Pharmaceutical Substances Syntheses, Patents, Applications - Part 60 pptx

Desipramine D 591 Desipramine ATC: NO~AAOI Use: ant~depressant RN: 50-47-5 MF: CIXH22NZ MW: 266.39 EINECS: 200-040-0 LD,: 22 mgkg (M, i.v.); 448 mglkg (M, p.o.), 29 mgkg (R, I.v.); 375 mglkg (R, p.0.) CN: 10,l I-dihydro-N-methy1-5H-dibenz[b,flazep1ne-5-propanam1ne monohydrochloride RN: 58-28-6 MF: C,,H2,N2 . HCI MW: 302.85 EINECS: 200-373-1 LDN: 37 mgkg (M, i.v.); 315 mglkg (M, p.0.); 19 mgkg (R, i.v.); 87 1 mgkg (R, p.0.); 25 mglkg (dog, I.v.) 10.1 1-dihydra-5H- prapane 5-(3-chloropropy1)- dibtnz[b.f]ozepine (1) 10.1 1-d~hydro-5H- d~benz[b.f]azep~ne 3-(benzylmethyl- amino)propyl chloride (from 1-bromo-3-chloro- propone and benzylmethylomine) I Desipramine NaNH2 Hz. Pd-C b sodium amide v L~/CH~ + cI ,R O-CH, 4 a23 LNICH3 I CH3 A 0 0ACH3 imipramine ethyl (q v.1 chloroformote Reference(s): a FR-M 796 (Geigy; appl. 3.9.1960; CH-prior. 4.9.1959). GB 908 788 (Geigy; appl. 1960; CH-prior. 1959). DE 1 I89 550 (Geigy; appl. 1960; CH-prior. 1959). b US 3 454 698 (Colgate-Palmolive; 8.7.1969; prior. 25.5.1960). US 3 454 554 (Colgate-Palmolive; 8.7.1969; prior. 25.5.1960). c DE 1 288 599 (Geigy; appl. 13.3.1962; CH-prior. 14.3.1961). DE 1 445 800 (Geigy; appl. 2.3.1962; CH-prior. 3.3.1961). Desipramine I Formulation(s): drg. 25 mg; tabl. 25 mg 592 D Desloratadine Trade Name(s): D: Pertofran (Novartis F: Pcrtofran (Novartis; as J: Pertofran (Fujisawa) Pharma) hydrochloride) USA: Norpramin (Hoechst Petylyl (ASTA Mcdica GB: Pertofran (Geigy); wfm Marion Roussel; as AW D) I: Nortimil (Chiesi) hy drochloride) Desloratadine (Sch-34117) Use: non-sedating antihistamine metabolite of loratadine RN: 100643-71-8 MF: C,,H,,CIN, MW: 310.83 CN: 8-Chloro-6,11 -dihydro-1 1 -(4-piperidinylidene)-5H-benz[5,6]cyclohepta[l,2-blpyridine laratadine (q. v.) YH3 BrCN __* cyonogen bromide I Desloratadine 1 Desloratadine u 8-chloroazotadine (cf. lorotadine) Reference(s): a,b WO 8 503 707 (Schering Corp.; appl. 8.2.1985; USA-prior. 15.2.1984) polymorphs: WO 9 901 450 (Schering Cop; appl. 1.7.1998; USA-prior. 2.7.1997). eye drops containing loratadine metabolites: WO 9 848 803 (Schering-Plough K.K.; WO-prior. 25.4.1997). treatment of allergic rhinitis and asthma with desloratadine: WO 9 834 61 1 (Sepracor; appl. 10.2.1998; USA-prior. 11.2.1997). WO 9 620 708 (Sepracor; appl. 1 1.12.1995; USA-prior. 30.12.1994). transdermal dosage system: DE 4 442 999 (Hexal Pharma; D-prior. 