Protheobromine P 1741 Reference(s): a Stoll, A. et al.: Helv. Chim. Acta (HCACAV) 16, 703 (1933). Stoll, A.; Kreis, W.: Helv. Chim. Acta (HCACAV) 34, 1431 (1951). Stoll, A. et al.: Helv. Chim. Acta (HCACAV) 35, 2495 (1952). DRP 646 930 (Ciba; appl. 1933; CH-prior. 1932). US 3 361 630 (Knoll; 2.1.1968; appl. 30.10.1964; D-prior. 2.11 .l963). b Louw, P.G.J: Nature (London) (NATUAS) 163,30 (1949). Zoller, P.; Tamm, Ch.: Helv. Chim. Acta (HCACAV) 36, 1744 (1953). Formulation(s): drg. 0.25 mg, 0.5 mg Trade Namefs): D: Talusin (Knoll) F: Talusin (Biosedra); wfm I: Caradrin (Boehringer Ing.); wfm Neogratusminal (Simes)- comb.; wfrn Stellarid (Zambeletti); wfrn Talusin (Knoll); wfm Teostellarid (Zambe1etti)- comb.; wfrn Urgilan (Simes); wfrn J: Apocerpin (Kotani) Bunosquin (Seiko) Caradrin (Kowa) Cardiolidin (Nichiiko) Cardion (Nippon Chemiphar) Cardon (Kanto) Mitredin (Nippon Shoji) Procardin (Mohan) Procillan (Hokuriku) Proherz (Shinshin) Pros Tab. (Mita) Proscillar (Toyo Jozo) Prosiladin (Sawai) Proslladin (Zeria) Proszin (Teisan) Scillaridin (Moroshita) Silamarin A (Wakamoto) Stellarid (Tobishi-Mochida) Talusin (Dainippon) USA: Talusin (Knoll); wfm Tradenal (Knoll); wfrn Protheobromine ATC: C03BD Use: diuretic, cardiotonic RN: 50-39-5 MF: C,,,H,,N,O, MW: 238.25 EINECS: 200-034-8 LD,,: 580 mgkg (M, s.c.) CN: 3,7-dlhydro- I-(2-hydroxypropy1)-3,7-dimethyl-1 H-purine-2,6-dione Referencefs): DE 1 067 025 (Degussa; appl. 23.8.1955). propylene theobrornine Formulation(s): drg. 50 mg, 100 mg Protheobrornine Trade Name(sj: D: Cordabromin-Digoxin I: Antelin (OFF)-comb.; wfm Tebe (Simes); wfm (Homburg)-comb.; wfm Idromin (Amaldi); wfm oxide 1742 P Prothipendyl Prothipendyl ATC: NOSAX07 Use: psychosedative, neuroleptic RN: 303-69-5 MF: ClhHL@3S MW: 285.42 LD,,,: 415 mglkg (M, p.0.); 25 mgkg (R, i.v.) CN: N,N-dimethyl-1OH-pyrido[3,2-b][l,4]benzothiazine-l0-propanamine monohydrochloride RN: 1225-65-6 MF: CIhH19N3S . HC1 MW: 321.88 EINECS: 214-958-4 LD,,,: 1 10 mglkg (R, i.v.); 610 mglkg (R, p.0.) 2. FH3 CH3 - 1. sodium omide 2. 3-dimethylomino propyl chloride Prothipendyl I DE 1 001 684 (Degussa; appl. 1954). US 2 974 139 (Degussa; 7.3.1961; D-prior. 