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 . 4&apos ;-( 2.5-dihydro- 5-0 x 0- 2-acetyl- 5-( 2.5-dihydro- 5-( 2.5-dihydro-50x 0- 3-furyl )-2 &apos ;-( 2-oxopropaxy )- 5-0 ~ 0-3 -furyl)-S-rnethyl- 3-furyl )-2 -( 1 -hydroxyethyl )- ocetophenone (I) benzofuran 3-methylbenzofuran. 4-( 4-rnethoxyphenyl )- ocetyl 2'-hydroxy-4&apos ;- 2-0 x 0-2 .5-dihydro- chloride (2.5-dihydro-50x 0- furon 3-furyl)ocetophenone d' I, 0 boranote 4&apos ;-( 2.5-dihydro- 5-0 x 0- 2-acetyl- 5-( 2.5-dihydro-. 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)-