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Pharmaceutical Substances Syntheses, Patents, Applications - Part 18 ppt

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complexes with zinc, cobalt or manganese sulfate resp.. Nebacetin Yamanouchi- Prednitracin CIBA Cicatrex Glaxo Neobac Dermapharm Tonsilase Media-comb.. 174 B Baclofen Collunovar SynthC1

Trang 1

Aztreonam A 171

1 CIS03H, 2-picoline CH2C12

2 V CH2CI2

b

iCH"'

XI

N1-sulfo-NZ-benzyloxycorbonyl-0-rnethylsulfonyl-

L-threoninornide tetrabutylornrnoniurn salt (XII)

VIII

K2C03, C2H4C12, H20 H2, Pd-C CZH,OH N-hydroxybenzotriozole, DCC

w

Reference(s):

US 4 386 034 (Squibb; 31.5.1983; prior 10.2.1982)

US 4 529 698 (Squibb; 16.7.1985; prior 5.11 ,1984)

US4 625 022 (Squibb; prior 25.11.1986; 2.2.1981)

DOS 3 104 145 (Squibb; appl 6.2.1981; USA-prior 29.8.1980)

GB 2 071 650 (Squibb; appl 6.2.1981; USA-prior 7.2.1980,29.9.1980)

Formulation(s): amp 2 g; inj powder 500 mg, 1 g, 2 g; lyo for inf 2 g; vial 1 g13 ml

Trade Narnefs):

D: Azactam (Bristol-Myers GB: Azactam (Bristol-Myers J: Azactam (Squibb; 1987)

Squibb; 1985) Squibb; 1986) USA: Azactam (Bristol-Myers

F: Azactam (Sanofi Winthrop) I: Axactam (Squibb; 1984) Squibb; 1987)

Trang 2

172 B Bacampicillin

Use: antibiotic (broad spectrum penicillin) RN: 50972-17-3 MF: CzIHz7N,07S MW: 465.53

CN: [2S-[2a,5a,6~(S*)]]-6-[(aminophenylacetyl)a~no]-3,3-~methyl-7-oxo-4-thia-l-

azabicyclo[3.2.0]heptane-2-carboxylic acid 1 -[(ethoxycarbonyl)oxy]ethyl ester

monohydrochloride

RN: 37661-08-8 MF: CzIHz7N,07S HCl MW: 501.99 EINECS: 253-580-4

LD,,: 184 m g k g (M, i.v.); 8529 m g k g (M, p.0.);

176 m g k g (R, i.v.); 10 g k g (R, p.0.)

azidocillin sodium salt

(9 v.)

1 -chloroethyl ethyl carbonote

Referencefs):

DAS 2 144 457 (Astra; appl 4.9.1971; S-prior 17.9.1970, 20.1 1.1970)

US 3 873 521 (Astra; 25.3.1975; S-prior 17.9.1970; 20.11.1970)

US 3 939 270 (Astra; 17.2.1976; S-prior 17.9.1970; 20.1 1.1970)

6-(D-a-azidaphenylacetamido)-

Formulation(s): f c tabl 400 g, 800 mg; susp 125 mg (as hydrochloride)

Bacampicillin

Trade Name(s):

D: Ambacamp (Pharmacia & Penglobe (Lematte et

Penglobe (Astra; 1977) GB: Ambaxin (Upjohn; 1980) J:

penicillanic acid 1 -ethoxycarbonyl-

oxyethyl ester (1)

Bacacil (Pfizer) Penglobe (Bracco) Bacacil (Pfizer Taito) F: Bacampicine (Pharmacia & I: Ambaxin (Upjohn) Penglobe (Yoshitomi) Upjohn) Amplibac (Schwarz) USA: Spectrobid (Pfizer; 1981)

Use: polypeptide antibiotic (mainly topical application)

RN: 1405-87-4 MF: C66H,o,N17016S MW: 1422.72 EINECS: 215-786-2

LD,,,: 360 mglkg (M, i.v.); >3750 mglkg (M, p.0.)

CN: bacitracin

Trang 3

Bacitracin B 173

RN: 22601-59-8 MF: Ch6H103Ni7016S MW:

Bacitracin A

1422.72 EINECS: 245-1 15-9

"Bacitracin" is submitted as mixture of bacitracin A with other bacitracins

From culture of Bacillus subtilis and purification on ion-exchangers

Referencefs):

US 2498 165 (US-Secret of War; 1950; appl 1946)

US 2 828 246 (Commercial Solvents Corp.; 1958; appl 1956)

purijication:

US 2 457 887 (Ben Venue Labs.; 1949; appl 1947)

US 2 609 324 (Commercial Solvents Corp.; 1952; appl 1949)

US 2 774 712 (S B Penick & Co.; 1956; appl 1955)

