Pharmaceutical Substances Syntheses, Patents, Applications - Part 18 ppt

Aztreonam A 171 1. CIS03H, 2-picoline. CH2C12 2. V. CH2CI2 b iCH"' XI N1-sulfo-NZ-benzyloxycorbonyl-0-rnethylsulfonyl- L-threoninornide tetrabutylornrnoniurn salt (XII) VIII. K2C03, C2H4C12, H20 H2, Pd-C. CZH,OH N-hydroxybenzotriozole, DCC w-VI b mr b IX Reference(s): US 4 386 034 (Squibb; 31.5.1983; prior. 10.2.1982). US 4 529 698 (Squibb; 16.7.1985; prior. 5.11 ,1984). US4 625 022 (Squibb; prior. 25.11.1986; 2.2.1981). DOS 3 104 145 (Squibb; appl. 6.2.1981; USA-prior. 29.8.1980). GB 2 071 650 (Squibb; appl. 6.2.1981; USA-prior. 7.2.1980,29.9.1980). Formulation(s): amp. 2 g; inj. powder 500 mg, 1 g, 2 g; lyo. for inf. 2 g; vial 1 g13 ml Trade Narnefs): D: Azactam (Bristol-Myers GB: Azactam (Bristol-Myers J: Azactam (Squibb; 1987) Squibb; 1985) Squibb; 1986) USA: Azactam (Bristol-Myers F: Azactam (Sanofi Winthrop) I: Axactam (Squibb; 1984) Squibb; 1987) 172 B Bacampicillin Bacampicillin ATC: JOlCA06 Use: antibiotic (broad spectrum penicillin) RN: 50972-17-3 MF: CzIHz7N,07S MW: 465.53 CN: [2S-[2a,5a,6~(S*)]]-6-[(aminophenylacetyl)a~no]-3,3-~methyl-7-oxo-4-thia-l- azabicyclo[3.2.0]heptane-2-carboxylic acid 1 -[(ethoxycarbonyl)oxy]ethyl ester monohydrochloride RN: 37661-08-8 MF: CzIHz7N,07S . HCl MW: 501.99 EINECS: 253-580-4 LD,,: 184 mgkg (M, i.v.); 8529 mgkg (M, p.0.); 176 mgkg (R, i.v.); 10 gkg (R, p.0.) azidocillin sodium salt (9. v.) 1 -chloroethyl ethyl carbonote Referencefs): DAS 2 144 457 (Astra; appl. 4.9.1971; S-prior. 17.9.1970, 20.1 1.1970). US 3 873 521 (Astra; 25.3.1975; S-prior. 17.9.1970; 20.11.1970). US 3 939 270 (Astra; 17.2.1976; S-prior. 17.9.1970; 20.1 1.1970). 6-(D-a-azidaphenylacetamido)- Formulation(s): f. c. tabl. 400 g, 800 mg; susp. 125 mg (as hydrochloride) Bacampicillin Trade Name(s): D: Ambacamp (Pharmacia & Penglobe (Lematte et Upjohn; 1981) Boinot) Penglobe (Astra; 1977) GB: Ambaxin (Upjohn; 1980) J: penicillanic acid 1 -ethoxycarbonyl- oxyethyl ester (1) Bacacil (Pfizer) Penglobe (Bracco) Bacacil (Pfizer Taito) F: Bacampicine (Pharmacia & I: Ambaxin (Upjohn) Penglobe (Yoshitomi) Upjohn) Amplibac (Schwarz) USA: Spectrobid (Pfizer; 1981) Bacitracin ATC: D06AX05; R02AB04 Use: polypeptide antibiotic (mainly topical application) RN: 1405-87-4 MF: C66H,o,N17016S MW: 1422.72 EINECS: 215-786-2 LD,,,: 360 mglkg (M, i.v.); >3750 mglkg (M, p.0.) CN: bacitracin Bacitracin B 173 bacitracin A RN: 22601-59-8 MF: Ch6H103Ni7016S MW: Bacitracin A 1422.72 EINECS: 245-1 15-9 "Bacitracin" is submitted as mixture of bacitracin A