Pvrantel P 1751 Tmde Name(s): F: Norbiline (Bellon)-comb. I: Norbiline (RhSne-Poulenc Rorer) Pyrantel ATC: P02CC01 Use: anthelmintic (nematodes) RN: 15686-83-6 MF: C,,H,,N,S MW: 206.31 EINECS: 239-774-1 LD,,: 175 mg/kg (M, p.0.); 170 mglkg (R, pa.); 2 dkg (dog, p.0.) CN: (E)-1,4,5,6-tetrahydro-l-methyl-2-[2-(2-thienyl)ethenyI]pyrimidine tartrate (1:l) RN: 33401-94-4 MF: ClIHl4N,S . C,H,O, MW: 356.40 EINECS: 251-501-8 LD,,: 2220 pg/kg (M, i.v.); 123 mglkg (M, p.0.); 170 mgkg (R, p.0.) pamoate (1: 1) RN: 22204-24-6 MF: CIIHl4N,S . C,,H,,O, MW 594.69 EINECS: 244-837-1 LD,: 62Q mglkg (M, i.p.1; 535 mglkg (R, i.p.) + ,c-coo, CH3COONH,, pyridine OHC ' NC NH2 thiophene-2- cyanoocetic carboxaldehyde acid 3-(2-thienyl). 3-(2-thieny1)- ocrylonitrile acrylamide (I) N-methvltri- methylenediomine propane sultone Reference(s): BE 658 987 (Pfizer; appl. 28.1.1965; GB-prior. 28.1 .l964, 13.8.1964, 26.9.1964). US 3 502 661 (Pfizer; 24.3.1970; prior. 14.2.1967, 5.6.1967, 9.11.1967). CH 404 677 (Dr. A. Wander; appl. 2.12.1960). CH 398 620 (Dr. A. Wander; appl. 16.8.1960). GB 980 853 (Dr. A. Wander; appl. 16.8.1961 ; CH-prior. l6.8.l960,2.I2.l960). NL 147 426 (Dr. A. Wander; appl. 24.5.1963; CH-prior. 25.5.1962, 8.6.1962, 5.12.1962, 15.2.1963). DE 1 280 879 (Wander; appl. 7.8.196 1; CII-prior. 16.8.1960, 2.12.1960). US3539573(Wander; 10.11.1970;CH-prior. 16.8.1960,2.12.1960,20.7.1961,25.5.1962,5.12.1962,15.2.1963, 22.3.1967, 11.7.1967, 3.11.1967). Hunziker, F. et al.: Helv. Chim. Acta (HCACAV) 50, 1588 (1967). Fomulation(s): chewing tabl. 250 mg; sol. 5 %; susp. 250 mg/5 ml, 720 mg; tabl. 125 mg, 250 mg (as pamoate) Trade Name(s): D: Helmex (Pfizer) Helmintox (Innotech I: Combantrin (Pfizer) F: Combantrin (Pfizer) International) J: Combantrin (Pfizer) GB: Combantrin (Pfizer); wfm 1752 P Pvrazinamide USA: Antiminth (Pfizer); wfm Antiminth (Roerig); wfm Combantrin (Pfizer); wlm Pyrazinamide ATC: J04AK01 Use: tuberculostatic, antibacterial RN: 98-96-4 MF: C,H,N,O MW: 123.12 EINECS: 202-717-6 LD,,: 1680 mgkg (M, i.p.); 2793 mglkg (M, s.c.) CN: pyrazinecarboxamide CHO I CHO glyoxol o-phenylene- quinoxoline pyrorine-2.3- pyrozine-2- diamine dicorboxylic corboxylic acid ocid (I) methyl pyrazine- Pyrozinomide 2-corboxylote Reference(s): DRP 632 257 (Merck; 1934). Hall, S.A. et al.: J. Am. Chem. Soc. (JACSAT) 62, 664 (1940). alternative synthesis via 2-cyanopyrazine (from 2-chloropyrazine): EP 122 355 (Servipharm; appl. 25.7.1983; CH-prior. 