Calcium dobesilate C 321 I b 1 -3-dibromo-5.5-di- methylhydantain 2. seporotion of isomers 3. H~C-@O~H .dioxane b 1. 2.4.6-collidine 1. KOH, THF 2. hv. THF H 3%,,, 3. KOH, CH30H UI * &"'3 \ = A , dioxane, HO / Calcitriol I Reference(s): US 3 993 675 (Hoffmann-La Roche Inc.; 23.1 1.1976; prior. 12.1 1.1973, 24.2.1975). alternative synthesis:. DOS 2 754 759 (Chugai Seiyaku; appl. 8.12.1977; J-prior. 8.12.1976). Semmler, E.J. et al.: Tetrahedron Lett. (TELEAY) 1972,4147. Barton, D.R. et al.: J. Chem. Soc., Chem. Commun. (JCCCAT) 1974, 203. synthesis of la,25-dihydroxycholesterol: DOS 2 453 648 (Hoffmann-La Roche; appl. 12.1 1.1974; USA-prior. 18.1 1.1973). Trade Name(s): D: ~~~&~l (Roche) I: Calcijex (Abbott) USA: Calcijex (Abbott) F: Rocaltrol (Roche) Rocaltrol (Roche) Rocaltrol (Roche Labs.) GB: Rocaltrol (Roche) J: Rocaltrol (Roche-Kyorin) Calcium dobesilate (Dobesilate de calcium) ATC: COSBXO1 Use: hemostatic (capillary protective) RN: 20123-80-2 MF: C,2H,,Ca0,0S2 MW: 418.41 EINECS: 243-531-5 LD,,: 775 mg/kg (M, i.v.); 7549 mglkg (M, p.0.); 7061 mgkg (R, p.0.) CN: 2,s-dihydroxy benzenesulfonic acid calcium salt (2: 1) 322 C Calcium hopantenate 0 hydrogen sulfite 1.4-benza- quinone (H.$oH) h2+ Calcium dabesilote Reference(s): US 3 509 207 (Lab. Om; 28.4.1970; CH-prior. 20.1.1966). Formulation(s): cps. 250 mg; tabl. 250 mg Trade Naine(s): D: Dexium (Synthelabo) I: Dobesifar (Farmila) Doxium (Delalande Dobica (OPW) Doxiproct-Plus (Delalande Isnardi) F: Doxium (SynthClabo) 1snardi)-comb. Calcium hopantenate ATC: N06B Use: cerebral activator RN: 17097-76-6 MF: C20H,,CaN20,0 MW: 504.59 CN: (R)-4-[(2,4-dihydroxy-3,3-dimethyl-l-oxobutyl)amino]butanoic acid calcium salt (2: 1) hopantenic acid RN: 18679-90-8 MF: C,,,H,,NOS MW: 233.26 LD,,: 2250 mgkg (M, i.p.); 5720 mglkg (M, route unreported) pantothenic acid (cf. colcium pantathenate) I Calcium hopantenate I coco,. H,O I calcium carbonate Reference(s): Kopelevich, V.M. et al.: Khim. Farm. Zh. (KHFZAN) 5, 21 (1971). JP 26 189 (64) (Takeda; appl. 23.10.1962). I(Ho%N70) H3C 6~ H o co2+ alternative syntheses: McFall Desha, C.; Fuerst, R.: Biochim. Biophys. Acta (BBACAQ) 86, 33 (1964). JP 732 (66) (Tanabe; appl. 25.2.1964). review: Nishizawa, Y.; Kodama, T.: Proc. Jpn. Acad. (PCACAW) 42,841 (1966). P Calcium pantothenate C 323 Trade Name(s): J: Hopate (Tanabe) Calcium pantothenate (Vitamin Bs) ATC: A1 lHA3 1 ; D03AX04 Use: growth factor RN: 137-08-6 MF: CIRH32CaN2010 MW: 476.54 EINECS: 205-278-9 LD,: 1443 mgkg (M, i.p.1; 2490 mg/kg (M, route unreported); 2500 mgkg (M, s.c.); 3500 mgkg (R, s.c.) CN: (R)-N-(2,4-dihydroxy-3,3-dimethyl-l-oxobutyl)-P-alanine calcium salt (2: 1) Pantothenic acid RN: 79-83-4 MF: C9HI7NO5 