Pharmaceutical Substances Syntheses, Patents, Applications - Part 153 ppsx

Oxitefonium bromide 0 1521 Oxitefonium bromide ATC: A03AB LJse: anticholinergic, antispasmodic RN: 17692-63-6 MF: C,,H,,BrN03S MW: 428.39 EINECS: 241-688-4 LD,,,: 27.5 mglkg (M, i.v.); 1050 mglkg (M, p.0.) CN: N,N-diethyl-2-[(hydroxyphenyl-2-thienylacetyl)oxy]-N-methylethanaminium bromide 0 AICIJ 0 0 phenylmognesium thiophene ethoxolyl chloride bromide 2-thicnylglyoxylic ocid ethyl ester rc 1 H3CvNJH, * 11 2-diethylamino- ethyl chloride a-hydroxy-a-phcnyl-2- a-hydroxy-a-phenyl-2- thiopheneacetic acid thiopheneocetic acid ethyl ester (I) a-hydroxy-a-phenyl-2-thiophene- methyl acetic ocid 2-diethylamina- bromide ethyl ester (11) I Oxitefoniurn bromide I Reference (s): US 2 541 024 (F. F. Blicke; 1951; prior. 1946). Blicke, F.F.; Tsao, M.U.: J. Am. hem. Soc. (JACSAT) 66, 1645 (1944). Trade Name(s): F: Bismutran (1SH)-comb.; Nihitor (ISH); wfm wfm VedrCnan (1SH)-comb.; wfm Oxitriptan (5-Hydroxy-L-tryptophan; Oxytriptanum) ATC: N06AB Use: antidepressant (psy siological serotonin precursor) RN: 4350-09-8 MF: C,,H,,N,O, MW: 220.23 EINECS: 224-41 1-1 LD,: 375 mglkg (M, i.v.); 1708 mgikg (M, p.0.); 27 mgkg (R, i.v.); 243 mgkg (R, p.0.) CN: 5-hydroxy-L-tryptophan 1522 0 Oxitriptan + o=c,, + FH3 dioxone. H~O HN, CH3 / N, '3'3 5-benzyloxyqromine (I) diethyl forrnomido- rnalonote 1. NoOH, H,O, A H 2. HCI COOH acrolein diethyl ocetornido- rnolanote Oxitriptan 0 1523 @ opticol resolution - benzyl (m) chloroforrnote 1. quinine 2. fraction01 crystollizotion of the quinine solts 3. HCI, extraction with ethyl ocetote VI I Oxitripton I @ microbiological oxidation of L-tryptophan q Bocillus subtilis (ATCC 21733) NH2 COOH L-tryptophan @ microbiological coupling with tryptophonose producing stroins Proteus rnorganii (IF0 3848) or - Erwinia herbicola (ATCC 21433) or CI NH~ Enterobacter cloacol (ATCC 7256) HO COOH Proteus rnorganii (IF0 3848) 01 Erwinia herbicola (ATCC 21433) or HO NH2 Enterobocter cloocol (ATCC 7256) VIII + '+ COOH Reference(s): a1 Ek, A,; Witkop, B.: J. Am. Chem. Soc. (JACSAT) 76,5579 (1954). preparation of 5-benzyloxyindole: Shaw, N.F. et al.: Biochem. Prep. (BIPRAP) 9, 12 (1962). a2 GB 845 034 (May & Baker; appl. 1957). b Morris, A.J.; Armstrong, M.D.: J. Org. Chem. (JOCEAH) 22, 306 (1957). c DOS 2 150 535 (Schering AG; appl. 6.10.197 1). d DE 2 461 188 (Ajinomoto; appl. 23.12.1974; J-prior. 29.12.1973). 1524 0 Oxitropium bromide alternative syntheses: DOS 2 15 1 088 (Kyowa Hakko; appl. 19.10.1971; J-prior. 26.10.1970). DAS 2 409 675 (Sagami; appl. 28.2.1974; J-prior. 1.3.1973). combination with benserazide: DOS 2 327 636 (Hoffmann-La Roche; appl. 30.5.1973; CH-prior. 