Pharmaceutical Substances Syntheses, Patents, Applications - Part 164 ppsx

Pifarnine P 1631 Picotarnide I Referencefs): , , FR 2 100 850 (Manetti Roberts; appl. 30.6.197 I; I-prior. 1.7.1970). DE 2 506 209 (Manetti Roberts; appl. 14.2.1975). - US 3 973 026 (Manetti Roberts; 3.8.1976; prior. 5.2.1975). BE 851 967 (Manetti Roberts; appl. 1.3.1977). Selleri. R. et al.: Chim. Ther. (CHTPBA) 6, 203 (1971). Formulation(s): tabl. 300 mg (as hydrate) Trade Name(s): I: Plactidil (Samil) Pifarnine ATC: A02B Use: peptic ulcer therapeutic, gastric acid secretion inhibitor RN: 56208-01-6 MF: C,7H,N,02 MW: 424.63 LD,: 500 mglkg (M, i.p.) CN: 1-(1,3-benzodioxol-5-ylmethyl)-4-(3,7,11-trimethyl-2,6,1O-dodecatrienyl)piperazine 1 -piperonyl- piperozine Reference (s): ES 452 269 (Boehringer Mannh.; appl. 12.1 1.1976). Bianchetti, A. et al.: Eur. J. Med. Chem. (EJMCA5) 9,555 (1974); 10,585 (1975). 1-brorno-3.7.1 1 -trimethyl- Trade Name(s): I: Pifazin (Pierrel); wfm Pifornine 2.6.10-dodecotriene 1632 P Pifoxime Pifoxime (Pixifenidurn) ATC: MOlAB Use: anti-inflammatory RN: 31224-92-7 MF: C,,H2,N203 MW: 276.34 LD,,: 1 gkg (M, P.o.) CN: 1-[[4-[1-(hydroxyimino)ethyl]phenoxy]acetyl]piperidine chloroacetic 4'-hydroxy- ocid ocetophenone 4-ocetylphenoxy- ocetic ocid (1) piperidine I Pifoxime Reference(s): US 3 907 792 (A. Mieville; 23.9.1975; CH-prior. 31.1.1969, 28.8.1969). Trade Name(s): F: Flamanil (Salvoxyl- Wander); wfm Piketoprofen ATC: M02AA Use: topical non-steroidal anti- inflammatory and analgesic, ketoprofen derivative RN: 60576-13-8 MF: C22H20N202 MW: 344.41 CN: 3-benzoyl-cr-methyl-N-(4-methylI2-pyridinyl)benzeneacetamide monohydrochloride RN: 59512-37-7 MF: C,,H2,N202. HC1 MW: 380.88 - - rnethylpyridine ([I) ketoprofen (1) (4. v-) Pildralazine P 1633 1. PCIJ 2. 1 0 n 1. phosphorous trichloride Reference(s): a GB 1 436 502 (A. Gallardo SA; appl. 10.4.1974; E-prior. 10.4.1973). b BE 882 7 1 1 (Fordonal SA; appl. 3 1.7.1980; E-prior. 25.2.1980). Formulation(s): aerosol 20 mglml Trade Name(s): E: Calmatel (Almirall; 1985) Pildralazine ATC: COlD . Use: hypotensive, vasodilator RN: 64000-73-3 MF: C8H,,N,0 MW: 197.24 CN: 6-[(2-hydroxypropyl)methylamino]-3(2H)-pyridazinone hydrazone N-methyl- 3.6-dichloro- 2-hydroxy- pyridazine propylamine OH yH3 2. OHC~ - -1 1. hydrazine MI hydrate hydroxypropyl)- methylomino]- pyridazine Pildralazine Pifferi, G.; Parravicini, F.; Carpi, C.; Dorigotti, L.: J. Med. Chern. (JMCMAR) 18, 741 (1975). DOS 2 154 245 (ISF; appl. 30.10.1971; I-prior. 