Griseofulvin G 981 Griseofulvin ATC: DOlAA08; DOlBAOl Use: antifungal antibiotic RN: 126-07-8 MF: C17H17C10h MW: 352.77 EINECS: 204-767-4 LD,: 280 mglkg (M, i.v.); >SO glkg (M, p.0.); 400 mg/kg (R, i.v.); >10 glkg (R, p.0.) CN: (1'S-truns)-7-chloro-2',4,6-trimethoxy-6'-methyspiro[benzofuran-2(3,1'-[2]cyclohexene]-3.4'dione Griseofulvin L From fermentation solutions of Penicillium patulum. Reference(s): GB 784 618 (Glaxo; appl. 28.3.1955). US 2 900 304 (ICI; 18.8.1959; GB-prior. 21.9.1956). US 3 038 839 (Glaxo; 12.6.1962; GB-prior. 2.3.1959). US 3 069 328 (Glaxo; 18.12.1962; GB-prior. 4.5.1960). US 3 069 329 (Glaxo; 18.12.1962; GB-prior. 4.5.1960). pharmaceuticul formulation with polyethyleneglycol: US 4 151 273 (Univ. of California; 24.4.1979; prior. 2.1.1970,2.12.1970, 13.4.1972, 3 1.10.1974, 13.6.1978). total syntheses: Brossi, A. etal.: Helv. Chim. Acta (HCACAV) 43, 1444 (1960). Day, A.C. etal.: Proc. Chem. Soc., London (PCSLAW), 1960, 284. Kuo, C.H. et al.: Chem. Ind. (London) (CHINAG), 1960, 1627. Stork, G. et al.: J. Am. Chem. Soc. (JACSAT) 84, 310 (1962). Formulation(s): cps. 125 mg, 250 mg; cream 5 gll0O g; tabl. 125 mg, 165 mg, 330 mg, 500 mg Trade Name(s): D: Fulcin S (Zeneca) Gricin Creme (LAW) Gricin Tabl. (ASTA Medica AWD) griseco (ct-Arzneimittel) Likuden M (Hoechst) F: Fulcine (Zeneca Pharma) GrisCfuline (Sanofi Winthrop) GB: Fulcin (Zeneca) Grisovin (Glaxo Wellcome) I: Fulcin (SIT) Griseofulvina (Scfm) Grisovina Fp (Teofarma) J: Grifulvin (Yamanouchi) Grisetin (Nippon Kayaku) Grisovin (Fujisawa) Guservin (Chugai) USA: Fulvicin PIG (Schering) Grifulvin V (Ortho Dermatological) Grisactin (Wyeth-Ayerst) Gris-PEG (Allergan) Guaiazulene ATC: SOIXAO~ (Guajazulene) Use: anti-inflammatory RN: 489-84-9 MF: CISHI, MW: 198.31 EINECS: 207-701-2 LDso: 1220 mg/kg (M, p.0.); 1550 mglkg (R, p.0.) CN: 1,4-dimethyl-7-(1-methylethy1)azulene 982 G Guaifenesin S. 130 "C ___* C"3 CH3 guaiol guaiene Guoiozulene (constituent of guaiocurn wood oil) Refererzce(s): CH 314 487 (Dr. B. Joos; appl. 1953). Formulation(s): cream; drg. 20 mg; ointment (ethanolic camomile extract) Trade Name(s): D: Azulon Kamillen Creme Thrombocid (bene- I: Azulon (Arrnour Med.); (ASTA Medica AWD) Arzneimitte1)-comb. wfm Azupanthenol (Parke F: Cicatryl (Evans Medical)- Azulon (Rorer); wfm Davis)-comb. comb. J: Azulon-Homburg (Daito) Garmastan (Protina) Pepsane (Rosa- Phytopharma)-comb. Guaifenesin ATC: R05CA03 (Guajacolglycerinather; Guaiphenesin) Use: muscle relaxant, expectorant RN: 93-14-1 MF: C,oH,404 MW: 198.22 EINECS: 202-222-5 LDs,,: 400 mglkg (M, i.v.); 690 mglkg (M, p.0.); 360 mglkg (R, i.v.); 