30.6.1972). Formulatiorz(s): cps. 100 mg Trade Name(s): D: Levothym (Promonta F: LCvotonine (Panpharma) Tript-OH (Sigma-Tau) Lundbeck) I: Oxyfan (Coli) Oxitropium bromide ATC: R03BB02 Use: anticholinergic, antiasthmatic RN: 30286-75-0 MF: C19H,BrN0, MW: 412.32 EINECS: 250-113-6 LD,,: 25.7mglkg(M,i.v.); 1.6g/kg(M,p.o.); 19 mgkg (R, i.v.); 2.25 gkg (R, p.0.); 40 mgkg (dog, i.v.); 3 glkg (dog, p.0.) CN: [7(S)-(1a,2~,4~,5a,7~)]-9-ethyl-7-(3-hydroxy-1-oxo-2-phenylpropoxy)-9-methyl-3-oxa-9- azoniatricyclo[3.3.1 .02s4]nonane bromide H H (-)-scopolamine phosgene (4- 4 (1) methyl I Oxitropium bromide I bromide I Reference(s): US 3 472 861 (Boehringer Ing.; 19.1.1971; D-prior. 26.1.1966). DOS 1 670 048 (Boehringer Ing.; appl. 26.1.1966). DE 1 795 8 18 (Boehringer Ing.; prior. 26.1.1966). Formulation(s): doses aerosol 0.1 mg; cps. 0.1 mg; inhalation sol. 1.5 mg; powder cps.0.l mgl5 mg; sol. 1.5 mglml Trade Nnme(s): D: Ventilate (Boehringer Ing.; F: Tersigat (3M Santt; 1984) 1983) Oxolamine 0 1525 Oxolamine ATC: R05DB07 Use: antitussive RN: 959-14-8 MF: C14H19N30 MW: 245.33 EINECS: 213-493-4 LD,,: 679 mglkg (M, p.0.); >2 glkg (R, p.0.) CN: N, N-diethyl-3-phenyl- 1,2,4-oxadiazole-5-ethanamine citrate (1:l) RN: 1949-20-8 MF: C,,H,,N,O~ C,HBO, MW: 437.45 EINECS: 217-760-6 LDso: 650 mgfkg (M, p.0.); 1650 mglkg (R, p.0.) _____* diethylomine benzomidoxime 3-chloro- 0-(3-chloro-I-oxopr0pyl)- propionyl benzamidoxime chloride Oxolamine I Reference(s): DE 1 097 998 (Angelini Francesco; appl. 30.9.1959). Forrnulation(s): syrup 1 %; tabl. 100 mg Trade Name(s): F: Prilon (Cassenne); wfm Perebron 1-Ciclina Proxybron (Cassenne)- (Angelini) comb.; wfm Tussibron (Sella) I: Gantrimex (Geymonat)- J: Flogobron (Intersint) comb. Oxamin (Violani- Oxolcv (Barlocco) Perebron (Angelini) Tussibron (Sella) numerous combination preparations Gantrimex ad scir Farmavigor) (Angelini; as phosphate) Oxarmin (Daiichi) Oxolinic acid (Acide oxolinique) ATC: G04AB04 Use: chemotherapeutic (Proteus bacteria infections, gyrase inhibitor) RN: 14698-29-4 MF: CI3H,,NOs MW: 261.23 EINECS: 238-750-8 LD,,: 1890 mgkg (M, p.0.); 525 mg/kg (R, p.0.); > 1 glkg (dog, p.0.) CN: 5-ethyl-5,8-dihydro-8-oxo-l,3-dioxolo[4,5-g]quinoline-7-carboxylic acid 1.2-methylene- 3.4-methylenedioxy- dioxybenzene 1-nitrobenzene 3.4-methylane- diaxyaniline (I) 1526 0 Oxomemazine ethoxymethylenernalonic [(1,3-benzodioxal-5-ylamino)- acid diethyl ester rnethylene]malonic acid diethyl ester 0 OH 1. NaOH, DMF C0 b " H3cA' ' O 2. ethyl iodide 4-hydroxy-6.7-methylene- dioxyquinoline-3-carboxylic acid ethyl ester (n) Oxolinic acid I Reference(s): US 3 287 458 (Warner-Lambert; 22.11.1966; appl. 27.4.1966; prior. 12.12.1963). alternative synthesis: DAS 2 103 805 (Sumitomo; appl. 27.1.1971 ; J-prior. 