Pharmaceutical Substances Syntheses, Patents, Applications - Part 14 pptx

Apraclonidine A 131 morphine Apomorphine CH3 Reference(s): Small, L. et a].: J. Org. Chem. (JOCEAH) 5, 334 (1940). Formulation(s): amp. 10 mg; inj. sol. 10 mg/l ml, 5 mg/l ml; tabl. 3 mg Trade Name(s): F: Apokinon (Aguettant) I: Apomor (Tariff. GB: Brilagel (Britannia; as Integrativo; as hydrochloride) hydrochloride) Apraclonidine (Aplonidine) ATC: SOlEA03 Usc: selective q-agonist (for postsurgical control of intraocular pressure) RN: 6671 1-21-5 MF: CyHl,,Cl,N4 MW: 245.1 1 CN: 2,6-dichloro-N1-2-imidazolidinylidene-1,4-benzenediamine monohydrochIoride RN: 7321 8-79-8 MF: CYH,,C1,N4. HC1 MW: 281.57 LD,,: 6 mglkg (M, i.v.); 3 mglkg (M, p.0.); 9 mglkg (R, i.v.); 38 mglkg (R, p.0.) dihydrochIoride RN: 73217-88-6 MF: C9H,,Cl,N4 .2HCI MW: 318.04 2.6-dichloro-4 nitroaniline CI S0Cl2. 5O2CI2 I 2. NH, thionyl chloride. CC13 1.ethylenediomine sulfuryl chloride H N-[4-(dichlaromethylene- amino)-3.5-dichloro- phenyl]trichloroacet- omide Referencefs): EP 81 924 (Alcon; appl. 19.1 1.1982; USA-prior. 20.1 1.1981). EP 81 923 (Alcon; appl. 19.11.1982; USA-prior. 20.1 1.1981). US 4 461 904 (Alcon; 24.7.1984; prior. 20.11.198 1). Ronot, B.; Leclerc, G.: Bull. Soc. Chim. Fr. (BSCFAS) Pt. 2,520 (1979). combination with P-receptor antagonist: EP 365 662 (Alcon; 26.4.1989; USA-prior. 26.4.1988). preparation of 2,6-dichloro-4-nitroaniline: Goldschmidt; Strohmenger: Ber. Dtsch. Chem. Ges. (BDCGAS) 55,2455 (1922). Pausadeer; Scroggie: Aust. J. Chem. (AJCHAS) 12,430,432 (1959). Fluerscheim: J. Chem. Soc. (JCSOA9) 93 1774 (1908). Datta; Miiller: J. Am. Chem. Soc. (JACSAT) 41, 2036 (1919). Koerner: Gazz. Chim. Ital. (GCITA9) 4,376 (1874). Kohn; Pfeifer: Monatsh. Chem. (MOCMB7) 48,236 (1927). Formulation(s): eye drops 0.5 %, 1 %; ophthalmic sol. 10 mglml Trade Name(s): D: Iopidine (Alcon) GB: Iopidine (Alcon) USA: Iopidine (Alcon; 1988); F: Iopidine (Alcon) wfm Aprindine ATC: COlBB04 Use: antiarrhythmic RN: 37640-71-4 MF: CI2,H3,N, MW: 322.50 LD,,: 274 mgkg (M, p.0.) CN: N-(2,3-dihydro-lH-inden-2-yl)-RP,N-diethyl-N-phenyl-l,3-propanediamine monohydrochloride RN: 33237-74-0 MF: CzZH3,N, . HCI MW: 358.96 EINECS: 251-418-7 LD,,: 17.1 mglkg (M, i.v.); 262 mglkg (M, p.0.); 16.6 mglkg (R, i.v.); 525 mglkg (R, p.0.) 2-indonone aniline (I) N-(2-indanylidene). 2-anilinoindane (11) aniline 1. NaNH2 rCH, + 1-11 2. J-diethylomino- propyl chloride 2-indanyl Aprindine methonesulfonote Aprobarbital A 133 Referenceis): DE 2 060 721 (Christiaens S. A.; appl. 10.1 2.1970; GB-prior. l9.l2.I968,26.ll.l970). Formulation(s): cps. 50 mg; inj. sol. 200 mg120 ml Trade Name(s): D: Amidonal (PCR F: Fiboran (Nycomed) Arzneimittel) I: Aspenone (Mitsui) Aprobarbital ATC: N05CA05 Use: hypnotic, sedative RN: 77-02- 1 MF: CloH,,N,03 MW: 210.23 EINECS: 200-997-4 LD,,: 200 mgkg (M, i.p.); 350 mgkg (M, s.c.) CN: 