with other bacitracins. From culture of Bacillus subtilis and purification on ion-exchangers. Referencefs): US 2498 165 (US-Secret. of War; 1950; appl. 1946). US 2 828 246 (Commercial Solvents Corp.; 1958; appl. 1956). purijication: US 2 457 887 (Ben Venue Labs.; 1949; appl. 1947). US 2 609 324 (Commercial Solvents Corp.; 1952; appl. 1949). US 2 774 712 (S. B. Penick & Co.; 1956; appl. 1955). US 2776 240 (Commercial Solvents Corp.; 1957; appl. 1954). US 2 834 71 1 (Commercial Solvents Corp.; 1958; appl. 1956). US 2 915 432 (Merck & Co.; 1959; appl. 1955). US 2 960 437 (Pfizer; 1960; appl. 1955). US 3 795 663 (Commercial Solvents Corp.; 5.3.1974; appl. 1.5.1972). US4 101 539 (IMC Chemical; 18.7.1978; appl. 17.10.1977). complexes with nickel salts: US 2 903 357 (Grain Processing Corp.; 1959; appl. 1958). Na-bacitracin methanesulfonate: US 3 205 137 (Warner-Lambert; 7.9.1965; appl. 19.3.1963). complexes with zinc, cobalt or manganese sulfate resp. sulfonates: US 3 384 631 (Spofa; 21.5.1968; appl. 23.6.1965; CSSR-prior. 26.6.1964). complexes with metal methanesuljnates: US 3 441 646 (Commercial Solvents; 29.4.1969; appl. 22.1.1965). complex with calcium or magnesium alkylbenzenesulfonates: US 3 891 615 (Commercial Solvents; 24.6.1975; appl. 25.10.1973). Formulation(s): amp. 50000 iu; vial 5000 iu; nasal ointment 300 iu; ointment 300 iu, 500 iu; powder 300 iu Trade Namefs): D: Anginomycin (MIP Frubienzym (Boehringer Polyspectran (A1con)- Pharma) 1ng.)-comb. comb. Batrax (Gewo)-comb. Nebacetin (Yamanouchi)- Prednitracin (CIBA Bivacyn (medphano) comb. Vision)-comb. Cicatrex (Glaxo Neobac (Dermapharm) Tonsilase (Media)-comb. Wellcome)-comb. Neotracin (CIBA Vision) F: Bacicoline (Merck Sharp & Dohme-Chibret)-comb. T' 174 B Baclofen Collunovar (SynthC1abo)- comb. Lysopaine ORL (Boehringer 1ng.)-comb. Maxilase Bacitracine (Sanofi Winthrop)-comb. Oropivalone (Jouveina1)- comb. Pimafucort (Beytout)- comb. generics GB: Cicatrin (Glaxo Wellcome)-comb. Polyfax (Dominion)-comb. I: Bimixin (Lusofarmaco)- comb. Enterostop (Teafarma)- comb. Orobicin (Fu1ton)-comb. J: Bacitracin (Ono) USA: Betadine (Purdue Frederick) Cortisporin (Burroughs I Wellcome)-comb. Neosporin (Glaxo Wellcome; Warner- Lambert) Polysporin (Warner- , Lambert) generics Baclofen ATC: M03BXO1 t Use: muscle relaxant (antispasmodic) RN: 1134-47-0 MF: C,,H12ClN02 MW: 213.66 EINECS: 214-486-9 LD,,,: 3 1 mgkg (M, i .v.); 200 mglkg (M, p.0.); 78 mglkg (R, i.v.); 145 mglkg (R, p.0.) CN: P-(aminomethyl)-4-chlorobenzenepropanoic acid oldehyde ethyl acetoacetole ClW O~CH~ 3-(4-chlorapheny1)- glutoric ocid (1) I C I 3-(4-chlorophenyl)- 3-(4-chloropheny1)- Baclofen glutaric anhydride glutarimide ethyl 4-chlorocinnamate nitromethone (11) Hz. Raney-Ni 11 O~CH~ % CI Reference(s): a US 3 47 1 548 (Ciba; 7.10.1969; CH-prior. 