28.1.1970, 18.2.1970, 23.2.1970,24.2.1970). Formulation(s): tabl. 0.75 g Trade Name(s). D: Nidantin (GodeckeISasse); Oxolina (Rorer); wfm Uroxol (Ausonia); wfm wfm Pelvis (Coli); wfm Uroxol mite (Ausonia); F: Urotrate (Parke Davis) Tilv~s (Scharper); wfm wfm GB: Prodoxol (Warner); wfm Tiurasin (Bouty) USA: Utibid (Warner); wfm I: Decme (Poli); wfin Uritrate (Parke Davis); wfm Ossian (Bioindustria); wfm Uroxin (Von Boch); wfm Oxomemazine ATC: R06AD08 Use: antiallergic, antipruritic, sedative RN: 3689-50-7 MF: C,uH22N202S MW: 330.45 EINECS: 222-996-8 LD,,,: 35 mg/kg(M,i.v.); 140mg/kg(M,p.o.) CN: N,N,P-trimethyl- 1 OH-phenothiazine-1 0-propanamine 5,s-dioxide monohydrochloride RN: 4784-40-1 MF: C,uH22N,02S . HC1 MW: 366.91 EINECS: 225-330-4 amide phenothiazine 3-dirnethylornino-2- 10-(3-dimethylamino-2- rnethylpropyl chloride rnethylpropyl)phenothiozine (I) Oxprenolol 0 1527 Oxomemozine Formulation(s): syrup 150 mgl150 ml; tabl. 10 mg Trade Name(s): D: Aplexil (RhBne-Pou1enc)- Imakol (RhBne-Poulenc); Toplexil (ThCrap1ix)-comb. comb.; wfm wfm J: Dysedon (Meiji) Imakol (Rhodia Pharma); F: Rectoplexil (Th6raplix)- wfm comb. Oxprenolol ATC: C07AA02 Use: beta blocking agent RN: 6452-71-7 MF: C15H,,N03 MW: 265.35 EINECS: 229-257-9 LD,,: 20mgkg(M, i.v.); 375 mglkg (M, p.0.) CN: 1-[(1-methylethyl)amino]-3-[2-(2-propenyloxy)phenoxy]-2-propanol hydrochloride RN: 6452-73-9 MF: CL5H2,N03 . HCI MW: 301.81 EINECS: 229-260-5 LD,,,: 20 mgkg (M, i.v.); 33 mgkg (R, i.v.); 214 mglkg (R, p.0.); 15 mgkg (dog, i.v.) 2-allyloxyphenol (1) epichloro- hydrin (11) isopropyl- Oxprenolol omine (1V) 1528 0 Oxybuprocaine Reference(s): DE 1 242 596 (Ciba; prior. 19.8.1965). US 3 483 221 (Ciba; 9.12.1969; CH-prior. 10.9.1964). CH 451 144 (Ciba; appl. 10.9.1964). CH 451 115 (Ciba; appl. 10.9.1964). CH 451 915 (Ciba; appl. 10.9.1964). GB 1 077 603 (Ciba; appl. 23.8.1965; CH-prior. 10.9.1964). Formulation(s): f. c. tabl. 20 mg, 40 mg, 80 mg, 160 mg (as hydrochloride) Trade Name(s): D: Trasicor (Novartis) Trasitensine (Novartis; as Trasicor (Ciba) numerous generics and hy droch1oride)-comb. Trasitensin Retard (Ciba)- combination preparations GB: Slow Trasicor (Novartis) comb. F: Trasicor (Novartis; 1975) Trasicor (Novartis; 1970) J: Trasacor (Ciba-Geigy- Trasipressol (Novartis; Trasidrex (Novartis Fama; . Takeda) 1977)-comb. 1978)-comb. USA: Trasicor (Ciba-Geigy); I: Tensilene (Caber)-comb. wfm Oxybuprocaine (Benoxinate) ATC: D04AB03; SO1 HA02 Use: local anesthetic RN: 99-43-4 MF: C,,H,N,O, MW: 308.42 LD,,: 7800 kg/kg (M, i.v.) CN: 4-amino-3-butoxybenzoic acid 2-(diethy1amino)ethyl ester monohydrochloride RN: 5987-82-6 MF: C,,H2,N20,. HCI MW. 344.88 EINECS: 227-808-8 LD,,: >6.8 mgkg (M, i.v.); >5.6 mglkg (R, i.v.) butyl bromide 3-hydroxy-4-nitro- 3-butyloxy-4-nitrobenzoic benzoic ocid ethyl acid ethyl ester ester Oxybutynin 0 1529 0-c~~ thionyl 0-c~~ 2-dieihylornino- NO, chloride NO, ethanol 3-butyloxy-4-nitro- 3-butyloxy-4-nitra- benzoic acid (1) benzayl chloride No, 3-buiyloxy-4-nitrobenloic ocid 2-diethylominoethyl ester (11) Oxybuprocaine Reference(s): GB 654 484 (Dr. A. Wander AG; appl. 1948; CH-prior. 