Trade Names: I : Botropase Ravizza J: Defibrase Tobishi- Reptilase Lepetit Fujisawa... Formulations: cream 0.025 %; dose aerosol 0.05 pg, 0.25 pglpuff; nasal spray 0.05pgIpuff; powder
Trang 1Batroxobin B 181
1 DIC/HOEt
2 separation of diastereorners
by crystollizotion
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:
J P 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)
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)
Trang 2182 B Beclamide
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
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
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
2 ethanol
Trang 3Beclometasone B 183
CHCIJ, KOH
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
beclometosone 21 -acetate (I)
Trang 4184 B Beclometasone
F) + ~ 3 ~ 7 O pyridine p 3O°C
H,O HCIO,
1
propionic onhydride
Re ference(s):
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)
Trang 5Befunolol B 185 Propaderm (Shin Nihon; USA: Beclovent (Glaxo Vancenase (Schering-
Salcoat (Fujisawa) Beconase (Glaxo
Soluroid (Nikken) Wellcome; as dipropionate)
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.)
b 1
2-hydroxy-3- chloro- 2-acetyl-7- 2 epichlorohydrin, piperidine
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 m g h l
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)
Trang 61 8 6 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
Micomplex (Schiapparelli J: Kanendomycin (Meiji
Trang 7Bemegride B 187
8
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
H O O C C O O H
C H 3 methyl ethyl ethyl cyanaacetate 2.4-dicyano-3-
glutarimide
(CH,-C0),0
I
anhydride H 3 C
C H 3
Y
H 3 C
C H 3
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)
Trade Narnefs):
D: Eukraton (Nordmark); wfm F: MCgimide (Aspros- GB: Megimide (Nicholas); wfm
Nicholas); wfm J: Antibarbi (Tanabe)
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
(aminosulfonyl)oniline aldehyde
Trang 8188 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)-
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 m g k g (M, i.v.); 160mg/kg(M, p.0.);
184 m g k g (R, p.0.)
Referencefs):
US 2 394 770 (American Cyanamid; 1946; prior 1942)
Trade Name(s):
D: Brondiletten (Albert- I: Pre Ciclo (Ibis)-comb.; I:
Perasthman (Polypharm)- Sirenitas (Benvegna)-
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.)
Trang 9I Benazepril B 189
NaOCH3
H O - ~ ~ C H ~
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
I
B,/hO-CH3
3-chloro-2.3.4.5-te-
trohydro-1H-1 -benz-
trohydro-1 H - l - b e n z - ozepin-2-one
0
($-cH3 2 resolution with
ethyl 3-ozido-
2.3.4.5-telrahydro-
2-oxo-1H-1 -benz-
ethyl (3s)-3-amino- 2.3.4.5-tetrohydro- 2-oxo-1H-1 -benz- azepin-1 -ocetote
Trang 101190 B Bencyclane
1 NaBH4
reference(^):
Watthey, J.W.H et a].: J Med Chem (JMCMAR) 28, 1511 (1985)
US 4 410 520 (Ciba-Geigy; 18.10.1983; prior l l 8 l 9 8 l , 9 l l I 9 8 l , 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)
F: Briazide (Pierre Fabre)- Tensanil (Zyma) Lotensin (Ciba)-comb with
Briem (Pierre Fabre) Beecham)-comb Lotrel (Ciba)-comb with
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 m g k g (M, i.v.); 446 mglkg (M, p.0.);
41 m g k g (R, i.v.); 414 mglkg (R, p.0.)
+
l-benzyl- cycloheptonol
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