Pharmaceutical Substances Syntheses, Patents, Applications - Part 20 ppsx

Bendacort
B
191
Trade Natne(s):
D:
Card-Fludilat (Thiemann)- Novo-Card-Fludilat I: Angiociclan (Organon
comb. with digoxin (Thiemann)-comb.
Italia)
Fludilat (Thiemann)
F: Fludilat (Organon); wfm
J:
Halidor (Sumitomo; as
fumarate)
-
-
Bendacort
ATC: D07XA
(Bendacortone) Use: glucocorticoid
RN: 53716-43-1 MF: C3,H4,N20, MW: 626.75 EINECS: 258-710-3
CN:
(11~)-ll,l7-dihydroxy-21-[[[[I-(phenylmethyl)-lH-indazol-3-yl]oxyJacetyl]oxy]pregn-4-ene-3~2O-dione
,&J
+
3,
o
-
H
H
0'
."s
cpN

hydrocortisone bendozolic
(4.
v.)
ocid chloride
(q.
v.
bendozoc)
I
Bendacort
Reference(s):
DOS
2
601 367 (Angelini; appl. 15.1.1976; I-prior. 13.2.1975).
Formulation(s):
cream 3
%;
ointment 3
%
Trade Name(s):
I:
Versacort (Angelini)
Bendazac
(Bindazac; Acido bendazolico)
ATC: M02AA11; SOlBC07
Use: anti-inflammatory
RN: 20187-55-7 MF: C,,H,,N20, MW: 282.30 EINECS: 243-569-2
LD,: 380 mglkg (M, i.v.); 1105 mglkg (M, p.0.);
304 mglkg
(R,
i.v.); 1200 mglkg

(R,
p.0.)
CN:
[[1-(phenylmethy1)-1H-indazol-3-yl]oxy]acetic
acid
sodium
salt
RN: 23255-99-4 MF: C,,H,,N,NaO, MW: 304.28 EINECS: 245-528-4
i:?COOH
aN
______,
1.
potossiurn hydroxide
OH
2.
brornoocetic acid
07
COOH
1
-benzyl-3-
hydroxy-
1H-
indorole
Bendozoc
'
192
B
Bendroflumethiazide
Reference(s):
US 3 470 194 (Angelini Francesco; 30.9.1969; I-prior. 29.8.1966).

starting material:
Palazzo, G. et al.: J. Med. Chem. (JMCMAR)
9,
38 (1966).
use in ointments, lotions etc.:
US 3 470 298 (Angelini Francesco; 30.9.1969; prior. 29.1.1969, 24.5.1968, 3.1.1967)
(Bendacort,
q.
v.)
Formulation(s):
cream 1
%,
3
%;
ointment 1
%,
3
%
Trade Name(s):
I: Bendaline (Ange1ini)- Versus (Angelini)
comb. with lysine J: Zildasac (Chugai)
Bendroflumethiazide
(Bendrofluazide)
ATC: C03AAOl
Use: diuretic, antihypertensive
RN: 73-48-3 MF: C15H,4F3N304S2 MW: 421.42 EINECS: 200-800-1
LD,,,: 395
mglkg (M, i.v.); >10 glkg
(M,
p.0.)

CN:
3,4-dihydro-3-(phenylmethyl)-6-(trifluoromethyl)-2H-l,2,4-benzothiadiazine-7-sulfonamide
1,l-dioxide
3-trifluoromethyl-
4-omino-6-trifluoro- 2.4-diominosulfonyl-
aniline
methyl-1,3-benzene- 5-trifluoromethyloniline
(I)
disulfochloride
Reference(s):
US 3 265 573 (Squibb; 9.8.1966, appl. 27.7.1962).
US 3 392 168 (Lovens Kemiske Fabrik; 9.7.1968; GB-prior. 13.8.1958).
Holdrege, C.T. et al.:
J. Am. Chem. Soc. (JACSAT) 81,4807 (1959).
phenylocelyl
chloride
Formulation(s):
cps. 1.25 mg, 2.5 mg; tabl. 2.5 mg, 5 mg
Bendroflumethiozide
Trade Name(s):
D:
Docidrazin (Rhein-Pharma; Dociretic (Thiemann).
Zeneca)-comb. comb.
Pertenso (Fournier
Pharma)-comb.
Benexate
B
193
Repicin (Boehringer 1ng.)-
comb.