1510 mglkg (R, p.0.); 335 mglkg (dog, i.v.) CN: 3-(2-methoxyphenoxy) 1,2-propanediol guaiacol (I) 3-chloropropane- Guoifenesin 1.2-diol Guaifenesin 0 + I glycide Reference (s): GB 628 497 (British Drug Houses; appl. 1948). Marle. E.R.: J. Chem. Soc. (JCSOA9) 101, 305 (1912). Yale, H.L. et al.: J. Am. Chem. Soc. (JACSAT) 72,3710 (1950). Guajacol G 983 Formulation(s): cps. 200 mg; elixir 200 mg15 ml; sol. I00 mg; syrup 100 mg, 200 mgl15 ml; tabl. 200 mg, 600 Trade Natne(s): D: Anastil (Eberth)-comb. Bricantyl (Astra)-comb. with terbutaline sulfate Dolestan forte (Whitehall- Much)-comb. Fagusan (Spreewald Pharma) Gufen (Steigerwald) Nephulon (Redel) Pulmotin (Serum-Werk Bernburg) Wick Daymed (Wick Pharma)-comb. Wick Formel 44 (Wick Pharma) Wick Kinder Formel 44 (Wick Pharma) F: Bronchospray (Tissot)- comb. Catabex (Darcy)-comb. Dimetane expectorant (Whitehall)-comb. Hexapneuminel-composC (Dams)-comb. Nortussine (Norgine Pharma)-comb. Polaramine pectoral (Schering-Plough)-comb. Pulmofluide (Phygi&ne)- 1: comb. Rectoplexil (ThCrap1ix)- comb. SCdophon pectoral (Mayoly-Spindler)-comb. Toplexil (Th6raplix)-comb. numerous combination preparations GB: Bricanyl compound (Astra)-comb.; wfrn Dimotane expect. (Robins)- comb.; wfrn Entair (Duncan, Flockhart)- comb.; wfrn Franol expect. (Winthrop)- comb.; wfrn Lotussin (Sear1e)-comb.; wfrn Nethaprin expect. (Merrell Dow)-comb.; wfrn Noradran (Norma)-comb.; wfrn Pholcomed expect. (Medo); wfm J: Broncovanil (Scharper) Chymoser Balsamico (Serono)-comb. Donatiol (AG1PS)-comb. Fepramol (Schwarz)-comb. Idropulminal-composta (IS11 Lanactin scir. (Lepetit). comb. Polarmin Espet. scir. (Essex)-comb. Pumilene (Montefarmac0)- comb. Resyl (Ciba) Rettocistin (Edmond)- comb. Ribexen Espet. (Formenti). comb. Robitussin (Proter) Torfan (Abbott)-comb. Tuscalman Berna (Bema)- comb. Ventolin Espet. (G1axo)- comb. Fustosil (Kyoto) Robitussin (Robins); wfrn USA: numerous combination Terpoin (Hough, preparations Hoseason); wfrn Guajacol ATC: ROSCA (Gaiacol; Guaiacolina; Guajol; Methylcatechol) Use: expectorant, antiseptic RN: 90-05-1 MF: C,H,O, MW: 124.14 EINECS: 201-964-7 LD,,,: 170 mglkg (M, i.v.); 621 mglkg (M, p.0.); 520 mglkg (R, p.0.) CN: 2-methoxyphenol phenylacetate RN: 41 12-89-4 MF: Cl,Hl,O, MW: 242.27 PY '0 - cotechol (I) Guojacol L I + HO-CH, 984 G Guanabenz Reference(s): Ullmanns Encykl. Tech. Chem., 4. Aufl., Vol. 18,226. Forrnulation(s): amp. 50 mg, 75 mg; drg. 100 mg; inhalation sol. 75 mg; syrup 50 mg; suppos. 