Pyrovalerone P 1761 Enbol (Merck-Chugai) Neuroxin (Yamanouchi) Neurotin (Nakataki) Piritiomin (Hishiyama) Pyrovalerone ATC: NO~BA Use: central stimulant RN: 3563-49-3 MF: C,,H,,NO MW: 245.37 CN: l-(4-methylphcnyl)-2-(l-pyrrolidinyl)-l-pentanone hydrochloride . - RN: 1147-62-2 MF: C,,H,,NO . HCI MW: 281.83 EINECS: 214-556-9 LD,,: 43 mgkg (M, i.v.); 350 mgkg (M, p.0.); 47 mglkg (R, i.v.); 620 mgkg (R, p.0.) pyrrolidine H3C 4'-methylvaleraphenone 2-bromo-4'-methyl- valerophenone Reference(s): GB 933 507 (Thomae; appl. 4.4.1961; D-prior. 7.4.1960). GB 927 475 (Dr. A. Wander; appl. 18.5.1961; CH-prior. 24.5.1960). Formulation(s): cps. 20 mg Trade Name(s): F: Thymergix (JoulliC); wfm Pyrrobutamine ATC: R06AX08 Ube: antihistaminic RN: 91-82-7 MF: C2,H,2CIN MW: 311.86 EINECS: 202-101-7 CN: I-[4-(4-chlorophenyl)-3-phenyl-2-butenyl]pyrrolidine phosphate (1:2) RN: 135-31-9 MF: C,oH22CIN . 2H304P MW: 507.84 EINECS: 205-1 85-3 LD,: 54 mglkg (M, i.v.); 11 16 mgkg (M, p.0.) acetophenone poroform- pyrrolidine 3-pyrrolidino- aldehyde propiophenone (I) 1762 P Pyrrocaine I + 4-chlorobenzyl- Pyrrobutomine magnesium chloride Reference(s): US 2 655 509 (Eli Lilly; 1953; prior. 1951). Formulation(s): tabl. 15 mg Trade Name(s): D: Copyronilum (Li1ly)- USA: Co-Pyronil (Dista)-comb.; comb.; wfm wfm GB: Co-Pyronil (Li1ly)-comb.; Co-Pyronil (Lil1y)-comb.; wfm wfm Pyrrocaine ATC: NOlRR Use: local anesthetic RN: 2210-77-7 MF: C,,H,,,N20 MW: 232.33 CN: N-(2,h-dimethylpheny1)-1-pyrrolidineacetamide monohydrochloride RN: 2210-64-2 MF: C,,HIoN,O . HC1 MW: 268.79 EINECS: 218-642-7 2 6-dlmethyl- chloroocetyl a-chloro-2.6- Pyrrocaine anil~ne chlor~de dmethyl- oceton~l~de Refer-ence(s): Lofgren, N. et al.: Acta Chem. Scand. (ACHSE7) 11, 1724 (1957). Fonnulntion(s): vial 2 % Trade Name(s): USA: Dynacaine (Graham); wfm Endocaine (Endo); wfm Pyrrolnitrin ATC: DOlAA07 Use: antibiotic, antifungal RN: 1018-71-9 MF: C,,H,C12N,02 MW: 257.08 EINECS: 213-812-7 LD,,,: 1 g/kg (M, p.o.1; >2 g/kg (R, p.0.) CN: 3-chloro-4-(3-chloro-2-nitrophenyl)-1 H-pyrrole Pyrvinium embonate P 1763 1-(2-nitro-3- diethyl omino- chlorapheny1)- malonote 1,3-butanedione H~C~~CH~ ;:Ef$ Ho@:ooH A I -+ ___, + 1. sulfuryl \ NO, \ \ chloride C I NO2 C I NO2 CI I Pyrrolnitrin US 3 428 648 (Fujisawa; 18.2.1969; J-prior. 