Pharmaceutical Substances Syntheses, Patents, Applications - Part 151 pptx

Ornipressin 0 1501 Ornipressin ATC: HOIBAOS (Omipresina; Orpressin) IJse: vasoconstrictor RN: 3397-23-7 MF: C,,H,,N,,0,2S, MW: 1042.21 EINECS: 222-253-8 CN: 8-L-ornithinevasopressin TY~ Phe 7 8 9 Z OH H Tos Z Tos Z Glu Pro Om G IY R Tos: -2G~~3 0 NP: Ornipressin FR 1 396 607 (Sandoz; appl. 3.4.1964; CH-prior. 5.4.1963). Huguenin, R.L.; Boissonnas, R.A.: Helv. Chim. Acta (HCACAV) 46, 1669 (1963). Bodanszky, M. et al.: J. Am. Chem. Soc. (JACSAT) 86,4452 (1964). 1502 0 Orotic acid Formulation(s): amp. 2.5 iu10.5 ml, 2.5 iu/5 ml Trade Name(s): D: Por 8 Sandoz (Novartis Pharma) Orotic acid (Acide orotique) ATC: A14B Use: metabolic therapeutic, electrolyte carrier RN: 65-86-1 MF: C,H,N204 MW: 156.10 EINECS: 200-619-8 LD,,,: 770mg/kg(M, i.v.);2g/kg (M.p.0.) CN: 1,2,3,6-tetrahydro-2,6-dioxo-4-pyrimidinecarboxylic acid potassium salt RN: 24598-73-0 MF: C,H3KN204 MW: 194.19 EINECS: 246-341-0 LD,,,: 10.9 g/kg (R, p.0.) magnesium salt RN: 34717-03-8 MF: C,,H,MgN40R MW: 334.48 zinc salt RN: 60388-02-5 MF: C,,H,N,O,Zn MW: 375.57 EINECS: 262-207-4 choline orotate RN: 24381-49-5 MF: CSH,,NO . CSH3N204 MW: 259.26 EINECS: 246-213-4 L-lysine orotate KN: 28003-86-3 MF: C,H,,N2O2. C,H4N204 MW: 302.29 EINECS: 248-771-4 diketene (1) y-chlorooceto- ocetyl chloride I Orotic ocid I 1. OHC-COOH . NoOH 0 2. HCI H$J+-CN + NoOCN d H2NKN*cN H 1. glyoxylic acid ominoaceto- sodium cyon0te hydantoic acid nitrile nitrile Orotic acid 0 1503 H Orotic acid HOOC 0 COOH rnaleic acid rnonoureide 5-brornodihydro- orotic ocid 11 , CH3COOH H trichloroocetyl 0 0 chloride cc13 acetyl chloride uracil (N) Reference(s): a DAS 1 770 117 (Diamalt; appl. 2.4.1968). DAS 2 025 247 (Lonza; appl. 23.5.1970; CH-prior. 28.5.1969). b DAS 2 502 951 (Diamalt; appl. 24.1.1975). US 4 113 950 (Diamalt; 12.9.1978; D-prior. 24.1.1975). c CH 595 351 (Lonza; appl. 7.5.1975). d US 4 064 126 (Lonza; 20.1 2.1977; CH-prior. 1 1.8.1975). DOS 2 540 275 (Lonza; appl. 24.2.1977; CH-prior. 11.8.1975). alternative syntheses: jbm oxalacetic acid ester and urea: Miiller: J. Prakt. Chem. (JPCEAO) 56, 488 (1897). Behrend: Justus Liebigs Ann. Chem. (JLACBF) 378, 165 (1910). US 2 937 175 (RhBne-Poulenc; 17.5.1960; F-prior. 18.1.1956). DE 1 034 640 (RhBne-Poulenc; appl. 1956). from aspartic acid: Nye, F. et al.: J. Am. Chem. Soc. (JACSAT) 69, 1382 (1947). from glyoxylic acid and hydantoin: US 4062 847 (Diamalt; 13.12.1977; D-prior. 