US 2776 240 (Commercial Solvents Corp.; 1957; appl 1954)

US 2 834 71 1 (Commercial Solvents Corp.; 1958; appl 1956)

US 2 915 432 (Merck & Co.; 1959; appl 1955)

US 2 960 437 (Pfizer; 1960; appl 1955)

US 3 795 663 (Commercial Solvents Corp.; 5.3.1974; appl 1.5.1972)

US4 101 539 (IMC Chemical; 18.7.1978; appl 17.10.1977)

complexes with nickel salts:

US 2 903 357 (Grain Processing Corp.; 1959; appl 1958)

Na-bacitracin methanesulfonate:

US 3 205 137 (Warner-Lambert; 7.9.1965; appl 19.3.1963)

complexes with zinc, cobalt or manganese sulfate resp sulfonates:

US 3 384 631 (Spofa; 21.5.1968; appl 23.6.1965; CSSR-prior 26.6.1964)

complexes with metal methanesuljnates:

US 3 441 646 (Commercial Solvents; 29.4.1969; appl 22.1.1965)

complex with calcium or magnesium alkylbenzenesulfonates:

US 3 891 615 (Commercial Solvents; 24.6.1975; appl 25.10.1973)

Formulation(s): amp 50000 iu; vial 5000 iu; nasal ointment 300 iu; ointment 300 iu, 500 iu; powder 300 iu Trade Namefs):

D: Anginomycin (MIP Frubienzym (Boehringer Polyspectran (A1con)-

Batrax (Gewo)-comb Nebacetin (Yamanouchi)- Prednitracin (CIBA

Cicatrex (Glaxo Neobac (Dermapharm) Tonsilase (Media)-comb Wellcome)-comb Neotracin (CIBA Vision) F: Bacicoline (Merck Sharp &

Dohme-Chibret)-comb

Trang 4

174 B Baclofen

Collunovar (SynthC1abo)-

comb

Lysopaine ORL

(Boehringer 1ng.)-comb

Maxilase Bacitracine

(Sanofi Winthrop)-comb

Oropivalone (Jouveina1)-

comb

Pimafucort (Beytout)-

comb

generics GB: Cicatrin (Glaxo Wellcome)-comb

Polyfax (Dominion)-comb

I: Bimixin (Lusofarmaco)- comb

Enterostop (Teafarma)- comb

Orobicin (Fu1ton)-comb

J: Bacitracin (Ono)

USA: Betadine (Purdue Frederick) Cortisporin (Burroughs I

Wellcome)-comb

Neosporin (Glaxo Wellcome; Warner- Lambert)

Polysporin (Warner- ,

Lambert) generics

Use: muscle relaxant (antispasmodic) RN: 1134-47-0 MF: C,,H12ClN02 MW: 213.66 EINECS: 214-486-9

LD,,,: 3 1 m g k g (M, i .v.); 200 mglkg (M, p.0.);

78 mglkg (R, i.v.); 145 mglkg (R, p.0.)

CN: P-(aminomethyl)-4-chlorobenzenepropanoic acid

oldehyde

ethyl acetoacetole ClW O ~ C H ~

3-(4-chlorapheny1)- glutoric ocid (1)

I

C I

3-(4-chlorophenyl)- 3-(4-chloropheny1)- Baclofen

glutaric anhydride glutarimide

ethyl 4-chlorocinnamate nitromethone (11)

Hz Raney-Ni

CI

Reference(s):

lJS 3 634 428 (Ciba; 11.1.1972; CH-prior 9.7.1963, 22.5.1964)

b JP 45 016 692 (Uchimaru, F et al.; Daiichi Seiyku; appl 10.6.1970); C.A (CHABAS) 73, 7 7 6 1 7 ~ (1970)

Trang 5

Balsalazide sodium B 175

conlbination with ncuroleptics:

US 3 947 579 (Nelson Research & Dev.; 30.3.1976; appl 3.6.1974)

US 3 978 216 (Nelson Research & Dev.; 31.8.1976; prior 3.6.1974, 16.7.1975)

US 4 138 484 (Nelson Research & Dev.; 6.2.1979; prior 3.6.1974, 16.7.1975, 16.8.1976,25.7.1977)

Fonnulation(s): inj sol 0.05 mgll ml, 10 mgl20 ml, 10 mg15 ml; intrathecal inj 50 pglml, 0.05 mglml,

10 mgl20 ml, 10 mg15 ml; liquid 5 mgl5 ml; tabl 5 mg, 10 mg, 25 mg

Trade Name(s):

D: Lebic (Isis Puren) GB: Lioresal (Novartis)

Lioresal (Novartis Pharma) I: Lioresal (Ciba)

F: LiorCsal (Novartis) J: Gabalon (Daiichi)

Lioresal (Novartis)

