Pinazepam P 1641 Pinazepam ATC: NO~BAI~ Use: tranquilizer RN: 52463-83-9 MF: ClxH,,ClN20 MW: 308.77 EINECS: 257-934-9 LD,,: 1302 mgkg (M, p.0.); 5819 mglkg (R, p.0.) CN: 7-chloro- 1,3-dihydro-5-phenyl- 1 -(2-propyny1)-2H- I ,4-benzodiazepin-2-one 7-chloro-1.3-dihydro- 5-phenyl-2H-1.4-bento- diozepin-2-one (cf. diazepam synthesis) 2-propynyl bromide Reference(s): DOS 2 339 790 (Zambeletti; appl. 6.8.1973; I-prior. 9.8.1972). GB 1 406 946 (Zambeletti; valid from 28.6.1973; I-prior. 9.8.1972). alternative synthesis: US 3 842 094 (Delmar Chem.; 15.10.1974; prior. 3 1.8.1972). Formulation(s): cps. 2.5 mg, 5 mg, 10 mg Trade Name(s): 1: Domar (Teofarma) Pindolol ATC: C07AA03 Use: beta blocking agent RN: 13523-86-9 MF: Cl,H,,N2O2 MW: 248.33 EINECS: 236-867-9 LD,,: 22.6 mglkg (M, i.v.); 235 mgkg (M, p.0.); 51 mglkg (R, i.v.); 263 mglkg (R, p.0.) CN: 1-(1H-indol-4-yloxy)-3-[(l-methylethyl)amino]-2-propanol epichloro- hydrin 1642 P Pioglitazone Reference(s): DE 1 620 342 (Sandoz; prior. 26.1.1966). US 3 471 515 (Sandoz; 7.10.1967; CH-prior. 1.2.1965). CH 453 363 (Sandoz; appl. 1.2.1965). Formulation(s): amp. 0.4 mgl2 rnl; eye drops 5 mglml, 10 mg/5 ml; s. r. tabl. 20 mg; tabl. 2.5 mg, 5 mg, 10 mg, 15 mg Trade Name(s): D: Durapindol (durachemie) Visken (Novartis Pharma; I: Visken (Novartis Farma; Glauco-Stulln (Phar~na 1971) 1973) Stulln) F: Viskaldix (Novartis)-comb. J: Carviskcn (Sankyo) Pindoptan (Kanoldt) Visken (Novartis; 1971) USA: Visken (Sandoz; 1982); Viskaldix (Novartis GB: Viskaldix (Novanis)-comb. wfm Pharrna)-comb. Visken (Novartis; 1974) generics Pioglitazone (AD-4833; U 721 07) ATC: AIOBG03 Use: antidiabetic, insulinenhancer RN: 11 1025-46-8 MF: CL,H20N203S MW: 356.45 CN: (f)-5-[[4-[2-(5-Ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2,4-thiazolidinedione hydrochloride RN: 1 12529-15-4 MF: C19H20N203S . HCl MW: 392.91 2-(5-ethyl-2- 4-fluoro-l- pyridy1)ethonal (I) nitrobenzene CH30H I1 2. H~C,&~F~ 111 2. methyl acrylote 0 s H3C-COONa , H~C-OH H~c'-o_ elCH3 + Y-NH~ . n ' N \ Br HzN sodium acetate methyl 2-bromo-3-[4-[Z-(5- thioureo ethyl-2-pyridyl)ethoxy]phenyl]- propionote (111) MI 2N HCl 3 b H3Cx mSgO HCI 0 i I/ 0 0 0") 1 Pioglitorone hydrochloride Pioglitazone P 1643 4-lluoro- benzonitrile CN Raney-Ni, oq. HCOOH formic acid 4-[z-(5-ethylpyridin- 2-yl)ethoxy]benzonitrile 4-[Z-(5-ethylpyridin- 2-yl)ethoxy]benzaldehyde (V) 2.4-thiozolidine- dione &ccH, Cl- , oq, NoOH \CH3 I + H,C- '\;acH3 0 benzyltributyl- N 0' "0 ammonium chloride (VII) ("w (Q) VII, oq. NoOH HO 4-hydroxy- benzoldehyde Pioglitozone NaBH,, aq. NoOH, DMF. COCI,, silicagel VI Pioglitazone Reference(s): a Sohda, T. et al.: Arzneim Forsch. (ARZNAD) 40 (I), 37-42 (1990). EP 193 256 (Takeda; appl. 15.1.1986; J-prior. 