Pharmaceutical Substances Syntheses, Patents, Applications - Part 59 ppsx

Defibrotide D 581 Formulation(s): amp. 500 mg; inj. powder 500 mg; lyo. 500 mg, 2 g Trade Name(s): D: Desferal (Ciba) I: Desferal (Ciba-Geigy) USA: Desferal (Novartis; as F: Desfkral (Ciba-Geigy) J: Desferal (Novartis-Takeda) mesylate) GB: Desferal (Novartis) Defibrotide RN: 8371 2-60-1 MF: unspecified MW: unspecified CN: defibrotide; polydeoxytibonucleotides from bovine lung Extraction from mammalian organs with aqueous solution of Zn salts. Reference(s): DE2 154278 (Crinos; appl. 3.11.1971; I-prior. 3.11.1970). DE 2 154 277 (Crinos; appl. 3.1 1 .I97 1; I-prior. 3.11 1970). US 3 829 567 (Crinos; 13.8.1974; I-prior. 3.1 1.1970). US 3 899 481 (Crinos; 12.8.1975; I-prior. 3.1 1.1970). EP 263 155 (Crinos; 10.4.1987; I-prior. 17.4.1986). ATC: B0I AX01; B06A Use: antithrombotic, cholinergic channel modulator, stimulates fibrinolysis medical use for renal dialysis patients: EP317 766 (Crinos; appl. 20.10.1988; I-ptior. 23.10.1987): medical use for treatment of myocardial ischaemia: EP 152 148 (Crinos; appl. 11.2.1985; I-prior. 16.2.1984). medical use for treatment ~Jperipheral arterial disease: EP 137 543 (Crinos; appl. 7.9.1984; I-prior. 12.9.1983). medical use for treatment of acute renal in.~~~ficiency: EP 137 542 (Crinos; appl. 7.9.1984; I-prior. 12.9.1983). Formulation(s): vial 200 rng Trade Name(s): I: Dasovas (Carlo Erba) Noravid (Rousscl; 1986) Prociclide (Crinos; 1986) Deflazacort ATC: I 102~~ 13 (Azacort; Oxazacort) Use: glucocorticoid, anti-inflammatory RN: 14484-47-0 MF: C2,H3,NO6 MW: 441.52 EINECS: 238-483-7 LD,,,: 5200 mgkg (M, p.0.) CN: (1 1P,16P)-21-(acety1oxy)-1 l -hydroxy-2'-methyl-5'H-pregna- 1,4-dieno[17,16-dloxazole-3,20-dione S 582 D Dehydrocholic acid 0 '. H2N\NKCHs 1. AI[OCH(CH~)~I~, H cyclohexonone 2. NaBH, 3. Li2COs I3.HCI 1. semicorbozide 1. aluminum 2. bromine 3. lithium carbonate nNPCH3 2.HsC-COOH .HsC 1. iodine, 2,2'-ozoisobutyronitrile 2. triethylammonium ocetate I Deflozocort Keference(s1: GB 1 077 393 (Lepetit; appl. 22.4.1965). Nathansohn, G. et al.: J. Med. Chem. (JMCMAR) 10,799 (1967). synthesis of I7~-azido-3P,16~-diacetoxy-5a-pregnane- I 1,20-dione: Nathansohn, G. et al.: Gazz. Chim. Ital. (GCITAY) 35, 1338 (1965). ulternative synfhesis: US 3 624 077 (Lepetit; 30.1 1.1971; GB-prior. 1 l.l.lY66). Nathansohn, G. et al.: Steroids (STEDAM) 13, 383 (1969). Fornrulution(s): tabl. 6 mg, 30 mg Trade Nume(s): D: Calcort (Albert-Roussel, I: Deflan (Guidotti) Hoechst) Flantadin (Lepetit) Dehydrocholic acid (Acide dehy drocholique) ATC: A05 Use: choleretic, liver protective drug RN: 81-23-2 MF: C,,H3,0s MW: 402.53 EINECS: 201-335-7 LD,,,: 1492 mgkg (M, i.v.); 3100 mglkg (M, p.0.); 750 mglkg (R, i.v.); 4 gkg (R, p.0.) CN: (5P)-3,7,12-trioxocholan-24-oic acid cholic ocid Dehydrocholic ocid US2966499 (Merck & Co.: 27.12.1960; prior. 