9.6.1963; 22.5.1964). lJS 3 634 428 (Ciba; 11.1.1972; CH-prior. 9.7.1963, 22.5.1964). b JP 45 016 692 (Uchimaru, F. et al.; Daiichi Seiyku; appl. 10.6.1970); C.A. (CHABAS) 73, 77617~ (1970). Balsalazide sodium B 175 conlbination with ncuroleptics: US 3 947 579 (Nelson Research & Dev.; 30.3.1976; appl. 3.6.1974). US 3 978 216 (Nelson Research & Dev.; 31.8.1976; prior. 3.6.1974, 16.7.1975). US 4 138 484 (Nelson Research & Dev.; 6.2.1979; prior. 3.6.1974, 16.7.1975, 16.8.1976,25.7.1977). Fonnulation(s): inj. sol. 0.05 mgll ml, 10 mgl20 ml, 10 mg15 ml; intrathecal inj. 50 pglml, 0.05 mglml, 10 mgl20 ml, 10 mg15 ml; liquid 5 mgl5 ml; tabl. 5 mg, 10 mg, 25 mg Trade Name(s): D: Lebic (Isis Puren) GB: Lioresal (Novartis) Lioresal (Novartis Pharma) I: Lioresal (Ciba) F: LiorCsal (Novartis) J: Gabalon (Daiichi) Lioresal (Novartis) Balsalazide sodium (BX-66 1 -A) ATC: DO8 Use: anti-inflammatory RN: 82101-18-6 MF: C,,H,,N,Na,O, MW: 401.29 CN: 5-[[4-[[(2-carboxyethyl)amino]carbonyl]phenyl]azo]-2-hydroxybenzoic acid disodium salt @)-free acid RN: 80573-04-2 MF: C,,H,,N,O, MW: 357.32 4-nitrobenzoyl ,L-alonine chloride N-(4-nitrobenzoyl) p-olanine (I) 1. NoN02. HZO, HCI. 5 'C COOH H , Pd-C. C H OH L a H2N%gc"CooH I, sodium nitrite + 11 ""-0 0 2. salicylic acid N-(4-aminobenz0yl)- palanine COOH I OyONa Refcrence(s): DE 3 128 819 (Riorex Lab.; appl. 21.7.1981; GB-prior. 21.7.1980,7.7.1981). (11) Formulation(s): cps. 750 mg (as disodium salt) Balsalazide sodium Trade Name(s): GB: Colazide (Astralmanuf. by Salix) 176 B Bambuterol Bambuterol (KWD-2183) ATC: R03CC12 Use: P2-receptor agonist, orally active lipophilic terbutaline ester prodrug, 1 long lasting bronchodilator RN: 81732-65-2 MF: C,,H,,N,OS MW: 367.45 CN: dimethylcarbamic acid 5-[2-[(1,1-dimethylethyl)amino]-l-hydroxyethyl]-l,3-phenylene ester monohy drochloride RN: 81732-46-9 MF: CI,H2,N,0s . HCI MW: 403.91 3',5'-dihydroxy- dimethyl- acetophenone carbamoyl chloride 3',5'-bis(dimethy1corb- amoyloxy)acetophenone (I) I Bombuterol EP 43 807 (Draco; appl. 30.6.1981; GB-prior. 9.7.1980,29.5.1981). DOS 3 163 871 (Draco; appl. 23.1.1981; GB-prior. 