Methapyrilene M 128 1 Methapyrilene (Thenylpyramine) ATC: R06AC05 Use: antihistaminic RN: 91-80-5 MF: Cl4Hl9N,S MW: 261.39 EINECS: 202-099-8 LD,,: 20mgkg(M,i.v.); 182mglkg(M, p.0.) CN: N,N-dimethyl-N-2-pyridinyl-N-(2-thienylmethy1)-1,2-ethanediamine monohydrochloride RN: 135-23-9 MF: ClpH,,N3S . HCl MW: 297.85 EINECS: 205-184-8 LD,,,: 17.5 mglkg (M, i.v.); 182 mgkg (M, p.0.); 200 mglkg (R, p.0.) fumarate (2:3) RN: 33032-12-1 MF: Cl4HI9N,S . 3/2C4H404 MW: 871 .OO EINECS: 251-351-3 Reference(s): Weston, A.W.: J. Am. Chem. Soc. (JACSAT) 69,980 (1947). US 2 581 868 (Monsanto; 1952; prior. 1946). N.N-dimethyl-N'- 2-thienyl- firnurate: GB 694 805 (Monsanto; valid from 1950; USA-prior. 1949). Methapyrilene Formulation(s): cps. 50 mg, 100 mg (as hydrochloride) (2-pyridyl). methyl I ethylenediarnine chloride Trade Name(s): D: Contac Liquid (Vonora)- comb.; wfrn Copyronilum (Lilly)- comb.; wfrn Sedanoct (Woe1m)-comb.; wfrn tiffaforte (Tiffapharm; as fumarate); wfrn I: Co-Pyronil (Lilly); wfrn USA: Allerest (Pharmacraft; as fumarate)-comb.; wfrn Brexin (Savage)-comb.; w fm Citra (Boyle)-comb.; wfm Co-Pyronil (Dista)-comb.; wfrn Ephed-Organidin (Wallace); wfrn Excedrin P.M. (Bdstol- Myers; as fumarate)-comb.; wfm Hista-Clopane (Lil1y)- comb.; wfrn Histadyl E.C. (Lilly; as fumarate)-comb.; wfrn Histadyl Fum. (Lilly; as fumarate); wfrn Histadyl Pulvules (Lilly); wfrn Methaqualone ATC: NO5CMO1 Use: hypnotic RN: 72-44-6 MF: Cl,H14N,0 MW: 250.30 EINECS: 200-780-4 LD,o: 420 mgkg (M, p.0.); 185 mgkg (R, p.o.1 CN: 2-methyl-3-(2-methylpheny1)-4(3H)-quinazolinone 1282 M Methazolamide monohydrochloride RN: 340-56-7 MF: CI,Hl,N,O . HC1 MW: 286.76 EINECS: 206-43 1-2 LD,,): 120 mglkg (M, i.v.); 400 mgkg (M, p.0.); 120 mgkg (R, i.v.); 410 mglkg (R, p.0.) P0ClJ , phosphorus oxychloride N-acetyl- 0-toluidine anlhranilic acid Methaqualone I Reference(s): GB 843 073 (Labs. Toraude; appl. 22.8.1958; USA-prior. 9.5.1958). Klosa, J.: J. Prakt. Chem. (JPCEAO) [4], 20,283 (1963). Formula~ion(s): tabl. 200 mg Trade Narne(s): D: Normi-Nox (Herbrand); wfrn Optinoxan (Robisch); wfrn Revonal (Cascan); wfrn F: Divinoctal (1.S.H.)-comb.; wfrn Isonox (Uc6pha)-comb.; wfrn Mandrax (Houd6)-comb.; wfrn Mandrax (1.S.H.)