Pharmaceutical Substances Syntheses, Patents, Applications - Part 138 docx

Moxestrol M 1371 3,4-dirnethoxy- 1 -nitro- benzoldehyde propane 1 -(3,4-dirnethoxy- phenyl)-2-nitro- 1 -butanal (I) . pyridine Zn, HCOOH 1 - H3C-0*CH3 0 H3C-0 - 11 phenylacetyl OH chloride 2-ornino-1-(3.4- dirnethoxypheny1)- 1 -butanal POC13, xylene A OH (11) 1 Moxoverine Reference (s): GB 1 030 022 (Orgamol; appl. 7.5.1963; CH-prior. 16.6.1962). Formulation(s): amp. 150 mgI5 ml; drg. 100 mg, 150 mg (as hydrochloride) Trade Name(s): D: Certonal (Serturner) Kallaterol (Ursapharm)- Kollateral (Ursapharm) comb. I: Eupaverina (Bracco); wfm Moxestrol ATC: G03CB04 Use: estrogen RN: 34816-55-2 MF: C,,H,O, MW: 326.44 CN: (1 1~,17a)-ll-methoxy-l9-norpregna-l,3,5(10)-trien-20-yne-3,17-diol 3,17-dioxo-l lp- hydroxy-4.9- estrodiene 1372 M Moxifloxacin hydrochloride CH3 H i( + acetylene, HO ' potassium tert- (1) amylote I Moxestrol I Reference(s): US 3 579 545 (Roussel-Uclaf; 18.5.197 1; F-prior. 7.9.1966,9.12.1966, 28.2.1967, 9.3.1967). FR-M 6 182 (Roussel-Uclaf; appl. 28.2.1967). Azadian-Boulanger, G.; Bertin, D.: Chim. Ther. (CHTPBA) 8,451 (1973). sturting muteriul: Joly, R. et al.: C. R. Seances Acad. Sci., Ser. C (CHDCAQ) 258, 5669 (1964) (total synthesis). Formulution(s): tabl. 50 ~g Trude Nume(s): F: Surestryl (Roussel-Uclaf) Moxifloxacin hydrochloride (Bay-12-8039) ATC: JOlMA14 Use: fluoroquinolone antibacterial RN: 186826-86-8 MF: C2,H2,FN3O4. HC1 MW: 437.90 CN: 1-Cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-[(4~,7~-octahydro-6H-pyrrolo[3,4-b]pyridin-6-y1]- 4-0x0-3-quinolinecarboxylic acid base RN: 151096-09-2 MF: CZlH,FN,O4 MW: 401.44 pyridine-2.3- dicarboxylic ocid 1. L-(+)-tartaric acid. DMF 2. crystallization 3. (mother liquors), NoOH 1. HZ. Pd-C H 4. D-(-)-tartaric acid (crystallization) 5. NaOH (S.S)-u Moxifloxacin hydrochloride M 1373 2,4,5-trifluoro- potassium monoethyl 3-methoxybenzoyl moionote chloride (IV) ethyl 2-(2.4.5-trifluoro- 3-methoxybenzoyl)acetote (V) /CH3 0 - Y v + NH2 , vl cyclopropyl- 0 0 amine triethyl orthoformote 1. NoF, DMF '0 y 1. 111. base 2. H+ 2. HCI vCH3 F COOH 0 0 0 1 -cyclopropyl-6,7- difluoro-8-methoxy- 4-0x0-1.4-dihydro- quinoline-3-corboxylic acid H N \ I I COOH 0 Moxifloxocin hydrochloride @ synthesis of IV pentofluoro- benzonitrile 1. CH3COOH. H2S0,. KCN 2. H2S0, 3. SOCI?. benzene VI1 ___* 1374 M Moxisylyte DMF, acetonitrile, Fa + ,I1 diozobicyclo[2.2.2]actone b VIU F COOH 0 1 -cyclopropyl-6,7,8- trifluaro-1.4-dihydro- 4-0x0-3-quinoline- carboxylic acid 1. H,C OH, THF. 2. HCI, H20 cH3 COOH 0 vnl \ Reference (s): a DE 4 208 792 (Bayer AG; appl. 19.3.1992; D-prior. 19.3.1992). aa EP 241 206 (Sankyo; appl. 31.3.1987; J-prior. 31.3.1986). b EP 550 903 (Bayer AG, appl. 28.12.1992; D-prior. 19.3.1992). DE 19 751 948 (Bayer AG; appl. 24.1 1.1997; D-pnor. 24.11.1997). formulution with controlled release of moxifloxacin: DE 19 546 249 (Bayer AG; appl. 12.12.1995; D-prior. 