500 mg (as phenylacetate) Trade Name(s): D: Anastil (Eberth) 1: Eucaliptina (Zoja)-comb. gcnerics Dalet Med Balsam Fosfaguaiacol (0gna)- J: Hustosil (Kyoto- (Mauermann)-comb. comb. Sumitorno)-comb. Infekt-Komplex Ho-Fu- Lacotocol (0gna)-comb. Complex (Pharrna Lipobalsamo (Parke Liebermann)-comb. Davis)-comb. Guanabenz ATC: C02 Use: antihypertensive RN: 505 1-62-7 MF: C,H,CI,N, MW: 23 1 .O9 EINECS: 225-750-8 CN: 2-[(2,6-dichlorophenyl)methylene]hydrazinecarboximidamide monoacetate RN: 23256-50-0 MF: C,H,CI,N, . C2H402 MW: 291.14 EINECS: 245-534-7 LD,,,: 260 mglkg (M, p.0.); 238 mglkg (R, p.0.) 2.6-dichloro- orninoguonidine benzoldehyde carbonate Refc.rencc(s): DOS I 802 364 (Wyeth; appl. 10.10.1968: USA-prior. 12.10.1967). Baum, T. et a].: Experientia (EXPEAM) 25,1066 (1969). Formulation(s): tabl. 4 mg, 8 mg, 16 mg (as acetate) Trade Name(s): D: Wytensin (Wyeth); wfm Rexitenel-plus (LPB); wfrn USA: Wytensin (Wyeth-Ayerst; 1. Rexitene (LPB); wfm J: Wytens (Nippon Shoji) as acetate) Guanadrel ATC: C02 Use: antihypertensive RN: 40580-59-4 MF: C,,H,,N,O, MW: 213.28 CN: (1,4-dioxaspiro[4.S]dec-2-y1methyl)guanidine Guancthidine sulfate G 985 sodium hydride 2-chloromethyl- (1) 1.4-dioxospiro- [4.5]decone NH N,H,. OH- I hydrozine S-methylthiouroniurn sulfate 2-ominomethyl- Guanodrel 1.4-dioxospiro- [4S]decane Referencers): FR 1 522 153 (Cutter Lab.; appl. 2.5.1967; USA-prior. 3.5.1966) Formulation(s): tabl. 10 mg, 25 mg (as sullate) Trade Name(s): USA: Hylorel (Medeva; as sulfate) Guanethidine sulfate ATC: ~02~~02; SOIEXOI Use: antihypertensive RN: 60-02-6 MF: CIOH2?N4. 1/2H204S MW: 494.71 EINECS: 200-452-0 LD,,: 18 mgkg (M, i.v.); 1 100 mg/kg (M, p.0.); 23 mgkg (R, i.v.); 1 g/kg (R, p.0.) CN: [2-(hexahydro-l(2H)-azocinyl)ethyl]guanidine sulfate (2: 1) guanethidine RN: 55-65-2 MF: C,,H,,N, MW: 198.31 EINECS: 200-241-3 chloro- octahydro- octohydro- acetonitrile azocine ozocine- 1 - ocetonitrile 1 -(2-amino- ethy1)octa- hydroozocine (I) S-methylthio- uranium sulfate I Guanethidine sulfote I 986 G Guanfacine Reference(s): US 2 928 829 (Ciba; 15.3.1960; prior. 10.6.1958). alternative svntheses: US 3 006 913 (Ciba; 31.10.1961; appl. 10.6.1959). US 3 055 882 (Ciba; 25.9.1962; appl. 10.6.1959). Formulation(s): eye drops 5 %, 10 %tabl. 10 mg, 25 mg Trade Narnefs): D: Esimil (Novartis Pharma). F: Ismtline (CIBA Vision J: Ismelin (Novartis-Takeda) comb. Ophthalmics) USA: Esimil (Novartis)-comb.; Suprexon (CIBA Vision)- GB: Ganda (Chauvin)-comb. wfm comb. Ismelin (Novartis) lsmelin (Novartis); wfrn Thilodigon (A1con)-comb. I: Visutensil (Merck Sharp & Dohme) Guanfacine ATC: C02CC Use: antihypertensive, a-adrenoceptor agonist RN: 291 10-47-2 MF: C,HyC12N,0 MW: 246.10 EINECS: 249-442-8 LD,,: I65 mglkg (M, p.0.) CN: N-(aminoiminomethyl)-2,6-dichlorobenzeneacetamide monohydrochloride RN: 291 10-48-3 MF: C,HyC12N,0 . HC1 MW: 282.56 EINECS: 249-443-3 LD,,: 25 mgkg (M, i.v.); 16 mglkg (M, p.0.); 5800 pglkg (R, i.v.); 210 mgkg (R, p.0.) 