2.1 2.1994). Trade Name(s): IJSA: DCL (Schering-Plough; 2000) Deslorelin D 593 Deslorelin Use: GnRH-agonist (for treatment of precocious puberty) RN: CN: 57773-65-6 MF: CHH,,N,7012 MW: 1282.48 6-~-tryptophan-9-(N-ethyl-L-prolinamide)-lO-deglycinamide luteinizing hormone-releasing factor (pig) Tos: Tosyl Boc: tert-butoxycorbonyl C12BzI: 2.4-dichlorbbenzyl Bzl: benzyl DNP: 2,4-dinitrophenyl Boc- Boc- Boc OH H- Boc Boc- H H CI2BzI Boc \CI,B~I -OH H \BZI \CI~BZI \C12~z~ \C~I 'OH b~, H,C' I Deslorelin I *rq Pro Resin Bac OH CI- Boc Boc- H H Tos Boc \TOS OH H \TOS \TOS as 0s 594 D Desmopressin Rrj'irence(s): DOS 2 830 629 (Salk Inst.; appl. 12.7.1978; USA-prior. 14.7.1977, 26.6.1978). US 4 218 439 (Salk Inst.; 19.8.1980; appl. 26.6.1978; prior. 14.7.1977). Formulation(s): vial 500 pg Trade Name(s): GB: Somagard (Monmouth; USA: Somagard (Roberts; 1990); 1991); wfm wfm Desmopressin ATC: HOlBA02 Use: antidiuretic RN: 16679-58-6 MF: C46HwN14012S2 MW: 1069.24 EINECS: 240-726-7 CN: I -(3-mercaptopropanoic acid)-8-D-argininevasopressin acetate (1:2) RN: 16789-98-3 MF: C4,HwN,40,2S2. 2C2H402 MW: 1189.34 Z-D-Arg(Tos)-OH Gly-OEt . HCI Z-D-Arg(Tos)-Gly-OEt (1) D-Arg(Tos)-GIy-OEt Np: 0~0~ Z-Pro-D-~rg(T0s)-GIy-OE~ (U) Z-Pr0-O-Arg(Tos)-Gly-~H~ (111) Desmopressin D 595 2-Asn-Cys(Bz1)-Pro-D-Arg(Tos)-Gly-NH (V) Z-Cln-Asn-Cys(Bz1)-Pro-D-Arg(Tas)-Cly-NH (VI) + . I '3'3 CH3 Tyr-Phe-OMe . HCI Bzl-Mep-ONp BzI-Mep-Tyr-Phe-OMe (VII1) Bzl-Mep-Tyr-Phe-NH-NH2 (M) 596 D Desogestrel 1. HBr. CH,WOH 2. DMF. N(C2HS),, pH 8.0 15 "C 1. No, liq. NH3, -40 OC 2. CH,COOH, pH 6.8 3. K3[WCN),l 4. purification on sephadex Referenceis): US 3 454 549 (Sandoz; 8.7.1969; CH-prior. 17.7.1964). US 3 497 49 1 (Ceskoslovenska Akad.; 24.2.1970; CS-prior. 15.9.1966). Huguenin, R.L.; Boissonas, R.A.: Helv. Chim. Acta (HCACAV) 49,695 (1966). DOS 2 723 453 (Ferring; appl. 24.5.1977; S-prior. 24.5.1976). DOS 2 749 932 (Ferring; appl. 8.1 1.1977; S-prior. 12.1 1.1976). GB I 539 317 (Ferring; appl. 20.5.1977; S-prior. 24.5.1976). GB 1 539 318 (Ferring; appl. 4.1 1.1977; S-prior. 12.1 1.1976). Formulation(s): amp. 4 kg; doses spray 0.1 mg; tabl. 0.1 mg, 0.2 mg Trade Namefs): D: DDAVP (Ferring) GB: DDAVP (Ferring) USA: DDAVP (Rh6ne-Poulenc Minirin (Ferring) I: Minirin (Ferring) Rorer; as acetate) F: Minirin (Ferring; as J: Desmopressin (Kyowa acetate) Hakko) Desogestrel ATC: G03AA Use: progestogen, oral contraceptive (in combination with ethinylestradiol) RN: 54024-22-5 MF: C,,H,,O MW: 310.48 EINECS: 258-929-4 CN: (17a)-13-ethyl-] 1-methyIene-18,19-dinorpregn-4-en-20-yn-17-01 OH + & ii G Pb(OCOCti3)4, lead tetraacetate, I2 b I eo iadine 1 lp-hydroxy-A4- ethylene estrene-3.17-dime glycol Desonide D 597 fl + H3C-big& + 1.N2H4 0 2. CrOJ b 11 H H 1. hydrarine to \ 2. chromium(Vl) ('1 oxide methylmognesium bromide ) 111 1. 