Batroxobin
B
181
1.
DIC/HOEt
2.
separation of diastereorners
by
crystollizotion
VtI
b
Referencefs):
a
DE
2904 552 (Yamanouchi Pharm.; appl. 7.2.1979; J-prior. 14.2.1978).
b
CN
85 107 590 (Faming Zhuanli Sheqing Gonhai S.; appl. 11.10.1985; J-prior. 24.1.1985).
alternative syntheses:
Hirose,
Y.;
Kariya, K.; Sasaki,
I.;
Kuronom
Y;
Achiwa,
K.:
Tetrahedron Lett. ('TELEAY)
34
(37), 5915 (1993).
JP

6
279 409 (Mercian Corp.; J-prior. 26.3.1993).
JP
7
070 066 (Amano Pharma Co.; prior. 3.9.1993).
alternative synthesis of optically active
I-benzyl-3-hydroxypyrrolidine:
JP
9 263 578 (Koei Chemical Co.; appl. 29.3.1996).
X-ray structure and synthesis of all enantiomers:
Tamazawa, K ct al.:
J.
Med. Chem. (JMCMAR)
29
(12), 2504 (1986)
Formulation(s):
tabl. 5 mg, 10 mg, 15 mg (as hydrochloride)
Trade Name(s):
J:
Hypoca R (Yamanouchi;
1992)
Batroxobin
ATC: B02BX03
Use: anticoagulant, fibrinolytic
RN:
9039-61-6 MF: unspecified
MW:
unspecified EINECS: 232-918-4
LD,,:
384 @kg (M, i.v.);

210 pglkg (R, i.v.);
380 pglkg (dog, i.v.)
CN:
bothrops atrox serine protcinase
Fibrinolytic effecting protcasc cnzyme from the poison secretion (venom) of
Bothrops atrox
with glycoprotein
structure.
It
has thrombin similarly endopeptidase activity.
hrification by chromatographic methods.
Reference(s):
US
3 849 252 (Pentapharm; 19.11.1974; CH-prior. 18.1.1971).
DOS
2 201 993 (Pentapharm; appl. 17.1.1972; CH-prior. 18.1.1971).
Formulation(s):
amp. 20
iu.
Trade Name(s):
I:
Botropase (Ravizza)
J:
Defibrase (Tobishi-
Reptilase (Lepetit) Fujisawa)
182
B
Beclamide
Beclamide
ATC: N03AX30

Use: antiepileptic, anticonvulsant
RN: 501-68-8 MF: C,,HI,C1NO MW: 197.67 EINECS: 207-927-1
LD,,,:
1
g/kg (M, p.0.);
770 rndkg (R, i.v.); 3200 rndkg
(R,
p.0.)
CN:
3-chloro-N-(phenylrnethy1)propanarnide
benzylomine 3-chloropropionyl
I
Beclomde
chloride
Referencefs):
US 2 569 288 (American Cyanamid; 1951; prior. 1949).
Formularion(s):
drg. 330 rng, 500 mg
Trade Name ( s):
D: Neuracen (Promonta); wfm
F:
PosCdrine (Aron); wfm
Posedrin (Promonta); wfm GB: Nydrane (Rona); wfm
I:
Posedrine (Aron); wfm
Beclobrate
ATC: B04AC
Use: hyperlipidemic
RN: 55937-99-0 MF: C2,,H2,C10,
MW:

346.85 EINECS: 259-912-4
CN:
(+)-2-[4-[(4-chlorophenyl)rnethyl]phenoxy]-2-rnethylbutanoic
acid ethyl ester
4-chlorobenzyl phenol 4-chloro-4'-hydroxy-
chloride
diphenymethone
(I)
2. ethanol
2-methyl- ethyl 2-rnethyl-
butyric acid butonoote
ethyl 2- rnethyl-2-
Beclobrote
bromobutyrote
(Il)
Beclometasone
B
183
CHCIJ,
KOH
I
+
H3C~~~3
-
0
ethyl methyl
ketone
Reference(s):
DOS
2 461 069 (Siegfried; appl. 23.12.1974; CH-prior. 27.1 2.1973, 28.3.1 974,3.10.1974, 18.11.1974).