MW: 219.24 EINECS: 201-229-0 LD,: 910 mglkg (M, i.v.); 10 glkg (M, p.0.); 830 mglkg (R, i.v.); >10 glkg (R, p.0.) CN: (R)-N-(2,4-dihydroxy-3,3-dimethyl-l-oxobutyl)-P-alanine monosodium salt RN: 867-8 1-2 MF: C,H,,NNa05 MW: 241.22 EINECS: 21 2-768-6 L isobutyr- form- 8-hydroxy- 'pantonitrile' (I) aldehyde aldehyde pivololdehyde racernate resolution with optical active ornines (e.g. ephedrine, a-phenyl- ethylamine, norephedrine) DL-panto- lactone (11) racemization (e.g. by boiling with NaOC2H5) b U D-panto- lactone (111) acrylic acid 8-olanine (N) CO(OH)~ or NoOH or aq. NH3 H2N*CN -P IV propionitrile 324 C Calcium pantothenate Reference(s): DL-pantolactone: Glaser: Monatsh. Chem. (MOCMB7) 25,46 (1904). Stiller et al.: J. Am. Chem. Soc. (JACSAT) 62, 1785 (1940). Reichstein, Griissner: Helv. Chim. Acta (HCACAV) 23,650 (1940). Carter; Ney: J. Am. Chem. Soc. (JACSAT) 63, 312 (1941). US 2 552 530 (Upjohn; 1958; appl. 1954). US 2 863 878 (Union Carbide; 1958; appl. 1954). GB 857 128 (Nopco; appl. 1958; USA-prior. 1958). US 2 967 869 (Nopco; 1961; appl. 1958). IJS 3 024 250 (Nopco; 1962; appl. 1958). DOS 2 758 883 (BASF; appl. 30.12.1977). US 4 082 775 (Soc. Chim. des Charbonnages; 4.4.1978; F-prior. 7.7.1975). GB 1 490 680 (Soc. Chim. des Charbonnages; appl. 21.6.1976; F-prior. 7.7.1975). US 4 095 952 (VEB Jenapharm; 20.6.1978; prior. 19.10.1972,4.6.1974, 16.3.1976, 15.10.1976). extraction ofpantolactone from aqueous solutions with methyl tert-butyl ether: DOS 2 809 179 (BASF; appl. 3.3.1978). D-pantolactone: racemate resolution with ephedrine: US 2 460 239 (Nopco; 1949; appl. 1945). US 2 460 240 (Nopco; 1949; appl. 1945). with ~-(+)-l-(4-nitrophenyl)-2-aminopropane-1,3-diol: DD 16 982 (R. Ring; appl. 1957). DD 32 628 (W. Braune et al.; appl. 25.3.1963). with 1-a-phenylethylamine: US 3 185 710 (Nopco; 25.5.1965; appl. 6.9.1961). with d-3-aminomethylpinane: GB 1 495 162 (BASF; appl. 29.1.1975; D-prior. 30.1.1974,9.11.1974) with d-norephedrine and derivatives: DAS 2 558 508 (Alps; appl. 24.12.1975; J-prior. 19.2.1975). US 4 045 450 (Alps; 30.8.1977; J-prior. 19.2.1975). by fractional crystallization of ammonium pantoate: FR 1 522 111 (Fuji Chemical; appl. 9.5.1967; J-prior. 10.5.1966). of guanidinium pantoate: DOS 2 838 689 (A. E. C.; appl. 5.9.1978; F-prior. 5.9.1977). of lithium pantoate: US 4 115 443 (VEB Jenapharm; 19.9.1978; prior. 17.10.1973, 10.1.1975, 25.3.1976). FR-appl. 2 23 1 638 (VEB Jenapharm; appl. 3 1.5.1974; DDR-prior. 