-comb.; wfrn GB: Revonal (Merck); wfrn J: Hyminal (Eisai) Meroctan (Sanwa) Nene (Sankyo) . Normorest (Doitsu-Aoi) Orzolon (Kobayashi) USA: Parest (Parke Davis); wfrn Quaalude (Rorer); wfrn Somnafac (Cooper); wfrn Sopor (Arnar-Stone); wfrn Methazolamide ATC: C03; SOlEC Use: diuretic (carboanhydrase inhibitor) RN: 554-57-4 MF: C5H8N403Sz MW. 236.28 EINECS: 209-066-7 LD,,,: >I glkg (M, i.v.) CN: N-[5-(aminosulfonyl)-3-methyl-1,3,4-thiadiazol-2(3H)-ylidene]acetamide 3-ocetylomina-5- methyl benzylthio- 1,3.4- iodide thiodiazole Methozolomide Methdilazine M 1283 Reference(s): US 2 783 241 (American Cyanamid; 1957; prior. 1955). Formulation(s): tabl. 50 mg Trade Name(s): F: Neptazane (ThCraplix); J: Neptazane (Lederle) generics wfm USA: Neptazane (Lederle); wfm Methdilazine ATC: R06AD04 Use: antiallergic, antihistaminic RN: 1982-37-2 MF: ClnHzoN,S MW: 296.44 EINECS: 217-841-6 LD,,,: 225 mg/kg (M, p.0.); 162 rnglkg (R, p.0.) CN: 10-[(l-methyl-3-pyrrolidinyl)methyl]-10H-phenothiazine monohydrochloride RN: 1229-35-2 MF: CInHzoN,S , HCI MW: 332.90 EINECS: 214-967-3 LD,,,: 190 mg/kg (M, p.0.); 260 rnglkg (R, p.0.) phenothiazine pH3 NoNH? sodium ' amide 1 -methyl- 3-chloromethyl- pyrrolidine I Methdilozine US 2 945 855 (Mead Johnson; 19.7.1960; prior. 21.10.1958). DE 1 049 382 (Cilag; appl. 1956; CH-prior. 1955). Fomulation(s): tabl. 8 mg (as hydrochloride) Trade Name(s): GB: Dilosyn (Duncan, USA: Tacaryl (Westwood); wfm Flockhart); wfrn Methenamine ATC: GO~AAOI (Formamine; Hexamethylentetramine; HMT; HHMTA; Use: 'dbacterial (urinary) Metenamine; Urotropin) RN: 100-97-0 MF: C,H,,N4 MW: 140.19 EINECS: 202-905-8 CN: 1,3,5,7-tetraazatricyclo[3.3.1. l3>']decane mandelate (1:l) RN: 587-23-5 MF: C,H,O, . C,HI2N4 MW: 292.34 EINECS: 209-597-4 1284 M Methestrol dipropionate hippurate (1:l) RN: 5714-73-8 MF: C,H9N03 - C6H,,N4 MW: 319.37 EINECS: 227-206-5 LD,,: 1500 mglkg (M, i.p.); 2870 mglkg (M, s.c.) Methenamine US 2 762 799 (J. Meissner; 1956; D-prior. 1952). US 2 762 800 (J. Meissner; 1956; D-prior. 1951). Formulation(s): f. c, tabl. 250 mg, 500 mg, 1000 mg; cream 13 g1100g; drg. 500 mg, 1000 mg Trade Name(s): D: Antihydral (Robugen) Mandelamine (Parke Davis) Urotractan (Klinge) F: Aromalgyl (Plantes et Mcdccines)-comb. Mictasol (J. P. Martin)- comb. Uromil (1prad)-comb. GB: Hiprex (3M Health Carc) I: Cinarbile cpr. (Benvegna)- comb.; wfm Elmitolo (Bayer); wfrn Esamet (Tariff. Integrativo) Esation vitaminico (Lafare); wfrn Etiliodina B 1 (Ceccarel1i)- comb.; wfrn Jodoibs (Benvcgna); wfrn Mictasol (Zoja)-comb.; wfrn Tionamil (0gna)-comb.; wfrn J: Hexamine(Mohan; . Nisshin-Yamagata) USA: Urcx (3M; as hippurate) Uro-Phosphate (ECR) Mandclamine (Warner Chilcott Professional Products; as mandelate) Urised (Po1yMcdica)- comb. Uroqid-Acid (Beach; as mandclatc) Methestrol dipropionate ATC: GO~C Use: estrogen RN: 84-13-9 MF: C2,H,,04 MW: 410.55 CN: 4,4'-(1,2-diethyl-1,2-ethanediyl)bis[2-methylphenol] dipropanoate meihestrol RN: 130-73-4 MF C2,H2,02 MW: 298.43 3'-methyl-4'- propionyloxy- propiophenone Methocarbamol M 1285 acetyl chloride Melhestrol dipropionate Reference(s): Niederl, V. et al.: J. Am. Chem. Soc. (JACSAT) 70, 508 (1948). alternative syntheses: Marson, L.M.: Bull. Chim. Farm. (BCFAAI) 102,3 17 (1963). Burckhalter, J.H.; Seiwald, R.J.: J. Org. Chem. (JOCEAH) 24,445 (1959). Formulation(s): 4 x l mglday (oral) Trade Name(s): USA: Meprane (Reed & Carnrick); wfm Methocarbamol ATC: M03BA03 Use: muscle relaxant RN: 532-03-6 MF: C1,H,,N05 MW: 241.24 EINECS: 208-524-3 LD,,,: 774 mglkg (M, i.v.); 812 mglkg (M, p.0.); 1320 mgkg (R, p.0.); 2 gk (dog, p.0.) CN: 3-(2-methoxyphenoxy)-1,2-propanediol I -carbarnate I. COCI, I guoifenesin (4. v.1 2. NH HO~O 1. phosgene OH Methocarbamol OH Reference(s): US 2 770 649 (Robins; 1956; prior. 1955). Yale, H.L. et al.: J. Am. Chem. Soc. (JACSAT) 72, 3710 (1950). Formulation(s): amp. 100 mglml; tabl. 250 mg, 500 mg, 750 mg; tabl. (USA) 325 mg, 400 mg in comb. with aspirin Trade Name(s): D: Ortoton (Bastian-Werk) GB: Robaxin (Shire) Miowas (Wassermann); F: Lumirelax (Jumer Sa)- I: Miowas (IFI); wfm w fm comb. J: Carbametin (Uji) 1286 M Methohexital Carxin (Kanto) Nichirakishin S (Nichiiko) Robaxisal (Robins)-comb. Methocabal (Zeria) Ohlaxin (Ohta) generics Methocal (Daiko) USA: Robaxin (Robins) Methohexital (Methohexitone) ATC: NOlAFOl;NO5CA15 Use: narcotic RN: 18652-93-2 MF: C,,H,,N,O, MW: 262.31 CN: (+)- I-methyl-5-(l-methyl-2-pentynyl)-5-(2-propenyl)-2,4,6(1H,3H,5H)-pyrimidinetrione sodium salt RN: 60634-69-7 MF: C14H17N2Na0, MW: 284.29 H~C~M~B~ 0 H PBr, rCGCH + OHC-CH, b ~CEC< I H3C ethylmagnesium H3C CH, phosphorus(lil)' 1-butyne acetaldehyde bromide J-~~~~~-P~~~ bromide 2-bromo-3-hexyne (I) (11) methylurea Methohexitol R<fe~nce(s): US 2 872 448 (Eli Lilly; 3.2.1959; prior. 4.4.1956). Forn~ulation(s): vial 100 mg, 500 mg (as sodium salt) Trade Name(s): D: Brevimytal-Natrium (Lilly) GB: Brietal Sodium (Lilly) USA: Brevital Sodium (Jones F: Brietal (Lilly); wfm Medical Industries) Methotrexate M 1287 Methotrexate (Amethopterin) ATC: NO1 AFOI ; N05CA15 Use: antineoplastic (folic acid antagonist) RN: 59-05-2 MF: C20H22N805 MW: 454.45 EINECS: 200-413-8 LD,,,: 65 mglkg (M, i.v.); 146 mglkg (M, p.0.); 14 mglkg (R, i.v.); 