19.1.1985). b,cEP 506 273 (Takeda; appl. 16.3.1992; J-prior. 25.3.1991). Momose, Y. et al.: Chem. Pharm. Bull. (CPBTAL) 39 (6), 1440-1445 (1991). c EP 186 340 (Takeda; appl. 26.6.1997; J-prior. 27.6.1996). d WO 9 313 095 (Upjohn; appl. 4.12.1992; USA-prior. 20.12.1991). synthesis of metabolites: Tanis, S.P. et a].: J. Med. Chem. (JMCMAR) 39 (26), 5053-5063 (1996). WO 9 322 445 (Upjohn; appl. 21.4.1993; USA-prior. 5.5.1992). Trade Name(s): USA: Actos (TakedaILilly; 1999) Pipamazine ATC: A04 Use: anti-emetic RN: 84-04-8 MF: C2,H2C1N,OS MW: 401.96 EINECS: 201-512-9 LD,,: 370 mglkg (M, p.0.); 620 mgtkg (R, p.0.) CN: 1-[3-(2-chloro-l0H-phenothiazin-lO-yl)propyl]-4-piperidinecarboxamide 1. NaNH2 2. Br-C' - 1. sodium amide 2-chloro- phenothiozine I + 2. 1 -bromo-3-chloro- propane 2-chlaro-10-(3-chlora- propy1)phenothiazine (I) K2C0,. Nal piperidine-4- carboxamide Reference(s): US 2 957 870 (Searle; 25.10.1960; prior. 5.1 1.1957). DE 1 089 386 (Searle; appl. 8.11.1957; USA-prior. 15.1 1.1956). Trade Name(s): F: Nausidol (GrCmy- USA: Momidine (Searle); wfm Longuet); wfm Pipamperone (Floropipamide) ATC: NOSAW5 Use: neuroleptic RN: 1893-33-0 MF: C2,H3,FN302 MW: 375.49 LD,,: 66 mglkg (M, i.v.); 490 mgkg (M, p.0.); 48 mglkg (R, i.v.); 160 mgkg (R, p.0.) CN: 1 '-[4-(4-fluorophenyl)-4-oxobutyl][1,4'-bipiperidine]-4'-carboxamide I-benzyl-4- potossium piperidine 1 -benzyl-4-cyono- 1 -benzyl-4- piperidone cyanide hydrochloride 4-piperidino- piperidinopiperidine- piperidine 4-carboxamide (1) butyrophenone 4-piperidino- piperidine-4- carboxomide I Pipornperone Reference(s): US 3 041 344 (Janssen; 26.6.1962; prior. 1.12.1960). DE 1 235 319 (Janssen; appl. 28.1 1.1961; USA-prior. 1.12.1960). Westeringh, C. van de et at.: J. Med. Chem. (JMCMAR) 7,619 (1964). Formulation(s): syrup 20 mgl5 ml; tabl. 40 mg (as dihydrochloride) Trade Name(s): D: Dipiperon (Janssen-Cilag) F: Dipiperon (Janssen-Cilag; I: as dihydrochloride) J: Piperonil (Lusofarmaco) Propitan (Eisai) Pipazetate (Pipazethate) ATC: ROSDBI 1 Use: antitussive RN: 2167-85-3 MF: C,,H,,N,O,S MW: 399.52 EINECS: 218-508-8 LD,,: 13.14 mgtkg (M, i.v.) CN: 10H-pyrido[3,2-6][1,4]benzothiazine-lO-carboxylic acid 2-[2-(1-piperidiny1)ethoxylethyl ester monohydrochloride RN: 6056-1 1-7 MF: C2,H,5N303S . HCI MW: 435.98 EINECS: 227-980-4 LD,,: 16 mglkg (M, i.v.); 214 mgkg (M, p.0.); 17 mglkg (R, i.v.); 530 mgkg (R, p.0.); 8 mgkg (dog, i.v.); 80 mglkg (dog, p.0.) 