Sali-Aldopur,
-
forte
(Hormosan)-comb.
Sotaziden (Bristol-Myers
Squibb)
Spirostada comp. -forte
(Stadapharm)-comb.
Tensoflux (Hennig)-comb.
F:
Naturine (Leo)
Precyclan-Leo (Leo)-comb.
Tensionorme (Leo)-comb.
GB: Aprinox (Knoll)
Corgaretic (Sanofi
Winthrop)-comb.
Inderetic (Zeneca)-comb.
Inderex (Zeneca)-comb.
Neo-Naclex (Goldshield)
Prestim (Leo)-comb.
Tenben (Galen)-comb.
I: Idrexin-Na (Vermont); wfm
Menserene
(Squibb)-
comb.; wfm
Notens (Farge); wfm
Polidiuril (Bios); wfm
Salural (Icb); wfm
Sodiuretic (Squibb); wfm
J:

Centyl (Leo-Sankyo)
Benexate
(TA-903)
ATC:
A02BX
Use:
cytoprotective agent (for treatment of
gastric ulcer), chymotrypsin inhibitor
RN: 78718-52-2 MF: C2,H2,N304 MW: 409.49
LD,,:
7600 mgkg (M, p.0.);
8010 mgkg (R, p.0.)
CN:
trans-2-[[[4-[[(aminoiminomethyl)amino]methyl]cyclohexyl]carbony]oxy]benzoic
acid phenylmethyl
ester
monohydrochloride
RN: 78718-25-9
MF:
CZ3Hz7N3O4. HCI MW: 445.95
monotosyIate
RN: 82576-86-1 MF: Cz3Hz7N304. C7H,03S MW: 581.69
monohydrochloride, clathrate with P-cyclodextrin (1:l)
RN: 86157-91-7 MF: C2,HZ7N3O4
.
HCI
.
C42H70035 MW: 1580.93
tranexarnic S-methyl-
trans-4-(guanidinornethy1)-

acid
(q.
v.)
thiouroniurn cyclohexanecarboxylic acid
(I)
chloride
1.
DCC
I
+
1.
dicyclohexylcarbodiirnide
2.
8-cyclodextrin
benzyl salicylate
194
B
Benfluorex
HOl HOl HOl HOl
I
Benexate
DE 3 035 086 (Nippon Chemiphar; appl. 17.9.1980; J-prior. 20.9.1979, 26.12.1979).
US 4 348 410 (Nippon Chemiphar, Teikoku Chem.; 7.9.1982; J-prior. 20.9.1979, 26.12.1979).
preparation of the clathrate with
P-cyclodextrin:
EP 78 599 (Teikoku Chem.; appl. 27.8.1982; J-prior. 1.9.1981).
alternative synthesis:
JP 57 035 556 (Nippon Chemiphar; 26.2.1982; prior. 8.8.1980).
JP 88 051 146 (Nippon Chemiphar; 13.10.1988; prior. 8.8.1980).
Satoh, T. et al.: Chem. Pharm. Bull. (CPBTAL) 33,647 (1985).

Formulation(s):
cps. 200 mg
Trade Name(s):
J: Loumiel (Teikoku; as Ulgut (Shionogi)
hydrochloride P-
cyclodextrin clathrate)
Benfluorex
ATC: B04AA; ClOAX04
Use: appetite depressant
RN: 23602-78-0 MF: CIyH2,F,NO2 MW: 351.37 EINECS: 245-777-9
LD,,: 2300 mglkg (M, p.0.)
CN:
2-[[1-methyl-2-[3-(trifluoromethyl)phenyl]ethy1]amin0]ethan01
benzoate (ester)
hydrochloride
RN: 23642-66-2 MF: CIyH2,F,NO2~ HC1 MW: 387.83 EINECS: 245-801-8
LD,,,: 108 mgkg (M, i.p.)
H
chloride
2-amino-1
-
ethylene 2-[1-methyl-2-(3-tri-
Benfluorex
(3-trifluoromethyl- oxide fluoromethylphenyl)-
phenyl)propane ethylomino]ethonol
(cf. fenfluromine
synthesis)
Benfotiamine
B
195