9.4.1958). Formulation(sJ: amp. for i.v. and i.m. inj. 1 g/5 ml H,O (as sodium salt); tabl. 250 mg D: Decholin (Cassella-Riedel) numerous combination Decholin (Miles); wfm Eupond N (Ferring) preparations Decholin Sodium (Dome); Felacomp (Veda)-comb. J: Dehychol (Nippon Eiyo) wfm numerous combination Dehydrochol (Kanto; Gastroenterase (Wallace)- Sawai; Hokuriku) comb.; wfm F: Dycholiurn (ThCraplix); Hydrochol (Kyorin) Hepahydrin (Great USA: Atrocholin (Glaxo); wfm Southern); wfm GB: Dehydrocholin (Duncan, Bilax (Drug Industries)- Ketochol (Searle): wfm Flockhart); wfm comb.; wfm Neocholan (Dow); wfm I; Certobil (Metapharma)- Cholan (Pennwa1t)-comb.; Neolax (Central)-comb.; wfm wfm Debridat (Sigma-Tau)- Cholan-DH (Pennwalt); Sodium Dchydrocholate wfm (City Chem.); wfm Heparbil (Montefarmaco)- Cholan-HMB (Pennwa1t)- Sodium Dehydrocholate comb.; wfm (Endo); wfm Delavirdine mesilate (U-90152s) ATC: J05AG02 Use: antiviral, HIV- I reverse transcriptase inhibitor RN: 147221-93-0 MF: C22H2xN60,S . CH403S MW: 552.68 CN: 1-[3-[(I-Methylethyl)amino]-2-pyridinyl]-4-[[5-[(methysulfonyl)amino-1W-indol-2-yl]- carbonyllpiperazine monornethanesulfonate base RN: 136817-59-9 MF: C22H28N603S MW: 456.57 Boc-0, aceton~trile Boc CI NO2 H N-' di-tert-butyl HN d~carbonote 2-chlom- piperozine 1 -(3-nitro-2- 3-nitropyridine pyridy1)piperazine '. - Q 2.H3CKCH, 0 , NoCN . BH3 , CH30H g b 2. acetone, sodium cyonoborohydride I / 584 D Demecarium bromide 5-nitroindole- 2-corboxylic ocid 3. H3C-S03H , ocetonitrile 111 b 2. methonesulfonyl chloride . H3C-S03H Delovirdine rnesilote ~omero, D.L. et al.: J. Med. Chem. (JMCMAR) 36, 1505 (1993). WO 9 109 849 (Upjohn; USA-prior. 28.12.1989). Pedersen, O.S.; Pedersen, E.B.: Synthesis (SYNTBF), 2000,479. water clathrates: WO 9 422 836 (Upjohn + Co.; appl. 15.3.1994; USA-prior. 26.3.1993). novel crystal form: WO 9 528 398 (Upjohn + Co.; appl. 1.3.1995; USA-prior. 15.4.1994). combination with HIV-protease inhibitors: WO 9 726 880 (Pharmacia + Upjohn; appl. 10.12.1996; USA-prior. 26.1.1996). WO 9 616 675 (Rega Inst.; appl. 29.1 1.1995; USA-prior. 30.11.1994). combination and use with other reverse transcriptme inhibitors: WO 9 409 781 (Upjohn + Co.; appl. 10.9.1993; USA-prior. 28.10.1992). Fonnulation(s): tabl. 100 mg Trade Narne(s): USA: Rescriptor (Pharmacia & Upjohn; 1997) Demecarium bromide ATC: SOlEB04 Use: cholinesterase inhibitor RN: 56-94-0 MF: C,,H,,Br,N404 MW: 716.60 EINECS: 200-301-9 LD,,: 6490 pglkg (M, p.0.) CN: 3,3'-[I, I0-decanediylbis[(methylimino)carbonyloxy]]bis[N,N,N-trimethybenzenaminium] dibromide Demeclocycline D 585 phosgene 1 ,lo-bis(rnethylorn~no]decane 3-dimothylarnlno- phenol sodlurn salt methyl Dernecoriurn bromide bmrnide Reference(s): US 2789 891 (Osten: Stickstoffwerke; 1957; A-prior. 