5-(1-methylethyl)-5-(2-propenyl)-2,4,6(1H,3H,5H)-pyrimidinetrione monosodium salt RN: 125-88-2 MF: C,,H,,N,NaO, MW: 232.22 EINECS: 204-760-6 LD,,: 85 mgkg (R, i.p.) 5-isoprapyl- ollyl bromide barbituric acid I Aproborbitol / Reference(s): US 1 444 802 (Hoffmann-La Roche; 1923; appl. 1921). Formulation(s): elixir 40 mg; tabl. 20 mg, 40 mg, 80 mg Trade Name(s): D: Allional (Hoffmann-La Nervisal (Lappe)-comb.; Vita-Dor (Steigerwald). Roche)-comb.; wfm wfm comb.; wfm Mandotrilan-"Porte" Nervolitan (Kette1hack)- USA: Alurate (Roche); wfm (Hen@-comb.; wfm comb.; wfm Nervinum Stada (Stada)- Resedorm (Lappe)-comb.; comb.; wfm wfm Aprotinine (Trasylol; Triazinin; Zymofren) ATC: B02AB Use: proteinase inhibitor, kallikrein inhibitor RN: 9087-70-1 MF: C2R4H432N8407YS7 MW: 6511.55 EINECS: 232-904-9 LD,,: >50 ml/kg (M, i.p.); >50 mlkg (M, s.c.); >40 mllkg (R, i.p.); >40 mlkg (R, s.c.) CN: trypsin inhibitor (ox pancreas basic) antagosan RN: 9050-74-2 MF: C284H432N8407YS7 MW: 651 1.55 iniprol 134 A Aranidipine ox pancreas basic RN: 12407-79-3 MF: C284H4,2N,407,S, MW: 65 1 1.55 ox pancreas basic reduced RN: 11061-94-2 MF: C,,,H4,,N,407,S, MW: 6517.60 By extraction of animal lymph glands, parotid glands, pancreas, liver, milt and blood serum with dilutcd acetic acid-ethanol-mixtures upon removal of fat and proteins. Refererzce(s): US 2 890 986 (Bayer; 16.6.1959; D-prior. 29.5.1954). Formulation(s): amp. 200000 KIU; inj. sol. 100000 KIU/IO ml, 500000 KIU/SO ml Trade Name(s): D: Antagosan (Hoechst) Biscol (Lab. Franpis du Trasylol (Bayer) Beriplast (Centeon Fractionement ct dcs J: Trasylol (Bayer-Yoshitomi; Pharma)-comb. Biotechno1ogies)-comb. as solution) Tissucol (Immuno) Trasylol (Bayer-Pharma) USA: Trasylol Injection (Bayer) Trasylol (Bayer Vital) I: Antagosan (Behring) F: Antagosan (Hoechst Fase (Astra-Simes) HoudC) Kir Richter (Lepetit) Aranidipine (MPC- 1304) ATC: C04 Use: antihypertensive, calcium channel blocker RN: 86780-90-7 MF: C,,H,,N207 MW: 388.38 LD,,: 143 mg/kg (M, p.0.); 1459 mgkg (R, p.0.); 3333 mgkg (dog, p.0.) CN: 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylic acid methyl 2-oxopropyl ester n NaH, benzene 0 diketene 2,2-(ethylene- 2,2-(ethy1enedioxy)- dioxy)- 1 -propano1 propyl ocetoocetote (I) n H3C 6 , cH,coou, benzene piperidine, acetic acid 2-nitro- benzoldehyde 2,2-(ethy1enedioxy)- propyl 2-(2-nitro- benzy1idene)acetoacetate (11) H2N CH 1. C2H50H, A 2. CH,COOH. H20 I1 + '(., . CH3 methyl 3- aminocratonate Arginine aspartate A 135 NH,. CH,OH CZH50H. A I + - Reference(s): a Ohno, S. eta].: Chem. Pharm. Bull. (CPBTAL) 34(4), 1589-1606 (1986). b FR 2 514761 (Maruko Seiyaku; appl. 19.10.1982; J-prior. 19.10.1981). topical ophthalmic formulation: WO 9 323 082 (Alcon Lab.; appl. 12.5.1993; USA-prior. 