1 -azaphenothiozine phosgene 1 -azaphenothiozine- 10-corbonyl chloride (I) 1646 P Pipebuzone 2-(2-piperidinoeth0wy)- ethanol Pipazetate I Reference(s): DE 1 055 538 (Degussa; appl. 15.6.1957). US 2 989 529 (Degussa; 20.6.1961; D-prior. 15.6.1957). Formrrlution(s): drops 40 mg; suppos. 10 mg; syrup 10 mg/5 ml (as hydrochloride) Trade Name(s): D: Selvigon (ASTA Medica GB: Selvigon (Smith Kline & I: Selvigon (RhBne-Poulenc AWD) French); wfm Rorer) Pipebuzone ATC: MOI AA; SOIBC Use: anti-inflammatory, antipyretic, analgesic RN: 273 15-91 -9 MF: C2,H3,N4O2 MW: 420.56 EINECS: 248-398-7 CN: 4-butyl-4-[(4-methyl-l-piperazinyl)methyl]-l,2-diphenyl-3,5-pyr~zolidinedione phenylbutazone form- I-rnethyi- Pipebuzone (4. v.) aldehyde piperazine Referenceis): DE 1 958 722 (Lab. Dausse; appl. 22.1 1.1969; F-prior. 25.11.1968, 19.2.1969). Formulation(s): cps. 150 mg; suppos. 300 mg Trade Name(s): F: ~larzone-~ausse (Dausse); wfm Pipecuronium bromide P 1647 Pipecuronium bromide ATC: M03AC06 Use: muscle relaxant, non-depolarizing neuromuscular blocker RN: LD~O: CN: 52212-02-9 MF: C,,H,,Br,N404 MW: 762.71 EINECS: 257-740-4 55300 nglkg (M, i.m.1; 70600 ndkg (M, i.p.); 29700 ngkg (M, i.v.); 22 mgkg (M, p.0.); 60500 nag (M, s.c.); 450 pglkg (R, i.p.); 173 pg (R, i.p.); 173 pg (R, i.v.) 4,4'-[(2P,3a,5a,16~,17P)-3,17-bis(acetyloxy)andrastane-2,16-diyl]bis[l, 1-dimethylpiperazinium] dibromide perbenzoic acid 5a-ondrost -2 - isopropenyl 17-acetoxy-5~- en-17-one acetate androsta-2.16-diene 2a.3a:I 6a.l la-diep- piperazine I Pipecuranium bromide 1 1 NaBH, 3. methyl bromide axy-l7,+acetoxy-5~- I androstane (I) H Br- Reference(s): DE 2 337 882 (Richter Gedeon; appl. 26.7.1973; H-prior. 27.7.1972). NL 7 3 10 389 (Richter Gedeon; appl. 26.7.1973; H-prior. 27.7.1972). Tuba, 2.: Arzneim Forsch. (ARZNAD) 30,342 (1980). Formulation(s): vial 10 mgl10 ml Trade Name(s): USA: Arduan (Organon: 1990) Pipemidic acid (Acide pipemidique; Piperamic acid) ATC: G04AB03 Use: chemotherapeutic (urinary tract infcctions), antibacterial RN: 51940-44-4 MF: Cl,H,,N503 MW: 303.32 EINECS: 257-530-2 LD,: 300 mglkg (M, i.v.); 5 glkg (M, p.0.); 529 mg/kg (R, i.v.); 16 glkg (R, p.0.); >2 dkg (dog, p.o.1 CN: 8-ethyl-5,8-dihydro-5-0x0-2-(I -piperazinyl)pyrido[2,3-qpyrimidine-6-caboxylic acid trihydrate RN: 72571-82-5 MF: Cl,H,,N,O,. 