1954). Fonnulation(s): collyre 0.25 %, 0.5 %, 1 % Tmde Name(s): D: Tosmilen (Lentia); wfm GB: Tosmilen (Astra): wfm J: Tosmilen (Chugai) I? Tomilhe (Chibret); wfm Tosmilen (Sinclair); wfm USA: Humorsol (Merck) Demeclocycline (Demethylchlortetracycline) ATC: D06AAOl: JOl AAOl Use: antibiotic RN: 127-33-3 MF: C2,H21CIN20, MW: 464.86 EINECS: 204-834-8 LD,,: 79 mgkg (M, i.v.); M.75 gkg (R, p.0.) CN: [4S-(&,4aa,5aa,6P,12aa)]-7-chloro-4-(dimethyamino)-l,4,4a,5,5a,6,11,12a-octahydro-3,6,10,12,12a- pentahydroxy-1 ,l l-dioxo-2-naphthacene carboxamide monohydrochloride RN: 64-73-3 MF: C,,H,,CIN,O, . HCI MW: 501.32 EINECS: 200-592-2 LD,: 275 mgkg (M, i.v.); 2150 mglkg (M, p.0.); 94 mgkg (R, i.v.); 2372 mglkg (R, p.0.) 586 D Demegestone From fermentation solutions of a Streptomyces aureofuciens mutant. Reference(s): US 2 878 289 (American Cyanamid; 17.3.1959; prior. 28.5.1956). US 3 012 946 (American Cyanamid; 12. 12. 1961; appl. 16.11.1960). US 3 019 172 (American Cyanamid; 30.1.1962; appl. 14.3.1960). US 3 050 446 (American Cyanamid; 21.8.1962; appl. 28.7.1960). US 3 154 476 (Olin Mathieson; 27.10.1964; appl. 29.4.1963). DE 1 041 21 3 (American Cyanamid; appl. 24.5.1957; USA-prior. 28.5.1956). McCormick, J.R.D. et al.: J. Am. Chem. Soc. (JACSAT) 79,4561 (1957). Formulation(s): tabl. 150 mg, 300 mg (as hydrochloride) Trade Nante(s): D: Demebronc (Lederle)- comb. Ledermycin (Novalis Arm) Lederstatin (Novalis Arm.)-comb. F: Ledermycine (Lederle- Novalis); wfm GB: Deteclo (Wyeth)-comb. Ledermycin (Wyeth) I: Demebronc (Cyanamid)- comb. Dcmctraciclina (Libral); wfm Detracin (Sierochimica); dm Detravis (Vis); wfm Dimeral (Panther-Osfa Chemie); wfm Diuciclin (Benvegna); wfm Elkamicina (Biotrading); wfm Fidocin (Farmaroma); wfm Isodemetil (Isola-Ibi); wfm Latornicina (Farber-Ref); wfm Ledermicina (Cyanamid) Lesten (Serono)-comb.; w fm Magis-Ciclina (Tiber); wfm Mirciclina (Francia Farm.); wfm Neo-Cromacdin (Panther- Osfa Chemre) Oldem (Firma)-comb. Tetradek (SIT) Tollerclin (Scalari) Varibiotic (Cyanamid)- comb. Veraciclina (Am) numerous combination preparations J. DemethylchlorTetracycline (Kaken) Ledermy cin (Lederle) USA: Declomycin (Lederle Labs.; as hydrochloride) Demeges tone ATC: G03DB05 Use: progestogen RN: 101 16-22-0 MF: C2,Hz80z MW: 3 12.45 EINECS: 233-320-6 CN: 17-methyl-19-norpregna-4,9-diene-3,20-dione 3-rnethoxy-20-0x0-19-nor- pregna-1,3.5(10).16-tetroene (I) (from estrone 3-methyl ether) Denopamine D 587 H0 CH3 1. c~o,. ocetone O CH, 1. Li, NH, 2. CH,COOH, ocetone 1 &CH~ 1 n 1, chrornium(Vl) 1 oxide Demegestone u Referencefs): US 3 453 267 (Roussel-Uclaf; 1.7.1969; F-prior. 31.12.1964,25.2.1965, 24.3.1965, 14.6.1965. 