21.3.1983). Formulation(s): cps. 500 mg; drg. 300 mg in comb. with rifapiam, isoniazide; f. c. tabl. 500 mg; tabl. 100 mg, 500 mg Trade Name(s): D: Pyrafat (Fatol) F: ' Pirilbne (Marion Merrell) I: Piraldma (Bracco) Pyrazinamid (Hefa Rifater (Marion Merrel1)- J: Pyramide (Sankyo) Pharma) comb. USA: Rifater (Hoechst Marion Pyrazinamid "Lederle" GB: Rifater (Hoechst)-comb. Merrel1)-comb. (Lederle) Zinamide (Merck Sharp & genencs Rifater (Griinentha1)-comb. Dohme) Pyridinol carbarnate (Pyricarbate) ATC: C04AX49 Use: antiarteriosclerotic RN: 1882-26-4 MF: C,,HISN30, MW: 253.26 EINECS: 217-538-9 LD,,,: 3100 mgkg (M, p.0.); 1230 mgkg (R, p.0.); 1 gfkg (dog, p.o.1 CN: 2,6-pyridinedimethanol bis(methy1carbamate) - Pyridinol carbarnate P 1753 starting product: dioicolinic acid 2.6-bis(hydroxymethyI)- pyridine (I) 2.6-bis(acetoxyrnethyI)- pyridine C12, H2S0, azobisisobutyronitrile H~O/H+ I1 - CI~CI , , / 2.6-bis(chloromethyl)- pyridine final product: Reference(s): FR 1 396 624 (M. Inoue; appl. 13.4.1964; J-prior. 13.4.1963) AT 258 953 (M. Inoue; appl. 13.4.1964; J-prior. 13.4.1963). AT 258 954 (M. Inoue; appl. 13.4.1964; J-prior. 13.4.1963). AT 258 955 (M. Inoue; appl. 8.1 1.1965). methyl isocyanate alternative syntheses Lfrom 2,6-bis(hydroxymethy1)pyridine and N,W-dimethylurea]: DOS 2 263 812 (Rocador S. A.; appl. 28.12.1972; E-prior. 28.12.1971). Pyridinol carbamale yl- and y,-modifications: DOS 2 702 772 (Richter Gedeon; appl. 24.1.1977; H-prior. 24.1.1976). GB 1 548 334 (Richter Gedeon; appl. 2 1.1.1977; H-prior. 24.1.1976). 2.6-bis(hydroxymethy1)pyridine: a FR 1 396 624 (M. Inoue; appl. 13.4.1964; J-prior. 13.4.1963). b Bockelheide, V.; Linn, W.J.: J. Am. Chem. Soc. (JACSAT) 76, 1286 (1954). c FR 1 394 362 (Merck & Co.; appl. 3 I .3.1964; USA-prior. 2.4.1963). 1754 P Pyridofylline alternative syntheses: DAS 2 460 039 (Richter Gedeon; appl. 19.12.1974; H-prior. 29.12.1973) DAS 2 614 400 (Richter Gedeon; appl. 2.4.1976; H-prior. 2.4.1975). Fortnulation(s): tabl. 250 mg Trade Name(s): F: Angioxine (Roussel); wfm I: Cicloven (AGIPS) J: Anginin (Banyu) Pyridofylline ATC: COl D Use: coronary vasodilator RN: 53403-97-7 MF: C9H,2N406S . C8HIIN03 MW: 473.46 EINECS: 258-521 -6 LD,,: 1 glkg(M,i.v.); 1600mg/kg(M,p.o.) CN: 3,7-dihydro- l,3-dimethyl-7-[2-(sulfooxy)ethyl]-1H-purine-2,6-dione compd. with 5-hydroxy-6-methyl- 3,4-pyridinedimcthanol (1 : 1) pyridoxine CHC13. CIS03H chlorosulfonic acid CZHJOH Reference(s): FR-M 828 (J. Debarge; appl. 23.12.1960). Trade Name(s): F: Atherophyllinc (Merrell); wfm 0-[2-(7-theophyllinyl)ethyl] hydrogen sulfote (I) Pyridofyllinc Pyridostigmine bromide ATC: N07AA02 Use: parasympathomimctic (cholinesterase blocker), antiniyasthenic, vagotonic RN: 101-26-8 MF: CYH11BrN20Z MW: 261.12 EINECS: 202-929-9 LDs,,: 1500 pglkg (M, i.v.); 16 mglkg (M, p.0.) CN: 3-[[(dimethylamino)carbonyl]oxy]-I-methylpyridinium bromide Pyridoxine P 1755 3-hydroxy- dimethyl- 3-(dimethylamino- pyridine carbomoyl corbony1oxy)- chloride pyridine Reference(s1: CH 246 834 (Roche; appl. 1945). US 2 572 579 (Roche; 1951; CH-prior. 