Pramiverine P 1681 '33 n3L yL"3 2. HCI. H20 I F ,-NYCH3 - HCI I " CH3 I Promirocelom hydrochloride I Reference (s): BE 864 269 (Parke Davis & Co.; appl. 7.3.1978; USA-prior. 3.3.1977). US 4 145 347 (Parke Davis & Co; 20.3.1979; USA-prior. 3.3.1 977). Butler, D.E.; Nordin, 1.C.; L'Italien, Y.J.; Zweisler, L.; Poschel, P.H.; Mamott, J.G.: J. Med. Chem. (JMCMAR) 27,684 (1984). Formulation(s): tabl. 600 mg (as sulfate) Trade Name(s): I: Neupramir (Lusofarmaco) Pramistar (Firma) Remen (Parke Davis) Pramiverine ATC: A03A IJse: antispasmodic RN: 14334-40-8 MF: C,,H,,N MW: 293.45 CN: N-(I -methylethyl)-4,4-diphenylcyclohexanamine hydrochloride RN: 14334-41-9 MF: CZIHz7N . HCl MW: 329.92 EINECS: 238-284-5 LDjo: 25 mgkg (M, i.v.); 346 mglkg (M, p.0.); 26 mglkg (R, i.v.); 623 mglkg (R, p.0.); 20 mgkg (dog, i.v.); 140 mgkg (dog, p.0.) diphenyl- methyl vinyl 4.4-diphenyl-2- acetaldehyde ketone cyclohexen-1 -one Promiverine Reference(s): DE 1 793 61 1 (Merck AG; appl. 15.12.1964). Formulation(s): amp. 2 mg12 ml; drg. 2 mg; drops 2 mglml; suppos. 6 mg (as hydrochloride) Trade Name(s): D: Sistalgin (Cascan); wfm I: Sistalgin (Bracco)-comb.; wfm 1682 P Pramocaine Pramocaine (Pramoxine) ATC: C05AD07 Use: local anesthetic RN: 140-65-8 MF: C,,H,,NO, MW: 293.41 EINECS: 205-425-7 LDso: 79 mgkg (M, i.v.) CN: 4-[3-(4-butoxyphenoxy)propyl]morpholine hydrochloride RN: 637-58-1 MF: C,,HnN03. HC1 MW: 329.87 EINECS: 21 1-293-1 LDso: 79.5 mglkg (M, i.v.); 1050 mgkg (M, p.0.) Reference(s): US 2 870 151 (Abbott; 1959; prior. 1954). Wilson, J.W. et al.: J. Org. Chem. (JOCEAH) 16, 792 (1951). 4-butoxyphenol 3-rnorpholino- Formulation(s): cream 1 g1100 g; gel 1 g1100 g (as hydrochloride) Pmmocaine Trade Nume(s): I): Proctofoam HC Anusol (Warner-Lambert) Prax (Ferndale) (Trommsdorffl-comb.; wfm Caladryl (Warner-Lambert) Proctofoam (Schwarz) F: Tronothane (Abbott) Cortane-B OTIC (Blansett) Promasone (Ferndale) I: Tronotene (Abbott) Cortic (Everett) Zoto-HC (Horizon) USA: Analpram-HC (Ferndale) Epifoam (Schwarz) propyl chloride Pranlukast (ONO-1078; RS-411; SB-205312) . ATC: R03DC02 Use: antiallergic, antiasthmatic, leukotriene D,-antagonist RN: 103177-37-3 MF: C27HuNs04 MW: 481.51 CN: N-[4-oxo-2-(1H-tetrazol-5-yl)-4H-l-benzopyran-8-yl]-4-(4-phenylbutoxy)benzamide hydrate (2:l) RN: 150821-03-7 MF: C2,H2,N504 . 1/2H20 MW: 981.04 monosodium salt RN: 103 180-28-5 MF: C,,H,,N,NaO, MW: 503.49 NaN3 NO2 0 1. NH3 NO, pyridinivm chloride wnCH3 2. p0c'3 , @CN OM , / 0 0 0 ethyl 8-nitro-4- 2-cyano-8- 8-nitro-2-(tetro- 0x0-l -benzopyran- nitro- l-benzo- 2-carboxylate pyron-4-one zol-5-yl)-1 -benzo- pyron-4-one (I) h Pranoprofen P 1683 I Pronlukost I synthesis of I1 NH HN'~~ (c~~~c-0~ H~C CH~OH 0 0 0 0 1. NaOCH3. CH,OH 0 0 ethyl I -trityl- carboxylate Trt: Reference(s): a EP 173 516 (0no Pharm.; 1.12.1993; J-prior. 22.1 1.1984). Nakai, H. et al.: J. Med. Chem. (JMCMAR) 31, 84-91 (1988). b EP 0 716 088 (Sumitomo Chem.; appl. 23.6.1995; J-prior. 23.6.1994). synthesis of intermediates type 11: WO 9 532 199 (SmithKline Beecham; appl. 30.1 1.1995; GB-prior. 