12.12.1995). Formulation(s): f. c. tabl. 400 mg Trade Name(s): D: Avalox (Bayer) Avelox (Bayer; 1999) Tovan (Bayer AG) Moxisylyte ATC: C04AX10 Use: vasodilator (peripheral) (Thymoxamine) RN: 54-32-0 MF: C,,H,,NO, MW: 279.38 EINECS: 200-204-1 LDS,,: 225 mglkg (M, p.0.) CN: 4-[2-(dimethy1amino)ethoxy J-2-methyl-5-(1-methylethy1)phenol acetate (ester) hydrochloride RN: 964-52-3 MF: C,,H,SNO, .HCI MW: 315.84 EINECS: 213-519-4 LD,,,: 28 mgtkg (M, i.v.); 225 mg/kg (M, p.0.); 32 mgkg (R, i.v.); 740 mgkg (R, p.0.); 54.5 mgkg (dog, i.v.) NO H3C#CH3 NaN02, HCl , H3c#H3 n2S n3C 3 0 1 CH, ' H3C CH30H aceticu CH,OH CH30H onhydride (I) ihyrnol 4-nitroso- thymol *-amino- thymol Moxonidine M 1375 4-ocetamido- thymol (11) 1. NoOC,H, 2. CI-~/CHJ I CH3 2. 2-(dimethylomi- no)ethyl chloride NoNOz I pyridine H3C I I I Moxisylyte Rqference(s): DE 905 738 (Diwag; appl. 1943). combination with steroids (e. g. ,for treatment of asthma): . GB 1 535 531 (W. R. Warner & Co.; appl. 17.10.1975; valid from 15.10.1976). Forrnulation(s): drg. 30 mg; tabl. 30 mg, 40 mg, 60 mg, 120 mg (as hydrochloride) Trade Name(s): D: Vasoklin (Godecke); wfm Icavex (ASTA Medica) J: Moxyl (Fujirebio) F: Carly the (ASTA Medica) GB: Erecnos (Fournier) Thimozil (Kohjin) Erecnos (DCbat) I: Arlitene (ASTA Medica) Moxonidine (BDF-5895) ATC: CO2ACO5 Use: antihypertensive, presynaptic a,- adrenoceptor agonist RN: 75438-57-2 MF: C,H,,ClN5O MW: 241.68 LD,,,: 320 mglkg (M, p.0.); 115 mglkg (Rf, p.0.); 143 mglkg (Rm, p.0.) CN: 4-chloro-N-(4,5-dihydro-lH-imidazol-2-yl)-6-methoxy-2-methyl-5-pyrimidinamine 1. POC13, HNO, CH3 OACH , POCI, b 1 0 H CI I -ocetylimidazolidin- 2-one 2-methyl-5-nitro- 5-omino-2-methyl- 4.6-dihydroxy- 4.6-dichloro- pyrimidine pyrimidine 1376 M Mupirocin 0 N, CH, + CH3-ONa J. H CI 0 CH3 4.6-dichloro-2-methyl- 1 Moxonidine I 5-(1 -ocetyl-2-imidozolin- 2-ylamino)pyrirnidine (I) Reference(s): DOS 2 849 537 (Beiersdorf; appl. 15.1 1.1978). DOS 2 937 023 (Beiersdorf; appl. 13.9.1979). synthesis of 5 amino-2-methyl-4,6-dichloropyrimidine: Huber, W.; Holscher, H.A.: Chem. Ber. (CHBEAM) 71B, 87 (1938). Ochiai, E.; Kashida, Y.: Yakugaku Zasshi (YKKZAJ) 62,97 (1942). medical use for promoting growth: DOS 3 904 795 (Beiersdorf; appl. 17.2.1989). combination with hydrochlorothiazide, triamterene: EP 317 855 (Beiersdorf; appl. 12.1 1.1988; D-prior. 24.1 1.1987). Formularion(s): f. c. tabl. 0.2 mg, 0.3 mg, 0.4 mg Trade Name(s): D: Cynt (Beiersdorf-Lillyl Physiotens (Solvay F: Physiotens (Solvay Lilly; 1991) Arzneimittel; 1991) Pharma) GB: Physiotens (Solvay) Mupirocin (Pseudomonic acid) ATC: D06AX09; ROI AX06 Use: antibiotic RN: 12650-69-0 MF: C,6H,0, MW: 500.63 LD,,: 1638 mgkg (M, i.v.); 5 g/kg (M, p.0.); 1310 mglkg (R, i.v.); 5 glkg (R, p.0.) CN: [2S-[2u(E),3~,4~,5a[2R*,3R*(IR*,2R*)]]]r9-[[3-methyl-I-oxo-4-[tetrahydro-3,4-dihydroxy-5-[[3-(2- hydroxy- l-methylpropyl)oxiranyl]methyl]-2H-pyran-2-yl]-2-butenyl]oxy]nonanoic acid Mupirocin I Fermentation of Pseurlomonas~uorescens NCIB 10586. Reference(s): DE 2 227 739 (Beecham; GB-prior. 