135 mglkg (R, p.0.) CN: N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-~-glutamic acid H , Raney-Ni +NH2 qooH COOH + IN 0 , 0 i ,I COOH L-glutamic 4-nitrobenzoyl acid (I) chloride COOH (+#pNH2 + I0 COOH N-(4-aminabenzoy1)- L-glutomic acid (11) CHO + + &AB, 2,3-dibromo- propanal I Zn, NaOH HCHO + I0 COOH acid 2.4.5.6-tetroamino- pyrimidine NH2 0 Methotrexate NaOH, Zn aNH2 + HCHO - FH3 HCOOH, reflux HOOC HOOC nNH A 4-aminobenzoic form- 4-(methylamino)- acid aldehyde benzaic acid YH3 SOCI,, toluene YH3 nN\cHO A HOOC ' clpN\cHO 0 1288 M Methotrexate 1. (V) . No2C03. toluene SOCI~ O-CH~ 2. HCI. C~H~OH I + H,C"OH .NH2 * HCI C 0' 0-CH, diethyl L-glutamate hydrochloride diethyl N-(4-methyl- omino)benzoyl-L- glutornote (VI) H2N N, NH, O2 (oir) ,N N NH2 + HOJNqx *HBr H2N NH2 "'Hz 2,4,5,6-tetroomino- 1,J-dihydroxy- 2.4-diomino-6-(hydroxy- pyrimidine dihydrobromide ocetone methy1)pteridine hydro- bromide (WI) (C6H5)3P. Br2, dimethylocetomide VII b triphenylphosphine NH2 dimethylacetamide Vlll + VI - 'methotrexate ester" (IX) I. NoOH. C2H50H 2. HCI IX Reference(s): Seeger, D.R. eta].: J. Am. Chem. Soc. (JACSAT) 71, 1753 (1949). alternative syn~heses: Piper, J.R.; Montgomery, J.A.: J. Heterocycl. Chem. (JHTCAD) 11, 279 (1974). Chaykowsky, M. et al.: J. Med. Chem. (JMCMAR) 17, 1212 (1974). DOS 2 741 270 (US-Secr. of Commerce Nat. Techn. Inform. Service; appl. 14.9.1977; USA-prior. 17.1 1.1976). US 4 057 548 (J. Wiecko; 8.1 1.1977; prior. 11.1 1.1975,30.3.1976). US 4 067 867 (J. Wiecko; 10.1.1978; prior. 11.1 1.1975,30.3.1976, 8.10.1976). US 4 080 325 (US-Secr. of Health; 21.3.1978; appl. 17.11.1976). DOS 2 741 383 (Lonza; appl. 14.9.1977; CH-prior. 12.8.1977). various syntheses of N-(4-methylaminobenzoy1)-L-glutamic acid: DOS 2 824 01 1 (Lonza; appl. 1.6.1978; CH-prior. 12.8.1977). US 3 892 801 (American Cyanamid; 1.7.1975; appl. 11.9.1974). US 4 136 101 (American Cyanamid; 23.1.1979; prior. 3.2.1978). Formulation(s): amp. 5 mg, 25 mg, 50 mg, 200 mg, 500 mg, 100 mg, 5000 mg; tabl. 2.5 g, 7.5 g, 10 g (as disodium salt) Trade Name(s): D: Farmitrexat (Pharmacia & Lantarel (Lederle) generic Upjohn) Metex (medac) F: Ledertrexate (Lederle) Methoxamine M 1289 Mtthothrexate Roger GB: Maxtrex (Pharmacia & I: generic Bellon (RhGne-Poulenc Upjohn) J: generic Rorer Bellon) Methotrexate (Wyeth) USA: Rheumatrex (Lederle) generic generic generic Methoxamine ATC: COlCAlO Use: sympathomimetic, vasoconstrictor RN: 390-28-3 MF: CllH17N03 MW: 211.26 EINECS: 206-867-3 LD,,: 30 mgfkg (M, p.0.) CN: or-(I-aminoethy1)-2,s-dimethoxybenzenemethanol hydrochloride RN: 61-16-5 MF: C,,H17N0, . HCl MW: 247.72 EINECS: 200-499-7 LD,,: 5030 pglkg (M, i.v.) 0, '33 2',5'-dimethoxy- propiophenone Methoxarnine I US 2 359 707 (Burroughs Wellcome; 1944; prior. 