9.7.1980,29.5.1981). (alternative synthes~s given). Formulation(s): tabl. 10 mg, 20 mg; sol. 0.1% Trade Namefs): D: Bambec (Astra) Bamethan (Butylnorsynephrine; Butyloctopamine) ATC: C04AA31 Use: sympathomimetic, vasodilator RN: 3703-79-5 MF: C,,Hl,N02 MW: 209.29 EINECS: 223-043-9 LD,,,: 72 mgkg (M, i.v.); 562 mglkg (M, p.0.); 80 mgkg (R, i.v.) CN: a-[(butylamino)methyl]-4-hydroxybenzenemethanol sulfate (2:l) RN: 5716-20-1 MF: CI2Hl9NO2. 1/2H2S04 MW: 516.66 EINECS: 227-214-9 LD,,: 72 mgkg (M, i.v.); 1600 mglkg (M, p.0.); >I500 mgkg (R, p.0.) Bamifylline B 177 benzoyl 4'- hydroxy- 4'-benzoyloxy- chloride ocetophenone acetophenone butylornine N-(4-benzoyloxy- phenocyl)butylomine 4-benzoyloxy- phenocyl bromide (1) Corrigan, J.R. et al.: J. Am. Chem. Soc. (JACSAT) 67, 1894 (1945). D: Emasex (Eurim Pharma)- comb. Heweven (Hevert) Medigel (Medice)-comb. Theo-Hexanicit (Astral Promed) Vasoforte N Kapseln (Krugmann) F: Escinogel (Doms-Adrian)- comb. GB: Vasculit (Boehringer Ing.); wfm I: Vasculat (Boehringer Ing.; as sulfate) J: Bloodbin (Nakataki) Butibatol (Hishiyama) Butosin (Kobayashi) Cyclate (Hokuriku) Garmin (Fuso) . Pan Line (Maruishi) Pericardin (Santen- Yamanouchi) Simpelate (Seiko Eiyo) Valtolmin (Sanwa) Vasculat (Tanabe; as sulfate) Vasolat (Kanto) Vasolen (Toho) Vasstol (Nichiiko) Yonomol A (Sawai) Bamifylline ATC: R03BA; R03DA08 Use: bronchodilator, coronary vasodilator RN: 2016-63-9 MF: C,,H,,N,O, MW: 385.47 CN: 7-[2-[ethyl(2-hydroxyethyl)aminolethyl]-3,7-dihydro-1,3-dimethyl-8-(phenylmethyl)-1H-purine-2,6~ dione monohydrochloride RN: 20684-06-4 MF: C,,H,N,O, . HCl MW: 421.93 EINECS: 243-967-6 178 B Bamipine Reference(s): BE 602 888 (A. Christiaens S.A.; appl. 21.4.1961; GB-prior. 22.4.1960). ethanol Fonnulation(s): inj. sol. 300 mgf5 ml; suppos. 250 mg, 750 mg; tabl. 300 mg Barnifylline Trade Name(s): D: Trentadil (Fresenius); wfm Trentadil injectable (Evans I: Bamifix (Chiesi) F: Trentadil (Evans Medical) Medical) Briafil (Alfa Wassermann) Trentadil (Scdaph); wfm GB: Trentadil (Armour); wfm Bamipine ATC: D04AA 15; R06AXO I Use: antihistaminic RN: 4945-47-5 MF: C,,H2,N2 MW: 280.42 EINECS: 225-587-2 LD,,: 250 mglkg (M, p.0.) CN: l-methyl-N-phenyl-N-(phenylmethyl)-4-piperidinamine monohydrochloride RN: 1229-69-2 MF: C,,H,N,. HCI MW: 316.88 LD,,: 60 mgkg (M, i.v.); 750 mglkg (M, p.0.); 460 mgkg (R, p.0.); 189 mglkg (dog, p.0.) lactate (1:l) RN: 61670-09-5 MF: C,,H2,N,. C,H,O, MW: 370.49 aniline 1 -methyl- 1-methyl-4- 4-piperidone phenylimino- piperidine CH3 I + 1. sodium amide 2. benzyl chloride EINECS: 262-887-2 1 -methyl-4-anilino- piperidine (I) Reference(s): US 2 683 714 (Knoll AG; 1954; D-prior. 