12.6.1971). US 3 977 943 (Beecham; 31.8.1976; appl. 7.7.1975; prior. 27.3.1974). US 4 071 536 (Beecham; 31.1.1978; prior. 12.6.1971). Fuller, A.T. et al.: Nature (London) (NATUAS) 234,416 (1971). structure: Chain, E.B. et al.: J. Chem. Soc., Chem. Commun. (JCCCAT) 20,847 (1974) Muzolimine M 1377 Formulation(s): cream 20 mglg; ointment 2 % (as calcium salt) Trade Name(s): D: Turixin (SmithKline GB: Bactroban (SmithKline J: Bactroban (SmithKline Beecham) Beecham) Beecham) F: Bactroban (SmithKline I: Bactroban (SmithKline USA: Bactroban (SmithKline Beecham; 1985) Beecham) Beecham; 1988) Muzolimine ATC: CO~CDOI Use: diuretic RN: 55294-15-0 MF: C,,H,,CI,N,O MW: 272.14 EINECS: 259-573-2 CN: 5-amino-2-[1-(3,4-dichlorophenyl)ethyl]-2,4-dihydro-3H-pyrazol-3-one H 2. HZ, Ni-kieselguhr 3. HCI c - 1. ocetylhydrazine 0 3',4'-dichloro- acetophenone ethyl 8-amino-8- ethoxyocrylate ethylhydrazine (I) H3cgz: O-3 N"2 Muzolimine DE 2 366 559 (Bayer; pripr. 17.4.1973). DOS 2 363 139 (Bayer; appl. 19.12.1973). Moller, E.; Horstmann, H.; Meng, K.: Pharmatherapeutica (PHARDW) 1,540 (1977). US 3 957 814 (Bayer; 18.5.1976; appl. 15.4.1974; D-prior. 17.3.1973). synthesis of 1-(3,4-dichloropheny1)ethylhydrazine: DE 1 003 215 (Hoechst; appl. 1954). Houben-Weyl 10/2,47. Formulation(s): tabl. 20.7 mg, 31 mg, 248 mg Trade Narne(s): D: Edrul (ZymaIBayer; 1985); I: Edrul (Bayropharm; 1983); wfm wfm 1378 M Mycophenolate mofetil Mycophenolate mofetil (ME-MPA; RS-61443) ATC: L04AA06 Use: anti-inflammatory, immunosuppressive RN: 128794-94-5 MF: C,,H,,NO, MW: 433.50 CN: (E)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methy1-3-0x0-5-is0benz0furanyl)-4-methyl-4-hexen0ic acid 2-(4-morpho1inyl)ethyl ester hydrochloride RN: 116680-01-4 MF, (E)-6-(1.3-dihydro-4-hydroxy- 6-methoxy-7-methyl-5-oxo- 5-isobenzofuronyl)-4-methyl- 4-hexenoic acid 2-morphalino ethanol (11) C,,H,,NO,. HCI MW: 469.96 CH2C12. DMF mycophenolic acid chloride (I) CH3 Mycophenolote mofetil Reference(s): US 4 727 069 (Syntex; appl. 30.1.1987; USA-prior. 30.1.1987). preparation by azeotmpic water removal from I and II: US 5 247 083 (Syntex; appl. 10.7.1992; USA-prior. 10.7.1992). treatment of allograft rejection: US 4 786 637 (Syntex; appl. 22.1.1988; USA-prior.30.1.1987,4.9.1987, 22.1.1988, 17.8.1988). immunoassays,for mycophenolic acid derivatives: WO 9 602 004 (Behringwerke AG; appl. 29.6.1995; USA-prior. 7.7.1994). high dose oral suspension: WO 9 509 626 (Syntex; appl. 27.9.1994; USA-prior. 1.10.1993). high-dosage unit formulation obtained by hot-meltjlling: WO 9 426 266 (Syntex; appl. 10.5.1994; USA-prior. 13.5.1993). intravenous fornzulation using crystalline anhydrous mycophenolate mofetil: WO 9 507 902 (Syntex; appl. 12.9.1994; USA-prior. 15.9.1993). combination of immunosuppressives: WO 9 202 229 (SmithKline Beecham Corp.; appl. 7.8.1991; USA-prior. 