4.6.1973). racemization of L-pantolactone: US 2 976 298 (Nopco; 1961; appl. 1958). US 2 434 061 (Merck & Co.; 1948; appl. 1945). US 2 463 734 (Nopco; 1949; appl. 1945). US 2 967 869 (Nopco; 1961; appl. 1958). Calusterone C 325 p-alanine: a US 2 376 334 (Univ. of California; 1945; appl. 1941). DAS 2 232 090 (Tokyo Fine Chem.; appl. 30.6.1972). b US 2 336 067 (Lederle; 1943; appl. 1942). US 2 377 401 (Lederle; 1945; appl. 1942). US 2 461 842 (Sharpies Chemicals; 1949; appl. 1943). US 2 819 303 (Nopco; 1958; appl. 1953). US 2 935 524 (Nopco; 1960; appl. 1957). DE 1 084 730 (Degussa; appl. 1959). US 2956 080 (Meick & Co.; 1960; appl. 1953). DAS 2 223 236 (VEB Jenapharm; appl. 12.5.1972; DDR-prior. 4.6.1971). DAS 2 232 090 (Tokyo Fine Chemical; appl. 30.6.1972). .calcium pantothenate: DE 875 359 (Roche; appl. 1941; CH-prior. 1940). DE 873 089 (E. Merck AG; appl. 1941; USA-prior. 1940). GB 571 915 (Lederle; appl. 1943; USA-prior. 1942). US 2 809 213 (Chemkk Labs.; 1957; appl. 1954). DAS 1 041 967 (Pfizer; appl. 1954; USA-prior. 1953). US 2 957 025 (Pfizer; 1960; appl. 1953). US 2 780 645 (Comm. Solvents Corp.; 1957; appl. 1954). US 2 935 528 (Nopco; 1960; appl. 1957). purification: US 2 390 499 (Lederle; 1945; appl. 1942). US 2 496 363 (Merck & Co.; 1950; appl. 1948). US 2 957 025 (Pfizer; 1960; appl. 1953). GB 1 51 1 216 (Diamond Shamrock; appl. 1.2.1977). DOS 2708 016 (Diamond Shamrock; appl. 24.2.1977). Fomulation(s): cps. 6 mg, 10 mg, 50 mg; ophthalmic ointment 25 mglg Trade Name(s): D: Kerato Biciron (S & K numerous combination Lasonil H (Bayer)-comb. Pharma) preparations J: Panto (Daiichi) numerous combination GB: combination preparations numerous combination preparations . I: Fisiolax (Manetti Roberts)- preparations F: Modane (RPR Cooper)- comb. USA: Mega-B (Arco) comb. Lasaproct (Bayer)-comb. Calusterone ATC: G03BA; L02A Use: androgen, antineoplastic (mamma carcinoma) RN: 17021-26-0 ME C2,H3202 MW: 316.49 CN: (7~,17~)-17-hydroxy-7,17-dimethylandrost-4-en-3-one J,7.17,7-diocetoxy-17a-methyl- methyl- 7-0x0-5-ondrostene lithium 326 C Camazepam 1.00 . A1[OC(CH3)3]3 2. Hz, Pd-C I * 1. cyclohexonone. oluminum tri tert-butylate Colusterone Referenceis): US 3 029 263 (Upjohn; 10.4.1962; prior. 22.12.1958,6.6.1958) (synthesis of starting material is also described). alternative synthesis: US 3 341 557 (Upjohn; 12.9.1967; prior. 5.6.1961, 6.1 1.1960, 6.6.1958). Formulation(s): tabl. 50 mg Trade Nameis): USA: Methosarb (Upjohn); wfm ' Camazepam ATC: N05BA15 Use: sedative, tranquilizer RN: 36104-80-0 MF: C,,H,,ClN,O, MW: 371.82 EINECS: 252-866-6 LD,,,: 970 mglkg (M, p.0.); >4 glkg (R, p.0.) CN: dimethylcarbamic acid 7-chloro-2,3-dihydro-l-methyl-2-oxo-5-phenyl-1H-l,4-benzodiazepin-3-y1 ester 6-chloro-2-chloro- 7-chloro-5-phenyl- methyl-4-phenyl- 1.3-dihydro-2H-1.4- quinazoline 3-oxide benzodiazepin-2-one (cf. chlordiozepoxide 4-oxide synthesis) 1. (CH,CO),O phenyl chlorofarmate 2-one 4-oxide (I) 1.4-benzodiazepin-2-ane B Camostat C 327 Reference(s): DOS 2 142 181 (Siphar; appl. 23.8.1971; CH-prior. 