Pharmaceutical Substances Syntheses, Patents, Applications - Part 156 docx

Pamidronic acid P 155 1 Trade Name(s): D: Taxol (Bristol-Myers GB: Taxol (Bristol-Myers J: Tax01 (Bristol-Myers Squibb) Squibb) Squibb) F: Taxol (Bristol-Myers I: Taxol (Bristol-Myers USA: Taxol (Bristol-Myers Squibb) Squibb) Squibb) Pamidronic acid (APD) ATC: M05BA03 Use: calcium metabolism rcgulator (treatment of Paget's disease, hypercalcemia of malignancy) RN: 40391-99-9 MF: C,H,,NO,P, MW: 235.07 EINECS: 254-905-2 CN: (3-amino-1-hydroxypropylidene)bis(phosphonic acid) disodium salt RN: 57248-88-1 MF: C,H,NNa207P, MW: 279.03 EINECS: 260-647-1 phosphorous trichloride I p-orninopropionic Pornidronic ocid ocid phosphite H,PO,, POCI, or PCI, - H,P04. PCI, I + Reference(s): a DOS 2 130 794 (Benckiser; appl. 22.6.1971). b DOS 2 658 961 (Benckiser; appl. 24.12.1976). DOS 2 943 498 (Henkel; appl. 27.10.1981). c EP 82 472 (Henkel; appl. 15.12.1982; D-prior. 23.12.1981). crystalline disodium salt: JP 61 043 196 (Ciba-Geigy; appl. 6.8.1984). controlled-release granule: CA 2 024 63 1 (Ciba-Geigy; appl. 7.9.1989). pharmaceuticalform~Llation ofdisodium pamidronatefor controlling calcium deposition and treatment oj calcium metabolism disorders: DOS 2 405 254 (Henkel; appl. 4.2.1974). DOS 2 553 963 (Henkel; appl. 1.12.1975). AT 538 31 1 (Henkel; appl. 2.1.1981). 1552 P Pancuronium bromide topical pharmaceutical formulation: EP 407 345 (Ciba-Geigy, Henkel; appl. 28.6.1990; CH-prior. 7.7.1989). synergistic combination with cytostatics: DOS 3 804 686 (Henkel, DKFZ; appl. 15.2.1988). Formulation(s): amp. 15 mg/5 ml, 30 mg/5 ml, 60 mg/5 ml, 90 mg15 ml, 15 mg/lO ml, 30 mg/lO ml, 60 mg/lO ml, 90 mg/lO ml (as disodium salt) Trade Narne(s): GB: Aredia (Novartis; 1989) J: Aredia (Ciba-Geigy) I: Arcdia (Novartis Farma) USA: Aredia (Novartis) Pancuronium bromide ATC: M03ACOI Use: ganglionic blockcr, anticonvulsant RN: 15500-66-0 MF: C,5HmBr,N,0, MW: 732.68 EINECS: 239-532-5 LDs,,: 13 j.~g/kg (M, i.v.); 21.2 mglkg (M, p.0.); 153 pglkg (R, i.v.); 202 mgkg (R, p.0.) CN: 1 ,I '-[(2~,3a,5a,16~,17~)-3,17-bis(acetyloxy)androstane-2,l6-diyl]bis[l-methylpiperidinium] dibromide 5u-ondrost-2- isopropenyl 17-acetoxy-5a-ondrosto- en-17-one ocetote 2.1 6-diene (I) 2. Br-CH, 111 - 1. acetic anhydride 2, methyl bromide NoBH,, CH30H. THF sodium borohydride 0 Br- Poncuronium bromide Pantethine P 1553 Reference(s): NLappl. 6 602 098 (Organon; appl. 17.2.1966; GB-prior. 19.2.1965). US 4 177 190 (Richter Gedeon; 4.12.1979; H-prior. 