13.5.1992). Formrrlution(s): gran. 20 mg/g (2 %) Trade Name(s): J: Bec (Maruko; Bristol- Sapresta (Taiho) Myers Squibb) Arginine aspartate ATC: A13A Use: liver dysfunction therapeutic, tonic RN: 7675-83-4 MF: C6H14N402 MW: 174.20 EINECS: 231-656-8 CN: L-aspartic acid compd. with L-arginine (1:l) H $2 H2N,,,, COOH H N NdCOOH + H 2 HzN,,, 2 -l' [COOH NH Very pure preparations are obtained by treatment of L-aspartic acid loaded strong basic anion-exchange resins with an aqueous solution of L-arginine hydrochloride. L-arginine L-ospartic acid Reference(s): DAS 1 518 033 (Mundipharma; appl. 17.9.1965; F-prior. 14.1.1965). Arginine asporiate Formulation(s): tabl. 1 g; sol. 1 g/10 ml, 1 &/5 ml; tabl. 500 mg, 1 g Trade Name(s): D: Argihepar (Chephasaar); F: Sargenor (ASTA Medica) I: Glutargin (Terapeutico wfm M.R.)-comb. 136 A Arginine pidolate Sargenor (ASTA Medica) Arginine pidolate (Arginine pyroglutamate) ATC: A13A Use: tonic, cerebrostimulant RN: 64855-91-0 MF: C6H,,N402. C5H,N03 MW: 303.32 EINECS: 265-253-3 CN: 5-0x0-proline compd. with L-arginine (1: 1) DL-pyroglutamic L-arginine acid Arginine pidolate DAS 2 416 339 (Manetti Roberts; appl. 4.4.1974; I-prior. 4.4.1973). GB 1 421 089 (Manetti Roberts; appl. 27.3.1974; I-prior. 4.4.1973). Provenzano, P.M. et al.: Arzneim Forsch. (ARZNAD) 27, 1553 (1977). use as sexual tonic: DOS 3 125 512 (Manetti Roberts; appl. 29.6.1981; I-prior. 30.6.1980). Formulation(s): lyo. 500 mg, 1 g; tabl. 500 mg Trade Name(s): I: Adiuvant (Manetti Roberts) Detoxergon Polvere Detoxergon Fiale (Ba1dacci)-comb. (Ba1dacci)-comb. Neoiodarsolo (Ba1dacci)- comb. Arotinolol (S-596) ATC: C07AA Use: P-adrenoceptor blocker, antihypertensive, antianginal RN: 52560-77-7 MF: C,~H,,N;O~S~ MW: 37 1.55 LD,,,: >360 mglkg (M, i.p.); 86 mglkg (M, i.v.); >5000 mglkg (M, p.0.) CN: 5-[2-[[3-[(1,l-dimethylethyl)amino]-2-hydroxypropyl]thio]-4-thiazo1y1]-2-thiophenecarboxamide hydrochloride RN: 80416-73-5 MF: C15H2,N302S, . xHC1 MW: unspecified 1. SOCI, O O Br,. CH,COOH 1. thionyl '~cWNH~ bromine chloride 5-acetylthiophene- 2-carboxylic acid Ascorbic acid A 137 omrnoniurn butylornino- 2-rnercopto-4-(5- dithiocorbomote 2-proponol corbornoyl-2-thienyl)- (from tert-butyl- thiozole ornine and epi- chlorohydrin) Arotinolol Reference(s): DOS 2 341 753 (Sumitomo; appl. 17.8.1973; J-prior. 17.8.1972, 5.4.1973). US 3 932 400 (Sumitomo; 13.1.1976; J-prior. 17.8.1972, 5.4.1973). Hara, Y. et al.: J. Pharm. Sci. (JPMSAE) 67, 1334 (1978). Formulation(s): tabl. 10 mg Trade Narners): J: Almarl (Surnitomo; 1986) Ascorbic acid (Acide ascorbique; Vitamin C) ATC: AIlGAOl Use: antiscorbutical vitamin. antioxidant RN: 50-81-7 MF: C6H8O6 MW: 176.12 EINECS: 200-066-2 LDS,,: 518rnglkg (M,i.v.); 3367 mg/kg(M,p.o.); >4 glkg (R, i.v.); 11.9 glkg (R, p.0.) CN: I ascorbic acid monopotassium salt RN: 15421-15-5 MF: C6H7K06 MW: 214.21 EINECS: 239-432-1 monosodium salt RN: 134-03-2 MF: C6H7Na0, MW: 198.11 EINECS: 205-126-1 calcium salt (2:l) RN: 5743-27-1 MF: C,2Hl,Ca0,, MW: 390.31 EINECS: 227-261-5 magnesium salt (2:l) RN: 