21.5.1994). combination with PAF-antagonisls: EP 469 477 (Hoffmann-La Roche; appl. 26.7.199 1 ; USA-prior. 2.8.1990). Formulation(s): cps. 112.5 mg (as hydrate) Trade Name(s): J: Onon (Ono; 1995) Pranoprofen RN: 52549-17-4 MF: Cl,H,,NO, MW: 255.27 LD,,: 447 mglkg (M, p.0.); 59.5 mglkg (R, p.0.) CN: a-methyl-5H-[I]benzopyrano~2,3-b]pyridine-7-acetic acid ATC: MOlAE Use: anti-inflammatory, analgesic 1684 P Pranoprofen POCI, HOOC phosphorus HOOC oxychloride 0 2-chloro- phenol 2-phenoxy- 5-0x0-5H-[I]- nicotinic nicotinic acid benzopyrono- acid [2.3-blpyridine (I) HCI amalgam OH 5H-[l]benzo- pyrano[2.3-b]- pyridine 7-chloromethyl- potassium 5H-[I Ibenzopyrono- cyanide [2.3-b]pyridine (11) methyl iodide Reference(s): FR 2 193 593 (Yoshitomi; appl. 19.7.1973; J-prior. 21.7.1972, 13.1.1973,3.4.1973). DOS 2 337 052 (Yoshitomi; appl. 20.7.1973; J-prior. 21.7.1972, 13.1.1973,3.4.1973). US 3 931 205 (Yoshitorni; 6.1.1976; appl. 18.7.1973; J-prior. 21.7.1972). HCI r 4 synthesis qf 5-hydroxy-5H-[1 Jbenzopyrano[2,3-blpyridine: Mann, F.G.; Reid, J.A.: J. Chem. Soc. (JCSOA9) 1952, 2057. H3cm COOH ~rano~rofen' Formulation(s): cps. 75 mg Trade Name(s): J: Niflan (Yoshitomi; 1981) Prasterone P 1685 Prasterone ATC: A14AA07 Use: anabolic, androgen RN: 53-43-0 MF: C,,H,,O, MW: 288.43 EINECS: 200-175-5 LD,,: >10 gkg (M, p.0.); >10 glkg (R, p.0.) CN: (3fl)-3-hydroxyandrost-5-en-17-one H3 1. NH20H . HCI, pyridine, C2H50H 2. S0Cl2 b 1. hydroxylamine hydrochloride 2. thionyl chloride 16-dehydropregnenolone ocetate ( cf. pregnenolone synthesis) 1 Prasterone 1. NH20H 2. POCI3, pyridine b 1. hydroxylamine 2. phosphoryl chloride pregnenolone ocetate (9. v.) 1. OH- & 2. H~O/H+ 2. HOCl n * H H HO ' Reference (s): Ullmanns Encykl. Tech. Chem., 4. Aufl., Vol. 13, 30. from cholesterol: Ullmanns Encykl. Tech. Chem., 3. Aufl., Vol. 8,648. Rosenkranz, G. et al.: J. Org. Chem. (JOCEAH) 21,520 (1956). US 2 335 61 6 (Parke Davis; 1943; prior. 1941). Formulation(s): amp. 200 mglml 1686 P Prasterone enanthate - - - - Trade Name(~): D: Gero Hormetten (Hormon- Gyno Hormetten (Hormon- I: Gynodlan (Schering, as Chemie; as sulfate)-comb.; Chemie; as sulfate)-comb.; valerate) wfm wfm J: Mylis (Kanebo) GB: Diandrone (Organon); wfm Prasterone enanthate ATC: ~14~~07; GO~EAO~ Use: androgen RN: 23983-43-9 MF: C26H4001 MW: 400.60 EINECS: 245-970-8 CN: (3P)-3-[(I-oxoheptyl)oxy]androst-5-en-17-one prasterone (9. v.1 enanthic anhydride I Prosterone enonthate Reference(s): BE 721 825 (Schering AG; appl. 4.10.1968; D-prior. 4.10.1967). ZA 686 1 12 (Schering AG; appl. 20.9.1968; D-prior. 4.10.1967). GB 1 246 639 (Schering AG; valid from 30.9.1968; D-prior. 