Balsalazide sodium

(BX-66 1 -A)

ATC: DO8 Use: anti-inflammatory

RN: 82101-18-6 MF: C,,H,,N,Na,O, MW: 401.29

CN: 5-[[4-[[(2-carboxyethyl)amino]carbonyl]phenyl]azo]-2-hydroxybenzoic acid disodium salt

@)-free acid

RN: 80573-04-2 MF: C,,H,,N,O, MW: 357.32

4-nitrobenzoyl ,L-alonine

chloride

N-(4-nitrobenzoyl) p-olanine (I)

1 NoN02 HZO, HCI 5 ' COOH

H , Pd-C C H OH

L a H2N%gc"CooH I , ""-0 sodium nitrite + 11

0 2 salicylic acid

N-(4-aminobenz0yl)- palanine

Refcrence(s):

DE 3 128 819 (Riorex Lab.; appl 21.7.1981; GB-prior 21.7.1980,7.7.1981)

(11)

Formulation(s): cps 750 mg (as disodium salt)

Balsalazide sodium

Trade Name(s):

GB: Colazide (Astralmanuf by

Salix)

Trang 6

176 B Bambuterol

Bambuterol

(KWD-2183)

ATC: R03CC12 Use: P2-receptor agonist, orally active lipophilic terbutaline ester prodrug, 1

long lasting bronchodilator RN: 81732-65-2 MF: C,,H,,N,OS MW: 367.45

CN: dimethylcarbamic acid 5-[2-[(1,1-dimethylethyl)amino]-l-hydroxyethyl]-l,3-phenylene ester

monohy drochloride

RN: 81732-46-9 MF: CI,H2,N,0s HCI MW: 403.91

3',5'-dihydroxy- dimethyl-

acetophenone carbamoyl

chloride

3',5'-bis(dimethy1corb- amoyloxy)acetophenone (I)

I Bombuterol

EP 43 807 (Draco; appl 30.6.1981; GB-prior 9.7.1980,29.5.1981)

DOS 3 163 871 (Draco; appl 23.1.1981; GB-prior 9.7.1980,29.5.1981)

(alternative synthes~s given)

Formulation(s): tabl 10 mg, 20 mg; sol 0.1%

Trade Namefs):

D: Bambec (Astra)

Bamethan

(Butylnorsynephrine; Butyloctopamine)

ATC: C04AA31 Use: sympathomimetic, vasodilator RN: 3703-79-5 MF: C,,Hl,N02 MW: 209.29 EINECS: 223-043-9

LD,,,: 72 m g k g (M, i.v.); 562 mglkg (M, p.0.);

80 m g k g (R, i.v.)

CN: a-[(butylamino)methyl]-4-hydroxybenzenemethanol

sulfate (2:l)

RN: 5716-20-1 MF: CI2Hl9NO2 1/2H2S04 MW: 516.66 EINECS: 227-214-9

LD,,: 72 m g k g (M, i.v.); 1600 mglkg (M, p.0.);

>I500 m g k g (R, p.0.)

Trang 7

Bamifylline B 177

benzoyl 4'- hydroxy- 4'-benzoyloxy-

chloride ocetophenone acetophenone

butylornine N-(4-benzoyloxy-

phenocyl)butylomine

4-benzoyloxy- phenocyl bromide (1)

Corrigan, J.R et al.: J Am Chem Soc (JACSAT) 67, 1894 (1945)

D: Emasex (Eurim Pharma)-

comb

Heweven (Hevert)

Medigel (Medice)-comb

Theo-Hexanicit (Astral

Promed)

Vasoforte N Kapseln

(Krugmann)

F: Escinogel (Doms-Adrian)-

comb

GB: Vasculit (Boehringer Ing.);

wfm I: Vasculat (Boehringer Ing.;

as sulfate) J: Bloodbin (Nakataki) Butibatol (Hishiyama) Butosin (Kobayashi) Cyclate (Hokuriku) Garmin (Fuso)

Pan Line (Maruishi)

Pericardin (Santen- Yamanouchi) Simpelate (Seiko Eiyo) Valtolmin (Sanwa) Vasculat (Tanabe; as sulfate)

Vasolat (Kanto) Vasolen (Toho) Vasstol (Nichiiko) Yonomol A (Sawai)

Use: bronchodilator, coronary vasodilator RN: 2016-63-9 MF: C,,H,,N,O, MW: 385.47

CN: 7-[2-[ethyl(2-hydroxyethyl)aminolethyl]-3,7-dihydro-1,3-dimethyl-8-(phenylmethyl)-1H-purine-2,6~

dione

monohydrochloride

RN: 20684-06-4 MF: C,,H,N,O, HCl MW: 421.93 EINECS: 243-967-6

Trang 8

178 B Bamipine

Reference(s):