Reference(s):
DE
1 593 991 (Science Union; appl. 14.4.1967; GB-prior. 15.4.1966).
FR
1 517 587 (Science Union; appl. 5.4.1967; GB-prior. 15.4.1966).
FR-M 6 564 (Science Union; appl. 3.7.1967; GB-prior. 15.4.1966).
US
3 607 909 (Science Union; 21.9.1971; GB-prior. 15.4.1966).
Formulation(s):
drg. 150 mg; tabl. 150 mg
Trade Namels):
F:
Mediator (Biopharma) I: Mcdiaxal (Servier) Minolip (Master Pharma)
Benfotiamine
ATC: AllDB
Use: neurotropic analgesic
RN: 22457-89-2 MF:
C,,H,,N,O,PS MW: 466.46 EINECS: 245-013-4
LD,,:
2200 mgkg
(M,
i.v.); 15 glkg (M, p.0.)
CN:
benzenecarbothioic acid
9[2-[[(4-amino-2-methyl-5-pyrimidiny
1)methy l]formylamino]-
1
-[2-
(phosphonooxy)ethyl]-
I

-propenyl] ester
2.
benzoyl chloride
I
I
______,
OH
1.
orthophosphoric acid
thiamine
(4.
v.)
CH,
NH,
xtzxxcH3
0-PO~H,
Benfotiamine
I
Referencels):
DE
1
130 81 1 (Sankyo Kabushiki Kaisha; appl. 14.4.1960; J-prior. 14.4.1959, 17.10.1959, 3.1 2.1959).
Formulation(s):
tabl. 40 mg, 50 mg, 100 mg, 300 mg
Trude Name(s):
D: Milgamma (Worwag)- Vitalgesic (Clin-Midy)-
I:
Tridodilan (Rousse1)-comb.
comb. comb.; wfm J: Biotamin (Sankyo)
Milneuron

(Worwag)- Vitanevril (Clin-Comar-
comb. Byla); wfrn
F:
Vitalgesic (Clin-Comar- Vitanevril (Clin-Midy);
Byla)-comb.; wfm wfm
Benfurodil hemisuccinate
ATC: COlD
Use: cardiotonic, vasodilator
RN: 3447-95-8 MF:
C,,H1807 MW: 358.35 EINECS: 222-367-8
LD,,: 520 mglkg (M, p.0.)
CN: butanedioic acid
mono[l-[5-(2,5-dihydro-5-oxo-3-furanyl)-3-methyl-2-benzofuranyl]ethyl]
ester
196
B
Benidipine
"9
6
chloroocetone
4-(4-rnethoxyphenyl)-
ocetyl 2'-hydroxy-4'-
2-0x0-2.5-dihydro- chloride (2.5-dihydro-50x0-
furon
3-furyl)ocetophenone
d'
I,
0
boranote
4'-(2.5-dihydro-5-0x0-

2-acetyl-5-(2.5-dihydro-
5-(2.5-dihydro-50x0-
3-furyl)-2'-(2-oxopropaxy)-
5-0~0-3-furyl)-S-rnethyl-
3-furyl)-2-(1 -hydroxyethyl)-
ocetophenone
(I)
benzofuran 3-methylbenzofuran (11)
succinic
I
Benfurodil hernisuccinbe
anhydride
1
Reference(s):
FR
1 408 721 (Clin-Byla; appl. 7.2.1964).
US
3 355 463 (Clin-Byla; 28.11.1967; F-prior. 7.2.1964).
Formulation(s):
amp. 2.5 %/2 ml; tabl. 150 mg
Trade Name(s):
F: Eucilat (Clin-Comar-Byla);
wfm
Benidipine
(KW-3049)
ATC: C02DE
Use: calcium antagonist, antihypertensive,
antianginal
RN: 105979-17-7 MF: C2uH,,N30, MW: 505.57
CN:

(R*,R*)-(+)-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyndinedicarboxylic
acid methyl
1-
(phenylmethy1)-3-piperidinyl
ester
monohydrochloride
RN: 91599-74-5 MF: C2uH,IN,06
.
HCI MW: 542.03
LD,,:
21.5 mg/kg
(M,
i.p.); 2.5 mglkg (M, i.v.); 322 mglkg (M, p.0.); 33.5 mgkg (M, s.c.);
15.1 mglkg (R, i.p.); 4.4 mgkg (R, i.v.); 87.6. mgkg (R, p.0.); 276 mgkg (R, s.c.)
3-hydroxy- benzyl
piperidine chloride
N-benzyl-3-piperi-
dinyl ocetoacetate (I)
Benmoxin
B
197
3-nitrobenz- methyl 3-amino-
aldehyde cratonate
I
Benidipine
Reference(s):
EP
63 365 (Kyowa Hakko; appl. 15.4.1982; J-prior. 17.4.1981).
alternative synthesis:
EP

106 275 (Kyowa Hakko; appl. 5.10.1983; J-prior. 15.10.1982.27.1.1983; 3.6.1983).
Formulation(s):
tabl. 2 mg, 4 mg, 8 mg
Trade Name(s):
J:
Coniel (Kyowa Hakko;
1991)
Benmoxin
ATC: N06A
Use: antidepressant
RN: 7654-03-7 MF: C,,H,,N,O MW: 240.31 EINECS: 231-619-6
LD,,: 250 mglkg (M, p.0.);
675 mgkg
(R,
p.0.)
CN:
benzoic acid
2-(1-pheny1ethyl)hydrazide
acetophenone benzoyl- acetoph5nane Benmaxin
hydrazine benzoylhydrazone
Refe rence(s):
GB
919 491 (ICI; appl. 1958; valid from 1959).
FR
1 314 362 (ICI; appl. 1959; GB-prior. 1958).
Trade Name(s):
F:
Neuralex (Millot); wfm
Benorilate
(Benorylate; Benorilato)

ATC: N02BA10
Use: analgesic, antirheumatic
RN:
5003-48-5 MF: C,,HI,NOs MW: 3 13.3
1
EINECS: 225-674-5
LD,,: 1551 mgkg (M, p.0.);
3500 mgkg
(R,
p.0.)
CN: 2-(acety1oxy)benzoic acid 4-(acety1amino)phenyl ester
198
B
Benoxaprofen
Rqference(s):
US 3 431 293 (Sterling Drug; 4.3.1969; GB-prior. 9.4.1964).
FR
1
436 870 (Sterwin; appl. 8.4.1965; GB-prior. 9.4.1964).
0-acetyi- paracetamal
Formulation(s):
gran.
2
g; powder 2 g; susp. 2 g, 400 mg; tabl. 750 mg
Benorilate
Trade Name(s):
D: Benortan (Winthrop); wfm Salipran (Evans Medical) I: Bentum (Zambon); wfm
F: Benortan (Winthrop); wfm GB: Benoral (Sanofi Winthrop) Winolate (Winthrop); wfm
solicyloyl chloride
(4.

v.1
Benoxaprofen
ATC: MOlAE06
Use: non-steroidal anti-inflammatory,
analgesic
RN: 5
1234-28-7 MF: C,,H,,ClNO, MW: 301.73 EINECS: 257-069-7
LD5,,: 800 mglkg (M, p.0.);
1
18 mglkg (R, p.0.)
CN:
2-(4-chloropheny1)-a-methyl-5-benzoxazoleacetic
acid
1.
NaNO,,
HCI
1.
HNO,
gNH2
2.ti2S04
H3Cg0H
2.
H,,
Pd-C
H3C C N CN H3C$x::2 C
N
2-(4-aminophenyl)-
2-(4-hydrorypheny1)- 2-(3-omino-4-hydroxy-
propionitrile propionitrile
phenyl)propianitrile