15.12.1970). Trade Name(s): I: Atensil (ISF); wfm 1634 P Pilocarpine Pilocarpine ATC: N07AXOl; SOlEBOl Use: parasympathomimetic, miotic RN: 92-1 3-7 MF: C, ,H16N202 MW: 208.26 EINECS: 202- 128-4 LD,,,: 61.9 mglkg (M, i.v.); 119 mglkg (M, p.0.); 88.5 mglkg (R, i.v.); 402 mg/kg (R, p.0.) CN: (3S-cis)-3-ethyldihydro-4-[(1-me~hyl-1H-imidazol-5-yl)methyl]-2(3H)-furanone monohy drochloride RN: 54-7 1-7 MF: C, ,H,,N,O, . HCI MW: 244.72 EINECS: 200-212-5 LD,,,: 150 mglkg (M, i.v.); 200 mglkg (M, p.0.) borate RN: 16509-56-1 MF: C,,H,&O, . xBH303 MW: unspecified mononitrate RN: 148-72-1 MF: CllH16N20, . HNO, MW: 271.27 EINECS: 205-723-7 LD,,,: 345 mglkg (M, i.v.); 91 l mglkg (R, p.0.) By extraction of Juborandi leaves (especially Pilocurpus microphvllus Stapf.) and isolation as hydrochloride. Reference(s): Ullmanns Encykl. Tech. Chem., 3. Aufl., Vol. 3,277. BIOS Final Reports No. 766, 233. parnoate: DAS 2 462081 (Merck & Co., appl. 16.12.1974; USA-prior. 17.12.1973, 31.10.1974) Formulation(s): eye drops 0.5 %, 1 %, 2 %, 3 %, 4 %; eye ointment 10 mg/g, 20 mg/g, 30 mglg; gel 40 mglg (as hydrochloride) Trade Nume(s): D: Isopto-Pilocarpin (Alcon) Pilocarpol (Winzer) Pilomann (Mann) Spersa carpin (CIBA Vision) Vistacarpin (Pharm- Allergan) numerous generics and combination preparations F: Chibro-Pilocarpine (Merck Sharp & Dohme-Chibret) Isopto-Pilocarpine (Alcon) Pilo (Chauvin) Pilocarpine Martinet (CIBA Vision Ophthalmics) GB: Isoptocarpin (Alcon) Minims Pilocarpine (Chauvin; as nitrate) Ocusert Pilo (Dominion) Pilogel (Alcon) Salagen (Chiron) Sno-Pilo (Chauvin) I: Dropilton (Bruschettim) Liocarpina (SIFI) Pilocarpina Lux (Allergan) Pilogel (Alcon) Pilotonina (Farmila) Salagen (Chiron Italia) generics J: generic preparations USA. Salagen (MGI) Pilsicainide P 1635 Pilsicainide (SUN- 1 165) ATC: COlBC Use: class Ic antiarrhythmic RN: 88069-67-4 MF: C,,H,N,O MW: 272.39 LD,,): 17 mgkg (M, i.v.); 175 mglkg (M, p.0.); I8 mglkg (R, i.v.); 255 mglkg (R, p.0.); 53 mgkg (dog, p.0.) CN: N-(2,6-dimethylphenyl)tetrahydro-1H-pyrrolizine-7a(5H)-acetamide monohydrochloride RN: 88069-49-2 MF: C,,H,N,O . HCI MW: 308.85 LD,,): 222 mg/kg (M, p.0.); 410 mglkg (M, s.c.); 260 mglkg (R, p.0.); 87 mgkg (rabbit, p.0.); 50 mglkg (dog, p.0.) H3cQ H2N 0 + (COOH CH, ' + 2. 2.6-dimethyl- ' COOH aniline (1) 1H-2.3.5.6- molonic 7a-carboxymethyl- tetrahydro- acid pyrrolizidine pyrrolizine I Pihicainide I Reference(s): EP 89 061 (Suntory; appl. 15.3.1983; J-prior. 16.3.1982). US 4 564 624 (Suntory; 14.1.1986; appl. 10.3.1983; J-prior. 16.3.1982). JP9 167 591 (Suntory; appl. 11.3.1983). Formulation(s): cps. 25 mg, 50 mg (as hydrochloride) Trade Name(s): J: Sunrythm (Suntory; Daiichi Seiyaku; 199 1) Pimefylline ATC: COlD Use: vasodilator RN: 10001-43-1 MF: C,,H,8N,02 MW: 314.35 LD,,,: 402 mgkg (M, i.v.); 1900 mglkg (M, p.0.) CN: 3,7-dihydro- 1,3-dimethyl-7-[2-[(3-pyridinylmethyl)amino]ethyl]- 1 H-purine-2,6-dione 1636 P Pimeprofen nicotinate (1:l) RN: 10058-07-8 MF: C,sH,8N602. C6HSN02 MW: 437.46 EINECS: 233-185-3 LD,,: 470 mglkg (M, i.v.); 2530 mglkg (M, p.0.); 3700 mgkg (R, p.o.1 theophylline 1,2-dibromo- 7-(2- bromoethyl)- ethane theophylline (1) Reference(s): US 3 350 400 (Eprova; 31.10.1967; CH-prior. 