Moclobemide M 1351 Isolation from cultures of Eupenicillium hrefeldianum NRRL 5734. a Amberlite IRA-41 l/pH 10. b Chromatography on DEAE-Sephadex A-25. / Mizoribine BE 799 805 (Toyo Jozo; appl. 31.1 1.1973; J-prior. 21.5.1973). DOS 2 326 916 (Toyo Jozo; appl. 23.5.1973; J-prior. 21.5.1973). Mizuno, K. et al.: J. Antibiot. (JANTAJ) 27,775 (1974). conrrolled-release formulation: JP 59 227 817 (Toyo Jozo; appl. 7.6.1983). Formulation(s): f. c. tabl. 10 mg; tabl. 10 mg Trade Narne(s): J: Bredinin (Toyo Jozo) Moclobemide (Ro-11-1163) RN: 71320-77-9 MF: C,,H,,CIN202 MW: 268.74 LD,,,: 707 mgkg (R, p.0.) CN: 4-chloro-N-[2-(4-morpholinyl)ethyl]benzamide benzoyl morpholine (I) chloride ATC: N06AG02 Use: antidepressant, reversible nonhydrazide MAO- A-inhibitor, antiparkinsonian I Moclobemide ( 1352 M Modafinil ReJerence(s): DE 2 706 179 (HoCCmann-La Roche; appl. 14.2.1977; A-prior. 16.2.1976). GR 1 5 12 194 (Hoffmann-La Roche; appl. 24.5.1978; A-prior. 16.2.1976, 2.9.1976, 20.4.1977, 17.2.1976, 4.6.1976). medical use for treatment ~Jcognitive disorders: IJS 4 906 626 (Hoffmann-La Roche; 6.3.1990; appl. 13.1.1989; CH-prior. 8.12.1988). Formulation(s): f. c. tabl. 150 mg, 300 mg; tabl. 100 mg, 150 mg. 300 mg Trade Name(s); D: Aurorix (Roche) F: Moclamine (Produits GB: Manerix (Roche) Roche) I: Aurorix (Roche) Modafinil (CRL-40476) RN: 68693-11-8 MF: ClsH,SN02S MW: 273.36 CN: 2-[(diphenylmethyl)sulfinyl]acetamide racemate RN: 11 21 11-49-6 MF: ClsH15N02S MW: 273.36 (+)-form RN: 11 21 11-47-4 MF: Cl,H15N02S MW: 273.36 (-)-form RN: 11211 1-43-0 MF: CI5HI5NO2S MW: 273.36 'benzhydrol 1. SOCI, 2. aq. NH3 3. HZOZ I. ATC: N06BA07 Use: psychostimulant, a,-adrenoceptor agonist (treatment of narcolepsy and idiopathic hypcrsomnia) 2-(diphenylrnethyl- thio)acetic acid (I) I Modafinil 2. (CHJ2SO4. NoHC03 3. aq. NH3 I b Reference(s): DE 2 809 625 (Laboratoire L. Lafon; appl. 5.10.1978; GB-prior. 31.3.1977). EP 233 106 (Laboratoire L. Lafon; appl. 19.8.1987; F-prior. 3 1.1.1986). use of modafinil as neuroprotective agent: EP 462 004 (Laboratoire L. Lafon; appl. 18.12.1991; F-prior. 14.6.1990). use for treatment of urinary and fecal incontinence: EP 594 507 (Laboratoire L. Lafon; appl. 27.4.1994; F-prior. 23.1.1992). use as a brain anti-ischemia: EP 547 952 (Laboratoire L. Lafon; appl. 23.6.1993; F-prior. 13.12.1991). use for treatment of sleep apnea and ventilation problems of central origin: WO 9 500 132 (Laboratoire L. Lafon; appl. 5.1.1995; F-prior. 22.6.1993). rise for modifying feeding behavior: WO 9 501 171 (Laboratoire L. Lafon; appl. 12.1.1995; 30.6.1993). Formulation(s): tabl. 100 mg Trade Name(s): F: Modiodal (Lafon) Moexipril ATC: c09~A13; CO~AB 13 (CI-925; RS- 10085 (base); RS-10085-197; SPM-925) Use: antihypertensive (ACE inhibitor) RN: 103775-10-6 MF: C27H,4N,07 MW: 498.58 . CN: [3S-[2[R*(R*)],3R*]]-2-[2-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]-l-oxopropyl]-l,2,3,4-tetrahydro- 