1.8.1975). Formufulion(s): amp. 1 mglml, 4 mgl2 ml, 8 mg4 ml; vial 10 mg Trade Name(s): D: Pancuronium Curamed Pancuronium ratiopharm GB: Pavulon (Organon Teknika) (Schwabe-Curamed) (ratiopharm) I: Pavulon (Organon Teknika) Pancuronium "Organon" F: Pavulon (Organon J: Myoblock (Sankyo) Amp. (Organon Teknika) Teknika); wfm USA: Pavulon (Organon) Pantethine ATC: ~11~~32 Use: growth factor RN: 16816-67-4 MF: C2,H,2N,0,S2 MW: 554.73 EINECS: 240-842-8 LD,,: 3400 mglkg (M, i.v.); >10 g/kg (M, p.0.); 3410 mglkg (R, i.v.); >10 gkg (R, p.0.) CN: [R-(R*,R*)J-N,N-[dithiobis[2,1-ethanediylimino(3-oxo-3,l-propanediyl)]]bis[2,4-dihydroxy-3,3- dimethylbutanamide] 0 H3C H~c,~L~~;H bN-Nb%o , OH hydrazine H ti OH hydrate 0-pantothenic acid D-pantothenic hydratide (1) methyl ester 1. HCI, NoN02 2. I b 2. cyatamine Pantethine P" 1. a& , pyridine 2. dicyclohexylcorbadiimide 3. purification by ion exchange + 2HCI '*NH, 1. 1 -hydroxybenzatriozole 2 colcium 0-pantothenate cystamine dihydrochloride Reference(s): a US 2 625 565 (Parke Davis; 1953; appl. 1951). b DAS 2 638 555 (Sago Pharmaceutical; appl. 26.8.1976; J-prior. 25.5.1976). 1554 P Pantoprazole sodium alternative syntheses: Wieland; Bokelmann: Naturwisscnschaften (NATWAY) 38,384 (1950). Wittle et al.: J. Am. Chcm. Soc. (JACSAT) 75, 1694 (1953). Viscontini et al.: Helv. Chim. Acta (HCACAV) 37,375 (1954). Bowman; Cavalla: J. Chem. Soc. (JCSOAY) 1954, 1171. Shimizu et al.: Chem. Pharm. Bull. (CPBTAL) 13, 180 (1965). Formulation(s): cps. 300 mg; tabl. 60 mg Trade name!.^): I: Analip (Iketon) Pantetina (Sanofi Carpantin (Sanofi Winthrop) Winthrop)-comb. J: Pantosin (Daiichi) Pantoprazole sodium (BY-1023; B 85 10-29; SK & F-96022) ATC: A02BC02; A02BD04 Use: antisecretory, gastric Hf/K+-ATPase inhibitor RN: 138786-67-1 MF: C,,H14F,N,Na04S MW: 405.36 LD,,,: 1000 mglkg (M, p.0.) CN: 5-(difluoromcthoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl]sulfinyl]-lH-benzimidazole sodium salt hydrate RN: 164579-32-2 MF: C,,H,,F,N,NaO,S .3/2H,O MW: 864.76 (+)-isomer RN: 160098- 11 -3 MF: C,,H,,F,N,NaO,S MW: 405.36 Isomer (-I-' RN: 160488-53-9 MF: C,,H,,F,N,NaO,S MW: 405.36 racemate RN: 142678-34-0 MF: ClhH,,F2N3NaO,S MW: 405.36 intermediate U H 0 0 4-(difluoromethoxy)- (1) aniline 1. HNO,, CH2C12 2. NaOCH,. H3C-OH NH2 3. H+ I: 1 ~&%SH F 0 Pantoprazole sodium P 1555 intermediate N 2-chloromethyl- 3.4-dimethoxy- pyridiniurn chloride (N) Pantoprozole sodium I Pantoprazole sodium I Reference(s): preparation ofpantoprazole: EP 134 400 (Byk Gulden Lomberg; appl. 1.5.1984; CH-prior. 3.5.1983). inhibitors of gastric acid secretion useful for treating and preventing ulcers: EP 166 287 (By k Gulden Lomberg; CH-prior. 16.6.1984). US 4 758 579 (Byk Gulden Lomberg; 19.7.1988; CH-prior. 16.6.1984). nonhygroscopic monohydrate salt: DE 4 018 642 (Byk Gulden Lomberg; appl. 12.12.1991; D-prior. 11.6.1990). pantoprazole sodium sesquihydrate lyophilisutes: DE 4 324 014 (Ryk Gulden Lomberg; D-prior. 