1945). '343 Pyridostigmine bromide Fomulation(s): amp. 1 mglml, 5 mglml; drg. 60 mg; s. r. tabl. 180 mg; syrup 60 mg15 ml; tabl. 60 mg Trade Name(s): D: Kalymin (ASTA Medica F: Mestinon (Roche) J: Mestinon (Nippon Roche) AWD) GB: Mestinon (Roche) USA: Mestinon (ICN) Mestinon (ICN) I: Mestinon (Roche) Regonol (Organon) Pyridoxine (Vitamin B,) ATC:' A I I HA02 Use: vitamin (enzym co-factor) RN: 65-23-6 MF: CsH,lN03 MW: 169.18 EINECS: 200-603-0 LD,: 545 mglkg (M, i.v.); 657 mglkg (R, i.v.); 4 glkg (R, p.0.) CN: 5-hydroxy-6-methyl-3,4-pyridinedimcthanol hydrochloride RN: 58-56-0 MF: CsH1,NO, . HCI MW: 205.64 EINECS: 200-386-2 LD,,: 660 mglkg (M, i.v.); 5500 mglkg (M, p.0.); 530 mglkg (R, i.v.); 4 glkg (R, p.0.); >SO0 mgkg (dog, p.0.) @ Marck + Co.: u H N CH~ % H2~x~~ci3~c~ oHc-NH2 'f + HO~CH~ COOH formom~de (111) DL-olanine (1) (11) DL-olonine ethyl esler hydrochloride N-formyl-DL-olanine ethyl ester (N) 5-ethoxy-4- (ocetol from isobutyroldehyde Pyridoxine + 2-butene-1.4-diol) rnethyloxozole 1756 P Pyridoxine cthyl 2-chloro- acetoacetote ethyl 4-methyl- 4-methyloxozole- 5-cyono-4- oxozole-5- 5-corboxomide methyloxozole (VII) corboxylote (VI) dihydro- 1 -3-dioxepin (ketol from ocetone + 2-butene-l,4-diol) @ BASF: 0 1. NoOH 2. A @:S"' 3-methylsulfonyl-2,s-dihydro- 4-methyl- oxoZolc (by addition of methonesulfonyl bromide to 2,s-dihydrofuron and subsequent HBr elimination with NoOH) 0 COOH + H3CAO+' CH3 COC12. (C&).+ I + 11+ I X VIIl COOH phosgene, triethyl- '0 O~CH~ omine I. NoOH 0 2. HCI 3.v ethyl 5-ethoxy-4-methyl- oxozole-2-corboxylote (VIE) Pyridoxine P 1757 Reference(s): review of pyridoxine syntheses: Konig, H.; Boll, W.: Chem Ztg. (CMKZAT) 100, 105 (1976). a Harris, E.E. et al.: J. Org. Chem. (JOCEAH) 27, 2705 (1962). DAS 1 470 022 (Merck & Co.; appl. 10.5.1962; USA-prior. 15.5.1961, 16.1.1962). US 3 227 721 (Merck & Co.; 4.1.1966; prior. 15.5.1961, 16.1.1962, 24.5.1965). US 3 227 724 (Merck & Co.; 4.1.1966; prior. 15.5.1961, 16.1.1962, 16.6.1964). b US 3 222 374 (Roche; 7.12.1965; prior. 22.5.1963, 20.1 1.1964). US 3 250 778 (Roche; 10.5.1966; appl. 29.11.1962). US 4 026 901 (Roche; 31.5.1977; appl. 30.4.1975). DOS 2 616 349 (Roche; appl. 14.4.1976; USA-prior. 30.4.1975). 5-cyano-4-methyloxazole: US 4 093 654 (Roche; 6.6.1978; appl. 31.3.1977). c DAS 2 143 989 (BASF; appl. 2.9.197 1). 3-methylsulfonyl-2,5-dihydrofuran: DOS 2 435 098 (BASF; 22.7.1974). d Maeda, J. et al.: Bull. Chem. Soc. Jpn. (BCSJA8) 42, 1435 (1969). alternative syntheses: from 5-ethoxy-4-oxazolylacetic acid: DAS 2 008 854 (Roche; appl. 25.2.1970; CH-prior. 25.3.1969). 4-methyloxazol from formimino ester hydrochloride and hydroxyacetone: GB 1 515 737 (BASF; appl. 22.1 0.1975; D-prior. 