BE
823 904 (Siegfried; appl. 18.1 1.1974; CH-prior. 27.12.1973).
US
4
153 803 (Siegfried; 8.5.1979; CH-prior. 27.12.1973, 28.3.1974, 18.1 1.1974).
Thiele,
K.
et al.: Arzneim Forsch. (ARZNAD) 29,711 (1979).
synthesis
of
1:
Klarmann,
E.
et al.: J. Am. Chem. Soc. (JACSAT)
54,
3315 (1932).
Huston, R.C. et al.:
J.
Am. Chem. Soc. (JACSAT)
55,4639
(1933).
synlhpsis
of
ethyl 2-methylbutanoate:
Gardner,
R.:
3.
Chem. Soc. (JCSOA9) 1938, 53.
Fonnulation(s):
tabl. 100 mg

Trade Narne(s):
CH:
Beclipur (Siegfried; 1988) Beclosclerin (Siegfried; Turec (Zyma; 1988)
1988)
Beclometasone
(Beclomethasone)
ATC: A07EA07; D07AC15; ROl ADO1
;
R03BAOI
Use: glucocorticoid
RN: 4419-39-0
MF:
C22H2,C10T
MW:
408.92 EINECS: 224-585-9
CN: (1 1P, 16P)-9-chloro-11,17,21
-trihydroxy-l6-methylpregna-l,4-diene-3,20-dione
dipropionate
RN: 5534-09-8
MF:
C28H3,C10,
MW:
-521.05 EINECS: 226-886-0
LD,,,:
>5
g/kg
(M,
p.0.);
>3.75 gikg
(R,

p.0.)
21 -acetoxy-17-hydroxy-16p
methylpregna- 1.4.9(11)-triene-
3,20-dione
(intermediate in syntheses
of betarnethasone,
q.v.)
beclometosone
21
-acetate
(I)
184
B
Beclometasone
F)
+
~3~7Op3
pyridine.
O°C
H,O.
HCIO,
1
propionic
onhydride
Re ference(s):
d3
/
CI
H
0

Beclometosone
Beclomethosone
dipropionote
a GB 912 378 (Merck
&
Co.; appl. 3.6.1959; USA-prior. 19.6.1958).
GB 912 379 (Merck
&
Co.; appl. 3.6.1959; USA-prior. 19.6.1958).
alternative synthesis:
GB 901 093 (Scherico; appl. 22.7.1958; USA-prior. 22.7.1957).
US 4 041 055 (Upjohn; 9.8.1977, appl. 17.1 1.1975).
b
BE 649 170 (Glaxo; appl. 11.6.1964; GB-prior. 11.6.1963).
FR 2 274 309 (Plurichemie; appl. 27.3.1975; P-prior. 27.3.1974, 10.3.1975).
medical use:
DOS 2 320 11
1
(Allen
&
Hanburys; appl. 19.4.1973; GB-prior. 20.4.1972).
Formulation(s):
cream 0.025
%;
dose aerosol (0.05 pg, 0.25 pglpuff); nasal spray (0.05pgIpuff); powder
inhaler
Trade Name(s):
D: AeroBec Autohaler (3M
MedicaIASTA Medica
AWD)

Beclorhinol (Lindopharm)
Becloturmant (Desitin)
Beconase (Glaxo)
Beconase
Aquosum
(Glaxo)
Beconase Dosier-Spray
(Glaxo)
Sanasthmax (Glaxo)
Sanasthmyl (Glaxo)
Sanasthmyl Dosier-Aerosol
Rotadish (Glaxo)
Viarox (By k Essex)
Viarox (Byk Gulden)
Viarox Dosier-Aerosol
(Byk Essex)
F: Beclojet (Promedica)
BCconase (Glaxo
Wellcome)
BCcotide (Glaxo
Wellcome)
Prolair Autohaler (3M
SantC)
Rhinirex (Irex)
Spir (Inava)
GB: Aerobec
(3M)
Asmabec (Evans)
Beclazone (Baker Norton)
Becloforte (Allen

&
Hanburys)
Becodisks (Allen
&
Hanbury s)
Beconase (Allen
&
Hanbury s)
Becotide (Allen
&
Hanburys)
Filair (3M)
Propaderm (Glaxo
Wellcome)
1: Becotide (Glaxo)
Bronco-Turbinal
(Valeas)
Cleniderm (Chiesi)
Clenigen (Chiesi)-comb.
Clenil (Chiesi)
Clenil spray (Chiesi)
Inalone (Lampugnani)
Menaderm (Menarini)
Proctisone (Chiesi)-comb.
Propaderm (Demcan)
Rino-Clenil (Chiesi)
Turbinal
(Valeas)
J:
Aldecin (Schering-Plough)