6,7-dimethoxy-3-isoquinolinecarboxylic acid monohydrochloride RN: 82586-52-5 MF: CUH,4N207. HC1 MW: 535.04 L-olonine tert-butyl ester ethyl 2-brorno- 4-phenylbutonoate N-[I (5)-ethoxycorbonyl- 3-phenylpropyl]-L-olonine tert-butyl ester (I) H3C-Ow~~@ , DCC, HOBt, CH2C12 CF3COOH L CH, =\ nl benzyl 1,2,3.4-tetrohydro- 8 6.7-dimethoxy-3(S)-iso- quinolinecorboxylote (11) 1354 M Mofebutazone benzyl 2-[N-[I (S)-ethoxycorbonyl- 3-phenylpropyl]-~-olon~l]-l ,2.3,4- tetrohydro-6.7-dimethoxy-3(S)- isoquinolinecorboxylote (111) 1. H2, Pd-C 2. HCI - Moexipril synthesis of the storting material 11: Hz, (R)-BINAP, rhodium(1) bis(norborn0diene)- 1. NaOH hexofluorophosphote H3C-0 2. HCI H3C-0 H3C-0 0, 0, CH3 CH3 methyl N-benzoyl- 3.4-dimethoxy-L- phenylolanine. 1. HCI H3C-0 2. + 0=CH2 r 11 H3C-0 2. benzyl olcohol (S)-2-amino-3-(3,4- dimethoxypheny1)- proponoic acid (N) Reference(s): EP 96 157 (Warner-Lambert; appl. 1.10.1981; USA-prior. 3.10.1980, 20.2.1981). EP 49 605 (Warner-Lambert; appl. 1 .lo. 1981; USA-prior. 3.10.1980). O'Reilly, N.J. et al.: Synthesis (SYNTBF) 7, 550-556 (1990). US 4 912 221 (Occidental Chemical Corp., appl. 27.10.1988). formulation stabilized with ascorbic acid: EP 264 887 (Warner-Lambert Co.; appl. 19.10.1987; USA-prior. 20.10.1986). Formulation(s): f. c. tabl. 7.5 mg, 15 mg; USA: f. c. tabl. 7.5 mg, 12.5 mg, 15 mg, 25 mg (in comb. with hydrochlorothiazide) (as hydrochloride) Trade Nume(s): D: Fempres (Isis Pharma) I: Femipres (Schwarz) USA: Uniretic (Schwarz) GB: Perdix (Schwarz) Primoxil (Bayer Italia) Univasc (Schwarz) Mofebutazone ATC: M01 AA02; M02AA02 Use: antirheumatic, anti-inflammatory. analgesic RN: 2210-63- 1 MF: C,,H,,N,O, MW: 232.28 EINECS: 218-641-1 LD,,,: 600 mglkg (M, i.v.); 1750 mglkg (R, p.0.) CN: 4-butyl-1-phenyl-3,5-pyrazolidinedione Mofezolac M 1355 sodium salt RN: 41468-34-2 MF: C,,H,,N,NaO, MW: 254.27 diethyl phenyl- butylrnolonote hydrozine GB 839 057 (Comm. Farmaceutica Milanese; appl. 27.11.1957; I-prior. 28.11.1956). Biichi, J. et al.: Helv. Chim. Acta (HCACAV) 36,75 (1953). Formulation(s): amp. 650 mgl3 ml (as sodium salt); cps. 200 mg; drg. 150 mg-comb.; f. c. tabl. 300 mg Trade Name(s): D: Diadin (Diadin) F: Arcobutina (Silbert et Monbutina (Lafare); wfm Mofesal (Medice) Ripen)-comb.; wfm Reumatox (Medosan); wfm Vasotonin (Merz)-comb. I: Chemiartrol (Gazzoni); wfm Mofezolac (N-22) ATC: M01; NO2 Use: anti-inflammatory, analgesic RN: 78967-07-4 MF: C,,H,,NO, MW: 339.35 ' LD,,: 1528 mgkg (M, p.0.); 887 mgkg (R, p.0.); 800 mgkg (dog, p.0.) CN: 3,4-bis(4-methoxypheny1)-5-isoxazoleacetic acid H 0 \ NH20H. CH,OH, NoOH. 70 OC b hydroxylornine cjb H3C-0 0-CH3 H3C-0 0-CH3 deoxyonisoin (I) - deoxyonisoin oxirne (U) 1. n-BuLi. THF. Mofezoloc -15 to 0 OC H3C n-BuLi. THF. 2. H C 0-CH, ' x -75 OC, co2 11 - H3C-0 0-CH, H3C-0 0-CH, 1356 M Molindone methyl 3-methoxyacrylote methyl 5-axo-4.5- bis(4-methoxypheny1)-3- pentenoote (IU) Reference(s): EP 26 928 (CDC Life Sciences Inc.; appl. 3.10.1 980; CA-prior. 