24.8.1970). US 3 799 920 (Siphar; 26.3.1974; CH-prior. 24.8.1970). US 3 867 529 (Siphar; 18.2.1975; CH-prior. 24.8.1970). (11) dimethylomine dlternative ~ynthesis (reaction of the 3-hydroxy-compd. with dimethylcarbamoyl chloride): DOS 2 558 015 (Siphar; appl. 22.12.1975; CH-prior. 6.3.1975). Camozepam precursors: GB 972968 (Roche; appl. 9.12.1960; USA-prior. 10.12.1959, 15 1.1960,26.4.1960, 27.6.1960). Stembach, L.H.; Reeder, E.: J. Org. Chem. (JOCEAH) 26,4936 (1961). Bell, S.C.; Childress, S.J.: J. Org. Chem. (JOCEAH) 27,562, 1691 (1962). Formulation(s): drg. 10 mg, 20 mg Trade Name(s): D: Albego (Boehringer Ing.); I: Albego (Simes); wfm wfm Limpidon (Crinos); wfm Camostat ATC: B02AB04 Use: trypsin inhibitor (for treatment of chronic pancreatitis) RN: 59721-28-7 MF: C2,H22N40, MW: 398.42 CN: 4-[[4-[(aminoiminomethyl)amino]benzoyl]oxy]benzeneacetic acid 2-(dimethylamino)-2-oxoethyl ester monomesyIate RN: 59721-29-8 MF: CzOHz2N4O5 . CH40,S MW: 494.53 LDS6 200 mgkg (M, i.v.); 3 g/kg (M, p.0.); 152 mfig (R, i.v.); 3 gkg (R, p.0.) b 0 HCI S0Cll 4-guanidino- 4-guanidinobenzoyl benzoic acid chloride hydrochloride (I) (4-hydroxyphenyl)- 2-bromo-N.N- N,N-dirnethylcorbarnoylmethyl acetic acid dimethyl- (4-hydroxyphenyl)ocetate (H) acetamide 328 C Camphotamide pyridine I + I1 4 Cornostot Reference(s): DOS 2 548 886 (Ono Pharmac.; appl. 31.10.1975; J-prior. 1.11.1974, 17.12.1974,27.5.1975). US 4 021 472 (Ono Pharmac.; 3.5.1977; J-prior. 1.1 1.1974, 17.12.1974, 27.5.1975). GB 1 472 700 (Ono Pharrnac.; appl. 23.10.1975; J-prior. 1.1 1.1974; 17.12.1974,27.5.1975). FR 2 289 181 (Ono Pharmac.; appl. 30.10.1975; J-prior. 1.11.1974, 17.12.1974, 27.5.1975). Formulation(s): gran. 200 mg Trade Narne(s): J: Foipan (Ono; 1985) Camphotamide (Camphetamide) ATC: NO6 Use: analeptic RN: 4876-45-3 MF: CllH17N20. CloH1504S MW: 424.56 EINECS: 225-484-2 LD,,,: 422 mglkg (M, i.v.) CN: 3-[(diethylamino)carbonyl]-I -rnethylpyridinium salt with 4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptane-2. sulfonic acid (1 : 1) nicethamide methyl carnphor- (4. v.) 3-sutfonote Carnphotamide Reference(s): FR 812 032 (Soc. Franc. de Rech. Biochimiques; appl. 1936). Trade Name(s): F: Tonicorine (Lernatte et Boinot); wfm Camylofin (Acamylophenin) ATC: A03AA03 Use: antispasmodic RN: 54-30-8 MF: C19H32N20, MW: 320.48 EINECS: 200-202-0 LD,,,: 760 mgkg (M, p.0.) 2 CN: a-[[2-(diethylamino)ethyl]amino]benzeneacetic acid 3-methylbutyl ester Candesartan cilexetil C 329 dihydrochloride RN: 5892-41-1 MF: C,,H3,N202. 