3H,O MW: 357.37 1648 P Pipemidic acid 4-omino-2-methyl- dieihyl elho~~rnethylene- thiopyrimidine molonote boiling diphenyl ether I b 1. NoOH or C2HSI/KOH or OMF + n 2. diethyl sulfote or ethyl iodide 8-ethyl-2-methylthio-5-0x0- piperozine Pipemidic acid 5,8-dihydropyrido[2,3-dl- pyrimidine-6-corboxylic acid (11) Reference(s): US 3 950 338 (Roger Bellon; 13.4.1976; appl. 31.7.1973; F-prior. 2.8.1972). DE 2 338 325 (Roger Bellon; prior. 1.8.1973). DOS 2 341 146 (6inippon; Gpl. 14.8.1973; J-prior. 14.8.1972, 19.12.1972, 22.12.1972, 26.12.1972, 27.12.1972,25.5.1973, 19.6.1973). US 3 887 557 (Dainippon; 3.6.1975; J-prior. 14.8.1972). US 3 962 443 (Dainippon; 8.6.1976; J-prior. 14.8.1972, 19.12.1972, 22.12.1972, 26.12.1972,27.12.1972, 25.5.1973, 19.6.1973). Mats~moto, J.; Minami, S.: J. Med. Chem. (JMCMAR) 18,74 (1975). precursor (8-ethyl-2-methylthio-5-oxo-5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid): DOS 2 143 369 (Dainippon; appl. 30.8.1971; J-prior. 29.8.1970) GB 1 129 358 (Dainippon; appl. 8.9.1966; J-prior. 8.9.1965, 10.9.1965). alternative synthesis: DOS 2 338 325 (Roger Bellon; appl. 1.8.1973; F-prior. 2.8.1972). Formulation(s): cps. 200 mg, 400 mg (as trihydrate) Trade Name(s): D: Deblaston (Madaus; 1978) F: Pipram (RhBne-Poulenc Rorer Bellon; 1975) I: Acipem (Caber) Diperpen (Francia Farm.) Filtrax (Ipso-Pharma) Pipeacid (Tosi-Novara) Pipedac (Teofarma) Pipefort (Lampugnani) Urosan (AGIPS) Pipemid (Gentili) Urosetic (Finmedical) Pipram (RhSne-Poulenc Urotractin (SmithKline Rorer; 1979) Beecham) Pipurin (NCSN) Uroval (Firma) Tractur (Damor) J: Dolcol (Dainippon; 1979) Urodene (O.F.F.) Uropimid (CT) Pipenzolate bromide P 1649 Pipenzolate bromide ATC: A03AB14 Use: anticholinergic, antispasmodic RN: 125-51-9 MF: C22H28BrN03 MW: 434.37 EINECS: 204-741-2 LDS,: 18 mgkg (M, i.v.); 1140 mglkg (M, p.0.); 18 mgkg (R, i.v.); 916 mgkg (R, p.0.) CN: I-ethyl-3-[(hydroxydiphenylacetyl)oxy]-1-methylpiperidinium bromide benzilic 1 -ethyl-3- acid chloropiperidine 1 Pipenzolate bromide 1 Reference(s): US 2 918 406 (Lakeside Labs.; 22.12.1959; appl. 8.4.1957; prior. 