5.10.1979). synthesis with C1CO2Et instead C02: JP 02 223 568 (Taiho Pharmaceuticals; appl. 20.11.1989; J-prior. 2.11.1988). EP 454 87 1 (Taiho Pharmaceuticals; appl. 19.1 1.1990; J-prior. 21.1 1.1989). JP 03 220 180 (Taiho Pharmaceuticals; appl. 24.1.1990; J-prior. 24.1.1990). EP 464 21 8 (Taiho Pharmaceuticals; appl. 22.1.1991; J-prior. 24.1.1990). transdermal formulations: JP 05 017 354 (Nichiban KK; appl. 3.7.1991; J-prior. 3.7.1991). stable injection solution: AT 391 415 (Kwizda; appl. 26.7.1989; A-prior. 26.7.1989). Trade Name(s): J: Disopain (Taiho- Yoshitomi) Molindone ATC: N05AE02 Use: tranquilizer, sedative RN: 7416-34-4 MF: C,,H,N202 MW: 276.38 CN: 3-ethyl-l,5,6,7-tetrahydro-2-methyl-5-(4-morpholinylmethyl)-4H-indol-4-one monohydrochloride RN: 15622-65-8 MF: C,,H,N2O2. HCI MW: 312.84 LD,,: 670 mgkg (M, p.0.); 261 mglkg (R, p.0.) HO-N o<z:: HN02 orti&-0-NO k' 0 methyl 0 CH, cyclohexone- ., d nitrite 1 -3-dione diethyl Molsidomine M 1357 3-ethyl-2-methyl- morpholine paraform- Molindone 4-0x0-4,5,6,7- aldehyde tetrahydroindol (I) Reference(s): DAS 1 545 774 (Endo Labs.; appl. 16.10.1965). US 3 491 093 (Endo Labs.; 20.1.1970; prior. 2.3.1964, 3.4.1964, 1 1.5.1966,29.11.1967). combination with amantadine (antidepressant): US 4 148 896 (Du Pont; 10.4.1979; appl. 22.2.1978). Formulation(s): sol. 20 mg/ml; tabl. 5 mg, 10 mg, 25 mg, 50 mg, 100 mg Trade Name(s): USA: Moban (Gate) Molsidomine ATC: COlDX12 Use: coronary vasodilator RN: 25717-80-0 MF: C,H,,N404 MW: 242.24 EINECS: 247-207-4 LD,,: 800 mgkg (M, i.v.); 830 mgkg (M, p.0.); 760 mglkg (R, i.v.); 1050 mgtkg (R, p.0.) CN: 5-[(ethoxycarbonyl)amino]-3-(4-morpholinyl)-1,2,3-oxadiazolium inner salt + HCHO + HCN + c- 4-amino- form- hydrogen morpholine oldehyde cyanide HN- H+ pyridine I + Molsidomine Reference(s): DAS 1 695 897 (Takeda; appl. 1.7.1967; J-prior. 4.7.1966). synthesis of 4-aminomorpholine: DAS 2 532 124 (Cassella; appl. 18.7.1975). US 3 769 283 (Takeda, 30.10.1973; J-prior. 4.7.1966). Formulation(s): amp. 2 mg; s. r. tabl. 8 mg; tabl. 1 mg, 2 mg, 4 mg 1358 M Mometasone furoate Trade Name(s): D: Corvaton (Hoechst; 1977) Molsidomine (Heumann; I: Molsidolat (Hoechst; duracoron (durachemie) ct-Arzneimittel; 1980); wfm Molsicor (betapharm) ratiopharm) Molsiton (Edmond); wfm Molsihexal (Hexal) J: Morial (Takeda; 1972) F: Corvasal (Hoechst; 1983) Mometasone furoate ATC: DO7AB Use: topical glucocorticoid, anti- inflammatory RN: 83919-23-7 MF: C,H3,Cl2O6 MW: 521.44 LD,,,: 300 mglkg (R, LC.) CN: (1 1 P, 16a)-9,2 1 -dichloro- 17-[(2-furanylcarbonyI)oxy]- I 1-hydroxy- 16-methylpregna- l,4-diene-3,20-dione mometasone RN: 105102-22-5 MF: C22H28C1204 MW: 427.37 2. HCIO,, CH30H 1. 