2HCI MW: 393.40 EINECS: 227-571-0 LD,: 49.2 mglkg (M, i.v.); 760 mglkg (M, p.0.); >.I5 glkg (R, p.0.) Reference(s): DE 842 206 (ASTA; appl. 1950). phenylglycine 2-diethylominoethyl Formulation(s): amp. 24 mglml; drg. 60 mg; suppos. 40 mg . Comylofin Avacan (Uji); wfrn Rugo (Hokuriku); wfrn iropentyl ester chloride hydrochloride Tmde Name(s): D: Avacan (ASTA Medica); Spasmo-Urolong wfm (Thiemann)-comb.; wfm Avafortan (ASTA Medics)- Ullus Apotheker Vetter comb.; wfm (Vetter)-comb.; wfm Avamigran (Degussa F: Avafortan (Lucien)-comb. Pharma1ASTA)-comb.; I: Avacan (Schering); wfm wfm J: Adopon (Kowa); wfm Candesartan cilexetil (TCV- 1 16) Use: antihypertensive, angiotensin I1 antagonist RN: 145040-37-5 MF: C3,H3,N,0, MW: 610.67 CN: (~)-2-ethoxy-l-[[2'-(1H-tetrazol-5-yl)[l,l'-biphenyl]-4-yl]methyl]-lH-benzimidazole-7-carboxylic acid 1-[[(cyclohexyloxy)carbonyl]oxy]ethyl ester 1. NoN,, DMF 1. H2S04 2. SOCI2. benzene H3C~0 o 2. HO$"H,. n + H~C-OH - CH3 & 1 sodium ozide ' 2. tert-butonol 3-nitrophtholic acid ethyl 2-chloro- formyl-3-nitro- benzoate NOH. THF ethyl 2-(tert-butoxy- 4-(2-cyonopheny1)- corbonylarnino)-3- benzyl bromide nitrobenzoate (I) (cf. losarton synthesis) 330 C Canthaxanthin 1. SnC12. CzH50H 2. ~~~-0~~~~~3 H~C-0 O CH3e CH3COOH + 2. ethyl orthocorbonote /h-0 ' N kH, ethyl 2-(2'-cyono- biphenyl-4-ylmethyl- amino)-3-nitrobenzoate (II) $: 1. H~C- N~ , toluene CH 2. NaOH. C$H,OH 3. Trt-CI . N(C2H5)3, CHlC12 + 1. trimethyltin azide 3. trityl chloride Trt : ethyl 1 -(2'-cyano- biphenyl-4-ylmethy1)- 2-ethaxybenzimidozole- 7-carboxylate (111) phenylmethyltetrazol-5-yl)- biphenyl-4-ylmethyl]- benzimidazole-7-corboxylic acid (IV) Reference(s): EP 459 136 (Takeda Chem. Ind.; appl. 19.4.1991 ; J-prior. 27.4.1990, 30.5.1990, 1.10.1990). 1. KpC03. DMF 2. HCI cyclohexyl 1 -iodoethyl Formulation(s): tabl. 4 mg, 8 mg, 16 mg /to Condesartan cilexetil Trade Name(s): D: Atacand (Astra/Promed) GB: Amias (Astra; Takeda) Blopress (Takeda) USA: Atacand (Astra) carbonate Canthaxanthin ATC: SOlJA Use: photoprotector, dye stuff RN: 514-78-3 MF: C4,,H,,0, MW: 564.85 EINECS: 208-187-2 LDso: 10 g/kg (M, p.0.) CN: P,P-carotene-4,4'-dione . 7-chloro-2,3-dihydro-l-methyl-2-oxo-5-phenyl-1H-l,4-benzodiazepin-3-y1 ester 6-chloro-2-chloro- 7-chloro-5-phenyl- methyl-4-phenyl- 1.3-dihydro-2H-1. 4- quinazoline 3-oxide benzodiazepin-2-one (cf. chlordiozepoxide 4-oxide synthesis). CN: (7~,17~ )-1 7-hydroxy-7,17-dimethylandrost-4-en-3-one J,7.17,7-diocetoxy-17a-methyl- methyl- 7-0 x 0-5 -ondrostene lithium 326 C Camazepam 1.00 . A1[OC(CH3)3]3 2. Hz, Pd-C I * 1 p.0.) CN: (R)-N-(2,4-dihydroxy-3,3-dimethyl-l-oxobutyl)-P-alanine monosodium salt RN: 86 7-8 1-2 MF: C,H,,NNa05 MW: 241.22 EINECS: 21 2-7 6 8-6 L isobutyr- form- 8-hydroxy- 'pantonitrile'