3.9.1965, 17.9.1965). US 3 547 959 (Roussel-Uclaf; 15.12.1970; F-prior. 27.12.1965). Joly, R. et al.: Bull. Soc. Chim. Fr. (BSCFAS) 1973, 2694. starting material: Bum, D.; Petrov, v.: J. Chem. Soc. (JCSOA9) 1962,364. total synthesis: Velluz, L. et al.: Tetrahedron (TETRAB)! 1966, Suppl. 8, part 11, 495 Formulation(s): tabl. 500 mg Trade Name(s): F: Lutionex (Roussel Diarnant) Denopamine (TA-064) ATC: COlCA IJse: orally active cardiostimulant, P,- receptor agonist RN: 71771-90-9 MF: C,,H,NO, MW: 317.39 LD,,: 198 mgkg (hl, i.v.); 5672 mglkg (M, p.0.); 9369 mglkg (R, p.0.) CN: (R)-a-[[[2-(3,4-dimethoxyphenyl)ethyl]amino]methyl]-4-hydroxybenzenemethanol hydrochloride RN: 64299-19-0 MF: CI,H,,NO,. HCI MW: 353.85 2-chloro-4'-benzyloxy- 3,4-dimethoxy- 2-(3,4-dimethoxyphenevlylomino)- ocetophenone phenethylomine 4'-benzyloxyocetophenone (I) 1. NoBH4 2. rocemote resolution with D(-)-acetylphenylolonine 3, H,. Pd-C I b J3i3TO-CH3 HO 0-CH, Denopamine 588 D Deptropine Reference(s): DOS 2 542 881 (Tanabe; appl. 25.9.1975). US 4 032 575 (Tanabe; 28.6.1977; appl. 1.10.1975). US 4 072 759 (Tanabe; 7.2.1978; appl. 10.1 1.1976; prior. 1.10.1975). Umino, N. et al.: Chem. Pharm. Bull. (CPBTAL) 27, 1479 (1979). enantioselective synthesis starting from optically active 4-hydroxyphenylglycine: JP 85 009 702 (Tanabe; appl. 14.1 1 .l977). JP 85 009 703 (Tanabe; appl. 14.1 1.1977). Ikezaki, M. et al.: Yakugaku Zasshi (YKKZAJ) 106, 80 (1986). Formulation(s): gran. 5 %; tabl. 5 mg, 10 mg Trade Name(s): J: Kalgut (Tanabe; 1988) Deptropine (Dibenzheptropine) ATC: R06AX16 Use: antihistaminic, anticholinergic RN: 604-51-3 MF: C2,HZ7NO MW: 333.48 EINECS: 210-069-0 CN: endo-3-[(l0,11-dihydro-5H-dibenzo[a,~cyclohepten-5-yl)oxy]-8-methyl-8-azabicyclo[3.2.l]octane citrate (1:l) RN: 2169-75-7 MF: CZ3Hz7NO . C6H80, MW: 525.60 EINECS: 218-516-1 LD,,: 32 mgkg (M, i.v.); 300 mgkg (M, p.0.); 445 mgkg (R, p.0.); 75 mgkg (dog, p.0.) methobromide RN: 10139-98-7 MF: CZ4H3,BrNO MW: 428.41 LD,,: 1150 pgkg (M, i.v.); 680 mgkg (M, p.0.); 1200 pglkg (R, i.v.); 800 mglkg (R, p.0.); 71 mgkg (dog, p.0.) methiodide RN: 38146-43-9 MF: C,,H,,INO MW: 475.41 phthalic phenylacetic anhydride ocid 2-(2-phenylethy1)- benzoic ocid (1) poiyphosphoric acid NaBH, I + (y'$ J (-J-Jy%" 0 OH 5-0x0-l0,11 -di- 5-hydroxy-l0,l 1- [a.d]cycloheptene benzo[a,d]cycla- heptene Deptropine I tropine er et al.: J. Med. Pharm. Chem. (JMPCAS) 4,335 (1961). Formulation(s): tabl. 1 mg hde Name(s): GB: Brontina (Brocades); wfm Brontisol (Brocades)- I: Brontin (Forment~) comb.; wfm Dequalinium chloride ATC: DO8AHOI; GOlACO5; R02AA02 Use: bacteriostatic, antifungal !" RN: 522-51-0 MF: C,oH40CI,N4 MW: 527.58 EINECS: 208-330-9 LD,,: 1900 pglkg (M, i.v.) t 1; CN: I ,l'-(1 ,l0-decanediyI)bis[4-amino-2-methyquinolinium] dichloride 