Becloderm (Kobayashi)
Beconase (Glaxo)
Becotide (Nippon Glaxo)
Becotide (Glaxo)
Belg (Kowa)
Betozon (Ohta)
Betozon (Ohta Seiyaku)
Entyderma (Taiyo)
Hibisterin (Nippon Zoki)
Korbutone (Nippon Glaxo)
Mulunet (Tatsumi)
Befunolol
B
185
Propaderm (Shin Nihon; USA: Beclovent (Glaxo Vancenase (Schering-
Jitsugyo-Glaxo Fuji;
as
Wellcome) Plough; as dipropionate)
dipropionate)
Beconase (Glaxo Vanceril (Schering; as
Rhinocort (Fujisawa) Wellcome) dipropionate)
Salcoat (Fujisawa) Beconase (Glaxo
Soluroid (Nikken) Wellcome; as dipropionate)
Befunolol
ATC: C07AA; SOlED06
Use: P-adrenoceplor blockcr
RN: 39552-01-7 MF: C,,H2,N04 MW: 291.35
LD,,: 100-105 mglkg
(M, i.v.)
CN:

(+)-1-[7-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]-2-benzofuranyl]ethanone
hydrochloride
RN: 39543-79-8 MF: C16H21N04 . HCI MW: 327.81
LD,,:
65 mgkg (M, i.v.); 950 mglkg (M, p.0.);
922 mglkg (R, p.0.)
H
C
H
C
'0
1.HBr
'0
2.
<CI
,
CH,
KOH
b
1
CHO
0
1.
hydrobrornic acid
2-hydroxy-3- chloro-
2-acetyl-7-
2.
epichlorohydrin, piperidine
rnethoxy- ocetone methoxybenzo-
benraldehyde furon

Reference(s):
DOS 2 223 184 (Kakenyaku Kako; appl. 12.5:1972; J-prior. 13.5.1971, 14.7.1971, 28.10.1971,6.1.1972).
US 3 853
923
(Kakenyaku Kako; 10.12.1974; J-prior. 13.5.1971, 14.7.1971, 28.10.1971,6.1.1972).
US 4056 626 (Kakenyaku Kako; 1.1 1.1977; J-prior. 6.1.1972; 13.5.1971).
(f)-2-ocetyl-7-glycidyl-
isopropyl-
synthesis of
2-acetyl-7-methoxybenzofuran:
Bergel et
al.:
J.
Chem. Suc. (JCSOA9), 1944,261
Befunolol
Formulution(s):
eye drops 2.5 mglml, 5 mghl
axybenzoiuron
(I)
arnine
Trude Name(s):
D:
Glauconex (Alcon; 1984)
1:
Betaclan (Angelini)
F:
Bentos (CIBA Vision J: Bentos (Kaken; as
Ophthalmics; 1987) hydrochloride; 1983)
186
B

Bekanamycin
Bekanamycin
(Kanamycin
B)
ATC: A07AA; JOIKD; SO1 AA
Use: aminoglycoside antibiotic
RN: 4696-76-8 MF: C,8H,7N,01, MW: 483.52 EINECS: 225-170-5
LD,,: 136 rnglkg (M, i.v.)
CN:
0-3-amino-3-deoxy-cx-~-glucopyranosyl-(l+6)-0-[2,6-diamino-2,6-dideoxy-a-~-glucopyranosyl-
(I
+4)]-2-deoxy-D-streptamine
sulfate
(1:l)
RN: 29701-07-3 MF: C,8H,7N,0,0. H2S04
MW:
581.60
LD,,: 112 mglkg (M, i.v.);
141 mglkg (R, i.v.); >10 g/kg (R, p.0.)
Fermentation of
Streptornyces kanamyceticus
(ATCC 12853) and precipitation with
sodium dodecylphenylsulfonate.
Reference(s):
DAS 1 115 413 (H. Urnezawa; appl. 1958; USA-prior. 1957).
US 2 967 177 (Bristol-Myers; 1961; prior. 1958).
US 3 032 547 (Merck
&
Co., 15.1.1962; prior. 12.9.1958).
alternative synthesis:

US 2 931 798 (H. Umezawa et al.; 1960; J-prior. 1956).
US 2 936 307 (Bristol-Myers; 1960; prior. 1957).
total synthesis:
Umezawa, S. et al.: Bull. Chem. Soc. Jpn. (BCSJAR) 42, 537 (1969).
structure:
Ito, T.: J. Antibiot., Ser. A (JAJAAA) 17, 189 (1964).
review:
Wakazawa,
T.
et al.:
J.
Antibiot., Ser. A (JAJAAA) 14A, 180, 187 (1961).
Formulation(s):
cps. 250 rng; gran. 250 mg; powder; susp. 200 mg
Trade Name(s):
I: Kanendos (Crinos; as Visumicina (Merck Sharp
sulfate)
&
Dohme)-comb.
Micomplex (Schiapparelli J: Kanendomycin (Meiji
Seark-comb. Seika; as sulfate)
Bemegride
B
187
8
Bemegride
ATC: R07AB05
Use: antidote for barbiturate poisoning,
analeptic
RN: 64-65-3 MF: C,H,,N02 MW: 155.20 EINECS: 200-588-0