17.7.1993). oral multiple-unit tablet for treatment of gastrointestinal injlammation: W09 601 624 (Astra; appl. 25.1.1996; S-prior. 8.7.1994). pharmaceutical compositions for inhibition of gastric acid secretion in animals: WO 9 425 070 (Astra; appl. 10.1 1.1994; S-prior. 30.4.1993). new pantoprazole tablets andpellets: EP 519 365 (Byk Gulden Lomberg; appl. 23.12.1992; CH-prior. 17.6.1991; HU-prior. 13.6.1992). treating viral infections such as herpes infections by H+/K+- or ATPase-inhitiors: WO 9 529 897 (Searle & Co.; appl. 9.1 1.1995; USA-prior. 29.4.1994). 1556 P Papaverine use of (-)-pantoprazole for treating gastric disorders: WO 9 424 867 (Sepracor Inc.; appl. 10.11.1994; USA-prior. 27.4.1993). use of (+)-pantoprazole for treating gastric disorders: WO 9 425 028 (Sepracor Inc.; appl. 10.1 1.1994; prior. 27.4.1993). rectal antiulcer composition containing benzimidazole derivatives: EP 645 140 (Takeda Chem. Ind.; appl. 29.3.1995; J-prior. 30.3.1994, 31.8.1995). synthesis of 3,4-dialkoxypyridines: AT 394 368 (Byk Gulden Lomberg; appl. 25.3.1992; A-prior. 4.8.1990). Fonnulation(s): amp. 40 mg; tabl. 40 mg Trade Name(s): D: Pantozol (Byk Gulden) F: Inipaup (Synthklabo) Rifun (Sanol, Schwarz USA: Protonix (American Home Pharma) Products) Papaverine ATC: G04BE02; G04BE52 Use: antispasmodic, vasodilator RN: 58-74-2 MF: C,oH,tN04 MW: 339.39 EINECS: 200-397-2 LD,,: 25 mglkg (M, i.v.); 162 mglkg (M, p.0.); 13.3 mg/kg(R,i.v.); 325 mgkg(R, p.0.) CN: 1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxyisoquinoline hydrochloride RN: 61-25-6 MF: CzoHz,N04 . HCI MW: 375.85 EINECS: 200-502-1 LD,,,: 14.4 mg/kg (M, i.v.); 130 mglkg (M, p.0.); 20 mg/kg (R, i.v.); 68.8 mg/kg (R, p.0.) KCN H3cr0n + O=CH1 , H3cH0aCN H3CL0 0 potassium H3CL0 cyonide verotrole form- 3.4-dimethoxybenzyl hornoverotronitrilc (I) oldchyde chlorlde Hz, Roney-Ni homoverotrylornine (11) hornoverotric ocid N-homoverotrylhornoverotromide (El) Paracetamol P 1557 3,4-dihydropapoverine I Papaverine I Referencefs): Budesinsky-Protiva, 87. combination with adenosin monophosphate: US 3 823 234 (C.E.R.M.; 9.7.1974; F-prior. 16.5.1971). Formulation(s): amp. 60 mgl2 ml; multiple-dose vial 30 mglml Trade Name(s): D: Artegodan (Artesan); wfrn Atropaverin (Saemann); wfrn Nyxanthan (Abbott)-comb.; wfrn Optenyl (Stroschein); wfrn Panergon (Mack); wfrn Papaverin Hameln (Hameln); wfrn Paveron (Karlspharma); wfrn Spastretten (Tropon); wfrn Vascleran (Klinge)-comb.; wfrn numerous combination preparations F: Acticarbine (Warner- Lambert)-comb. Albatran (Beaufour) OxadilCne (Evans Medical)-comb. PapavCrine Aguettant (Aguettant) GB: Aspace (Hoechst)-comb. I: Antispasmina (Recordati)- comb. Monotrean (Sankyo Pharma)-comb. generics J: Papermin Inj. (Sanwa)- comb. numerous generic preparations USA: Papaverine Hydrochloride (Lilly; as hydrochloride) Parace tam01 (Acetaminophenol) ATC: N02BEOI Use: analgesic, antipyretic RN: 103-90-2 MF: C,H,NO, MW: 151.17 EINECS: 203-157-5 LD,,: 338 mglkg (M, p.0.); 2404 mgkg (R, p.0.) CN: N-(4-hydroxypheny1)acetamide classical route: w Hz, Roney-Ni 1 noH H2N (I$ H3c N / ocid H phenol (I) 4-nitrophenol 4-orninophenol ( ~orocetarnol V O~ 1. EtOAc. SOC12 l+n H1F2_ qCpOH *pH . 0.5 n2so+ 2. KI. 50 "C hydroxylarnine 0 sulfate 4'-hydroxy- ocelophenone 1558 P Paraflutizidc Referencefs): Ullmanns Encykl. Tech. Chem., 3. Aufl., Vol. 13,297. Ullmanns Encykl. Tech. Chem., 4. Aufl., Vol. 7, 543. US 2 998 450 (Warner-Lambert; 1961; appl. 1958). DAS 2 121 164 (Howard Hall; appl. 29.4.197 1; USA-prior. 29.4.1970). ncvfylntion with ketene: DRP 453 577 (M. Bergmann; appl. 1925). pharmaceutical,formulations: US 4 097 606 (Bristol-Myers; 27.6.1978; appl. 8.10.1975). combination with phenyltoloxamine: US 3 173 835 (Endo; 16.3.1965; appl. 19.3.1963). Formulation(s): cps. 500 mg; powder 500 mg, 600 mg; sol. 200 mg/5 ml; suppos. 125 mg, 250 mg, 500 mg, I g; susp. 125 mg, 250 mg, 500 mg, 1000 mg; syrup 120 mg15 ml, 200 mg15 ml, 2 g1100 ml; tabl. 200 mg, 270 mg, 350 mg, 500 mg Tmde Nanze(s): D: Ben-u-ron (bene- Arzncimi ttcl) Captin (Krewel Meuselbach) Doregrippin (Rentsch1er)- comb. Enelfa (Dolorgiet) Mono Praecimed (Molimin) nilnOcen (Zcppcnfeldt) Paedialgon (Cephasaar) Paracetamol (Hexal; Heumann; Stada) Paracetamol-ratiopharm (ratiopharm) Py romed (Sanofi Winthrop) RubieMol (RubiePharm) Toga1 (Togal) Treupel P (ASTA Medica AWD) numerous combination preparations F: Afkradol Oberlin (Oberlin) Dafalgan (UPSA) Doh prane (ThCraplix) Efferalgan 500 1- pkdiatrique (UPSA) ParacCtamol SmithKline Beecham (SmithKline Beecham) combination preparations GB: Alvedon (Novex) Calpol (Warner-Lambert) Disprol (Reckitt & Colman) Medinol (Seton) Panaleve (Pinewood) Salzone (Wallace) further combination preparations I: Acetamol (Abiogen Pharma) Alsogil (Also)-comb. Antiflu (Byk Gulden)- comb. Antinevralgico Penegal (Fama)-comb. Baby Rinolo (Lepetit)- comb. Doloflex (B yk Gulden)- comb. Efferalgan (Ursamedica) Fluciwas (1FT)-comb. Fluental (Camillo Corvi)- comb. Fluvaleas (Valeas)-comb. Lonarid (Boehringer 1ng.)