24.1.1975). fermentatively: US 3 086 917 (Kyowa Hakko; 23.4.1963; J-prior. 15.6.1960). lithium orotate: DOS 2 410 181 (Nadrol-Chemie; appl. 4.3.1974). Formulation(s): cps. 250 mg (as hydrochloride); cps. 60 mg in comb. with a-tocopherol acetate; tabl. 20 mg (as zinc salt), 40 mg (as zinc salt), 500 mg (as choline orotate) Trade Narne(s): D: Vigodana N (Loges)-comb. numerous combination Orolyl (Porcher-Lavril); Zinkorotat (Nadrol; as zinc preparations wfm salt) F: Lysortine (Thiraplix; as I: Oro B,, (Ripari-Gero)- Zinkorotat (Ursapharm; as lysine orotate); wfm comb. zinc salt) Oroturic (GrCmy-Longuet); J: Orodine (Takeda) wfm Orosan (Maruishi) 1504 0 Orphenadrine Orotics (Nippon Shinyaku) Orotopin (Fuso) Orotonsan (Ono) Urabon (Nissin) Vita-thirteen (Sumitomo) generic Orphenadrine ATC: M03BCOl; N04AB02 Use: antiparkinsonian, muscle relaxant RN: 83-98-7 MF: ClnH2,N0 MW: 269.39 EINECS: 201-509-2 LD,,,: 33 mgkg(M,i.v.); 125mg/kg(M,p.o.) CN: N,N-dimethyl-2-[(2-methylphenyl)phenylmethoxy]ethanamine hydrochloride RN: 341-69-5 MF: C,,H2,N0 . HCI MW: 305.85 EINECS: 206-435-4 LD,,,: 20 mgkg (M, i.v.); 100 mglkg (M, p.0.); 27.5 mglkg (R, i.v.); 255 mgkg (R, p.0.) citrate (1:l) RN: 4682-36-4 MF: ClnH2,N0 . C,HnO, MW: 461.51 EINECS: 225-1 37-5 2-methylbenzhydryl Z-dimethylamino- chloride ethanol Orphenadrine Reference(s): US 2 567 351 (Parke Davis; 1951; prior. 1946). US 2 991 225 (~rocades-~theema;; 4.7.1961; NL-prior. 1952). Bijlsma, U.G. et al.: Arzneim Forsch. (ARZNAD) 5,72 (1955). Formulation(s): amp. 60 mgl2 ml; s. r. tabl. 100 mg; tabl. 100 mg (as citrate) Trade Name(s): D: Norflex (3M Medica) GB: Biorphen (Bioglan; as J: Delenar (Schering- Norgesic (3M Medica)- hydrochloride) Shionogi)-comb. comb. Dis~pal (Yamanouchi; as USA: Norflex (3M; as citrate) F: Disipal (Beytout); wfm hydrochloride) Norgesic (3M; as citrate) Estomul (Jean Roy- I: Disipal (Yamanouchi) Freyssinge)-comb.; wfm Oseltamivir (GS 4104) ATC: JOlAH02 Use: antiviral, anti-influenza, neuramidase inhibitor RN: 196618-13-0 MF: C,,H2,N204 MW: 312.41 CN: (3R,4R,5S)-4-(Acetylamin0)-5-amino-3-(1 -ethylpropoxy)-1 -cyclohexene- 1-carboxylic acid ethyl ester phosphate RN: 2042.55-1 1-8 MF: C,,H2,N2O4 . H304P MW: 410.40 hydrochloride RN: 204255-09-4 MF: Cl,H2nN204 . HCI MW: 348.87 citrate RN: 209965-30-0 MF: C,,H2,N204. C,HRO, MW: 504.53 Oseltamivir 0 1505 HO COOH QOH + H3C-0 0-CH3 Tos-OH, ocetone HO."' X ____, OH H3C CH3 p-toluenesulfonic ocid (-)-quinic acid 2.2-dirnethoxy- propone 3.4-0-isopropylidene- 1,5-quinic loctone (I) SO2CI2. -20°C. pyridine. CH2CI2 - 11 sulfuryl chloride acid 0 ethyl 3.4-0-isopropylidene- 3-pentonone (111) ethyl 3.4-0-(1 -ethylpropylidene)- 5-0-(methonesuIfonyl)- shikimate (11) 5-0-(methonesulfonyl)- shikimate (N) FHl R s 1~~3~-~-~-~-~~3 BF~ n3c/ 'cn3 CH, 0 2. KHC03. aq. C2H50H 1v 1. trimethylsilyl triflote ethyl (3R,4R,5S)-4.5- epoxy-3-(1 -ethylpropoxy)- 1 -cyclohexene- 1 -corboxylote (V) 1. sodium ozide I 2. triphenylphosphine 1. NoN3, NH,CI. DMF 2. 0 0 H3cJ-oKcH3 , 2. ocetic anhydride 0 0,CH3 1. Hz. Roney-Ni. C2HSOH Aoc:H3 2. 8% H3PO+ , N3 1506 0 Otilonium bromide H~C-OH. SOCIZ, A H3C CH3 ___* H3C-0~0-CH3 H 0'" - ,,o.P\ OH 2.2-dimethoxy- 0 H OH propane (-)-shikimic ocid ethyl shikirnate ethyl 3.4-0- isopropylidene- shikirnote (VII) R H3C-S-CI , TEA 11 0 cryst. CH30H Ill. F3C-S03H Vll b 11 -b V -+ trifluoromethone- - sulfonic ocid Reference(s): a RohlofP, J.C. et al.: J. Org. Chem. (JOCEAH) 63, 4545-4550 (1998) WO 9 626 933 (Gilead Sciences; appl. 26.2.1996; USA-prior. 27.2.1995) US 5 886 213 (Gilead Sciences; 23.3.1999; USA-prior. 22.8.1997) US 5 859 284 (Gilead Sciences; 12.1.1999; USA-prior. 23.8.1996) b Federspiel, M. et al.: Org. Process Res. Dev. (OPRDFK) 3 (4). 266-274 (1999) Tmde Nurne(s): CH: Tami flu (Roche; 1999) Otilonium bromide ATC: A03AB06 Use: antispasmodic RN: 26095-59-0 MF: C2,H,,BrN20, MW: 563.58 EINECS: 247-457-4 LD,,,: 46.5 mglkg (M, i.v.); >I 500 mglkg (M, p.0.); 14.1 mg/kg (R, iv.); >I650 mglkg (R, p.0.) CN: N,N-diethyl-N-methyl-2-[[4-[[2-(octyloxy)benzoyl]amino~benzoyl]oxy]ethanam1nium bromide diaxone, pyridine -1 NH2 2-octyloxybenzoyl 4-ominobenzoic chloride acid 4-(2-octyloxybenzoyl- ornino)benzoic acid (I) 4-(2-octyloxybenzoylornino)- benzoyl chloride Oxaceprol 0 1507 methyl bromide Otilonium bromide Reference(s): DOS 1 643 458 (Menarini; appl. 15.9.1967; I-prior. 17.9.1966). US 3 536 723 (Menarini; 27.10.1970; I-prior. 27.9.1966). Ghelardoni, M. et a].: J. Med. Chem. (JMCMAR) 16, 1063 (1973). Formulation(s): amp. 150 mg; drg. 40 mg; suppos. 20 mg; tabl. 40 mg Trade Narne(s): 1: Spasen (Firma) Spasmomen (Menarini) Spasen Somatico (Firma)- Spasmomen Somatico comb. (Menarini)-comh. Oxaceprol ATC: D 1 I AXO~; MO I ~~24 (Aceprolinum; N-Acetyl-4-hydroxy-L-proline) Use: connective tissue therapcutic, antirheumatic RN: 33996-33-7 MF: C,H, ,NO, MW: 173.17 EINECS: 25 1-780-6 CN: trans- 1-acetyl-4-hydroxy-L-proline trans-L-hydroxy- ocetic anhydride proline H CH,COOH D coo, H C 0 CH, + 3KK + HO 0 0- Oxaceprol u 0 CH, ?