12.1.1965). 3-(aminomethyl)- Trade Name(s): I: Teonicon (Neopharmed); J: Teonicon (Neopharmed) wfm Pirnefy\line Pimeprofen (Ibuprofen piconol) pyridine ATC: MOIAE; M02AA Use: anti-inflammatory RN: 64622-45-3 MF: C,,H,,NO, - MW: 297.40 EINECS: 264-979-8 LD,,,: 1980 mglkg (M, p.0.); 1440 mgkg (R, p.0.); 74 glkg (dog, p.0.) CN: a-methyl-4-(2-methylpropy1)benzeneacetic acid 2-pyridinylmethyl ester ibuprofen sodium salt 2-chloromethyl- Pimeprofen (9. v.) pyridine Pimobendan P 1637 triethyl- CH3 amine 2-(4-isobutylphenyl)- P-hydroxy- propionyl chloride rnethyl- (from ibuprofen) pyridine Reference(s): DOS 2 658 610 (Hisamitsu; appl. 23.12.1976; J-prior. 24.12.1975). US 4 150 137 (Hisamitsu; 17.4.1979; J-prior. 24.12.1975). Formulation(s): cream 5 %; ointment 5 % Trade Name(s): J: Staderm (Torii) Vesicum (Hisamitsu) Pimobendan (UD-CG 1 15; UD-CG 1 15BS) ATC: COlCE Use: cardiotonic, PDE 111-inhibitor, vasodilator RN: 74150-27-9 MF: C,,H,,N402 MW: 334.38 LDso: >2 g/kg (M, p.0.); 72 mgkg (R, i.v.); 950 mgkg (R, p.0.) CN: 4,5-dihydro-6-[2-(4-methoxyphenyl)-1H-benzimidazol-5-yl]-5-methyl-3(2H)-pyrida~inone hydrochloride RN: 74149-75-0 MF: C19H18N402 . xHC1 MW: unspecified monohy drochloride RN: 77469-98-8 MF: C,yH,8N402. HCl MW: 370.84 racemate RN: 118428-36-7 MF: C,,HI,N4O2 MW: 334.38 LDS6 75 mgflcg (R, i.v.) (-)-enantiomer RN: 118428-37-8 MF: C,,H,,N402 MW: 334.38 LD,: 100 mglkg (R, i.v.) (+)-enantiomer RN: 118428-38-9 MF: C,,HI,N4O2 MW: 334.38 LD,,: 75 mgkg (R, i.v.) 4-anisoyl methyl 3-(4-amino- chlon'de 3-nitrobenzayl)- butyrate methyl 3-[4-(4-methoxy- benzoylarnino)-3-nitro- benzoyl]butyrate (I) 1638 P Pimozide hydrozine hydrate ,- A, 1 Pimobendon I Reference (s): EP 8 39 1 (Thomae GmbH; appl. 3.2.1980; D-prior. 25.8.1978, 1.6.1979). separatiun of enanliomers: DE 3 728 244 (Thornae GmbH; appl. 25.8.1987; D-prior. 25.8.1987). oral formulalion: DE 4 001 622 (Thomae GmbH; appl. 20.1.1990; D-prior. 20.1.1990). use for treatment of aslhma: DE 4 001 623 (Thomae GmbH; appl. 20.1.1Y90; D-prior. 20.1.1990). combination with P-blockers: EP 387 762 (Thomac GmbH; appl. 12.3.1990; D-prior. 16.3.1989). use for trealing erectile dysfunction: DE 4 338 948 (J. Carlen; appl. 15.1 1.1993; D-prior. l5.ll.1~93). Formulalion(s): cps. 1.25 mg, 2.5 rng Trade Nameis): J: Acardi (Nippon Boehringer) Pimozide ATC: NOSAG02 Use: neuroleptic RN: 2062-78-4 MF: C28H29F,N,0 MW: 461.56 EINECS: 218-171 -7 LD,,,: 14 mglkg (M, i.v.); 228 mglkg (M, p.0.); 90 mglkg (R, i.v.); 1 I00 mg/kg (R, p.0.); 32 mglkg (dog, i.v.); 40 mglkg (dog, p.0.) CN: 1 -[I -[4,4-his(4-fluorophenyl)butyl]-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one Pinacidil P 1639 4-lluorophenyl- cyclopropane- magnesium corboxylic ocid bromide ethyl ester 4.4-bis(4-fluoro- phenyl)butyl chloride bis(4-(luorophenyl)- 1,l -bis(4-fluorophenyl)- cyclopropylcorbinol 4-chioro-l -butene (1) _______* 1 -(4-piperidyl)-2-benz- imidozolonc (cf. benperidol synthesis) I Pimozide DAS 1 470 124 (Janssen; appl. 12.6.1963; USA-prior. 