- comb. Migranet (Ogna) Neofepramol (Istoria) Neouniplus (Angelin+ comb. Neoneoral (Hoechst Marion Rousse1)-comb. Omniadol (Montefarmaco)- comb. Panadol (Maggioni) Saridon (Roche)-comb. Tachipirina (Angelini) Verdal (Falqui)-comb. Zerinol (Fher)-comb. numerous generics and combination preparations J: Pyrinazin (Yamanouchi) USA: Phrenilin (Camrick)-comb. Tylenol with Codeine (Ortho-McNei1)-comb. numerous combination preparations and generics Paraflutizide ATC: C03 Use: diuretic RN: 1580-83-2 MF: C,,HI3CIFN,O4S2 MW: 405.86 EINECS: 216-426-7 CN: 6-chloro-3-[(4-fluorophenyl)methyl]-3,4-dihydro-2H-l,2,4benzothiadiazi1~~-7-sulfonamide 1,l-dioxide Paramethadione P 1559 Cl H 6-ornino-4-chlorobenzene- 2-(4-fluor0phanyl)- Poroflutizide 1,3-disulfonarnide ethanol (cf. chlorothiozide synthesis) Referenceis): GB 961 641 (Lab. Dausse; appl. 31.7.1962; F-prior. 3 1.7.1961). Formulation(s): drg. 2.5 mg Trade Name(s): D: Detensitral (Kar1spharma)- F: Divimax (Dausse)-comb.; Tensitral (Dausse)-comb.; comb.; wfm wfm wfm Paramethadione ATC: NO~ACOI (Isoethadione) . Use: antiepileptic RN: 115-67-3 MF: C,H,,NO, MW: 157.17 EINECS: 204-098-8 LD,,: 1 gfkg (M, p.0.) CN: 5-ethyl-3,5-dimethyl-2,4-oxazolidinedione H3C-)<0H H~C"OH , HCI H3C-b0 NOCN + H3CxO_~~3 H3C sodium H3C CN ethanol H C 0 cyanide methyl ethyl 2-hydroxy-2-methyl- ketone butyronitrile 2-hydroxy-2-methyl- butyric acid ethyl ester (1) ureo dirnethyl sulfate Poromethodione I Reft.rence(s): US 2 575 693 (Abbott; 195 1 ; appl. 1949). Formulation(s): cps. 150 mg, 300 mg; drops 300 mg Trade Nameis): F: Paradione (Abbott); wfm GB: Paradione (Abbott); wfm USA: Paradione (Abbott); wfrn Paramethasone ATC: H02AB05 Use: glucocorticoid RN: 53-33-8 MF: C2?HZ9FOj MW: 392.47 EINECS: 200-169-2 CN: (6a, I I P,16a)-6-fluoro- 1 1,17,21 -trihydroxy-16-methylpregna-l,4-dicnc-3,20-dione - - - - - - - - - - - - - 1560 P Paramethasone disodium phosphate RN: 2145-14-4 MF: C2,H2,FNa20RP MW: 516.41 EINECS: 218-410-5 acetate RN: 1597-82-6 MF: C2,H3,FO6 MW: 434.50 EINECS: 216-486-4 LDso: >I g/kg (M, p.0.) 16-dehydropreqnenolone methylmognesium ocetote iodide BF3, ether I + monoperphtholic a 3 - 11 boron ocid H3C 0 trifluaride 3p'-ocetoxy-5a.6a-epoxy- 16a- methylpreqnon-20-one 3,'3-0cetoxy-6p'-fluoro-5a- hydroxy- 16a-methylpregnon-20-one (11) ocetic anhydride (IU) 2. H!O/OH- b 1. monoper- phthalic ocid 68-fluoro-1 Ga-methylpregn-l7(20)- ene-3@,5a.20-triol triacetote (N) 5u-ocetoxy-68-fluoro- 38.17-dihydraxy-16a- methylpregnan-20-one (V) 1. Br2 2. Nal 3. potossium ocetote . 5 3-3 3-8 MF: C2?HZ9FOj MW: 392.47 EINECS: 20 0-1 6 9-2 CN: (6a, I I P,16a )-6 -fluoro- 1 1,17,21 -trihydroxy-16-methylpregna-l,4-dicnc-3,20-dione - - - - - - - - - - - - - 1560 . EINECS: 21 6-4 2 6-7 CN: 6-chloro- 3-[ (4-fluorophenyl)methyl ]-3 ,4-dihydro-2H-l,2,4benzothiadiazi1~ ~-7 -sulfonamide 1,l-dioxide Paramethadione P 1559 Cl H 6-ornino-4-chlorobenzene- 2-( 4-fluor0phanyl )-. 2. H!O/OH- b 1. monoper- phthalic ocid 68-fluoro-1 Ga-methylpregn-l7(20 )- ene-3@,5a.20-triol triacetote (N) 5u-ocetoxy-68-fluoro- 38.17-dihydraxy-16a- methylpregnan-20-one (V) 1.