4.10.1967). altertmtive synthesis: DOS 2 534 91 1 (Schering AG; appl. 1.8.1975). use against psoriasis: DOS 2 147 309 (Schering AG; appl. 17.9.1971). Form~dation(s): amp. 200 mg in comb. with estradiol valerate Trade Name(s): D: Gynodian Depot F: Gynodian Depot I: Gynodian Depot (Schering)-comb. (Schering)-comb.; wfm (Schering)-comb. Pravastatin (Eptastatin) ATC: ClOAA03 Use: cholesterol depressant, HMG-CoA- reductase inhibitor RN: 81093-37-0 MF: C,,H,,O, MW: 424.53 CN: [IS-[la(~S*,GS*),2a,6a,8~(R*),8aa]]-1,2,6,7,8,8a-hexahydro-P,6,6-trihydroxy-2-methyl-8-(2-methyl-l- oxobutoxy)-1-naphthaleneheptanoic acid monosodium salt RN: 81 131-70-6 MF: C,,H,,NaO, MW: 446.52 LD,,,: 201 1 mgkg (M, i.v.); 8939 mglkg (M, p.0.); 440 mglkg (R, i.v.); >12 gkg (R, p.0.) Pravastatin P 1687 hydroxylation by Mucor hiemolis or P. coccineus, R. solani, H3C Nocardia Reference(s): DE 3 122 499 (Sankyo; appl. 5.6.1981; J-prior. 6.6.1980, 8.9.1980, 19.9.1980, 22.8.1980). US 4 346 227 (Sankyo; 24.8.1982; appl. 5.6.1981; J-prior. 6.6.1980, 22.8.1980, 11.3.1980) Serizawa, N. et al.: J. Antibiot. (JANTAJ) 36, 604 (1983). mevastatin asymmetric synthesis: Daniewski, A.R. et al.: J. Org. Chem. (JOCEAH) 57, 7133 (1992). Provostatin pharmaceutical fortnulation with increased stabili~: EP 336 298 (Squibb; appl. 30.3.1989; USA-prior. 31.3.1988). combination with coenzyme Q10: US 4933 165 (Merck & Co.; 12.6.1990; appl. 8.1 1.1989). US 4 929 437 (Merck & Co.; 29.5.1990; appl. 2.2.1989). mevastatin (compactin): The Merck Index, 1 lth Ed., 6088 (Rahway 1989). Endo, A.: J. Med. Chem. (JMCMAR) 28,401 (1985). new production process: EP 877 089 (Gist-Brocades, EP-prior. 7.5.1997). WO 9 736 996 (Gist-Brocades; appl. 21.3.1997; EP-prior. 28.3.1996). WO 9 845 410 (Yungjin; appl. 30.6.1997; KR-prior. 10.4.1997). EP 776 974 (Sankyo; appl. 29.11.1996; J-prior. 29.1 1.1995). conversion of compactin by Actinomadura: WO 9 640 863 (MIT; appl. 4.6.1996; USA-prior. 7.6.1995). hydroxylation by Saccharopolysopra hirsuta: EP 649 907 (Bristo-Myers Squibb; appl. 18.10.1994; USA-prior. 22.10.1993). use for slowing progression of atherosclerosis: EP 671 170 (Bristol-Myers Squibb; appl. 21.2.1995; USA-prior. 11.3.1994). use for preventing restinosis: EP 459 453 (Squibb & Sons; appl. 29.5.1991; USA-prior. 31.5.1990). Formulation(s): tabl. 5 mg, 10 mg, 20 mg (as sodium salt) Trade Name(s): D: Liprevil (Schwarz/Sanol) GB: Lipostat (Bristol-Myers Selectin (Bristol-Myers Mevalotin (Sankyo) Squibb) Squibb; 1990) Pravasin (Bristol-Myers I: Aplactin (Mead Johnson) J: Mevalotin (Sankyo; 1989) Squibb; 1991) Prasterol (Malesci) USA: Pravachol (Bristol-Myers F: Elisor (Bristol-Myers Pravaselect (Menarini; Squibb; 1991) Squibb; 1991) 1990) Vasten (Specia; RhGne- Sanaprav (Sankyo Pharma) Poulenc Rorer; 199 1) Prazepam ATC: NO5BA11 Use: tranquilizer RN: 2955-38-6 MF: C,9H17CIN20 MW: 324.81 EINECS: 220-975-8 LD,,,: 2300 mglkg (M, p.0.); >4 glkg (R, p.0.); >4 glkg (dog, p.0.) CN: 7-chloro-l-(cyclopropylmethyl)-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one P CI C I '. lithium / alanate 2-amino-5-chloro- cyclapropane- benzophenone carbonyl chloride oxide benzophenone HZN-NHZ hydrozine 0 _____* n phthalimidoacetyl chloride 6 cl$2 Prazepam 1. NOH Br b 1. sodium hydride 2. cyclopropylmethyl bromide 7-chloro-2-0x0-5- phenyl-2.3-dihydro- 1 H-1.4-benzodiazepine (cf. diazepam synthesis) Praziauantel P 1689 Reference(s): a DAS 1 229 098 (Warner-Lambert; appl. 24.2.1964; USA-prior. 