4-amlno- quinaldine A9cl I + Dequaliniurn chloride Referencefs): GB 745 956 (Allen & Hanburys; appl. 1953). dequoliniurn iodide (I) Formulation(s): different tabl., creams, sol. and gels 590 D Deserpidine Trade Narne(s): D: Dequafungan Hautspray (Kreussler) Dequavagyn (Kreussler) Eriosept (Kreussler) Evazol (Ravensberg) Malty1 (Merckle) Optipect (Thiemann) Phylletten (Arznei Miiller- Rorer) Soor-Gel (Engelhard) Sorot (Ravensberg) Tonsillol (Merck1e)-comb. numerous combination preparations F: Humex Fournier Kinaldine (Labs. Urgo)-comb. Oroseptol (SmithKline Beecham)-comb. GB: Labosept (L.A.B.) I: Aperdan (Tiber)-comb. Decabis (Gazzoni) Dequadin (Eurospital) Dequadin (Importex) Faringina (SIT) Farmocillina (Zyma) Golosan (Lifepharma) Kinogen (Geymonat). comb. Lariquin (Manetti Roberts) Osangin (Antonetto) Rinospray (Midy)-comb. S terox (Granel1i)-comb, Transpulmina gola (Sigurta)-comb. J: Almani S (Tanabe)-comb. Dequadin Lozenges (Torii) Honkon-N (Zenyaku)- comb. Neues Troch (Toyo Pharmar) SP Troche (Meiji Seika) Deserpidine (Desmethoxyreserpine) ATC: C02AA05 Use: neuroleptic RN: 13 1-01-1 MF: C,,H,,N,O, MW: 578.66 EINECS: 205-004-8 LD,,,: 500 mglkg (M, p.0.); 15 mglkg (R, i.v.) CN: (3~,l6~,l~a,l8~,2Oa)-l~-methoxy-l8-[(3,4,~-trimethoxybenzoyl)oxy]yohimban- 16-carboxylic acid methyl ester 0 0/CH3 H3C\ I;, d0-cp-~~3 , N N% ,,to I / 0-CH3 \ Deserpidine a By extraction of Rauwolfia serpentina (L.) Beuth. roots, separation of in greater quantity available reserpine as heavy soluble thiocyanate and column chromatographic purification of the mother liquors. b By extraction of Rauwolfia canescens, R. hirsuta, R. tetraphylla, R. indecora, R. vornitoria Afz. or R cubana roots and purification by fractional crystallization andlor column chromatography on A1,0,. Reference (s): a US 2 887 489 (Ciba; 1959; CH-prior. 1956). b US 2 982 769 (Ciba; 1961; appl. 1955). Formulation(s): tabl. 0.25 mg; tabl. 0.25 mg (comb. with 5 mg methyclothiazide) Trade Name(s): F: Enduronyl (Abbott)-comb.; Harmony1 (Abbott); wfm Oreticyl (Abbott)-comb.; wfm USA: Enduronyl (Abbott)-comb.; wfm GB: Enduronyl (Abbott)-comb.; wfm wfm Harmony] (Abbott); wfm . RN: 101 1 6-2 2-0 MF: C2,Hz80z MW: 3 12.45 EINECS: 23 3-3 2 0-6 CN: 17-methyl-19-norpregna-4,9-diene-3,20-dione 3-rnethoxy-2 0-0 x 0-1 9-nor- pregna-1,3.5(10).16-tetroene (I) (from estrone 3-methyl. RN: 60 4-5 1-3 MF: C2,HZ7NO MW: 333.48 EINECS: 21 0-0 6 9-0 CN: endo- 3-[ (l0,11-dihydro-5H-dibenzo[a,~cyclohepten-5-yl)oxy ]-8 -methyl-8-azabicyclo[3.2.l]octane citrate (1:l) RN: 216 9-7 5-7 MF:. HIV- I reverse transcriptase inhibitor RN: 14722 1-9 3-0 MF: C22H2xN60,S . CH403S MW: 552.68 CN: 1-[ 3-[ (I-Methylethyl)amino ]-2 -pyridinyl ]-4 -[ [ 5-[ (methysulfonyl)amino-1W-indol-2-yl ]- carbonyllpiperazine