Pharmaceutical Substances Syntheses, Patents, Applications - Part 25 potx

D MA N-4-cyano-3-trifluorcmethylphenyl- 3-4-fluorophenylsuIfony1-2-hydroxy- 2-methylpropionomide N J-chloroper- benzoic acid V methocryloyl chloride 4'-cyono-3'-trifluoro methylme

Bicalutamide B 241

Bicalutamide

(ICI- 176334)

Use: non-steroidal antiandrogen, antineoplastic, anti(pr0state)cancer

RN: 90357-06-5 MF: CI8Hl4F4N2O4S MW: 430.38

CN: (f)-N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide

R-enantiomer

RN: 113299-40-4 MF: C1,H,,F4N,O4S MW: 430.38

S-enantiomer

RN: 113299-38-0 MF: C18H14F4N204S MW: 430.38

F

C H 2

thiophenol (I) F

methyl

methocrylate

methyl 2.3-epoxy- 2-rnethylpropionote

methyl Z-hydroxy- 2-methyl-3-(4-fluoro- pheny1thio)propionote (11)

aniline (Ill), thianyl chloride

D MA N-(4-cyano-3-trifluorcmethylphenyl)-

3-(4-fluorophenylsuIfony1)-2-hydroxy-

2-methylpropionomide (N)

J-chloroper-

benzoic acid (V)

methocryloyl

chloride

4'-cyono-3'-trifluoro methylmethocryl- onilide

NOH THF

H

4'-cyano-3'-trifluoro-

methyl-2.3-epoxy-2-

methyl-propiononilide (VI)

242 B Bietamiverine

Reference(s):

EP 100 172 (ICI; appl 8.7.1983; UK-prior 23.7.1982)

active enantiomer (R-(-)-bicalutamide),for treating e g prostare cancel; acne:

WO 9 519 770 (Sepracor Inc.; appl 27.7.1995; USA-prior 21.1.1994)

combination with progesterone antagonists:

DE 4 318 371 (Schering AG; 1.12.1994; D-prior 28.5.1993)

combination with sex steroid biosynthesis inhibitors:

WO 9 100 733 (Endorecherche Inc.; 24.1.1994; USA-prior 7.7.1 989)

Formulation(s): tabl 50 mg

Trade Name(s):

Bietamiverine

(Dietamiverin)

Use: antispasmodic

CN: a-phenyl-1-piperidineacetic acid 2-(diethy1amino)ethyl ester

dihydrochloride

LD,,: 55 m g k g (M, i.v.); 1247 mglkg (M, p.0.)

a-chlorophenyl- 2-diethylamino-

acetyl chloride ethanol

c I

2-phenyl-2-chloroacetic acid 2-(diethylamina)ethyI ester (I)

H

0

I - - - +

piperidine

ICH3

w 0 - N V c H 3

Bietamiverine

Reference(s):

DE 859 892 (Nordmark; appl 1950)

Trade Namefsi:

w fm

Use: antihypertensive

CN: (3~,16~,17a,l8~,20a)-1-[2-(diethylamino)ethyl~-11,17-dimethoxy-l8-[(3,4,5- trimethoxybenzoyl)oxy]yohimban-16-carboxylic acid methyl ester

Bifluranol B 243

bitartrate (1:l)

RN: 11 11-44-0 MF: C3,HS3N309 C4H606 MW: 857.95 EINECS: 214-180-5

1 NOH

2 p H 3

C I A J ' L C H s

-1 sodium hydride

2 2-diethylominoethyl

reserpine

(9 v.1

chloride

Reference(s):

FR 1 256 524 (Dautreville et Lebas et A Buzas; appl 13.2.1959)

FR-M 102 (Soc Nogentaise de Prod Chim et A Buzas; appl 3.8.1960)

Trade Namefs):

(Guidotti); wfm

Use: antiandrogen, treatment of benign prostatic hypertrophy

CN: (R*,S*)-4,4'-(1-ethyl-2-methyl-l,2-ethanediyl)bis[2-fluorophenol]

3-chloro-2- trans-2.3-bis(3-fluora-4-methoxy- pentanone phenyl)-2-pentene (11)

Bifluranol

i _l

244 B Bifonazole

3-chloro-2- (R*,S*)-2.3-bis(3-fluoro-4-rnethoxy-

pentonol pheny1)pentone

Reference(s):

DE 2 I10 428 (Biorex; appl 4.3.1971; GB-prior 16.3.1970)

US 4 051 263 (Biorex; 27.9.1977; GB-prior 16.3.1970)

Formulation(s): amp

Trade Name(s):

GB: Prostarex (Biorex); wfrn

Bifonazole

(Bifonazolum)

Use: topical antimycotic (inhibitor of erg~sterin biosynthesis in yeasts and dermatophytes)

LD,,: 57 rngkg (M, i.v.); 2629 mglkg (M, p.0.);

63 m g k g (R, I.v.); 1463 m g k g (R, p.o.);

>500 m g k g (dog, p.0.)