1.3.1963). US 3 192 199 (F. H. McMillan, J. Pattison; 29.6.1965; appl. 1.3.1963). b US 3 192 200 (H. M. Wuest; 29.6.1965; prior. 5.3.1963). alternative synthesis: Inaba, S. et al.: Chem. Pharm. Bull. (CPBTAL) 17, 1263 (1969). Formulation(s): drops 15 mglml; tabl. 10 mg, 20 mg, 40 mg Trade Name(s): D: Demetrin (Godecke; Parke GB: Centrax (Parke Davis); USA: Centrax (Parke Davis); Davis) wfm wfm Mono-Demetrin (Godecke; I: Prazene (Parke Davis) Verstran (Parke Davis; Parke Davis) Trepidan (Max Farma) Warner Chilcott); wfm F: Lysanxia (Parke Davis) J: Prazepam (Sumitomo Chem.) Praziquantel ATC: P02BAOl Use: anthelmintic RN: 55268-74-1 MF: C,,HXN2O2 MW: 312.41 EINECS: 259-559-6 LD,,: 2454 mglkg (M, p.0.); 2840 mglkg (R, p.0.); >200 mglkg (dog, p.0.) CN: 2-(cyclohexylcarbony1)-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinolin-4-one cC;':: ,' l-ominomethyl- 1,2.3,4-tetrahydro isoquinoline @ + isoauinoline + C'~ CI 150 OC - 4 cyciohexonecorbonyl chloride chloroocetic 1 -(N-corboxymethyl- N-cyclohexylcorbonyl- ominomethyl)-l.2,3,4- tetrahydroisoquinoline chloroocetyl chloride 1690 P Prazosin Reference(s): DOS 2 457 971 (E. Merck Patent GmbH; appl. 7.12.1974). DOS 2 362 539 (E. Merck Patcnt GmbH; appl. 17.12.1973). DOS 2 504 250 (E. Merck Patent GmbH; appl. 1.2.1975). DOS 3 01 1 156 (E. Merck Patent GmbH; appl. 22.3.1980). Formulation(s): f. c. tabl. 150 mg, 600 mg; tabl. 500 mg Trade Name(s): D: Biltricide (Bayer) Cysticide (Merck) I: Biltrizide (Bayer) Cesol (Merck) F: Biltricide (Bayer Pharrna) USA: Biltricide (Bayer) Prazosin ATC: C02CAOl Use: antihypertensive, a,-adrcncrgic blocker RN: 19216-56-9 MF: C,yH21N504 MW: 383.41 EINECS: 242-885-8 LD,,,: >400 mglkg (M, i.v.); >4 glkg (M, p.0.) CN: I-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-furanylcarbony1)piper~ine monohydrochloride RN: 19237-84-4 MF: C,yH21N504 . HCl MW: 419.87 ETNECS: 242-903-4 LD,: 92 mgkg (M, i.v.); 5 glkg (M, p.0.); 73 mglkg (R, i.v.); 1950 mgkg (R, p.0.); r700 mglkg (dog, p.0.) 2-ornino-4.5-di- sodium 2,4-dihydroxy-6,7- rnethoxybenzoic cyanate dirnethoxyquinazoline odd 2,4-dichloro-6.7- dirnethoxyquinazoline (I) 4-omino-2-chloro- 6,7-dimethoxy- quinozoline i Prazosin Reference(s): US 3 5 11 836 (Pfizer; 12.5.1970; appl. 13.12.1967; prior. 6.8.1965,7.6.1966). US 3 635 979 (Pfizer; 18.1.1972; prior. 6.8.1965,7.6.1966, 13.12.1967). US 3 663 706 (Pfizer; 16.5.1972; prior. 6.8.1965, 13.12.1967, 12.5.1970). DAS 1 620 138 (Pfizer; appl. 2.7.1966; USA-prior. 6.7.1965,7.6.1966). . @CN OM , / 0 0 0 ethyl 8-nitro- 4- 2-cyano- 8- 8-nitro- 2-( tetro- 0x0-l -benzopyran- nitro- l-benzo- 2-carboxylate pyron-4-one zol-5-yl )-1 -benzo- pyron-4-one (I) h Pranoprofen P 1683. CN: N-[4-oxo- 2-( 1H-tetrazol-5-yl )-4 H-l-benzopyran-8-yl ]-4 -( 4-phenylbutoxy)benzamide hydrate (2:l) RN: 15082 1-0 3-7 MF: C2,H2,N504 . 1/2H20 MW: 981.04 monosodium salt RN: 103 18 0-2 8-5 MF:. (dog, p.0.) CN: 7-chloro-l-(cyclopropylmethyl )-1 ,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one P CI C I '. lithium / alanate 2-amino-5-chloro- cyclapropane- benzophenone carbonyl