1,2-ethanedithiol 2. sodium (11) rnethylenetriphe- 11-rnethylene-18-methyl- borahydride nylphosphorane b4-estrene-3.1 7-dione oxide Reference(s): US 3 927 046 (Akzona; 16.12.1975; appl. 3.12.1973; NL-prior. 9.12.1972). DE2 361 120 (Organon; appl. 7.12.1973; NL-prior. 9.12.1972; 15.11.1973). NL 7 411 607 (Akzo; appl. 2.9.1974). Broek, AS. van den et al.: Recl. Trav. Chim. Pays-Bas (RTCPA3) 94,35 (1975). Formulation(s): tabl. 150 pg (in combination with ethinylestradiol) Trade Name(s): D: Biviol (Nourypharma)- comb. Cyclosa (Nourypharma)- F: comb. Cydeane (Mansanto)- comb. Lovelle (Organon)-comb. Marvelon (Organon; 198 1)- GB: comb. Oviol (Nourypharma)- comb. Cydeane (Momanto)- comb. Mercilon (Organon)-comb. Varnoline (Organon; 1984)- comb. Marvelon (Organon)-comb. Mercilon (Organon; 1982)- comb. I: Mercilon (Organon)-comb. Planum (Mer1arini)-comb. Practil (Organon)-comb. Securgin (Menarini)-comb. USA: Desogen (Organon) Ortho-Cept (Ortho-McNeil Pharmaceutical) Desonide (Prednacinolone) ATC: D07AB08; SOIBAI 1 Use: topical glucocorticoid RN: 638-94-8 MF: C,H,,O, MW: 416.51 EINECS: 21 1-351-6 LD,: 3710 mgkg (M, p.0.) CN: (1 lP,l6a)-ll,2l-dihydroxy-l6,l7-[(l-methylethylidenc)bis(oxy)]pregna-l,4-diene-3,20-dione C 598 D Desoximetasone OJH microbiolqical hydroxylation and dehydration 0JH [S. roseochromogenes ond A. simplex] , &OH Me H OH H H 0 0 ' hydrocortisone 16a-hydroxyprednisolone (I) (q v.) HCI 1 + + Desonide Reference(s): US 3 536 586 (Squibb; 27.10.1970; prior. 25.1.1968). US 2 990 401 (American Cyanamid; 27.6.1961; prior. 18.6.1958, 11.3.1958). Bernstein, S. et al.: J. Am. Chem. Soc. (JACSAT) 81, 4573 (1959). synthesis of hydrocortisone: Allen, W.S.; Bernstein, S.: J. Am. Chem. Soc. (JACSAT) 78, 1909 (1956). Bernstein, S.: Recent Prog. Horm. Res. (RPHRA6) 14, 1 (1958). alternative synthesis: US 3 549 498 (Squibb; 22.12.1970; prior. 2.4.1968). Formulation(s): cream 1 mg/g Trade Name(s): D: Sterax (Galderma) I: Cloressidina Reticus (Farm~la) F: Locapred (Pierre Fabre) (Farmacologico Milanese) Reticus Antim~cotico Locatrop (Pierre Fabre) -Desonix (Usar)-comb. (Farmila)-comb. TridCsonit (Dome- PR 100 (Farmacologico J: Tridesonit (Miles) Hollister-Stier) Milanese) USA: Des Owen (Galderma) GB: Tridesilon (Lagap); wfm Prenacid (SIFI) Tridesllon (Bayer) Desoximetasone (Desoximethasone) ATC: D07AC03; D07XC02 Use: topical glucocorticoid RN: 382-67-2 MF: C2,H2,F0, MW: 376.47 EINECS: 206-845-3 CN: (1 1 ~,16o1)-9-fluoro-11,21-dihydroxy-l6-methylpregna-l,4-diene-3,20-dione d Desoximetasone D 599 3a-ocetoxy-16-pregnene- - 11,20-dione (fmm deoxychol~c ac~d) H,C-MgBr, LiBr v methylmognesium bromide 3n-hydroxy-lea-methyl- pregnane- 1 1,20-dione (I) OMF. Li2C03. LiBr m , N sernicorbazide hydrochloride 21 -ocetoxy-l6a-methyl- pregno- 1.4-diene-3.11.20- trione 0 :: ~~~ocooH, o&:ir H3C-SO2-CI, DMF, pyridine b V H H H H i rnethonesulfonyl HN N 'IJ' 'N' ' / chloride 21 -ocetoxy-1 lp-hydroxy- 16-methyl-1,4-pregno- diene-3.20-dione 600 D Desoxycortone acetate N-Br , HCIO+ DMF INCH, - N-brornosuccin~rnide. perchlor~c oc~d 21-acetoxy-16u-methyl- 1,4.9(1 l)-pregnatriene- 3,20-dione (V) 1. AczO, pyridine 2. HZF2. DMF 3. NoHC03, CH30H . 2. hydrogen fluoride ( Desaximetosone I Reference(s): US 3 099 654 (Roussel-Uclaf; 30.6.1963; F-prior. 17.8.1960). DOS 1 159 441 (Roussel-Uclaf; appl. 4.8.1961; F-prior. 17.8.1960). FR 1 296 544 (Roussel-Uclaf; appl. 17.8.1960). Joly, R. et al.: Arzneim Forsch. (ARZNAD) 24, 1 (1974). synthesis of 21-acetoxy-1 l~-hydroxy-16a-methyl-l,4-pregnadien-3,20-dione: DOS 1 205 096 (Roussel-Uclaf; appl. 12.5.1961; F-prior. 14.5.1960, 16.5.1960). alternative synthesis: BE 614 196 (Schering AG; appl. 21.2.1962; D-prior. 22.2.1961). US 3 232 839 (Schering AG; 1.2.1966; D-prior. 22.2.1961, 27.6.1963). Formulation(s): cream 0.25 %, 0.05 %; lotion 0.25 %; ointment 0.35 % Trade Name(s): D: Topisolon (Hoechst) Topifram (Roussel USA: Topicort (Hoechst Marlon Topisolon (Hoechst)-comb. 'Diamant)-comb. Roussel) F: Topicorte (Roussel GB: Stiedex LP (Stiefel) Diamant) 1. Flubason (Hoechst) Desoxycortone acetate ATC: H02AA03 (Deoxycorticosterone acetate; Deoxycortone acetate) Use: mineralocorticoid RN: 56-47-3 MF: C23H3204 MW: 372.51 EINECS: 200-275-9 CN: 21-(acety1oxy)pregn-4-ene-3,20-dione desoxycortone RN: 64-85-7 MF: C2,H3,,O3 MW: 330.47 EINECS: 200-596-4 LD,,,: 1 g/kg (M, route unreported) . 2-Asn-Cys(Bz1)-Pro-D-Arg(Tos)-Gly-NH (V) Z-Cln-Asn-Cys(Bz1)-Pro-D-Arg(Tas)-Cly-NH (VI) + . I '3'3 CH3 Tyr-Phe-OMe . HCI Bzl-Mep-ONp BzI-Mep-Tyr-Phe-OMe (VII1) Bzl-Mep-Tyr-Phe-NH-NH2. Z-D-Arg(Tos)-OH Gly-OEt . HCI Z-D-Arg(Tos)-Gly-OEt (1) D-Arg(Tos)-GIy-OEt Np: 0~0~ Z-Pro-D-~rg(T0s)-GIy-OE~ (U) Z-Pr0-O-Arg(Tos)-Gly-~H~ (111) Desmopressin D 595 2-Asn-Cys(Bz1)-Pro-D-Arg(Tos)-Gly-NH. 38 2-6 7-2 MF: C2,H2,F0, MW: 376.47 EINECS: 20 6-8 4 5-3 CN: (1 1 ~,16o1 )-9 -fluoro-11,21-dihydroxy-l6-methylpregna-l,4-diene-3,20-dione d Desoximetasone D 599 3a-ocetoxy-16-pregnene- - 11,20-dione