10.8.1990, 5.12.1990). WO 9 1 19 498 (Du Pont Merck; appl. 5.6.1991; USA-prior. 6.1 1.1990). Formulation(s): cps. 250 mg; tabl. 500 mg Trade Name(s): D: CellCept (Roche) GB: CellCept (Roche) USA: CellCept (Roche) F: CellCept (Produits Roche) I: CellCept (Roche) Mycophenolic acid M 1379 Mycophenolic acid ATC: L04AA06 Use: antibiotic, antineoplastic, antiviral RN: 24280-93-1 MF: CI7H2,O6 MW: 320.34 EINECS: 246-119-3 LD,,: 1 glkg (M, p.0.); 450 mglkg (R, i.v.); 352 mgikg (R, p.0.) CN: (E)-6-(l,3-dihydro-4-hydroxy-6-methoxy-~-methyl-3-oxo-~-isobenzofuranyl)-4-methyl-4-hexenoic acid I Mycophenolic acid I By fermentation of Penicillium stoloniferum. Reference(s): BE 862 618 (Lilly; appl. 4.1.1978; USA-prior. 21.3.1977). GB 1 157 099 (ICI; valid from 31.7.1967; prior. 27.9.1966, 13.6.1967) structure: Logan, W.R.; Newbold, G.T.: J. Chem. Soc. (JCSOA9) 1957. 1946. use as immunosuppressive and anticancer agent: Williams, R.H.: J. Antibiot. (JANTAJ) 21,463 (1968). Suzuki, S. et al.: J. Antibiot. (JANTAJ) 22, 297 (1969). GB 1 157 100 (ICI; valid from 2.8.1967; prior. 27.9.1966). antiviral activily: Ando, K. et al.: J. Antibiot. (JANTAJ) 21,649 (1968). total synthesis: Birch, A.J.: J. Chem. Soc., Chem. Commun. (JCCCAT) 1969, 788. Canonica, L. et al.: Tetrahedron Lett. (TELEAY) 1971, 2691. review: Carter, S.B. et al.: Nature (London) (NATUAS) 223, 848 (1969). Trade Narne(s): USA: Melbex (Lilly); wfm Myrtecaine (Nopoxamine) ATC: NOlB Use: local anesthetic, antispasmodic RN: 7712-50-7 MF: C1,H3,NO MW: 265.44 EINECS: 231-735-7 LDS,: 48 mglkg (M, i.v.) CN: 2-[2-(6,6-dimethylbicyclo[3.l.l]hept-2-en-2-yl)ethoxy]-N,N-diethylethanamine lauryl sulfate RN: 76157-55-6 MF: C17H3,N0 . C12H2,04S MW: 531.84 1380 M Myrtecaine t I 1 NoNH2, toluene OH 2 I chloride hornornyrtenol 1 Myrtecoine I Reference(s): GB 861 900 (0. P. Gaudin; appl. 1959). Formulation(s): chewing tabl. 2.5 mg (as lauryl sulfate); cream 1 g1100 g, 10 gI100 g; tabl. 2.5 mg i Trade Name(s): D: Acidrine (Solvay Pharma)- Algesalona (Solvay AlgCsal SuractivC (Solvay comb. Pharma)-comb. Pharma)-comb. Algesal (Solvay Pharma)- F: Acidrine (Solvay Pharma)- I: Acidrine (Solvay Pharma)- 1 comb. comb. comb. . (E )-6 -( 1,3-dihydro-4-hydroxy-6-methoxy-7-methy 1-3 -0 x 0-5 -is0benz0furanyl )-4 -methyl-4-hexen0ic acid 2-( 4-morpho1inyl)ethyl ester hydrochloride RN: 11668 0-0 1-4 MF, (E )-6 -( 1.3-dihydro-4-hydroxy- 6-methoxy-7-methyl-5-oxo- 5-isobenzofuronyl )-4 -methyl- 4-hexenoic. 4-chloro-N-(4,5-dihydro-lH-imidazol-2-yl )-6 -methoxy-2-methyl-5-pyrimidinamine 1. POC13, HNO, CH3 OACH , POCI, b 1 0 H CI I -ocetylimidazolidin- 2-one 2-methyl-5-nitro- 5-omino-2-methyl-. 1-Cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy- 7-[ (4~,7~-octahydro-6H-pyrrolo[3,4-b]pyridin-6-y1 ]- 4-0 x 0-3 -quinolinecarboxylic acid base RN: 15109 6-0 9-2 MF: CZlH,FN,O4 MW: 401.44 pyridine-2. 3- dicarboxylic ocid 1. L-(+)-tartaric