon; appl. 2.4.1958; NL-prior. 10.4.1957).
alternative syntheses:
GB 875 549 (Organon; appl. 31 .l2.1959; NL-prior. 13.1.19.59).
US
2 878 267 (Organon; appl. 16.4.1958; NL-prior.
1
S.1957).
Formulation(s):
tabl. 5 mg
Trade Name(s):
D: Gestanon (Organon); wfm 1: Gestanon (Organon Italia)
GB: Gestanin (Organon); wfm
J:
Gestanon (Sankyo)
Alminoprofen
ATC: MOlAE16

Use: non-steroidal anti-inflammatory,
analgesic
RN:
39718-89-3 MF: C,,Hl,NO, MW: 219.28 EINECS: 254-604-6
LD,,: 2400 mglkg (M,
p.0.)
CN:
a-methyl-4-[(2-methyl-2-propenyl)amino]benzeneacetic
acid
68
A
Almitrine
1. HCI
YH3
CH3
2.HO-CH3
UCooH
+
0=CH2
+
COOH
,
I
O2N
HN\
CH3
4-nitrobenzene- form- dimethyl-
acetic ocid oldehyde
omine
Hp. Pd-C 2. NoOH

fl\CH3- &0\cH3
T=
H3cvN
02N
/
0
Hzt4
chloride
(1)
I
Alminoprofen
Referenceis):
Dumaitre, B. et al.: Eur. J. Med. Chem. (EJMCAS)
14,
207 (1979).
alternative synthesis:
FR
2 289 180 (Lab. Bouchara; appl. 17.5.1971).
Formulation(s):
tabl. I50 mg, 300 mg
Trade Name(s):
F: Minalfkne (Bouchara) J: Minalfen (Fujirebio)
Almitrine
ATC: R07AB07
Use: analeptic, respiratory stimulant
RN: 27469-53-0 MF: C,,H,,F,N, MW: 477.56 EINECS: 248-475-5
CN:
6-[4-[bis(4-fluorophenyl)methyl]-l-piperazinyl]-N,l\r-di-2-propenyl-1,3,5-triazine-2,4-diamine
1 -[bis(4-fluoropheny1)- cyonuric
methyllpiperozine chloride

2-[4-[bis(4-1luorophenyl)-
methyl]-1 -piperozinyl]-
4.6-dichloro-1 .3,5-triozine
(I)
H2N4~H2
.
NoOH
I
b
ollylomine
F
N yN
HNd'~~,
Alrnitrine
Aloxiprin
A
69
Reference(s):
FR
2
019 646 (Science Union; appl. 22.9.1969; GB-prior. 2.10.1968).
DOS
1 947 332 (Science Union; appl. 18.9.1969; GB-prior. 2.10.1968).
US
3 647 794 (Science Union; 7.3.1972; GB-prior. 2.10.1968).
GB 1 256 51 3 (Science Union; appl. 2.10.1968; valid from 30.9.1969).
Formulation(s):
f. c. tabl. 50 mg; vial 15 mg/5 ml; tabl.
50
mg

Trade Narne(s):
D: Vectarion (Servier; 1984)
F:
Duxil (Therval Mtdical; Vectarion (EuthCrapie;
1979)-comb. 1983)
Aloxiprin
ATC: BOIACIS; N02BA02
Use: analgesic
RN: 9014-67-9 MF: unspecified MW: unspecificd
CN: aloxiprin
polymeric condensotion product of aluminum oxide and ocetylsolicylic acid
aluminum isoprapylate acetylsalicylic ocid Aloxiprin
(q.
v-1
Reference(s):
Cummings,
A.J.
et al.:
J.
Pharm. Pharmacol. (JPPMAB)
15,
56 (1963).
Forrnulation(s):
tabl. 400 mg, 450 mg, 600 mg
Trade Name(s):
GB: Palaprin (Nicholas); wfm Palaprin forte (Nicholas);
wfm
Alphaprodine
(Alfaprodina)
ATC: N02AB

Use: analgesic
RN: 77-20-3
MF:
C,,H,,NO, MW: 261.37 EINECS: 201-011-5
CN:
cis-1,3-dimethyl-4-phenyl-4-piperidinol
propanoate (ester)
hydrochloride
RN: 561-78-4 MF: C,,H2,NO2. HCI MW: 297.83
LD,,,: 32 mgkg (M, i.v.);
25 mgkg (R, i.v.); 90 mglkg (R, p.0.);
36.2 mgkg (dog, i.v.)
70
A
Alpidem
bromo- phenyllithium
benzene
H
SO
11
+.
H~C/)~OY'CH~
L+
0
0
HSC
propionic anhydride
Alphaprodine
I
Reference(s):

US 2 498 433 (Hoffmann-La Roche; 19.50; prior. 1946)
starting material:
I
,3-dimethyl-4-piperidone:
Howton: J. Org. Chem. (JOCEAH) 10,277 (1945)
Formulation(s):
amp. 4
%,
6
%
Trade Name(s):
USA: Nisentil (Roche); wfm
Alpidem
ATC: N05B
Use: anxiolytic, o,-agonist
RN: 82626-01
-5
MF:
C2,Hz3CI2N3O
MW:
404.34
CN:
6-chloro-2-(4-chlorophenyl)-N,~propylimidazo[l,2-a]pyridine-3-acetamide
2-omino-5- 4'-chloro-2-brorno- 6-chloro-2-(4-chloro-
chloropyridine acetophenone phenyl)imidazo[l,2-a]-
pyridine
2.
NaCN
cI~~l 3.
HCI. CH3COOH

-
COOH
H,C-N,