Suprofen ATC: MOlAE07 Use: anti-inflammatory, analgesic RN: 40828-46-4 MF: C14H1201S MW: 260.31 EINECS: 255-096-9 LD,,,: 185 mglkg (M, i.v.); 590 mglkg (M, p.0.); 226 mglkg (R, i.v.); 70.6 mglkg (R, p.0.); > 160 &/-kg (dog, p.0.) CN: a-methyl-4-(2-thieny1carbonyl)benzeneacetic acid I - thlonyl fluorobenzene chloride aluminum thiophene- th~opnene- chloride 2-carboxyiic 2-carbonyl ocid chloride Suprofen I thiophene 4-ethylbenzoyl tetrachloride 4-eihylphenyl chloride 2-thienyl ketone (11) 1 NaCN 2. NDOH 11 O b N brorno- Reference(s) DOS 2 353 357 (Janssen; appl. 24.10.1973; USA-prior. 24.10.1972, 10.9.1973, 23.3.1974). Daele, P.G.H. van et al.: Arzneim Forsch. (ARZNAD) 25, 149.5 (1975). Trade Name(s): GB: Suprol (Cllag); wfm Sufenide (Italfarmaco); Lindrax (Taiho) 1: Erdol (Herdel); wfm wfm Mexaron (Toyo Yozo) Masterfin (DompC): wfm Sup101 (Cilag); wfm Sulplotin (Ichikawa Labs) J: Lindral (Taiho) USA: Suprol (Ortho); wfm 1952 S Surfactant TA Surfactant TA (Beractant) ATC: R07A Use: surfactant (for treatment of respiratory distress syndrome) RN: 108778-82- 1 MF: unspecified MW: unspecified LD,,,: 2000 mgkg (M, i.p.); 3000 mg/kg (M, p.0.) CN: beractant Production comprises (a) extracting mammalian lung slices with an electrolyte soln. (NaCl), (b) centrifuging the extract to collect a crude precipitation, (c) suspending the precipitate in water, adjusting specific gravity of the suspension with CaCI, and centrifuging the suspension to separate upper emulsion layer, (d) dialysing the emulsion and freeze-drying the dialysed soh, (e) treating the resultant powder with ethyl acetale, collecting the insoluble material and extracting the insoluble material with an organic solvent (CH,OH, CHCl,) and (Q concentrating the extract to give a solid. Referenre(s): DE 3 021 006 (Tokyo Tanabe; appl. 30.5.1980; J-prior. 2.6.1979). US 4 397 839 (Tokyo Tanabe; 9.8.1983; J-prior. 10.9.1981). Formulation(s): vial 120 mg (lyo.) Trade Name(s): J: Surfacten (Tokyo Tanabe; 1987) Suxamethonium chloride (Succinylcholine chloride) ATC: M03ABO1 Use: muscle relaxant RN: 71-27-2 MF: C,,H&12N204 MW: 361.31 EINECS: 200-747-4 LD,,,: 430 pglkg (M, i.v.) CN: 2.2'-[(I ,4-dioxo-1,4-butanediyl)bis(oxy)]bis[N,N,N-trimethylethanaminium] dichloride succinyl 2-dimethyl- bis(2-dimethylominoethyl) chloride ominoethanol succinote (I) Rqference(s): Tammelin, L.E.: Acta Chem. Scand. (ACHSE7) 7, 185 (1953). Walker, J.: J. Chem. Soc. (JCSOA9) 1950, 193. methyl suxamethonium-chloride - dry ampules: US 2 957 501 (Burroughs Wellcome; 1960; appl. 1958). US 2 957 609 (Burroughs Wellcome; 1960; appl. 1958). Suxamethonium chloride chloride Suxibuzone S 1953 Formulation(s): amp. 50 mg/5 ml, 100 mg/5 ml; vial 