1942). Formulation(s): amp. 20 mglml (as hydrochloride) Trade Name(s): D: Rolinex (Rohm Pharma)- GB: Vasoxine (Glaxo J: Mexan (Nippon Shinyaku) comb.; wfm Wellcome) USA: Vasoxyl (Glaxo Wellcome) I: Vasoxine (Wellcome); wfm Methoxsalen ATC: D05AD02; D05BA02 (Ammoidin; Methoxypsoralen; Methoxysalen; Use: radioprotector Xanthotoxin) RN: 298-81-7 MF: Cl2HILO4 MW: 216.19 EINECS: 206-066-9 CN: 9-methoxy-7H-furo[3,2-g][l]benzopyran-7-one 1290 M Methoxsalen from plant material: 8-geranylaxypsoralen is obtained by extraction from Arnrni rnajus with n-hexane, which is dealkylated with CH,COOH/H2S0, to 8-hydroxypsaralen and then is rnethylated with dimethyl sulfate pyrogallol chloroacetic 2-chloro-2'.3',4'- acid trihydroxy- acetophenane benzofuran 6,7-dihydroxy- cournaranane (I) 2.3-dihydro- xanthotoxol (n) 2,3-dihydro- 5,6-dic~ono- l,4-benzo- xanthotoxin I Methoxsalen quinane a US 2 889 337 (US-Secret. of Agriculture; 1959; appl. 1956). b US 4 129 576 (T. C. Elder; 12.12.1978; prior. 12.4.1976, 24.6.1976). US 4 129 575 (T. C. Elder; 12.12.1978; prior. 12.4.1976). alternative syntheses: US 4 150 042 (Roche; 17.4.1979; prior. 29.7.1977, 8.3.1978). US 4 107 182 (Roche; 15.8.1978; appl. 29.7.1977). US 4 147 703 (Roche; 3.4.1979; appl. 29.7.1977). DOS 2 820 263 (Thomae; appl. 10.5.1978). US 4 169 840 (Oy Star; 2.10.1979; SF-prior. 3.10.1977). Formulation(s): sol. 0.1 gI100 ml, 0.75 g/100 ml, 1.5 mg; tabl. 10 mg Trade Narne(s): D: Meladinine (Galderma) J: Meladinine (Nippon Shoji) Oxsoralen (ICN) F: MCladinine (Promedica) Oxsoralen (Taisho) Psoraderm-S (Sunlife) USA: &MOP (ICN) . inhibitor) RN: 55 4-5 7-4 MF: C5H8N403Sz MW. 236.28 EINECS: 20 9-0 6 6-7 LD,,,: >I glkg (M, i.v.) CN: N-[ 5-( aminosulfonyl )-3 -methyl-1,3,4-thiadiazol-2(3H)-ylidene]acetamide 3-ocetylomina- 5- methyl benzylthio-. CN: (+ )- I-methyl- 5-( l-methyl-2-pentynyl )-5 -( 2-propenyl )-2 ,4,6(1H,3H,5H)-pyrimidinetrione sodium salt RN: 6063 4-6 9-7 MF: C14H17N2Na0, MW: 284.29 H~C~M~B~ 0 H PBr, rCGCH + OHC-CH, b. 9 1-8 0-5 MF: Cl4Hl9N,S MW: 261.39 EINECS: 20 2-0 9 9-8 LD,,: 20mgkg(M,i.v.); 182mglkg(M, p.0.) CN: N,N-dimethyl-N-2-pyridinyl-N-(2-thienylmethy1 )-1 ,2-ethanediamine monohydrochloride RN: 13 5-2 3-9