BE 602 888 (A Christiaens S.A.; appl 21.4.1961; GB-prior 22.4.1960)

ethanol

Fonnulation(s): inj sol 300 mgf5 ml; suppos 250 mg, 750 mg; tabl 300 mg

Barnifylline

Trade Name(s):

D: Trentadil (Fresenius); wfm Trentadil injectable (Evans I: Bamifix (Chiesi)

F: Trentadil (Evans Medical) Medical) Briafil (Alfa Wassermann) Trentadil (Scdaph); wfm GB: Trentadil (Armour); wfm

Use: antihistaminic RN: 4945-47-5 MF: C,,H2,N2 MW: 280.42 EINECS: 225-587-2

LD,,: 250 mglkg (M, p.0.)

CN: l-methyl-N-phenyl-N-(phenylmethyl)-4-piperidinamine

monohydrochloride

RN: 1229-69-2 MF: C,,H,N, HCI MW: 316.88

LD,,: 60 m g k g (M, i.v.); 750 mglkg (M, p.0.);

460 m g k g (R, p.0.);

189 mglkg (dog, p.0.)

lactate (1:l)

RN: 61670-09-5 MF: C,,H2,N, C,H,O, MW: 370.49

aniline 1 -methyl- 1-methyl-4-

4-piperidone phenylimino-

piperidine

CH3

1 sodium amide

2 benzyl chloride

EINECS: 262-887-2

1 -methyl-4-anilino- piperidine (I)

Reference(s):

U S 2 683 714 (Knoll AG; 1954; D-prior 1949)

Trang 9

Barbexaclone B 179

Formulation(s): cream 20 mg; drg 20 mg; f c tabl 50 mg; gel 20 mg

Trade Nameis):

D: Bamipin (ratiopharm) F: Taumidrine (Knoll); wfm

Soventol (Knoll) I: Soventol (Knoll); wfm

Use: antiepileptic RN: 4388-82-3 MF: C,2H,2N203 MW: 232.24 EINECS: 224-504-7

LD,,: 334 mg/kg (M, p.0.);

306 mg/kg (R, p a )

CN: 5-ethyl-5-phenyl-2,4,6(1H,3H,SH)-pyrimidinetrione, compd with ( 9 - N , a -

dimethylcyclohexaneethanamine (1: I)

Reference ( s ) :

DE 1 120 452 (Knoll; appl 16.4.1960)

phenaborbitol (-)-propylhexedrine

Formulation(s): drg 100 mg, 25 mg

Barbexaclone

Trade Nurne(s):

D: Maliasin (Knoll) I: Maliasin (Ravizza)

Use: hypnotic RN: 57-44-3 MF: C8HI2N2O3 MW: 184.20 EINECS: 200-331-2

LD,,: 600 mg/kg (M, p a )

CN: 5,5-diethyl-2,4,6(1H,3H,5H)-pyrimidinetrione

monosodium salt

RN: 144-02-5 MF: C,H,,N,Na03 MW: 206.18 EINECS: 205-613-9

LD,,: 830 mglkg (M, i.v.); 800 mglkg (M, p.0.);

280 mglkg (R, i.v.1; 600 mglkg (R, p.0.)

diethyl

diethylrnolonate

Reference(s):

Fischer; Dilthey: Justus Liebigs Ann Chem (JLACBF) 335,338 (1904)

Trang 10

180 B Barnidipine

Formulation(s): tabl 250 mg, 500 mg

Trade Name(s):

D: Barbimetten (Hormosan); F: combination preparations; 1: Barbitt (Tariff Integrative)

Barnidipine

(Mepirodipine hydrochloride)

ATC: C08CA12 Use: antihypertensive agent, long active calcium antagonist

RN: 104757-53-1 MF: C2,H2,N,0, HC1 MW: 528.01

CN: [S-(R* , R * ) ] - l , 4 - D i h y d r o - 2 , 6 - d i m e t h y l - 4 - ( 3 - n i t r o p h e n y ~ b o x y i c acid methyl 1 -

(phenylmethy1)-3-pyrrolidinyl ester hydrochloride

free base

RN: 104713-75-9 MF: C2,H2,N,0, MW: 491.54

racemate

RN: 71863-55-3 MF: C2,H2,N,0, MW: 491.54

HO*,,, C O O H

C C O O H

L-molic acid

O v C H 3

2 LiAlH THF

a

1 benzylamine

2 lithium oluminum

hydride

o7

9 CH,COONo, 80°C

diketene (3s)-1 -benzyl-3-

hydroxypyrrolidine (I)

2 methyl 3-aminocrotonote (IV)

2 N

3 hydrolysis

_+

1 , tert-butyl acetoocetote m-nitro-

benzoldehyde (111)

Bornidipine

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