13.6.1962, 11.6.1963). FR-M 3 695 (Janssen; appl. 12.9.1963; USA-prior. 11.6.1963). US 3 196 157 (Janssen; 20.7.1965; appl. 11.6.1963). DD 243 284 (VEB Arzneimittelwerk Dresden; appl. 13.12.1985). Formulation(s): tabl. 1 mg, 2 mg, 4 mg Trade Name(s): D: Antalon (ASTA Medica F: Orap (Janssen-Cilag) J: Orap (Fujisawa) AWD) GB: Orap (Janssen-Cilag) USA: Orap (Gate) Orap (Janssen-Cilag) I: Orap (Jansscn-Cilag) Pinacidil (P-1134) ATC: C02DGOl Use: antihypertensive, vasodilator, potassium channel activator RN: 60560-33-0 MF: C,,H,,N, MW: 245.33 EINECS: 262-294-9 LD,,: 177 mdkg (M, i.v.); 412 mgtkg (M, p.0.); 155 mgkg (R, i.v.); 210 mg/kg (R, p.0.) CN: N-cyano-N-4-pyridinyl-N'-(1,2,2-trimethylpropyl)guanidine monohydrate RN: 8537 1-64-8 MF: C,,H,,N, . H20 MW: 263.35 LD,,: 600 rnglkg (M, p.0.); 570 mg/kg (R, p.0.) 1640 P Pinacidil 4-pyridyl 1.2.2-trimethyl- isothiocyonote propylornine N-(4-pyridy1)-N'- (1.2.2-trirnethylpr0pyl)- thloureo (I) (CHI DCC. H,CyNyCH3 CH3CH3 I + H2N-CN dicyclohexylcorbodiirnide. ethyldiisopropylarnine cyanamide (11) (CH3 COCIZ. H C N CH3 =YY CH3CH3 I - Pinacidil phosgene . ethyldi- isopropyl- Reference(s): DE 2 557 438 (Leo; appl. 19.12.1975; GB-prior. 20.12.1974). DE 2 560 633 (Leo; appl. 19.12.1975; GB-prior. 20.12.1974). GB 1 489 879 (Leo; appl. 20.12.1974). Petersen, H.J. et al.: J. Med. Chem. (JMCMAR) 21,773 (1978). Hansen, E.T.; Peterscn, H.J.: Synth. Commun. (SYNCAV) 14, 537 (1984). medical use for treatment of asthma: EP 207 606 (Lilly; appl. 15.5.1986; USA-prior. 17.5.1985). medical use for treatment of peripheral vuscular disease: EP 223 81 1 (Beecham; appl. 20.5.1986; GB-prior. 29.5.1985, 22.5.1985). combination with ACE inhibitors: EP 271 271 (Beecham; appl. 30.1 1.1987; GB-prior. 24.12.1986,6.12.1986). combination with P-blocker: EP 323 745 (Beecham; appl. 23.12.1988; CB-prior. 6.1.1988). sustained release formulation: DOS 3 404 595 (Leo; appl. 9.2.1984; DK-prior. 11.2.1983). Fonnulation(s): cps. 12.5 mg, 25 mg Trade Nume(s): DK: Pindac (Leo) . 4,5-dihydro- 6-[ 2-( 4-methoxyphenyl )-1 H-benzimidazol-5-yl ]-5 -methyl-3(2H)-pyrida~inone hydrochloride RN: 7414 9-7 5-0 MF: C19H18N402 . xHC1 MW: unspecified monohy drochloride RN: 7746 9-9 8-8 . -[ I -[ 4,4-his(4-fluorophenyl)butyl ]-4 -piperidinyl ]-1 ,3-dihydro-2H-benzimidazol-2-one Pinacidil P 1639 4-lluorophenyl- cyclopropane- magnesium corboxylic ocid bromide ethyl ester 4.4-bis(4-fluoro-. ester 4.4-bis(4-fluoro- phenyl)butyl chloride bis( 4-( luorophenyl )- 1,l -bis(4-fluorophenyl )- cyclopropylcorbinol 4-chioro-l -butene (1) _______* 1 -( 4-piperidyl )-2 -benz- imidozolonc