31.10.1974). Formulation(s): amp. 25 mg/2 ml, 50 mgl2 ml, 100 mgl2 ml, 300 mg; drg. 100 mg, 300 mg; f. c. tabl. 40 mg; tabl. 1 mg, 25 mg, 40 mg, 50 mg, 100 mg, 300 mg (as hydrochloride) Trade Name(s): D: F: GB: I: B,-ASmedic (Dyckerhofo B,-Vicotrat (Heyl) BYK (Roche Nicholas)- comb. Bonasanit (Weimer] Hexobion (Merck) Vitamin B, ratiopharm (ratiopharm) generics and circa 500 combination preparations Becilan (Specia) Dermo-6 (PharmadCveloppement) Pyridoxine Aguettant (Aguettant) Vitamine B, Richard (Richard) numerous combination preparations Complement Continus (Napp); wfm numerous combination preparations Acutil Fosforo (SmithKline Beecham) Adenoplex (Lepetit)-comb. Alcalosio (SIT)-comb. Antemesyl (Mo1teni)- comb. Antimicotico pom. derm. (IF1)-comb. Benadon (Roche) Benexol (Roche)-comb. Coxanturenasi (Teofarma)- comb. Detoxergon (Ba1dacci)- comb. Dobetin (Ange1ini)-comb. Emoferrina B,, os (Piam)- comb. Etanicozid (Piam)-comb. Furanvit (SIF1)-comb. Memosprint (Po1i)-comb. Menalgon (Menarini)- comb. Miazide B, (Wyeth- Leder1e)-comb. Midium (Glaxo)-comb. Mionevrasi forte (Boehringer Mannh.)- comb. Neogeynevral (Geymonat)- comb. Neuraben (Bioindustria)- comb. Neurobionta (Bracco)- comb. Sustenium (Menarini)- comb. Triferon (Sa1us)-comb. Trinevrina B, (Chidotti)- comb. Xanturenasi (Teofarma) J: Aderoxin (Sonybod-Torii) Pyridomin (Showa) Sandoxin (Sanko) numerous combination preparations USA: Aminoxin (Tyson) Beelith (Beach)-comb. Lurline (Fielding)-comb. Marlyn Formula 50 (Marl yn)-comb. Mega-B (Arco)-comb. 1758 P Pyrimethamine Pyrimethamine ATC: POlBDOl Use: chemotherapeutic (toxoplasmosis and malaria), antimalarial RN: 58-14-0 MF: CL2HI3C1N4 MW: 248.72 EINECS: 200-364-2 LDs,,: 92 mglkg (M, p.0.); 440 mglkg (R, p.0.) CN: 5-(4-chloropheny1)-6-ethyl-2,4-pyrimidinediamine orthoformote 4-chlorobenzyl cyonide methyl propionote guonidine Pyrimethornine u US 2 576 939 (Burroughs Wellcome; 1951; prior. 1950). US 2 602 794 (Burroughs Wcllcome; 1952; appl. 1950). US 2 680 740 (Rldne-Poulenc; 1954; F-prior. 1951). Formulation(s): tabl. 25 mg Trade Name(s): D: Daraprim (Glaxo Fansidar (Roche)-comb. USA: Daraprim (Glaxo Wellcome) Maloprim (Wellcome)- Wellcome) Pyrimethamin-Hey1 (Heyl) comb. Fansldar (Roche)-comb. F: Fansidar (Roche)-comb. I: - Metakelfin (Pharmacia & with sulfadioxine Malocide (Specia) Upjohn)-comb. GB: Daraprim (Burroughs J: Fansidar (Roche)-comb. Wellcomc) Pyrithione zinc (Zinc pyrithione) ATC: DllAX Use: antiseborrhoic, fungicide, bactericide RN: 13463-41-7 MF: C,,H,N,O,S,Zn MW: 317.71 EINECS: 236-671-3 LD,,,: 160 mg/kg (M, p.0.); 177 mglkg (R, p.0.); 600 mglkg (dog, p.0.) CN: (T-4)-bis(l-hydroxy-2(1H)-pyridinethionato-O,S)zinc I Pyrithyldionc P 1759 2-chloro- ocetic acid 2-chloro- 2-mercopto- 1 -hydroxy-2- pyridine pyridine pyridine pyridinethione (I) oxide oxide / Pyrithione zinc 1 Reference(s): GB 761 171 (Olin Mathieson; appl. 19.5.1954; USA-prior. 