2.6-dichlorophenyl- guanidine (I) I Guanfacine acetyl chlaride ethyl 2.6-dichloro- phenylocetale US 3 632 645 (Dr. A. Wander; 4.1.1972; appl. 23.9.1968; CH-prior. 26.9.1967). DE 1 793 483 (Dr. A. Wander; appl. 24.9.1968; CH-prior. 26.9.1967). Bream, J.B. et al.: Arzneim Forsch. (ARZNAD) 25, 1477 (1975). alternative syntheses: CH 5 11 816 (Dr. A. Wander; appl. 26.2.1969). CH 518 910 (Dr. A. Wander; appl. 14.1 1.1969). Guanoclor G 987 Formulationis): tabl. I mg, 2 mg (as hydrochloride) Trade Narne(s): D: Estulic-Wander (Novartis F: Estulic (Novartis; 1981) USA: Tenex (Robins; 1987) Pharrna; 1980) J: Estulic (Sandoz-Sankyo) Guanoclor ATC: Co2CCo5 Use: antihypertensive RN: 5001-32-1 MF: C,HI,CI2N,O MW: 263.13 EINECS: 225-667-7 CN: 2-[2-(2,6-dichlorophenoxy)ethyl]hydrazinecarboximidamide sulfate (2:l) RN: 551-48-4 MF: CyH,2C12N40 1/2H2S04 MW: 624.33 EINECS: 208-996-0 CI NaOH H+NH . H20 &OH + Br-Br + &"-'Eir A I Cl ,' CI hydrozine hydrote 2,s-dichloro- 1.2-dibromo- 2-(2,6-dichloro- phenol ethone phenoxy)ethyl bromide 0) S-methylthiouronium sulfate Guanoclor I BE 629 613 (Pfizer; appl. 14.3.1963; GB-prior. 15.3.1962,20.7.1962). US 3 271 448 (Pfizer; 6.9.1966; GB-prior. 15.3.1962, 20.7.1962). Augstein, J. et al.: J. Med. Chem. (JMCMAR) 8, 395 (1965). Formulation(s): tabl. 10 mg, 40 mg (as sulfate) Trade Name(s): GB: Vatensol (Pfizer); wfm USA: Vatensol (Pfizer); wfm Guanoxabenz ATC: CO2CCO7 Use: antihypertensive RN: 24047-25-4 MF: C,H,CI,N,O MW: 247.09 CN: 2-[(2,6-dichlorophenyl)methylene]-N-hydroxyhydrazinecarboximidamide NH2 HN ,& NHz I- NH2-OH. HCI, NOOH 2 'N s + I-CH, 4 H2N\ KS/CH3 D b I H hydroxylomine hydrochloride thiosemicarbozide methyl S-methylisothio- iodide sernicorbozide h"rlr;nr(;rl- 988 G Guanoxan hydroxyguonidine (I) benzoldehyde Reference(s): DOS 1 902 449 (Sandoz; appl. 18.1.1969; USA-prior. 22.1.1968, 10.7.1968, 16.9.1968). US 3 591 636 (Sandoz; 6.7.1971; prior. 22.1.1968, 10.7.1968, 16.9.1968). Formularion(s): vial 5 mg; tabl. 25 mg Trade Name(s): F: Benzerial (HoudC); wfm Guanoxan ATC: CO2CCO3 Use: antihypertensive RN: 2165-19-7 MF: Cl,H,,N,02 MW: 207.23 CN: [(2,3-dihy dro-1,4-benzodioxin-2-y1)methyIlguanidine sulfate (2: 1) RN: 5714-04-5 MF: C1,HI3N3O2. 1/2H2S04 MW: 512.54 LD,,: I6 1 mglkg (M, i.p.) NoOH SOC12 OH thionyl 0 chloride pyrocotechol epichlorohydrin 2-hydroxymethyl- 2-chloromethyl- 2.3-dihydro- 2.3-dihydro- 1.4-benzodioxin 1,4-benzodioxin (I) benzylomine 2-ominomethyl- 2,3-dihydro- 1,4-benzodioxin (11) Reference(s): US 3 247 221 (Pfizer; 19.4.1966; appl. 16.5.1963; GB-prior. 