100 mg/lO ml, 200 mg/lO ml Trade Name(s): D: Ly sthenon (Nycomed) GB: Anectine (Glaxo J: Relaxin (Kyorin) Pantolax (Schwabe- Wellcome) Succin (Yamanouchi) Curarned) I: Midarine (Glaxo USA: Anectine (Glaxo Succicuran (Rodleben) Wellcome) Wellcome) F: CClocurine (Pharmacia & Myotenlis (Pharmacia & Upjohn) Upjohn) Suxibuzone ATC: M02AA22 Use: antirheumatic RN: 27470-5 1-5 MF: CZ4Hz6N2O6 MW: 438.48 EINECS: 248-477-6 LD,,: 285 rnglkg (M, i.v.); 1200 mg/kg (M, p.0.); 305 mg/kg (R, i.v.); 1700 mg/kg (R, p.0.); 373 mglkg (dog, p.0.) CN: butanedioic acid mono[(4-butyl-3,5-dioxo-l,2-diphenyl-4-pyrazolidinyl)methyl] ester phenylbutozone form- Suxiburone (T v, aldehyde Reference(s): DE 1 936 747 (Lab. Dr. Esteve; appl. 18.7.1969; E-prior. 20.7.1968). Formulation(s): cream 7 % Trade Name(s): D: Solurol (Delalande); wfm F: Calibene (Carrion); wfm J: Danicon (Taiho-Fujisawa) Synephrine (Oxedrine) ATC: COlCAO8 Use: sympathomimetic, adrenergic, vasopressor RN: 94-07-5 MF: C9H,,N02 MW: 167.21 EINECS: 202-300-9 LDS,f 270 mglkg (M, i.v.) CN: 4-hydroxy-a-[(methylamino)methyl]benzenemethanol tartrate (2:l) RN: 16589-24-5 MF: C,H,,NO,. 1/2C4H606 MW: 484.50 EINECS: 240-647-8 HO~ + Nc-fcH3 AICI,. HCI b HOq N ,CH3 0 H phenol (methylamino)- 4'-hydroxy-2-methyl- ocetonitrile arninoocetophenone (I) 1954 S S yrosingopine Rejiwnce(s): US 2 585 988 (Hartford Nat. Bank; 1952; NL-prior. 1948). DRP 522 790 (H. Legerlotz; 1929). DRP 566 578 (Boehringer Ing.; 1927). DRP 569 149 (Boehringer Ing.; 1928). H2. Roney-Ni I- Ebrrndation(s): drg. 12.5 mg in comb.; eye drops 0.5 mglml, 1 mglml incomb.; nasal drops 1.5 mglml in comb.; sol. 100 mglg HOq N ,CH3 OH H Synephrine Trade Narne(s): D: Corpivas (Pascoe)-comb. F: Antalyre (Boehringer 1ng.)- Posine (Alcon)-comb. Dacrin (Chibret)-comb. comb. SCdacollyre (RhBne- Ophtalmln (Winzer)-comb. Dacryne (Martin-Johnson Poulenc Rorer Cooper)- Pasgensin (Pascoe)-comb. & Johnson-MSD)-comb. comb. Solupen (Winzer) Dacryoboraline (Mart~n- GB: Sympatol (Lewis); wfm Sympatol (Boehringer Ing.) Johnson & Johnson-MSD)- I: Sympatol (Boehringer Ing.) comb. Syrosingopine ATC: CO~LAO~ Use: antihypertensive RN: 84-36-6 MF: C35H42N20,1 MW: 666.72 EINECS: 201-527-0 LD,,,: 1293 mglkg (M, p.0.); 50 mglkg (R, i.v.); >2 glkg (R, p.0.) CN: (3P, l6~,l7a,l8~,2Oa)-~8[[4-[(ethoxycarbonyI)oxy]-3,~-dimethoxybenz0yl]0xy]-ll ,l7- dimethoxyyohimban-16-carboxylic acid methyl ester methyl rcscrpote 3,5-dimethoxy-4-ethmy- corbanyloxybenzoyl chlondc Reference(s): IIS 2 81 3 871 (Ciba 1957; appl. 1954). Lucas, R.A. et al.: J. Am. hem. Soc. (JACSAT) 81, 1928 (1959). Formulution(s): tabl. 1 mg in comb. with hydrochlorothiazide (25 mg); tabl. 0.5 mg Syrosingopine S 1955 Trade Name(s): 1: Flurizin (Snvio 1BN)- Novoserpina (Ghimas); Rosidil (Nippon comb.; wfm wfm Chemiphar) Ipodiuril (Ceccare1li)- Raunova (Zambeletti); wfm Tesamurin (Zensei) comb.; wfm Raunova Plus (Zambe1etti)- USA: Singoserp-Esidrix (Cibn); Neoreserpan (Panthox & comb.; wfm Burck); wfm J: Elumonon (Tatsumi) wfrn 1956 T Tacalcitol Tacalcitol (TV-02) ATC: DOSAX04 Use: antipsoriatic RN: 57333-96-7 MF: C,,H,O, MW: 416.65 CN: (1 a,3~,5Z,7E,24R)-9,1O-Secocholesta-5,7,10(19)-triene-l,3,24-triol & 03, -78 CH2C12, OC & dioxone Me ,,\H d Me ,,,H b 1 Me H Me H dichlorodi- H H H H cyanobenzo- HO ' HO ' quinone fucosterol (from brown olgoe) 1. HZOZ, NoOH, CH30H. 2. Li, liq. NH3 b 0 HO cholesto-l,4,6-triene- 3,24-dione (I) 2. opticol seporation _____, benzoyl chloride 5,5-dimethyl- hydontoin Tacrine T 1957 E2 526 981 (Teijin; 18.6.1975; J-prior. 18.6.1974). Synform (SNFMDF) 5 (I), 1-8 (1987). Morisaki, M. et al.: J. Chem. Soc., Perkin Trans. 1 (JCPRB4) 1975, 1421-1424. Formulation(s): ointment 4.17 ~glg (as hydrate); ointment 0.0002%, 0.0004% D: Curatoderm (Herrnal) J: Bonalfa (Teijin) GB: Curatoderm (Merck) Bonealfa (Fujisawa) ATC: N06DAO1 Use: acetylcholinesterase inhibitor, nootropic, antidementia RN: 321-64-2 MF: CI,Hl4N2 MW: 198.27 EINECS: 206-291-2 LD,: 20 mgkg (R, i. v.); 70 mglkg (R, p. 0.); 39.8 mgkg (M, p. 0.); 25 mgkg (M, s. c.) CN: 1,2,3,4-Tetrahydro-9-acridinamine hydrochloride RN: 1684-40-8 MF: CI,HI,N2. HC1 MW: 234.73 EINECS: 216-867-5 hydrochloride monohydrate RN: 7149-50-0 MF: C,,H,,N2. HC1 . H20 MW: 252.75 w H 1.2.3.4-tetro- Tocrine hydro-9- ocridone aniline ethyl 2-0x0- cyclohexone- carboxyiate Tacrine El 2-amino- cyclo- benzonitrile hexonone (I) H C a""' tic1 dNH2 + I u Tocrine '4'2 4-methylaniline hydrochloride 2-amino- banzarnide 1958 T Tacrolimus 1.2,3,4-tetrohydro- ocridine-9- corboxornide 1.2,3,4-tetrohydro- ocridine 1,2.3.4-tetrahydro- ocridine N-oxide Fe. CH,COOH I1 - US 3 232 945 (S. E. Massengill Co.; 1.2.1966; USA-prior. 13.8.1962). Albert; Gledhill: J. Soc. Chem. Ind., London (JSCIAN) 64, 169 (1945). Moore, J.A.; Kornreich, L.D.: Tetrahedron (TETRAB) 20, 127 (1963). Goncharenko, S.B; Kaganskii, M.M.; Portnov, Yu.N.; Granik V.G.: Pharm. Chem. J. (Engl. Transl.) (PCJOAU) 26,769 (1992). Girgis, N.S.; Pedersen, E.B.: Synthesis (SYNTBF) 5, 547 (1985). Ettel, V.; Neumann: Collect. Czech. Chem. Commun. (CCCCAK) 23,1319 (1958). SU 3 19 596 (Klimov, G.A.; Makar'eva, T.N.; Tilchenko, M.N.) Forrnulation(s): cps. 10 mg, 20 mg, 30 mg, 40 mg (as hydrochloride) Trade Name(s): D: Cognex (Parke Davis) F: Cognex (Parke Davis) USA: Cognex (Parke Davis) Tacrolimus ATC: LO~AAOS (FK-506; FR-900506; Fujimycin; L-679934) Use: immunosuppressant RN: 104987-1 1-3 MF: C44H,yN0,, MW: 