18.8.1950). Formulation(s): tabl. 5 mg Trade Nanie(s): F: Piptal (Roger Bellon); wfrn I: Piper (Panthox & Burck); USA: Piptal (Hoechst Marion GB: Piptal (M.C.P. wfm Roussel; Merrell-National); Pharmaceuticals); wfm Piptal (RBS Pharma); wfm wfm Piptalin (M.C.P. Piptal (Roger Bellon); wfm Pharmaceuticals)-comb.; J: Piptal (Chugai) wfrn Piperacetazine ATC: NOSAC Use: neuroleptie, antihistaminic RN: 3819-00-9 MF: C,,H,,N,O,S MW: 410.58 EINECS: 223-312-0 LD,,: 575 mgkg (M, p.0.); 390 mgkg (R, p.0.) CN: 1-[10-[3-[4-(2-hydroxyethyl)-1-piperidinyl]propyl]-10H-phenothiazin-2-yl]ethanone 1. NoNHZ or KOH 2. C'-Br C'? -, ,I& 2. l -brorno-3- a:dcH3 chloropropone 2-ocetyl-10-(3-chloro- propyl)phenothiozine (I) 1650 P Piperacillin Reference(s): CB 861 807 (Searle; appl. 6.8.1959; USA-prior. 7.8.1958). 4-(2-hydroxyethy1)- piperidine Forn~ulation(s): tabl. 10 mg HO Piperocetazine Trade Name(s): USA: Quide (Dow); wfm Piperacillin ATC: JOlCA12 Use: anlibiolic RN: 61477-96-1 MF: C2,H2,N507S MW: 517.56 EINECS: 262-81 1-8 LD,,: 5 g/kg (M, i.v.) CN: [2S-[2a,5a,6~(S*)]]-6-[[[[(4-ethyl-2,3-dioxo-1-piperaztnyl)carbonyl]amino]phenylacetyl]amino]-3,3- dimethyl-7-oxo-4-thia-l-azabicyclo[3.2.0]heptane-2-carboxylic acid 2. phosgene N-ethylethylene- diethyl oxalote 2.3-dioxo-1 -ethyl- diamine piperazine Reference(s): DOS 2 519 400 (Toyama; appl. 30.4.1975; J-prior. 9.5.1974, 13.5.1974, 31.5.1974, 13.8.1974,26.9.1974, 13.12.1974, 27.3.1975). DOS 2 824 610 (Toyama; appl. 5.6.1978; J-prior. 8.6.1977). GB 1508062(Toyama; appl. 28.4.1975; J-prior. 9.5.1974, 13.5.1974,31.5.1974,24.7.1974,7.8.1974,13.8.1974, 26.9.1974, 12.10.1974, 28.10.1974, 6.12.1974, 13.12.1974, 17.2.1975, 26.3.1975, 27.3.1975). US 4 1 12 090 (Toyama; 5.9.1978; J-prior. 13.12.1974). 0 0 2,3-dioxo-4-ethyl- ompicillin precursors: US 4 087 424 (Toyama; 2.5.1978; J-prior. 9.5.1974). Piperocillin 1 -piperozinecarbonyl (q v.1 chloride (I) . &apos ;-[ 4-( 4-fluorophenyl )-4 -oxobutyl][1,4'-bipiperidine ]-4 '-carboxamide I-benzyl- 4- potossium piperidine 1 -benzyl-4-cyono- 1 -benzyl- 4- piperidone cyanide hydrochloride 4-piperidino-. CN: (f )-5 -[ [ 4-[ 2-( 5-Ethyl-2-pyridinyl)ethoxy]phenyl]methyl ]-2 ,4-thiazolidinedione hydrochloride RN: 1 1252 9-1 5-4 MF: C19H20N203S . HCl MW: 392.91 2-( 5-ethyl- 2- 4-fluoro-l- pyridy1)ethonal. 5246 3-8 3-9 MF: ClxH,,ClN20 MW: 308.77 EINECS: 25 7-9 3 4-9 LD,,: 1302 mgkg (M, p.0.); 5819 mglkg (R, p.0.) CN: 7-chloro- 1,3-dihydro-5-phenyl- 1 -( 2-propyny1 )-2 H- I ,4-benzodiazepin-2-one