1947). Formulation(s): eye drops 2 mg, 4 mg/ml; sol. 10 mglml (as hydrochloride) Trade Name(s): D: Benoxinat 0,4 % Thilo (Alcon) Conjuncain ED0 (Mann) Novesine (CIBA Vision) Novesine Wander (Novartis Pharma) Oxbarukain (Chauvin ankerpharm) Oxybutynin Thilorbin (Thi1o)-comb. Opulets Benoxinate F: Ctbksine (Chauvin-Blache) (Alcon) Novksine (Merck Sharp & I: Novesina (Novartis Farma) Dohme-Chibret) I: Benoxil (Santen) GB: Minims Benoxinate Lacrimin (Santen) (Chauvin; as Primacaine (Hori-Morita) hydrochloride) USA: I)orsacaine (Dorsey); wfm ATC: G04BD04 Use: anticholinergic, antispasmodic RN: 5633-20-5 MF: C22H3,N03 MW: 357.49 CN: a-cyclohexyl-a-hydroxybenzeneacetic acid 4-(diethylamino)-2-butynyl ester hydrochloride RN: 1508-65-2 MF: C,,H,,NO,. HCI MW: 393.96 EINECS: 216-139-7 LD,,: 42 mgkg (M, i.v.); 725 mglkg (M, p.0.); 61 mgkg (R, i.v.); 460 mgkg (R, p.0.); >400 mglkg (dog, p.0.) a-cyclohexylphenylglycalic poroform- diethylomine ocid propargyl ester oldehyde Oxybutynin I 1530 0 Oxycodone a-cyclohexylphenylglycolic 1 -acetoxy-4-diethylomino- ocid methyl ester 2-butyne Reference(s): GB 940 540 (Mead Johnson; appl. 25.7.196 1 ; USA-prior. 26.7.1960,20.6.1961). Fortnulation(s): syrup 2.5 mgI5 ml; tabl. 2.5 mg, 5 mg (as hydrochloride) Trade Name(s): F: Ditropan (Synthelabo) Di tropan (Lorex) USA: Ditropan (Hoechst Marion Dxiptane (Dtbat) I: Ditropan (Synthelabo) Roussel) GR: Cystrin (Pharrnacia & J: Pollakisu (Kodama) Upjohn) Oxycodone ATC: N02AA05 Use: analgesic RN: 76-42-6 MF: C18H2,N04 MW. 315.37 EINECS: 200-960-2 LD,,,: 320 mgkg (M, i.p.); 426 mglkg (M, s.c.) CN: (5a)-4,5-epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one hydrochloride RN: 124-90-3 MF: C,,H2,N04 , HC1 MW: 351.83 EINECS: 204-717-1 codeine 14-hydroxycodeinone Oxycodone Reference(s): Ehrhart-Ruschig I, 118. DRP 41 1 530 (E. Merck AG; 1925). controlled release composition: US 5 266 331 (Euroceltique; 30.1 1.1993; appl. 27. Formulution(s): cps. 5 mg; s. r. tabl. 10 mg, 20 mg, 40 mg, 80 rng Trade Name(s): D: Eubine (Chemipharm); Scophedal (Merck)-comb.; GB: Proladone (Boots); wfm wfm wfm Eukodal (Merck); wfm F: Eubine (Promedica) . CN: [7(S )-( 1a,2~,4~,5a,7~) ]-9 -ethyl- 7-( 3-hydroxy-1-oxo-2-phenylpropoxy )-9 -methyl-3-oxa- 9- azoniatricyclo[3.3.1 .02s4]nonane bromide H H (-) -scopolamine phosgene ( 4- 4 (1) methyl I Oxitropium. 1469 8-2 9-4 MF: CI3H,,NOs MW: 261.23 EINECS: 23 8-7 5 0-8 LD,,: 1890 mgkg (M, p.0.); 525 mg/kg (R, p.0.); > 1 glkg (dog, p.0.) CN: 5-ethyl-5,8-dihydro-8-oxo-l,3-dioxolo[4,5-g]quinoline-7-carboxylic. analgesic RN: 7 6-4 2-6 MF: C18H2,N04 MW. 315.37 EINECS: 20 0-9 6 0-2 LD,,,: 320 mgkg (M, i.p.); 426 mglkg (M, s.c.) CN: (5a )-4 ,5-epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one hydrochloride