2.10.1954). Formulation(s): amp. 40 mg/2 ml; drg. 40 mg; drops 25 mgl0.5 ml; f. c. tabl. 80 mg (as hydrochloride) Trade Name(s): D: Dominal /-forte (ASTA GB: Tolnate (Smith Kline & J: Prosy1 (Kanto) Medica AWD) French); wfm Protionamide (Prothionamide) ATC: J04ADO1 Use: tuberculostatic, antibacterial RN: 14222-60-7 MF: C9H,,N2S MW: 180.28 EINECS: 238-093-7 LD,,: 1 glkg (M, p.0.); 1320 mgkg (R, p.0.) CN: 2-propyl-4-pyridinecarbothioamide diethyl 2-pentonone oxalate ocetamide ethyl 2,4-dioxa- Protirelin P 1743 1. POCI,, PC!, O@C" 3 _______* 2. HO-CH, NC 1. phosphotyl chloride, COOH COOH phosphorus(\/) chloride "TH3 0 O-CH~ 6-propyl-2- pyridone-4- carboxylic ocid ethyl 2-chloro-6- propylisonicotinote (U) ethyl 2-propyl- 2-propyliso- 2-propyliso- I Protionornide 1 isonicotinate nicotinomide nicotinonitrile Reference(s); GB 800 250 (Chimie et Atomistique; appl. 26.3.1957; F-prior. 27.3.1956, 19.4.1956, 6.8.1956, 7.12.1956). Libermann, S. eta].: C. R. Hebd. Seances Acad. Sci. (COREAF) 242, 2409,2412 (1956). Formulation(s): f. c. tabl. 250 mg; tabl. 125 mg, 250 mg . Trade Name(s): D: Ektebin (Hefa Pharma) GB: Trevintix (May & Baker); Tuberamin (Meiji) Isoprodion (Fato1)-comb. wfm Tuberex (Shionogi) Peteha Dragees (Fatol) J: Entelohl (Kyowa) Tubermide (Sankyo) F: TrCvintix (ThCraplix); wfm Prot~onamid (Lederle- Takeda) Protirelin (TRH; Thyroliberin; Tyroliberin) ATC: VO4CJO2 Use: antidepressant, thyroid diagnostic RN: 24305-27-9 MF: .C,,H2,N,O4 MW: 362.39 EINECS: 246-143-4 LD,,: 921 mg'kg (M, i.v.); >10 g/kg (M, p.0.); 514 mg/kg (R, i.v.); >5 g/kg (R, p.0.) CN: 5-0x0-L-prolyl-L-histidyl-L-prolinamide OH H mC-7- mi , DM my + ,I Mbh, H2N O\ 1 -hydroxy- N-ethyl- dicyclohexyl- benzotriazole rnorpholine carbodiimide benzylorycarbonyl 4.4'-dimethoxybenzhydryl 1744 P Protirelin 1 NoOH, dioxone, H20 Mbh, Mb h H 2-Gln(Mbh)-His-OMe (I) 2-Gln(Mbh)-His-OH (11) b 111 0 1-hydroxy- N-ethyl- dicyclohexyl- benzotriozole morpholine corbodiimide H-Pro-NU2 . UCI Irifluoroocetic ocid/onisole (9:1), reflux. 1.5 h Mbh, H 2-Gln(Mbh)-His-Pro-NH2 (III) / Protintin I Keference(s): synthesis: Konig, W.; Geiger, R.: Chem. Ber. (CHBEAM) 105,2872 (1 972). US 3 746 697 (K. Folkers et al.; 17.7.1973; prior. 19.9.1969). US 3 757 003 (K. Folkers et al.; 4.9.1973; prior. 18.12.1969). US 3 753 969 (K. Folkers et al.; 21.8.1973; prior. 22.12.1969). US 3 959 247 (Takeda; 25.5.1976; appl. 21.6.1974; J-prior. 2.7.1973) DE 2 431 331 (Takeda; appl. 22.5.1975; prior. 29.6.1974). starting material: Kbnig, W.; Geiger, R.: Chem. Ber. (CHBEAM) 103, 2041 (1970). Flouret, G.: J. Med. Chem. (JMCMAR) 13,843 (1970). use: as antidepressant: US 3 737 549 (Abbott; 5.6.1973; appl. 20.3.1972). DOS 2 313 635 (Abbott; appl. 19.3.1973; USA-prior. 