LD,,: 16 mglkg (M, i.v.); 41 mglkg (M, p.0.);
16 mgikg (R, i.v.)
CN:
4-ethyl-4-methyl-2,6-piperidinedione
HOOC COOH
0
0
Q
H3C LcH3
+
~~d~~~~~
CH3
methyl ethyl ethyl cyanaacetate 2.4-dicyano-3-
ketone ethyl-3-methyl-
glutarimide
(CH,-C0),0
I
acetic
y
"
.
anhydride
H3C
CH3
Y
H3C
CH3
3-ethyl-3-methyl-
glutaric acid
(I)

3-ethyl-3-methyl-
/
Bernegride
glutoric anhydride
Benica, W.S.; Wilson, C.H.O.:
J.
Am. Pharm. Assoc. (JPHAA3) 39,451,454 (1950).
Formulation(s):
amp. 5 mglml (5
%,
10
%)
Trade Narnefs):
D: Eukraton (Nordmark); wfm F: MCgimide (Aspros-
GB:
Megimide (Nicholas); wfm
Nicholas); wfm
J:
Antibarbi (Tanabe)
Bemetizide
ATC: C03E
Use: diuretic
RN:
1824-52-8 MF: C15H,6CIN304S2 MW: 401.90 EINECS: 217-357-5
LD,,: 345 mglkg (M, i.v.); >5 glkg (M, p.0.);
>5 glkg (R, p.0.)
CN:
6-chloro-3,4-dihydro-3-(1
-phenylethyl)-2H-l,2,4-benzothiadiazine-7-sulfonamide
1 ,l -dioxide

5-chlora-2,4-bis- hydratropic
Bernetizide
(aminosulfonyl)oniline aldehyde
(cf. chlorothiazide synthesis)
188
B
Benactyzine
Reference(s):
AT 230 382 (Dr. H. Voigt; appl. 8.3.1961; D-prior. 23.2.1961).
Topliss, J.G. et al.: J. Org. Chem. (JOCEAH)
26,
3842 (1961).
Jacobi, H.; Fontaine, R.: Arzneim Forsch. (ARZNAD)
16,
1186, 1332 (1966).
Formulation(s):
drg. 10 mg, 20 mg
Trade Name(s):
D: Dehydro sanol (Sano1)- Diucomb (Me1usin)-comb.
F:
Tensigradyl (Oberva1)-
comb. comb.; wfm
Benactyzine
ATC: N04A
Use: ataractic, neuroleptic, anticholinergic
RN: 302-40-9 MF: C2nH2sN03 MW: 327.42 EINECS: 206- 123-8
LD,,,: 100 mglkg (M, i.p.); 159 mg/kg (M, s.c.);
135 mg/kg (R, i.m.)
CN:
a-hydroxy-a-phenylbenzeneacetic

acid 2-(diethy1amino)ethyI ester
hydrochloride
RN: 57-37-4 MF: C20H2sN03
.
HC1 MW: 363.89 EINECS: 200-324-4
LD,,: 14.3 mgkg (M, i.v.); 160mg/kg(M, p.0.);
184 mgkg (R, p.0.)
ethyl benzilote 2-diethylomino-
ethanol
I
Benoctyzine
Referencefs):
US 2 394 770 (American Cyanamid; 1946; prior. 1942).
Formulation(s):
amp. 2 mglml,
0.3
%;
tabl.
1
mg
Trade Name(s):
D: Brondiletten (Albert-
I:
Pre Ciclo (Ibis)-comb.;
.I:
Rousse1)-comb.; wfm wfm
Perasthman (Polypharm)- Sirenitas (Benvegna)-
comb. comb.; wfm
Morcain (Tatsumi); wfrn
Parpon (Santen); wfrn

Benaprizine
(Benapry zine)
ATC: NO4
Use: antiparkinsonian
RN: 22487-42-9 MF: C2,H27N03 MW: 341.45
CN:
a-hydroxy-a-phenylbenzeneacetic
acid
2-(ethylpropy1amino)ethyl
ester
hydrochloride
RN: 3202-55-9 MF: C2,HZ7NO3. HC1 MW: 377.91
LD,,,: 500 mglkg (M, p.0.)
I
Benazepril
B
189
NaOCH3
HO-~~CH~
methyl benzilote 2-(ethylpropylomin0)- Benoprizine
ethonol
I
I
Reference{s):
US
3
746
743
(Beecham;
17.7.1973;