CN: 1-([1,1'-biphenyl]-4-ylphenylrnethyl)-lH-imidazole

monohydrochloride

sulfate

biphenyl benzoyl

chloride

(2)-4-phenylbenz- (-4)-4-(chlorophenyl- Bifonazole

hydro1 (I) rnethy1)biphenyl

Binedaline B 245

1 -1'-sulfinyl- bisirnidazole

Reference(s):

DOS 2 461 406 (Bayer; appl 5.12.1975; USA-prior 24.12.1974)

US 4 118 487 (Bayer; 3.1 1.1978; appl 5.12.1975; prior 24.12.1974)

effective mechanism:

Berg, D et al.: Arzneim.-Forsch (ARZNAD) 34 (I), 139 (1984)

Formulation(s): cream 10 mg (1 %); gel 10 mg; lotion 1 %; powder 10 mg (1 %); sol 10 mg (1 %)

Trade Name(s):

SantC)-comb

Binedaline

(Binodaline)

Use: antidepressant

LD,,; 54 mgkg (M, i.v.); 770 mglkg (M, p.0.);

27 mgkg (R, i.v.)

CN: N,N,N-trimethyl-N-(3-phenyl- l H-indol-1 -yl)- 1.2-ethanediamine

monohydrochloride

RN: 57647-35-5 MF: ClyHz,N3 HCl MW: 329.88 EINECS: 260-877-2

LD,: 54 mgkg (M, i.v.); 760 mglkg (M, p.0.);

26 mgkg (R, i.v.); 1160 m g k g (R, p.0.);

>20 mg/kg (dog, i.v.) -

1 N a N 0 2 , HCI

2 NH,

b

N-(3-phenylindal-1 -yl)

\

"% 4-phenyl-

cinnoline (1)

246 B Biotin

1 KOH

methyl 4-toluene-

NaH

_,

sulfonote

p 3

C , ~ N \

CH3

1 potassium hydroxide

2 2-(dimethylomino)- ethyl chloride

DOS 2 512 702 (Siegfried AG; appl 22.3.1975; CH-prior 29.3.1974)

US 4 204 998 (Siegfried AG; 27.5.1980; CH-prior 29.3.1974)

Schatz, F et al.: Arzneim.-Forsch (ARZNAD) 30,919 (1980)

synthesis of 1,4-dihydro-4-phenylcinnoline:

Simpson, J.C.F et al.: J Chem Soc (JCSOA9) 1945,646

Scheifele, H.J Jr et al.: Org Synth (ORSYAT) 32, 8 (1952)

Sternbach, L.H et al.: J Org Chem (JOCEAH) 26,4488 (1961)

Formulation(s): tabl 25.5 mg

Trade Name(s):

Biotin

(Vitamin B7; Vitamin H)

Use: growth factor, vitamin

CN: [3aS-(3aa,4~,6aa)]-hexahydro-2-oxo-1H-thieno[3,4-d]imidazole-4-pentanoic acid

fumoric ocid mesa-2.3-dibromo- cis-1,3-dibenzyl-

succinic ocid 2-axo-imidazolidine-

4.5-dicorboxylic ocid (1)

Biotin B 247

1 Zn CH3COOH

I

magnesium bromide

1.3-dibenzyl-4-(3-ethoxy- propy1idene)-cis-perhydro- thieno[3,4-d]imidozol-2-one (N)

HBr, CH3COOH

v

1 silver D-comphorsulfonote - AgBr

2 seporotion of diostereorners by crystollizotion

b 1,3-dibenzyl-2-0~0-3a,8b-cis-per-

hydrathieno[l',2':l 2]thieno[3.4-dl-

imidozolium bromide (V)

diethyl rnalonate

0

Biotin

rnolonic acid diethyl ester

248 B Biotin

cyclo- cis-1.3-dibenzyl-2-0x0-

hexonol imidazolidine-4.5-dicorboxylic

acid rnonocyclohexyl ester

4 H2, Raney-Ni

1 potassium thioacetote magnesium chloride 0-CH,

(3oS)-1,3-dibenzyl-4t-(3- rnethoxypropyl)-(3or.60~)- tetrohydrothieno[3,4-dl- imidozol-2-one (VIII)

1 HBr

Reference(s):

US 2 489 232 (Roche; 1949; appl 1946)