8.4.1965, 2.2.1965,4.12.1964,7.12.1964, 22.10.1964, 12.10.1964). Nakano, H. et al.: Tetrahedron Lett. (TELEAY) 1966, 737 (also further methods). isolalion from Pseudomonas: Anna, K. et al.: Agric. Biol. Chem. (ABCHA6) 28, 575 (1964). Formulalion(s): cream 1 % Trade Name(s): D: Antimy coticum Klinger Micutrin Beta (Monsanto)- (Dr. Klinger)-comb.; wfm comb. I: . Micutrin (Monsanto) J: Pyroace (Fujisawa) Pyrvinium embonate (Pyrvinium pamoate) ATC: PO2CX01 Use: anthelmintic RN: 3546-41-6 MF: C2,HZ8Nc 112C2,H,40, W'W: 1151.42 EINECS: 222-596-3 LD,,: 200 mgtkg (M, s.c.) CN: 6-(dimethylamino)-2-[2-(2,5-dimethyl-l-phenyl-1H-py~ol-3-yl)ethenyl]-I -methylquinolinium 4.4'- methylenebis[3-hydroxy-2-naphthalenecarboxylate] (2:l) chloride RN: 548-84-5 MF: C,,H2,ClN3 MW: 417.98 1,2-dimethyl-6-dimethyl- 2,5-dimethyl-1- pyrvinium iodide (I) ominoquinolinium iodide phenylpyrrole- 3-carboxaldehyde 1764 P Pyrvinium embonate AgCl + silver chloride I + - COOH Pywinium chloride lrl ernbonic acid I Pywinium ernbonate pyrvinium iodide and chloride: US 2 515 912 (Eastman Kodak; 1950; prior. 1946). pyrvinium embonate: US 2 925 417 (Parke Davis; 16.2.1960; prior. 6.1 1.1957). Formulafion(s): drg. 75.25 mg; susp.75.25 mg/5 ml Trade Name(s). D: Molevac (Parke Davis) F: Povanyl (Warner-Lambert) J: Poquil (Parke Davis- Pyrcen (Krewel I: Vanquin (Parke Davis) Sankyo) Meuselhach) USA: Povan (Parke Davis); wfrn Quazepam Q 1765 Quazepam (Sch-16134) ATC: N05CDIO Use: benzodiazepine hypnotic RN: 36735-22-5 MF: C17H,lC1F4N2S MW: 386.80 EINECS: 253-179-4 LDso: 845 mgkg (M, i.p.); >I370 mgkg (M, i.v.); >SO00 mgkg (M, p.0.); 2749 mglkg (R, i.p.); >5 g/kg (R, p.0.) CN: 7-chloro-5-(2-fluorophenyl)-1,3-dihydro-l-(2,2,2-trifluoroethyl)-2H-l,4-benzodiazepine-2-thione Y-fluorobenzo- phenone trichloromethone sulfonote (1) bramoacetyl 7-chloro-1 -(2.2.2-trifluoro- chloride ethyl)-1.3-dihydro-5-(2-1luorophenyl)- 2H-1,4-benzodiozepin-2-one (In) 4-chloro- oniline 4-chloro-N-(2,2,2- trifluoroethy1)- aniline RuO, I11 ruthenium Letroxide 2-fluoro- benzoyl chloride 1766 Q Quetiapine fumarate P2S5, dioxane + Refer~nce(s): US 3 845 039 (Schering Corp.; 29.10.1974; appl. 26.7.1972; prior. 7.8.1970). US 3 920 818 (Schering Corp.; 18.1 1.1975; appl. 31.7.1974; prior. 26.7.1972, 24.I.l972,7.8.l970). DOS 2 138 773 (Scherico; appl. 3.8.1971; USA-prior. 7.8.1970). Steinman, M. et al.: J. Med. Chem. (JMCMAR) 16, 1354 (1973). alternative synthesis: DOS 2 106 175 (Scherico; appl. 10.2.1971; USA-prior. 13.2.1970). Formulation(s): tabl. 7.5 mg, 15 mg Trade Name(s): I: Quaziurn (Schering- USA: Doral (Wallace) Plough; 1987) Quetiapine fumarate (ZD 5077; ZM 204636; ICI-204636) ATC: N05AH04 Use: antipsychotic RN: 11 1974-72-2 MF: C21H25N302S . 