1949). Barbexaclone B 179 Formulation(s): cream 20 mg; drg. 20 mg; f. c. tabl. 50 mg; gel 20 mg Trade Nameis): D: Bamipin (ratiopharm) F: Taumidrine (Knoll); wfm Soventol (Knoll) I: Soventol (Knoll); wfm Barbexaclone ATC: N03AA04 Use: antiepileptic RN: 4388-82-3 MF: C,2H,2N203 MW: 232.24 EINECS: 224-504-7 LD,,: 334 mg/kg (M, p.0.); 306 mg/kg (R, pa) CN: 5-ethyl-5-phenyl-2,4,6(1H,3H,SH)-pyrimidinetrione, compd. with (9-N,a- dimethylcyclohexaneethanamine (1: I) Reference (s): DE 1 120 452 (Knoll; appl. 16.4.1960) phenaborbitol (-)-propylhexedrine Formulation(s): drg. 100 mg, 25 mg Barbexaclone Trade Nurne(s): D: Maliasin (Knoll) I: Maliasin (Ravizza) (4. v.) (9. v.1 Barbital ATC: N05CA04 Use: hypnotic RN: 57-44-3 MF: C8HI2N2O3 MW: 184.20 EINECS: 200-331-2 LD,,: 600 mg/kg (M, pa) CN: 5,5-diethyl-2,4,6(1H,3H,5H)-pyrimidinetrione monosodium salt RN: 144-02-5 MF: C,H,,N,Na03 MW: 206.18 EINECS: 205-613-9 LD,,: 830 mglkg (M, i.v.); 800 mglkg (M, p.0.); 280 mglkg (R, i.v.1; 600 mglkg (R, p.0.) diethyl diethylrnolonate urea 1 Barbitol I Reference(s): Fischer; Dilthey: Justus Liebigs Ann. Chem. (JLACBF) 335,338 (1904). 180 B Barnidipine Formulation(s): tabl. 250 mg, 500 mg Trade Name(s): D: Barbimetten (Hormosan); F: combination preparations; 1: Barbitt (Tariff. Integrative) wfm wfm Veronidia (Vaillant); wfm Barnidipine (Mepirodipine hydrochloride) ATC: C08CA12 Use: antihypertensive agent, long active calcium antagonist RN: 104757-53-1 MF: C2,H2,N,0, . HC1 MW: 528.01 CN: [S-(R* ,R*)]-l,4-Dihydro-2,6-dimethyl-4-(3-nitropheny~boxyic acid methyl 1 - (phenylmethy1)-3-pyrrolidinyl ester hydrochloride free base RN: 104713-75-9 MF: C2,H2,N,0, MW: 491.54 racemate RN: 71863-55-3 MF: C2,H2,N,0, MW: 491.54 HO*,,, COOH CCOOH L-molic acid OvCH3 I .H2N 9 2. LiAlH THF a 1. benzylamine 2. lithium oluminum hydride o7 9 CH,COONo, 80°C + U diketene (3s)-1 -benzyl-3- hydroxypyrrolidine (I) 2. methyl 3-aminocrotonote (IV) 2. N 3. hydrolysis _____+ 1, tert-butyl acetoocetote m-nitro- benzoldehyde (111) Bornidipine . penicillin) RN: 5097 2-1 7-3 MF: CzIHz7N,07S MW: 465.53 CN: [2S-[2a,5a,6~(S*)] ]-6 -[ (aminophenylacetyl)a~no ]-3 , 3-~ methyl-7-oxo-4-thia-l- azabicyclo[3.2.0]heptane-2-carboxylic acid 1 -[ (ethoxycarbonyl)oxy]ethyl. RN: 201 6-6 3-9 MF: C,,H,,N,O, MW: 385.47 CN: 7-[ 2-[ ethyl(2-hydroxyethyl)aminolethyl ]-3 ,7-dihydro-1,3-dimethyl- 8-( phenylmethyl )-1 H-purine-2,6~ dione monohydrochloride RN: 2068 4-0 6-4 MF:. antihistaminic RN: 494 5-4 7-5 MF: C,,H2,N2 MW: 280.42 EINECS: 22 5-5 8 7-2 LD,,: 250 mglkg (M, p.0.) CN: l-methyl-N-phenyl-N-(phenylmethyl )-4 -piperidinamine monohydrochloride RN: 122 9-6 9-2 MF: C,,H,N,.