US 2 489 233 (Roche; 1949; appl 1947)

US 2 489 234 (Roche; 1949; appl 1947)

US 2 489 235 (Roche; 1949; appl 1947)

US 2 489 236 (Roche; 1949; appl 1947)

US 2 489 237 (Roche; 1949; appl 1948):

US 2 489 238 (Roche; 1949; appl 1948)

US 2 5 19 720 (Roche; 1950; appl 1948)

US 3 740 416 (Roche; 1973; CH-prior 29.1 1.1969)

newer syntheses:

DAS 2 331 244 (Sumitomo; appl 19.6.1973; J-prior 22.6.1972, 23.3.1973)

DAS 2 534 962 (Teikoku; appl 5.8.1975; J-prior 5.8.1974, 6.8.1974, 8.8.1974)

DOS 2 730 341 (Roche; appl 5.7.1977; USA-prior 12.7.1976)

DOS 2 807 200 (Roche; appl 20.2.1978; USA-prior 23.2.1977)

US 4 054 740 (Roche; 18.10.1977; prior 24.12.1974, 5.9.1975)

US 4 130 712 (Roche; 19.12.1978; prior 12.7.1976, 17.6.1977)

US 4 130 713 (Roche; 19.12.1978; prior 5.8.1977)

Lavielle, S et al.: J Am Chem Soc (JACSAT) 100, 1558 (1978)

Formrdation(s): amp 0.5 mg, 5 mg; cps 0.06 mg, 0.1 mg; drg 0.15 mg, 0.5 mg; tabl 5 mg, 10 mg

Trade Name(s):

Biperidene B 249

F: Alvityl (Solvay Pharma)-

comb

Azedavit (Whitehall)-

comb

Azinc complexe

(Arkopharrna)-comb

Berocca (Nicholas)

Biotine (Roche)

Cemtvit (BaxtersaIClintel

Parenttra1)-comb

~ l t v i t Vitamine B9 (Nicholas)-comb

Lofenalac (Bristol-Myers

Plenyl (0berlin)-comb

Soluvit (Pharmacia & I:

Upjohn)-comb

Survitine (Roche Nicholas)-comb

Vivamyne (Whitehall)- comb

generics Ketovite (Paines & Byrne)- comb

Biodermatin (Lafare) Diathymil (Dermalife) Havita (Kakenyaku) Mega-B (Arco) Megadose (Arco) combination preparations

Use: antiparkinsonian

RN: 514-65-8 MF: C21H2,N0 MW: 31 1.47 EINECS: 208-184-6

LD,,: 56 rnglkg (M, i.v.); 530 mgfkg (M, p.0.);

750 mglkg (R, p.0.);

340 mgkg (dog, p.0.)

CN: a-bicyclo[2.2.1]hept-5-en-2-yl-a-phenyl-l-piperidinepropanol

hydrochloride

LD,; 56 mglkg (M, i.v.); 530 mgkg (M, p.0.);

750 mgkg (R, p.0.);

340 mgkg (dog, p.0.)

lactate (1:l)

RN: 7085-45-2 MF: C,,H,,NO C3H60, MW: 401.55 EINECS: 230-388-9

LD,o: 61 mglkg (M, i v.)

acetophenone poroform- piperidine 3-piperidino-

hept-5-en-2-yl- Biperidene

magnesium chloride

cyclo- methyl 2-ocetyl- 2-(3-piperidinopropiany1)-

pentadiene vinyl ketone 5-norbornene 5-norbornene (U)

250 B Bisacodyl

phenylmagnesium

bromide

Reference(s):

US 2 789 110 (Knoll; 1957; D-prior 1953)

DE 1 005 067 (Knoll; appl 1953)

Formulation(s): amp 5 mglml; powder 1 YO; S r drg 4 mg; tabl 2 rng

Trade Narne(s):

Use: laxative

LD,,: 17.5 glkg (M, p.0.);

4.32 glkg (R, p.0.);

r 15 glkg (dog, p.0.)

CN: 4,4'-(2-pyridinylmethylene)bis[phenol] diacetate (ester)

pyridine-2- phenol 2-(4.4'-dihydroxy-

carboxaldehyde benzhydry1)pyridine

Reference(s):

DE 951 987 (Thomae; appl 1952)

US 2 764 590 (Thomae; 1956; D-prior 1952)

alternative synthesis:

DE 951 988 (Thomae; appl 1952)

Trade Name(s):

Bisacodyl I

Laxbene (Merckle) Laxoberal (Boehringer Ing.)

Mandrolax (Dolorgiet) Marienbader (RIAM) Mediolax (Medice) Pyrilax (Berlin-Chemie)