22.5.1962). Augstein, J. et al.: J. Med. Chem. (JMCMAR) 8,446 (1965). 5-methylthiouronium Formulation(s): tabl. 10 mg Guonoxon sulfate Gusperimus trihydrochloride G 989 Trade Namefsj: F: Envacar (Pfizer); wfm Envartse (Pfizer)-comb.; GB: Envacar (Pfizer); wfm wfrn USA: Envacar (Pfizer); wfm Gusperimus trihydrochloride ATC: LOI; LO^ (BMY-422 15- 1; BMS- 181 173; Deoxyspergualin Use: antineoplastic, immunosuppressive, hydrochloride; DSG; NKT-01; NSC-356894) multiple sclerosis therapeutic, S antiangiogenic, disease rnodifymg ! drug, systemic lupus erythematosus therapeutic i RN: 85468-01-5 MF: C17H37N703 . 3HCI MW: 496.91 LD,,: 35 mglkg (M, 1.v.) CN: 7-[(aminoiminornethyl)aminol-N-[2-[[4-[(3-aminopropyl)arnino]butyl]arnino]-1-hydroxy-2- 1 oxoelhyl]heptanamide S-(-)-form RN: 84937-45-1 MF: C,,H3,N70, . 3HC1 MW: 496.91 E LD,,: 35 mgkg (M, i.v.) : base (racemate) [ RN: 104317-84-2 MF: C,,H3,N,O3 MW: 387.53 : $-(-)-base i RN: 89149-10-0 ME C,,H3,N70, MW: 387.53 R-(+)-base 1 RN: 114760-38-2 MF: C,,H,,N,O, MW: 387.53 1 $(-)-hydrochloride f RN: 128488-79-9 MF: C,,H,,N,O, . xHC1 MW. unspecified / E I intermediate 1: ti2~wNH2 oB - H2N 0 CH3 1,4-butanediamine 0-benzyl S(4.6- N-benzyioxycarbonyl- dimethyl-2-pyrimidinyl) 1,4-butanedlamine (1) thiocarbonate intermediate V: 1. CH,OH thiocarbonate (11) 990 G Gusperimus trihydrochloride 3. oq. HCI IV H OH b 1. 2.2-diethoxyocetic acid H~N~N-N~OH H ' 2. 1 -hydroxybenzotriozole. 0 dicyclohexylcorbodiirnide N-[4-(3-orninopropylornino)hutyl]-2,2-dihydroxy- ethonornide lrihydrochloride (V) intermediate XI: 1. Na2C03 N-ethoxycarbanyl- ~hthalirnide - 1. oxolyi chloride 2, diazornethone di-N-phthaloyl- L-lysine (VI) 2.~00J3. 0 0 x 3. NO NO^. CH~COOH HOOC- VII b OH 0 1. hydrazine hydrate 2. N-benzyloxycarbonyl- (mn) succinimide 3. sodium nitrite 1. aq. NaOH 0/CH3 2. Hz. Pd-C H IX + ON, N A. NH, H2N-NyNH2 0 OH NH . pyrocotechol epichlorohydrin 2-hydroxymethyl- 2-chloromethyl- 2.3-dihydro- 2.3-dihydro- 1.4-benzodioxin 1,4-benzodioxin (I) benzylomine 2-ominomethyl- 2,3-dihydro- 1,4-benzodioxin (11) Reference(s):. 35 mglkg (M, 1.v.) CN: 7-[ (aminoiminornethyl)aminol-N-[ 2-[ [ 4-[ (3-aminopropyl)arnino]butyl]arnino ]-1 -hydroxy- 2- 1 oxoelhyl]heptanamide S- (-) -form RN: 8493 7-4 5-1 MF: C,,H3,N70, . 3HC1. 10431 7-8 4-2 MF: C,,H3,N,O3 MW: 387.53 : $-( -) -base i RN: 8914 9-1 0-0 ME C,,H3,N70, MW: 387.53 R-(+)-base 1 RN: 11476 0-3 8-2 MF: C,,H,,N,O, MW: 387.53 1 $ (-) -hydrochloride f RN: 12848 8-7 9-9