20.3.1972). a! impaired consciousness: DOS 2 61 1 976 (Takeda; appl. 20.3.1976; GB-prior. 3.4.1975, 26.1 1.1975). US 4 059 692 (Takeda; 22.1 1.1977; GB-prior. 3.4.1975, 26.1 1.1975). for abolition of schizophrenia: GB 1 540 574 (Takeda; appl. 23.5.1975; valid from 24.5.1976). injectable solutions (by use of sugar alcohols): DOS 2 743 586 (Takeda; appl. 28.9.1977; J-prior. 1.10.1976). Formulation(s): amp. 200 yg/2 rnl, 400 yg/2 ml; nasal spray 1 mg10.09 ml; tabl. 40 mg; USA: amp. 500 ~dml Protizinic acid P 1745 Trade Name(s): D: Antepan (Henning Berlin; TRH (Berlin-Chemie; Xantium (Wyeth-Lederle) 1980) Ferring; 1974) J: TRH (Tanabe) Relefact TRH (Hoechst; F: Stimu-T.S.H. (Roussel) TJSA: Thyrel TRH (Ferring) 1975) GB: Relefact (LH-RH/TRH ThyroliberidTRF Merck Hoechst; 1978); wfm (Merck; 1978) 1: Irtonin (Takeda) Protizinic acid (Acide protizinique) ATC: MOlAE Use: anti-inflammatory RN: 13799-03-6 MF: Ci7H17N03S MW: 315.39 EINECS: 237-453-0 CN: 7-methoxy-a,lO-dimethyl-lOH-phenothiazine-2-acetic acid 1. NaN02, HCI 0 2. .t . KOH ~~c-0 SK \ Br CI n c nBr + H~c\~~~~ + I 0 NH* 2. potassium 4'-chloro-3-nitro- ethylxanthogenote acetophenone onisole thiophenol Fe, CH,COOH K2C0,, Cu. OMF H3C\ 0 FH3 0 IJ C0) , N H3C\ H3C\ 0 morpholine 0 2-ocet9-7-methoxy- methyl 2-ocetyl-7-methoxy-10- phenothiozine (11) iodide (In) methyiphenothiozine diethyl carbonate 1746 P Protokylol Protirinic ocid Formulution(s): cps. 200 mg Trade Numu(s): F: Pirocrid (Thtraplix); wfm J: Piroarid (Mochidia) Protokylol ATC: R03A Use: p-sympathomimetic, bronchodilator RN: 136-70-9 MF: C,8H,,N0, MW: 33 1.37 EINECS: 205-2553 CN: 4-[2-[[2-(l,2-benzodioxol-5-yl)-l-methylethyl]amino]- 1-hydroxyethyll-l,2-benzenediol hydrochloride RN: 176-6945 MF: CIRI-I,,NO,. HCI MW: 367.83 EINECS: 205-254-8 LD,,,: 86.5 mglkg (M, i.v.); 785 mg/kg (M, p.0.); 71 mglkg (R, i.v.); 865 mgkg (R, p.0.) 2-chloro-T.4'-dihydroxy- I-methyl-2-(3.4- ocetophenone methylenedioxy- pheny1)ethylomine I Protokylol I Referertce(s): US 2 900 415 (Lakeside Labs.; 1959; prior. 1954). Form~rlation(s): aerosol 0.01 mg; drg. I mg; tabl. 1 mg (as hydrochloride) Trade Nume(s): D: atma-sanol (SanoWcomb.; I: Asmetil (Benvegna); wfm J: Caytine (Chugai) wfm Beres (Simes); wfm USA: Ventaire (Marion); wfm Protriptyline P 1747 Protriptyline ATC: N06AAll Use: antidepressant RN: 438-60-8 MF: C,,H,,N MW: 263.38 EINECS: 207-1 19-9 LD,,: 30 mgkg (M, i.v.); 269 mg/kg (M, p.0.); 240 mglkg (R, p.0.) CN: N-methyl-5H-dibenzo[n,d]cycloheptene-5-propanamine hydrochloride RN: 1225-55-4 MF: CI9H2,N. HC1 MW: 299.85 EINECS: 214-956-3 LD,,: 49 mgkg (M, i.v.); 21 1 mglkg (M, p.0.); 299 mglkg (R, p.0.) HoMN'CH3 + rH2 - HOufCH3 H CHO CHO thionyl CHO chloride 3-methylomino- form- 3-(N-formyl-N- 3-(N-formyl-N- I -propon01 omide methylamino)- methylomino)- 1 -propon01 prapyl chloride (I) omide CHO I n 5H-dibenzo[o.d]- cycloheptene Protriptyline I Reference(s): US 3 244 748 (Merck & Co.; 5.4.1966; prior. 3.7.1962). US 3 271 451 (Merck & Co.; 6.9.1966; appl. 3.7.1962). BE 617 967 (Merck & Co.; appl. 22.5.1962; USA-prior. 24.5.1961,25.9.196l). DE 1 287 573 (Me~ck & Co.; appl. 6.5.1963; USA-prior. 14.5.1962). DE 1 468 212 (Merck & Co.; appl. 21.5.1962; USA-prior. 24.5.196l,2S.Y.I96l). alternative syntheses: DE 1 288 599 (Geigy; appl. 13.3.1962; CH-prior. 14.3.1961, 30.3.1961). Engelhardt, E.L. et al.: J. Med. Chem. (JMCMAR) 11, 325 (1968). Formulution(s): tabl. 5 mg, 10 mg (as hydrochloride) Tmde Name(s): D: Maximed (Sharp & GB: Condordin (Merck Sharp & USA: Vivactil (Merck Sharp & Dohme); wfm Dohme) Dohme) F: Concordine (Merck Sharp I: Concordin (Merck Sharp & & Dohme); wfm Dohme); wfm Proxazole (Propaxoline) ATC: A03AX07 LJse: analgesic, anti-inflammatory, antitussive, antispasmodic, relaxant (smooth muscle) RN: 5696-09-3 MF: C,,H,SN,O MW: 287.41 CN: N,N-diethyl-3-(1-phenylpropyl)-1,2,4-oxadiazole-5-ethanamine 1748 P Proxymetacaine citrate (1:l) RN: 132-35-4 MF: CI7H2,N,O . C,H,07 MW: 479.53 EINECS: 205-059-8 LD,,,: 68 mgkg (M, i.v.); 1270 mglkg (M, p.0.); 1400 mgkg (R, p.0.) 2-phenyl- butyronitrile 2-phenylbutyr- 3-chloropropionyl omidoxime (I) chloride diethylomine Proxazole Reference(s1: US 3 141 019 (Angelini Francesco; 14.7.1964; A-prior. 29.9.1959). Formulalion(s): drops 5 %; tabl. 100 mg (as citrate); vial 30 mg/5 ml Trade Namefs): F: Mendozal (Bcaufour); wfm I: Toness (Angelini) J: Pirecin (Yoshitomi) Prox ymetacaine (Proparacai ne) ATC: SOlHAO4 Use: local anesthetic RN: 499-67-2 MF: C,,H2,N203 MW: 294.40 EINECS: 207-884-9 CN: 3-amino-4-propoxybenzoic acid 2-(diethy1amino)ethyl ester monohydrochloride RN: 5875-06-9 MF: CI6H2&V2O3. HC1 MW: 330.86 EINECS: 227-541-7 LD,,: 3371 pg/kg (M, i.v.) Proxyphylline P 1749 dhydroxy-3- propyl p-toluene- propyl 3-nitro- 3-nitro-4-propoxy- nitrobenzoic sulfonate 4-propoxybenzoate benzoic acid (I) acid 2-diethylamina ethyl chloride I Proxymetocaine I Reference(s): Clinton, R.O. et