29.5.1953). pyrithione: US 2 745 826 (Oh Mathieson; 15.5.1956; appl. 16.12.1953). Shaw, E. et al.: J. Am. Chem. Soc. (JACSAT) 72,4362 (1950). use: US 3 236 733 (Procter & Gamble; 22.2.1966; prior. 5.9.1963, 1.4.1965). US 3 281 366 (Procter & Gamble; 25.10.1966; prior. 25.8.1964.4.1 1.1965). Formulation(s): cream 1 gI100 g; shampoo 1 %, 2 % Trade Name(s): D: de-squaman hermal Ultrex antipelliculaire (Lab. USA: DHS Zinc (Person RL (Hermal) Pharmaeurop); wfm Covey) F: Fonderma (Doms); wfm GB: Polystar AF (Stiefe1)-comb. Head & Shoulders (Procter J: Merit (Kao) & Gamble) Pyrithyldione ATC: N05CE03 Use: hypnotic, sedative RN: 77-04-3 MF: C,H,,NO, MW: 167.21 EINECS: 201-000-5 LD,,: 780 mgkg (R, p.0.) CN: 3,3-diethyl-2,4(1 H,3H)-pyridinedione methyl ethyl 2.2-diethyl- ethyl 2.2-diethyl- formote ocetoocetate y-(hydroxymethy1ene)- ocetoacetote 1 1760 P Pyritinol Keference(s): US 2 090 068 (Hoffmann-La Roche; 1937; D-prior. 1935). Trade Name(s): D: Perscdon Roche (Roche): I: Hibersulfan (Ecobi)-comb.; wfm wfrn Pyritinol (Pyrithioxine) ATC: N06BX02 Use: neurotropic, nootropic RN: 1098-97-1 MF: C,,H20N20,S, MW: 368.48 EINECS: 214- 150- 1 CN: 3,3'-[dithiobis(methylene)]bis[5-hydroxy-6-methyl-4-pyridinemethanol] dihydrochloride monohydrate RN: 10049-83-9 MF: Cl6HmN2O4S2. 2HCl . H20 MW. 459.42 EINECS: 233-178-5 LD,,,: 221 mg/kg (M, i.v.); 5786 mglkg (M, p.0.); 300 mglkg (R, i.v.); 6 g/kg (R, pa.) 3.4- bis(bromomethy1)- 5-hydroxy-6-methyl- pyridine hydrobromide (from pyridoxine) potassium ethyl- xonthogenote HO Pyritinol US 3 010 966 (E. Merck AG; 28.1 1.1961; D-prior. 21.3.1958). DE 1 135 460 (E. Merck AG; appl. 21.3.1958). DE 1 197 455 (E. Merck AG; appl. 27.8.1960). alternative syntheses: DAS 1 210 429 (E. Merck AG; appl. 3.8.1963). DE 1 222 062 (E. Merck AG; appl. 8.2.1964). DE 1 227 908 (E. Merck AG; appl. 8.2.1964). DOS 1 695 402 (E. Merck AG; appl. 25.3.1967). Fomulation(s): amp. 200 mg; drg. 100 mg, 200 mg; susp. 80.5 mgf5 ml, 100 mg; syrup 100 mg (as hydrochloride) Trade Name(s): D: Ardeyceryl P F: Biontabol (Merck- I: Encefabol (Bracco) (Ardeypharm) C1Cvenot)-comb.; wfm J: Chioebon (Kyowa Encephabol (Merck) Enckphabol (Merck- Yakuhin) ClCvcnot); wfm Divalvdn (Nippon Kayaku) . isobutyroldehyde Pyridoxine + 2-butene-1.4-diol) rnethyloxozole 1756 P Pyridoxine cthyl 2-chloro- acetoacetote ethyl 4-methyl- 4-methyloxozole- 5-cyono- 4- oxozole- 5- 5-corboxomide methyloxozole. mglkg (dog, p.0.) CN: (T-4)-bis(l-hydroxy-2(1H)-pyridinethionato-O,S)zinc I Pyrithyldionc P 1759 2-chloro- ocetic acid 2-chloro- 2-mercopto- 1 -hydroxy- 2- pyridine pyridine pyridine. RN: 5340 3-9 7-7 MF: C9H,2N406S . C8HIIN03 MW: 473.46 EINECS: 25 8-5 21 -6 LD,,: 1 glkg(M,i.v.); 1600mg/kg(M,p.o.) CN: 3,7-dihydro- l,3-dimethyl- 7-[ 2-( sulfooxy)ethyl ]-1 H-purine-2,6-dione compd.