- HO Reference(s): GB 1 246 141 (P. and B. Coirre; appl. 30.8.1968; F-prior. 14.9.1967, 16.5.1968). DAS 1 795 327 (S.A.R.L. Franco-Chimie; appl. 13.9.1968; F-prior. 14.9.1967, 16.5.1968). DOS 2 139 476 (P. and B. Coirre; appl. 6.8.1971). For~nulation(s): f. c. tabl. 200 mg Trade Narne(s): D: AHP 200 (Chephasaar) F: Jonctum (Marion Merrell) 1508 0 Oxacillin Oxacillin ATC: JOlCFO4 Use: antibiotic RN: 66-79-5 MF: ClYH,yN3O5S MW: 401.44 EINECS: 200-635-5 LD,,,: 1490 mgkg (M, i.v.); 6500 mgkg (M, p.0.) CN: [2S-(2~,5~,6~)]-3,3-dimethyl-6-[[(5-methyl-3-phenyl-4-isoxazolyl)carbonyl]amino]-7-oxo-4-thia-1- azabicyclo[3.2.0]heptane-2-carboxylic acid monosodium salt monohydrate RN: 7240-38-2 MF: C,yHIRN3Na0,S . H20 MW: 441.44 benzoldehyde benzoldoxime benzhydroxirnic acid chloride (I) aceloacetic mid ethyl 5-methyl-3-phenyl- 5-methyl-3-phenylisoxo- ethyl ester isoxorale-4-corbaxylate zale-4-carbaxylic acid (Il) 11 thionyl chloride 5-methyl-3-phenyl- isoxazole-4-carbonyl chloride Oxacillin Refermce(s): US 2 996 501 (Beecham; 15.8.1961; GB-prior. 31.3.1960). GB 905 778 (Beecham; appl. 3 1.3.1960; valid from 14.3.1961). GB 958 478 (Beecham; appl. 28.2.1963: USA-prior. 13.3.1962). Formularion(s): cps. 250 mg, 500 mg; vial 0.5 g, 1 g (as sodium salt) Trade Name( s): D: Optocillin (Bayer Vital)- I: Penstapho (Bristol-Myers Oxacillin (Teva) comb. Squibb) Prostaphlin (Bristol); wfm Stapenor (Bayer Vital) J: Staphcillin V (Banyu) F: Bristopen (Bristol-Myers USA: Bactocill (Beecham- Squibb) Massengill); wfm Oxa flozane ATC: N06AX10 Use: antidepressant RN: 26629-87-8 MF: C14H,RF3N0 MW: 273.30 EINECS: 247-855-8 CN: 4-(1-methylethyl)-2-[3-(trifluoromethyl)phenyl]morpholine Oxaflumazine 0 1509 hydrochloride RN: 26629-86-7 MF: C,,H,,F,NO . HCI MW: 309.76 EINECS: 247-854-2 LD,,: 80 mglkg (M, i.v.); 365 mglkg (M, p.0.) CI+O*% bromine 2-chloroethyl vinyl ether 1 -brorno-2-(2-chloro- ethoxy)-2-(3-trifluoro- rnethylpheny1)ethone (I) phenylrnognesiurn (2-ch1oroethoxy)- bromide 1.2-dibrornoethone toluene, A isopropylarnine ( Oxoflozane DOS 1 910 477 (CERM; appl. 1.3.1969; F-prior. 