al.: J. Am. Chem. Soc. (JACSAT) 74, 592 (1952). US 1 317 250 (Parke Davis; 1919; appl. 1918). DRP 522 064 (Schering-Kahlbaum AG; appl. 1928). US 2 288 334 (Abbott; 1942; appl. 1940). Formulation(s): eye drops 5 mglml (as hydrochloride) Trade Nnme(s): D: Proparakain-POS GB: Mimius Proxymetacaine I: Visuanestetico (ISF); wfm (Ursapharm) (Chauvin) USA: Alcaine (Alcon); wfm F: Keracaine (Merck Sharp & Ophthaine (Bristol-Myers Ophthaine (Squibb); wfm Dohme-Chibret); wfm Squibb) Ophthetic (Allergan); wfm Proxyphylline ATC: R03DA03 Use: cardiotonic, bronchodilator RN: 603-00-9 MF:'C,oH14N403 MW: 238.25 EINECS: 210-028-7 LD,: 510 mglkg (M, i.v.); 1460 mglkg (M, p.0.); 430 mglkg (R, i.v.); 460 mg/kg (R, p.0.) CN: 3,7-dihydro-7-(2-hydroxypropy1)- 1,3-dimethyl-1 H-purine-2,6-dione theophylline (1) 1 -chloro-2- propanol Proxyphylline L 1750 Prozapine propylene oxide Reference(s): US 2 715 125 (Gane's Chem. Works; 1955; prior. 1953). Formulation(s): clysma 150 mg/5 ml, 300 mg/lO ml, 600 mg120 ml; s. r. tabl. 200 mg, 300 mg; suppos. 500 mg; tabl. 300 mg Trade Name(s): D: Antihypertonicum GB: Brontyl (Reckitt & 1: Pantafillina (TrommsdorfQ-comb. Colman); wfm (Farmacobiologico); wfm Neobiphyllin-Clys Thean (Astra); wfm J: Monophyllin (Yoshitomi) (Trommsdorff)-comb. Tomophyllin (Nichiiko) Prozapine (Hexadiphane) ATC: A03BA Use: choleretic, antispasmodic RN: 3426-08-2 MF: C,,H,,N MW: 293.45 EINECS: 222-325-9 CN: 1-(3,3-diphenylpropy1)hexahydro-1H-azepine hydrochIoride RN: 13657-24-4 MF: C,,H,,N . HCI MW: 329.92 EINECS: 237-143-5 ethylene hexahydro- 1 -(2-hydroxyethy1)- oxide 1 H-azepine hexohydro-1H- . azepine diphenyl- 2.2-diphenyl-4- ocetonitrile (hexohydro- IH-azepino). butyronitrile Reference(s): US 2 881 165 (Janssen; 1959; NL-prior. 1956). hexahydro-1 H- azepine (I) Prozapine Formrrlation(s): amp. 1 mgl5 ml, 2 mgl5 m1; syrup 1 mg (as hydrochloride) . chloride 3-methylomino- form- 3-( N-formyl-N- 3-( N-formyl-N- I -propon01 omide methylamino )- methylomino )- 1 -propon01 prapyl chloride (I) omide CHO I n 5H-dibenzo[o.d ]- cycloheptene. R03A Use: p-sympathomimetic, bronchodilator RN: 13 6-7 0-9 MF: C,8H,,N0, MW: 33 1.37 EINECS: 20 5-2 553 CN: 4-[ 2-[ [ 2-( l,2-benzodioxol-5-yl)-l-methylethyl]amino ]- 1-hydroxyethyll-l,2-benzenediol. dioxone, H20 Mbh, Mb h H 2-Gln(Mbh)-His-OMe (I) 2-Gln(Mbh)-His-OH (11) b 111 0 1-hydroxy- N-ethyl- dicyclohexyl- benzotriozole morpholine corbodiimide H-Pro-NU2 . UCI Irifluoroocetic