GB-prior.
22.8.1963).
Formulation{s):
tabl.
10
mg
(as
hydrochloride),
50
mg
Trade Name(s):
GB:
Brizin
(Beecham);
wfm
I:
Zinadril
(Smith
Kline
Beecham)
Benazepril
(Benzapril)
ATC:
C09AA07
Use:
antihypertensive
(ACE
inhibitor)
RN:
86541-75-5

MF:
C,H2,N20, MW:
424.50
CN:
[S-(R*,R*)]-3-[[l-(ethoxycarbonyl)-3-phenylpropy~]amino]-2,3,4,5-tetrahydro-2-oxo-lH-l-benzazepine-
1-acetic
acid
monohydrochloride
RN:
86541-74-4
MF:
C,H,,N,O,
.
HC1
MW:
460.96
ti
0
H,. Pd-C,
PCI5. xylene. 90 OC
CH3COOH, CH3COONa
I
2,3.4,5-tetrohydro-
3.3-dichloro-2.3.4.5-
1H-l -benz-
letrohydro- 1H-l-
azepin-2-one
benzozepin-2-one
B,/hO-CH3
H

0
H
0
0
NaN
,
DMSO. 80 OC KOH. THF
1
+
ethyl 11
3-chloro-2.3.4.5-te-
trohydro-1H-1 -benz-
ozepin-2-one (I)
3-ozido-2.3.4.5-te- bromoacetote
trohydro-1 H-l-benz-
ozepin-2-one
0
1.
Hz. Pd-C
($-cH3
2. resolution with
L-tortoric acid in CH,OH
NoOH. CH30H
ethyl 3-ozido-
2.3.4.5-telrahydro-
2-oxo-1H-1 -benz-
azepin-1 -ocetate (11)
ethyl (3s)-3-amino-
2.3.4.5-tetrohydro-
2-oxo-1H-1 -benz-

azepin-1 -ocetote
I
1190
B
Bencyclane
1.
NaBH4
2.
recrystallization
(35)-3-amino- ethyl 2-0x0-
I
-(corboxymethyl)- 4-phenylbutyrote Benozepril
reference(^):
Watthey, J.W.H. et a].: J. Med. Chem. (JMCMAR)
28,
1511 (1985).
US 4 410 520 (Ciba-Geigy; 18.10.1983; prior. ll.8.l98l,9.ll.I98l, 19.7.1982).
EP 72 352 (Ciba-Geigy; appl. 5.8.1982; USA-prior. 11.8.1981,9.11.1981).
EP 206 993 (Ciba-Geigy; appl. 9.6.1986; CH-prior. 13.6.1985)
1
Formulation(s):
f.
c. tabl. 5 mg, 10 mg, 20 mg (as hydrochloride)
Trade Natnefs):
D:
Cibacen (Novartis Pharma)
Cibadrex (Novartis)-comb. J: Cibacen (Novartis; as
Cibadrex (Novartis
1:
Cibadrex (Ciba-Geigy)- hydrochloride)

Pharrnal-comb. comb. USA: Lotensin (Ciba)
F: Briazide (Pierre Fabre)- Tensanil (Zyma)
Lotensin (Ciba)-comb. with
comb. Zinadur (Smith Kline Hydrochlorothiazide
Briem (Pierre Fabre) Beecham)-comb.
. Lotrel (Ciba)-comb. with
Cibactre (Novartis) Amlodipine
Bencyclane
ATC: ~04~x1
I
(Benciclano)
Use: antispasmodic, vasodilator
RN: 2179-37-5 MF: C,,H,,NO MW: 289.46 EINECS: 218-547-0
CN:
N,N-dimethyl-3-[[l-(phenylmethyl)cycloheptyl]oxy]-l-propanamine
fumarate
(I: 1)
RN: 14286-84-1
MF:
C,9H31N0. C4H404
MW.
405.54 EINECS: 238-204-9
LD,,:
45 mgkg (M, i.v.); 446 mglkg
(M,
p.0.);
41 mgkg (R, i.v.); 414 mglkg (R, p.0.)
benzylmog- cyclo-
nesium chloride heptanone
+

l-benzyl-
cycloheptonol
1.
NaNH2
2.
7%
C'-NCH,
b
1.
sodium omide
2.
3-dimethylomino-
propyl chloride
Reference(s):
HU 151 865 (Egyesiilt Gyogyszer; appl. 18.8.1963).
Bencyclone
J
1
Formulation(sj:
drg. 75 mg, 100 mg