(1)
pyridine
CN
4-chlorobenzoyl 2-(4-chloropheny1)-a-
chloride methyl-5-benzoxazole-
acetonitrile
inw well,
D.W. et al.:
J.
Med. Chem. (JMCMAR)
81,
53 (1975).
DOS 2 324 443 (Lilly; appl. 15.5.1973; GB-prior. 18.5.1972).
Trade Narne(s).
Benoxaprofen
D: Coxigon (Lilly); wfm F: Inflamid (Eli Lilly); wfm GB: Opren (Dista); wfm
Benperidol
B
199
Benperidol
(Benzperidol)
ATC: N05AD07
Use: neuroleptic
RN: 2062-84-2 MF:
C22H24FN302 MW: 38 1.45 EINECS: 218-172-2
LD,: 20 mglkg (M, i.v.); 432 mglkg (M, p.0.);
21 mgkg
(R,
i.v.)
CN:

1-[1-[4-(4-fluorophenyl)-4-oxobutyl]-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one
benzylornine ethyl ocrylote
H3C
3-ethoxycorbonyl-
0-phenylene-
I-(1
-benzyl-4-piperidyl)
1-benzyl-4-piperidone
(I)
diarnine
2-benzirnidazolone
1
-(4-piperidyl)- 4-chloro-4'-fluoro-
2-benzirnidozolone
(11)
butyrophenane
L
"nperida'
Reference(s):
GB
989 755 (Janssen; appl. 24.12.1962; USA-prior. 22.12.1961).
US 3 161 645 (Janssen; 15.12.1964; prior. 22.12.1961).
DE
1
470 120 (Janssen; appl. 19.12.1962; USA-prior. 22.12.1961).
Formulation(s):
amp.
2
mg; drops 2 mg; tabl. 0.25 mg,
2

mg; 5 mg; 10 mg
Trade Name(s):
D: Glianimon (Bayer Vital) Frenactil (Clin-Midy); wfm
F:
Frenactil (Clin-Comar-
GB:
Anquil (Janssen-Cilag)
Byla); wfm
I:
Psicoben (Ravizza); wfm
Benproperine
ATC: R05DB02
IJse: antitussive
RN: 2156-27-6 MF: C,,HnNO
MW:
309.45
LD,,: 1087 mglkg (M, p.0.)
CN:
l-[l-methyl-2-[2-(phenylmethyl)phenoxy]ethyl]piperidine
r
200
B
Benserazide
dihydrogen phosphate
RN: 19428-14-9
MF:
C,,H,,NO. H,PO, MW: 407.45 EINECS: 243-050-0
LD,,,: 32 mglkg (M, i.v.); 1 100 mglkg (M, p.0.)
2-benzylphenol propylene oxide
p-toluenesulfonyl

1
-(2-benzy1phenoxy)-
chloride
2-tosyloxypropone
Benproperine
I
SOCI,
CI
I
Benproperine
Reference(s):
DAS 1 420 955 (Pharmacia; appl. 24.4.1961; DK-prior. 28.4.1960).
US 3 117 059 (Pharrnacia; 7.1.1964; DK-prior. 28.4.1960).
Formulation(s):
drg. 33 mg; susp. 15 mg; syrup 24.4 mg
Trade Name(sJ:
.
,
D: Tussafug (Robugen)
I:
Blascorid Sosp. (Guidotti;
J:
Flaveric (Taito Pfizer; as
as embonate) phosphate)
Benserazide
RN: 322-35-0 MF: C,,H,,N,O, MW: 257.25
CN: DL-serine
2-[(2,3,4-trihydroxypheny1)methyllhydrazide
ATC: N04BA02
Use: antiparkinsonian (in combination

with levodopa), decarboxylase
inhibitor
monohy drochloride
RN: 14919-77-8 MF: C,,H,,N,05~ HCl MW: 293.71 EINECS: 238-991-9
LD,,: 5 glkg
(M,
p.0.);
5300 mgkg (R, p.o.1