1543 1-40-0 MF: C,,H,,MgOI2 MW: 374.54 EINECS: 239-442-6 Fe(I1) salt (2:l) RN: 24808-52-4 MF: C,,H,,FeO,, MW: 406.08 Hz. Roney-Ni H , H:$-~ Acetobocter suboxydons I CHO H 138 A Ascorbic acid CH, acetone diacetone-L-sorbose CH3 diocetone-2-0x0- L-gulonic acid (U) COOH ko 2-0x0-L- gulonic ocid HO 0 H Ascorbic ocid ~eichstein, T.; Griissner, A.: Helv. Chim. Acta (HCACAV) 17, 31 1 (1934). Ullmanns Encykl. Tech. Chem., 3. Aufl., Vol. 18,223 ff. Kirk-Othmer Encycl. Chem. Technol., 2. Ed. (15SWA8), Vol. 2, (1963-1971), p. 747 ff. Formul~ztion(s): amp. 562 mg; eff. tabl. 1 g; powder 1 g; tabl. 50 mg, 200 mg, 500 mg Trade Name(s): Ascorvit (Jenapharm) Cebion (Merck) Cetebe (SmithKline Beecham) Cevitt (Hermes) Vitamin C Phytopharma (OW) numerous combination preparations Ascofer (Gerda; as iron- salt) Laroscorbine (Roche Nicholas) Midy Vitamine C (SmithKline Beecham) Vi tascorbol (ThCraplix) generics (as salts) and numerous combination preparations Ferfolic SV (Sinc1air)- comb. Redoxon (Roche Consumer) Acidylina (1st. Italiano Ferm.) Agrumina (Also) Agruvit (Lepetit) Ascomed (Ripari-Gero) Ascorgil (Biomedica Foscama) Aster C (Corvi) Bio-Ci (Ceccarelli) C-Lisa (Lisapharma) C-Tard (Eurand-Mi) Cebion (Bracco) Cecon (Abbott) Cevit (Italfarmaco) Duo-C (Geymonat) Idro-C (Blue Cross) Lemonvit (Molteni) Rcdoxon (Roche) Vicifte (Iacopo Monico) Vicitina (CT) Vitamina C Vca (Bergamon) Vitamina C Vita (Synthelabo) combination preparations J: Ascoyl (Shionogi); wfm Hicee (Takeda); wfm Viscorin (Daiichi); wfm Vitacimin (Takeda); wfm numerous combination preparations USA: ACES Antioxidant Soft Gels (Carlson) Ce-Vi-Sol (Mead Johnson) Cevi-Bid (Geriatric Pharm.) Chromagen (Savage) CitraDerm (Pedinol) Ferancee (Stuart) Fero-Folic-500 (Abbott) Fero-Grad-500 (Abbott) Fetrin (Lunsco) Irospam (Fielding) Materna (Lederle Labs.) Trinsicon (UCR) Vi-Daylin ADC (Ross) Vitron-C (Fisons) numerous combination preparations Asparaginase A 139 Asparaginase (L-Asparaginase) ATC: LOIXX; LOlXXO2 Use: antineoplastic RN: 9015-68-3 MF: unspecified MW: unspecified EINECS: 232-765-3 LD,,,: 136 glkg (M, iv.); 7568 mglkg (R, i.v.); 227 mglkg (dog, i.v.) CN: asparaginase L-Asparagine-amidohydrolase. Relative mol mass 133000 + 5000. By separation from bacterial culture such as Escherichia coli, Serratia rnarcescens, Erwinia aroideae, Erwinia atrosepfica, Erwinia carotovora. Reference(s): Ho et al.: J. Riol. Chem. (JBCHA3) 245,3708 (1970). DAS 1 642 615 (Bayer; appl. 27.12.1967). DAS 1 942 833 (Secret. of Statc for Social Services, London; appl. 22.8.1969; GB-prior. 23.8.1968). DAS 1 942 900 (Secret. of State for Social Services, London; appl. 22.8.1969; GB-prior. 