804.03 CN: [3S-[3R*[E(lS*,3S*,4S*)],4S*,5R*,8S*,9E,l2R*,l4R*, 15S*,16R*,18S*,19S*,26aR*]]- 5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a-hexadecahydro-5,19-dihydroxy-3-[2-(4-hydroxy-3- methoxycyclohexyl)-1 -methylethenyl]-14,16-dimethoxy-4,10,12,18-tetramethyl-8-(2-propenyl)- 15,19- epoxy-3H-pyrido[2,1 -c][l,4]oxaazacyclotricosine-l,7,20,21(4H,23H)-tetrone Isolation: A fermentation broth of Streptomyces tsukubaensis No. 9993 is filtered and the mycelial cake is extracted with acetone. The filtrate is combined with the acetone extract and passed through a column of Diaion HP-20. The dilution with 75 % aqueous acetone, by evaporation gives an oily residue that is extracted with ethyl acetate and submitted to column chromatography over silica gel. Tacrolimus T 1959 synthesis intermediate V: 1. Hz, Ru2C14 Uq 1. hydrogen, RU~CI,[(S)-BINOL]~ 0, 2. lithium diisoprapylamide, CH3 allyl bromide 1. LiAIH4, THF n hydride 2. dichlorodicyano- (1) benzoquinone 1. N-iodosuccinimide OH/Y;' 1. oxalyl chloride 2. diisobutylalurninum hydride <(, 2. (E)-2-butenyltri- phenylstannane, boron trifluoride etherate 1. CH2C12 0 I 1 2. 03. CH30H. CH2CI2 + Tis-0-S-CF3 r V I I 0 2. ozone triisopropylsilyl trifluoromethane- sulfonate (1V) 1960 T Tacrolimus intermediate XI: ~CH~ pp+ H3C 0 CH3 H3cd 0 H CH3 H2C\ACH2 tert-butyl hydroperoxide. divinylcorbinol L(+)-diisopropyl tartrate, titonium isopropoxide (Shorpless epoxidotion) (2R.3S)-1.2-epoxy- 4-penten-3-01 (VI) 2. HCZ-07 CH3 BF3 . O(CzH5)z Ill bromide 2. ethoxyacetylene. boron trifluoride 0, CH, . 4-methoxy- etherote (WO benzyl bromide 1. CzH50H. HgClZ 2. TosOH, toluene (lactonization) 0 II 3.Tbs-0-8-CF3 1. CHZN2 0 2. BHJ. oq. NoOH (Cloisen reorrongement) 3. N, Ct$Clz Vlll 1. mercury(l1) chloride 2. p-toluenesulfonic acid 2. borone 3. tert-butyldimethylsilyl trifluoromethonesulfonote FH3 H Tbs: -?i&H3 CH3 CH3 1. LiAIH,. THF 2. cl%cl , CHzClz 0 H~C/ \CH~ (Swern oxidation) Tis - 0 j,,, KO-~%, . THF CH3 H3C-0 CH3 1. lithium oluminum hydride 0 2. oxolyl chloride, DMSO $C H (W 3. diethyl diozomethyl- (XI phosphonote . 15S*,16R*,18S*,19S*,26aR*] ]- 5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a-hexadecahydro-5,19-dihydroxy- 3-[ 2-( 4-hydroxy- 3- methoxycyclohexyl )-1 -methylethenyl ]-1 4,16-dimethoxy-4,10,12,18-tetramethyl- 8-( 2-propenyl )-. hydrochloride 2-amino- banzarnide 1958 T Tacrolimus 1.2,3,4-tetrohydro- ocridine- 9- corboxornide 1.2,3,4-tetrohydro- ocridine 1,2.3.4-tetrahydro- ocridine N-oxide Fe. CH,COOH I1 - US 3. RN: 168 4-4 0-8 MF: CI,HI,N2. HC1 MW: 234.73 EINECS: 21 6-8 6 7-5 hydrochloride monohydrate RN: 714 9-5 0-0 MF: C,,H,,N2. HC1 . H20 MW: 252.75 w H 1.2.3.4-tetro- Tocrine hydro- 9- ocridone