112C4H404 MW: 883.10 CN: 2-[2-(4-Dibenzo[bfi[I ,4]thiazepin- I1 -yl- 1 -piperazinyl)ethoxy]ethanol furnarate (2: 1) base RN: 1 11974-69-7 MF: C,,H,,N,O,S MW: 383.52 w 1. H,. Ronev-Ni, ethanol NOOH, &. , . 2. COC12, toluene b I CI HS a-chloronitro- thiophenol o-nitro- benzene diphenyl sulfide H 0 dimethylaniline dibenzo[b.f][l.4]- thiozepin- 11 (1 OH)-one Quetiapine ru~narate Q 1767 1. NoOH, xvlene. A O~OH 2. HooC*~~~~ (111). r' ethanol - Quetiopine lumorate 2. fumaric acid H N 11 -chlorodibenzo- I-[2-(2-hydroxy- [b,f][l,4]thiozepine (11) ethoxy)ethyl]- piperozine Quetiapine furnorote No2C03. Nol, 1 -propanal, U toluene H N piperozine 1 l -piperozino- dibenzo[b.f][l.4]- thiozepine Reference(s): a EP 240 228 (ICI; appl. 24.3.1987; GB-prior. 27.3.1986). b EP282236 (ICI; appl. 4.3.1988; GB-prior. 10.3.1987). synthesis of dibenzo[bd[1,4]thiazepin- IO(1lH)-one: Schmutze, J. et al.: Helv. Chim. Acta (HCACAV) 48, 336 (1965). sustained-release formulation: WO9745 124 (Zeneca; appl. 27.5.1997; GB-prior. 31.5.1996). pharmaceutical composition for treatment of psychoses: EP 830 864 (Eli Lilly; appl. 22.9.1997; USA-prior. 23.9.1996). Formrrlation(s): tabl. 25 mg, 100 mg, 150 mg, 200 mg Trade Nume(s): GB: Seroquel (Zeneca; 1997) USA: Seroquel (Zeneca; 1997) 1768 Q Quinagolide hydrochloride Quinagolide hydrochloride (CV-205502; SDZ-205502) ATC: G02CB04 Use: dopamine D,-receptor agonist, antiparkinsonian, prolactin secretion inhibitor RN: 94424-50-7 MF: CmH3,N303S . HC1 MW: 432.03 CN: (3a,4aa,lOa~)-(~)-N,N-diethyl-N-(1,2,3,4,4a,5.10,1Oa-octahydro-6-hydroxy-1-propylbenzo[g]quinolin- 3-y1)sulfamide monohydrochloride base (racemate) RN: 87056-78-8 MF: C2,H,,N,03S MW: 395.57 all diastereomers RN: 130793-78-1 MF: CmH33N,0,S . HCl MW: 432.03 base (all diastereomers) RN: 13O793-77-0 MF: C,H,,N,O,S MW: 395.57 30-diastereomers RN: 132071-86-4 MF: C20H,3N,0,S . HCI MW: 432.03 base (3P-diastereomers) RN: 132014-58-5 MF: C,oH,3N30,S MW: 395.57 J-methoxy- 2-tetrolone (I) S-phenyl benzene- thiosulfonote 1. CHJOH, NaOAc 2. n-BuLi. hexane. -70 OC 2. butyllithium 3. tert-butyl P-brornomethyl- acrylote ted-butyl 8-[1,2.3.4- tetrahydro-1 -1 -bis(phenyl- thio)-2-0x0-5-methoxy- 3-naphthyl]-a-methylene- propionotc (11) 1. Al, Hg. THF 2. H2N&.CH; HCI . No2HP0, - 2 H,O. CH30H 3. NaBH,CN. CHPH 11 (In) 1. CF3COOH 1. K,HPO,, cyclization 2. H2C=N2 , Et20 2. seporotion by HPLC 3. Zn. CH3COOH 111 + pb3 .N 0, 0 H,C CH3 - 2. H,. Pd-C 3. N2H, . H,O, CH30H 4. NOCI. -30 OC. THF . CH, 0. 