4.3.1968, 29.5.1968 18.6.1968,27.8.1968, 15.1 1.1968, 19.2.1969). US3637680(CERM; 25.1.1972;F-prior.4.3.1968,29.5.1968, 18.6.1968,27.8.1968, 15.11.1968, 19.2.1969). Busch, N. et a].: Eur. J. Med. Chem Chim. Ther. (EJMCAS) 11, 201 (1976). Formulation(s): drops 2 % Trade Narnefs): F: Conflictan (Solvay Pharma) I: Conflictan (Riom); wfm Oxaflumazine ATC: NOSAB Use: psychosedative RN: 16498-21-8 MF: C26H32F3N302S MW: 507.62 CN: 10-[3-[4-[2-(1,3-dioxan-2-yl)ethyl]-l-piperazinyl]propyl]-2-(trifluoromethyl)-1OH-phenothiazine hydrogen succinate (1:l) RN: 41761-40-4 MF: C26H32F,N,02S . C4H604 MW: 625.71 10-(3-pipera2inopropyl)- 2-(2-chloroethy1)- 2-trifluorornethyl- 1,3-dioxone phenothiozine (from acrolein, 1.3- (cf. fluphenozine propanediol ond HCI) synthesis) 1510 0 Oxaliplatin Reference(s): DAS 1 620 281 (Roussel-Uclaf; appl. 28.6.1965; F-prior. 29.6.1964,28.9.1964). Ratouis, R.; Boissier, J.R.: Bull. Soc. Chim. Fr. (BSCFAS) 1966, 2963. alternative synthesis: DOS 19 11 719 (S.I.F.A.; appl. 7.3.1969; F-prior. 8.3.1968). Trade Narne(s): F: Oxaflumine (Diamant); wfm Oxaliplatin (I -0HP; NSC-266046; RP-54780) ATC: LOlXA03 Use: antitumor RN: 61825-94-3 MF: C,H14N,04Pt MW: 397.29 LD,,,: 19.8 mg/kg (M, i.p.); 14.3-15.6 mglkg (R, i.p.) CN: [SP-4-2-(1R-trans)~(1,2-cyclohexanediamine-N,hr)[ethanedioato(2-)-O,O']platinum 1 (R),P(R)-di- aminocyclohexone Oxaliplatin Reference(s): Kidani, Y. et al.: J. Clin. Hematol. Oncol. (JCHODP) 7, 197 (1977). JP 53 03 1 648 (Kidani; appl. 25.3.1978; J-prior. 6.9.1976). JP 09 132 583 (Tanaku Kihinzobo Kogyo; appl. 20.5.1997; J-prior. 10.11.1995). as stable aqueous formulation: WO 9 604 904 (Dehiopharm SA; appl. 22.2.1996; CH-prior. 8.8.1994). in combination with cisplatin: WO 9 412 193 (Debiopharm SA; appl. 9.6.1994; CH-prior. 24.1 1.1992). Formulation(s): vial 50 mg, 100 mg Trade Narne(s): F: Eloxatin (Sanofi Winthrop) Transplatin (Debiopharm) Oxametacin ATC: MOIAB13 Use: anti-inflammatory, analgesic RN: 27035-30-9 MF: C,,H1,CIN,O, MW: 372.81 EINECS: 248-179-6 LD,,,: 92 mglkg (M, p.0.); 78 mglkg (R, p.0.) CN: 1-(4-chlorobenzoyl)-N-hydroxy-5-methoxy-2-methyl-1H-indole-3-acetamide . mid ethyl 5-methyl-3-phenyl- 5-methyl-3-phenylisoxo- ethyl ester isoxorale-4-corbaxylate zale-4-carbaxylic acid (Il) 11 thionyl chloride 5-methyl-3-phenyl- isoxazole-4-carbonyl chloride. 1649 8-2 1-8 MF: C26H32F3N302S MW: 507.62 CN: 1 0-[ 3-[ 4-[ 2-( 1,3-dioxan-2-yl)ethyl]-l-piperazinyl]propyl ]-2 -( trifluoromethyl )-1 OH-phenothiazine hydrogen succinate (1:l) RN: 4176 1-4 0-4 MF:. RN: 2703 5-3 0-9 MF: C,,H1,CIN,O, MW: 372.81 EINECS: 24 8-1 7 9-6 LD,,,: 92 mglkg (M, p.0.); 78 mglkg (R, p.0.) CN: 1-( 4-chlorobenzoyl)-N-hydroxy-5-methoxy-2-methyl-1H-indole-3-acetamide