23.8.1968). Formulation(s): inj. powder 10000 iul2.5 ml Trade Name(s): D: Erwinase (Ipsen Pharma) 1: Crasnitin (Bayer); wfm USA: Elspar (Merck) F: Kidrolase (Bellon) J: Leunasc (Kyowa Hakko) Aspartame LJse: sweetener (pharmaceutical agent) RN: 22839-47-0 MF: C,,H,,N,O, MW: 294.31 EINECS: 245-261-3 CN: N-L-a-aspartyl-L-phenylalanine 1-methyl ester L-osportic L-aspartic anhydride acid hydrochlaride I Aspartame (olong with aspartame ore formed up to 20% p-isomer. seporoted by crystallization) Refuence(s): DE 1 692 768 (Searle & Co.; prior. 16.2.1968). Mazur, R.H. et al.: J. Am. Chem. Soc. (JACSA'I') 91, 264 (1969). Ariyoshi, Y. et al.: Bull. Chem. Soc. Jpn. (BCSJA8) 46, 1893 (1973). DE 2 104 620 (Ajinomoto; appl. 1.2.1971; J-prior. 31.1.1970.23.2.1970, 26.6.1970) DAS 2 152 11 1 (Ajinomoto; appl. 19.10.1971; J-prior. 26.10.1970). DAS 2 233 535 (Ajinomoto; appl. 7.7.1972; J-prior. 9.7.1972). US 3 492 131 (Searle; 27.1.1970; appl. 18.4.1966). 140 A L -Aspartic acid alternative synthesis: US 4 238 392 (Pfizer; 9.12.1980; appl. 29.10.1979). US 4 173 562 (Monsanto; 6.1 1.1979; prior. 27.12.1976, 3 1.3.1978). EP 143 881 (Gema; appl. 6.7.1984; CH-prior. 7.9.1983). ,fermentative preparation from L-aspartic acid and L-phenylalanine methyl ester: US 4 506 011 (Toyo Soda; 19.3.1985; J-prior. 5.9.1981; 14.10.1981, 18.1.1982). purijication: US 3 798 207 (Ajinomoto; 19.3.1 974; J-prior. 26.10.1970). Formulation(s): eff. tabl. 20 mg; tabl. 18 mg Trade Name(s): D: Canderel (Wander) F: Candtrel (Monsanto; 1980) 1: Aspardolce Dolafic (Ganassini) Asparel Dietason (Formenti) Aspartina (Ilex) Bil Aspatame dolaf Hermesetas Gold (Pietrasanta) (Milanfarma) Dietoman aspartame Snel Miel (Fea) (Sterling Midy) Suaviter (Boehringer Dolcor aspartame Mannh.) (Gazzoni) Tac Aspartame (Also) Futura aspartame J: Pal-Sweet (Ajinomoto) (Farmacologico Milanese) L-Aspartic acid (L-2-Aminosuccinic acid; Acide aspartique) Use: non-essential proteinogenic amino acid (for infusion solutions and as salt former) RN: 56-84-8 MF: C,H,NO, MW: 133.10 EINECS: 200-291-6 LD,,: 6 glkg (M, i.p.1 CN: L-aspartic acid monopotassium salt RN: 11 15-63-5 MF: C4H6KN0, MW: 171.19 EINECS: 214-226-4 monosodium salt RN: 3792-50-5 MF: C,H,NNaO, MW: 155.09 EINECS: 223-264-0 magnesium salt (2:l) KN: 2068-80-6 MF: C,HI,MgN,O, MW: 288.50 EINECS: 218-191-6 magnesium salt (2:l) tetrahydrate RN: 7018-07-7 MF: C8HL2MgN2O8. 4H20 MW: 360.56 ammonium furnorote L-hparlic acid I Rcference(s): with immovable aspartase: Tosa, T. et al.: Biotechnol. Bioeng. (BIBIAU) 15.69 (1973). . antiarrhythmic RN: 3764 0-7 1-4 MF: CI2,H3,N, MW: 322.50 LD,,: 274 mgkg (M, p.0.) CN: N-(2,3-dihydro-lH-inden-2-yl)-RP,N-diethyl-N-phenyl-l,3-propanediamine monohydrochloride RN: 3323 7-7 4-0 MF: CzZH3,N,. Hakko) Aspartame LJse: sweetener (pharmaceutical agent) RN: 2283 9-4 7-0 MF: C,,H,,N,O, MW: 294.31 EINECS: 24 5-2 6 1-3 CN: N-L-a-aspartyl-L-phenylalanine 1-methyl ester L-osportic L-aspartic. chloride 5-acetylthiophene- 2-carboxylic acid Ascorbic acid A 137 omrnoniurn butylornino- 2-rnercopto- 4-( 5- dithiocorbomote 2-proponol corbornoyl-2-thienyl )- (from tert-butyl- thiozole