0 'CH, 'CH, Quinagolide hydrochloride Q 1769 1. N2H4 ' H20. CH,OH 2. NOCI. THF. -30 "C 3. HCI I Quinogolide hydrochloride preparation of 5-rnethoxy-2-tetralone 1,6-naphthalene- diol Reference(s): EP 77 754 (Sandoz; appl. 27.4.1983; CH-prior. 16.10.1982, 25.6.1982). US 4 565 818 (Sandoz; appl. 21.1.1986; CH-prior. 16.10.1981, 25.6.1982). preparation of 5-methoxy-2-tetralone: Abell, A.D. et al.: Aust. J. Chem. (AJCHAS) 51 (5), 398 (1998). Copinga, S. et al.: J. Med. Chem. (JMCMAR) 36 (20), 2891 (1993). Cornforth, Robinson: J. Chem. Soc. (JCSOA9) 1949 1855, 1861. Cornforth et al.: J. Chem. Soc. (JCSOA9) 689 (1942). use for treatment of nicotine addiction: FR 2 634 379 (Sandoz; appl. 26.1.1990; USA-prior. 22.7.1989). WO 9 000 896 (Sandoz; appl. 8.2.1990; USA-prior. 22.7.1988). use in cancer therapy: EP 373 658 (Sandoz; appl. 20.6.1990; GB-prior. 16.12.1988). Formulation(s): tabl. (containing quinagolide hydrochloride base equivalent) 0.025 ing, 0.050 mg, 0.075 mg, 0.150 mg Trade Name(s): D: Norprolac (Novartis F: Norprolac (Novartis) Pharma) GB: Norprolac (Novartis) 1770 Q Quinapril hydrochloride Quinapril hydrochloride ATC: C02EA; C09AA06 Use: non-sulfhydrg angiotensine converting enzyme inhibitor, antihypertensive RN: 82586-55-8 MF: C,,H3,N,O5. HC1 MW: 474.99 LD,,,: 504 mglkg (M, i.v.1; 1739 mglkg (M, p.0.); 107 mglkg (Rf, i.v.); 158 mgkg (Rm,i.v.); 3541 mglkg (R, p.0.) CN: [3S-[2[R*(R*)],3R*l]-2-[2-[[l-(ethoxycarbony-3-phenylpropyl]amino]-1-oxopropyl]-l,2,3,4-tetrahydro- 3-isoquinolinecarboxylic acid monohydrochloride monohydrate RN: 90243-99-5 MF: C2,H3,N20j. HCl . H,O MW: 493.00 quinapril RN: 85441-61-8 MF: C2,H,,N,05 MW: 438.52 (*)-ethyl 2-brorna- L-olonine 4-phenylbutonoote tert-butyl ester u 0 1. seporotion of diostereomers by 1. CF,COOH HOOC y~ crystollization from CH2C12 2. HCI 2. NaOAc I + 11 ethyl (S,S)-2-[(I dioxane. H,c&H~' conc. HpSO,. 0 OC 0=CH2 + N isobutylene form- L-phenyl- (5)-1,2,3,4-tetrohydro- oldehyde olonine 3-isoquinoline- corboxylic ocid (Ill) . CN: 7-chloro- 5-( 2-fluorophenyl )-1 ,3-dihydro-l-(2,2,2-trifluoroethyl )-2 H-l,4-benzodiazepine-2-thione Y-fluorobenzo- phenone trichloromethone sulfonote (1) bramoacetyl 7-chloro-1 -( 2.2.2-trifluoro-. EINECS: 22 2-5 9 6-3 LD,,: 200 mgtkg (M, s.c.) CN: 6-( dimethylamino )-2 -[ 2-( 2,5-dimethyl-l-phenyl-1H-py~ol-3-yl)ethenyl]-I -methylquinolinium 4.4&apos ;- methylenebis[3-hydroxy-2-naphthalenecarboxylate]. -( 2.2.2-trifluoro- chloride ethyl )-1 .3-dihydro- 5-( 2-1 luorophenyl )- 2H-1,4-benzodiozepin-2-one (In) 4-chloro- oniline 4-chloro-N-(2,2, 2- trifluoroethy1 )- aniline RuO, I11 ruthenium Letroxide 2-fluoro-