4-dimethylamino- pyridine 165-methyl-1.4,9(1 1)- 2-furoyl pregnatriene-l7a.21 -dial- chloride 3.20-dione 21 -acetate 17a.21-dihydraxy-1 &-methyl- 1,4,9(11)-pregnatriene-3.20- dime 17-(2-furoote) (I) 1. CH3S02CI 2. LiCI, DMF I - 1, mesyl chloride ;;:&o 0 'CI . HCIO, 1.3-dichloro-5.5- dirnethylhydontoin Mometasone furoate EP 57 401 (Schering Corp.; appl. 25.1.1982; USA-prior. 2.2.198 1). US 4 472 393 (Schering Corp.; 18.9.1984; appl. 29.7.1982; prior. 2.2.198 1). Shapiro, E.L. et al.: J. Med. Chem. (JMCMAR) 30, 1581 (1987). cream: EP 262 681 (Schering Corp.; appl. 1.10.1987; USA-prior. 2.10.1986). lotion: US 4 775 529 (Schering Corp.; 4.10.1988; appl. 21.5.1987) Monobenzone M 1359 Formulation(s): cream 0.1 %; lotion 0.1 %; ointment 0.1 % ( 1 mg/g) Trade Name(s): D: Ecural (Essex Pharma) I: Altosone (Essex Italia) USA: Elocon (Schering-Plough; GB: Elocon (Schering-Plough) Elocon (Schering-Plough) 1988) Nasorex (Schering- J: Ecotone (Schering-Plough) Plough)-comb. Flumeta (Shionogi) Monobenzone Use: depigmentant (melanin inhibitor against hyperpigmentation of skin) RN: 103-16-2 MF: C,,H,,O, MW: 200.24 EINECS: 203-083-3 LD,,: >600 mgkg (M, i.p.); 4500 mgkg (R, i.p.) CN: 4-(pheny1methoxy)phenol Reference(s): Schiff, H.; Pellizzari, G.: Justus Liebigs Ann. Chem. (JLACBF) 221, 365 (1883). HO KOH. C&OH DOH + B - hydroquinone benzyl bromide Formulation(s): cream 20 % aO Monobenzone Trade Name(s): D: Depigman (Hermal); wfm I: Dermochinona (chindin); USA: Benoquin (Elder) wfm Montelukast sodium (MK-476; MK-0476; L-70663 1) ATC: R03DC03 Use: antiallergic, antiasthmatic, leukotriene antagonist RN: 15 1767-02- 1 MF: C,,H,,ClNNaO,S MW: 608.18 CN: 1-[[[(I R)-1-[3-[(1E)-2-(7-Chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-(l-hydroxy-l- methylethyl)phenyl]propyl]thio]methyl]cyclopropaneacetic acid sodium salt acid RN: 158966-92-8 MF: C,,H,,ClNO,S MW: 586.20 + $ H,C 9- 0 8 CH3 acetic onhydride CI OHC 7-chloroquinoldine iaophthalaldehyde 1360 M Montelukast sodium toluene, THF + BrMg-,CH, - vinylmagnesium bromide Pd(OAc)*, LiOAc. DMF + Br palladium acetate Cl / N, \ \ / methyl 2-bromo- benzoate (-)-0-chlorodiisopinocarnpheylborane. THF b methyl 2-[3-[3-[(2E)-(7-chloro- quinalin-2-yl)vinyl]phenyl]-3- oxopropyl]benzoote (111) 1. THF, toluene 2. fi pH3 H3C-8-CI, H3CyNyCH3 0 H3C CH3 toluene, acetonltrile + BrMg-CH3 methylmagnesium bromide 1. BuLi. THF 2. DCHA 2-[l-(mercapto- methyl)cyclopropyl]- acetic acid (VI) 1. HOAc 2. NaOH. toluene/H20 I Montelukast sodium I . 1,2,3.4-tetrohydro- 8 6.7-dimethoxy-3(S)-iso- quinolinecorboxylote (11) 1354 M Mofebutazone benzyl 2-[ N-[I (S)-ethoxycorbonyl- 3-phenylpropyl ]-~ -olon~l]-l ,2.3, 4- tetrohydro-6.7-dimethoxy-3(S )- isoquinolinecorboxylote. acetate Cl / N, / methyl 2-bromo- benzoate (-) -0 -chlorodiisopinocarnpheylborane. THF b methyl 2-[ 3-[ 3-[ (2E )-( 7-chloro- quinalin-2-yl)vinyl]phenyl ]-3 - oxopropyl]benzoote (111) 1 Mofezoloc -1 5 to 0 OC H3C n-BuLi. THF. 2. H C 0-CH, ' x -7 5 OC, co2 11 - H3C-0 0-CH, H3C-0 0-CH, 1356 M Molindone methyl 3-methoxyacrylote methyl 5-axo-4. 5- bis(4-methoxypheny1 )-3 -