formulution with controlled release of moxifloxacin: DE 19 546 249 Bayer AG; appl... combination with hydrochlorothiazide, triamterene: EP 317 855 Beiersdorf; appl.. DMF mycophenolic a
Trang 1Moxestrol M 1371
3,4-dirnethoxy- 1 -nitro-
benzoldehyde propane
1 -(3,4-dirnethoxy- phenyl)-2-nitro-
1 -butanal (I)
pyridine
Zn, HCOOH
phenylacetyl
O H
chloride 2-ornino-1-(3.4-
dirnethoxypheny1)-
1 -butanal
POC13, xylene
A
O H
Reference (s):
GB 1 030 022 (Orgamol; appl 7.5.1963; CH-prior 16.6.1962)
Formulation(s): amp 150 mgI5 ml; drg 100 mg, 150 mg (as hydrochloride)
Trade Name(s):
D: Certonal (Serturner) Kallaterol (Ursapharm)- Kollateral (Ursapharm)
Use: estrogen
RN: 34816-55-2 MF: C,,H,O, MW: 326.44
3,17-dioxo-l lp-
hydroxy-4.9-
Trang 21372 M Moxifloxacin hydrochloride
CH3
acetylene,
HO ' potassium tert-
Reference(s):
US 3 579 545 (Roussel-Uclaf; 18.5.197 1; F-prior 7.9.1966,9.12.1966, 28.2.1967, 9.3.1967)
FR-M 6 182 (Roussel-Uclaf; appl 28.2.1967)
Azadian-Boulanger, G.; Bertin, D.: Chim Ther (CHTPBA) 8,451 (1973)
sturting muteriul:
Joly, R et al.: C R Seances Acad Sci., Ser C (CHDCAQ) 258, 5669 (1964) (total synthesis)
Formulution(s): tabl 50 ~g
Trude Nume(s):
F: Surestryl (Roussel-Uclaf)
Moxifloxacin hydrochloride
(Bay-12-8039)
ATC: JOlMA14 Use: fluoroquinolone antibacterial RN: 186826-86-8 MF: C2,H2,FN3O4 HC1 MW: 437.90
4-0x0-3-quinolinecarboxylic acid
base
RN: 151096-09-2 MF: CZlH,FN,O4 MW: 401.44
pyridine-2.3-
dicarboxylic
ocid
1 L-(+)-tartaric acid DMF
2 crystallization
3 (mother liquors), NoOH
1 HZ Pd-C H 4 D-(-)-tartaric acid (crystallization)
5 NaOH
(S.S)-u
Trang 3Moxifloxacin hydrochloride M 1373
2,4,5-trifluoro- potassium monoethyl
3-methoxybenzoyl moionote
chloride (IV)
ethyl 2-(2.4.5-trifluoro- 3-methoxybenzoyl)acetote (V)
/CH3
cyclopropyl-
0 0 amine triethyl orthoformote
1 NoF, DMF '0 y 1 111 base
1 -cyclopropyl-6,7- difluoro-8-methoxy- 4-0x0-1.4-dihydro- quinoline-3-corboxylic acid
H N
COOH
0
Moxifloxocin hydrochloride
@ synthesis of I V
pentofluoro-
benzonitrile
1 CH3COOH H2S0, KCN
2 H2S0,
3 SOCI? benzene
Trang 41374 M Moxisylyte
DMF, acetonitrile,
Fa + ,I1 diozobicyclo[2.2.2]actone b VIU
0
1 -cyclopropyl-6,7,8-
trifluaro-1.4-dihydro-
4-0x0-3-quinoline-
carboxylic acid
1 H,C OH, THF
2 HCI, H20 cH3
COOH
0
vnl
\
Reference (s):
a DE 4 208 792 (Bayer AG; appl 19.3.1992; D-prior 19.3.1992)
aa EP 241 206 (Sankyo; appl 31.3.1987; J-prior 31.3.1986)
b EP 550 903 (Bayer AG, appl 28.12.1992; D-prior 19.3.1992)
DE 19 751 948 (Bayer AG; appl 24.1 1.1997; D-pnor 24.11.1997)
formulution with controlled release of moxifloxacin:
DE 19 546 249 (Bayer AG; appl 12.12.1995; D-prior 12.12.1995)
Formulation(s): f c tabl 400 mg
Trade Name(s):
Use: vasodilator (peripheral) (Thymoxamine)
RN: 54-32-0 MF: C,,H,,NO, MW: 279.38 EINECS: 200-204-1
LDS,,: 225 mglkg (M, p.0.)
CN: 4-[2-(dimethy1amino)ethoxy J-2-methyl-5-(1-methylethy1)phenol acetate (ester)
hydrochloride
RN: 964-52-3 MF: C,,H,SNO, HCI MW: 315.84 EINECS: 213-519-4
LD,,,: 28 mgtkg (M, i.v.); 225 mg/kg (M, p.0.);
32 m g k g (R, i.v.); 740 m g k g (R, p.0.);
54.5 m g k g (dog, i.v.)
NO
' H3C CH30H
aceticu
Trang 5Moxonidine M 1375
4-ocetamido-
thymol (11)
1 NoOC,H,
2 CI-~/CHJ
I
CH3
2 2-(dimethylomi- no)ethyl chloride
pyridine
H3C
I Moxisylyte
Rqference(s):
DE 905 738 (Diwag; appl 1943)
combination with steroids (e g ,for treatment o f asthma):
GB 1 535 531 (W R Warner & Co.; appl 17.10.1975; valid from 15.10.1976)
Forrnulation(s): drg 30 mg; tabl 30 mg, 40 mg, 60 mg, 120 mg (as hydrochloride)
Trade Name(s):
D: Vasoklin (Godecke); wfm Icavex (ASTA Medica) J: Moxyl (Fujirebio)
F: Carly t h e (ASTA Medica) GB: Erecnos (Fournier) Thimozil (Kohjin)
Erecnos (DCbat) I: Arlitene (ASTA Medica)
Moxonidine
(BDF-5895)
ATC: CO2ACO5 Use: antihypertensive, presynaptic a,-
adrenoceptor agonist RN: 75438-57-2 MF: C,H,,ClN5O MW: 241.68
LD,,,: 320 mglkg (M, p.0.);
115 mglkg (Rf, p.0.); 143 mglkg (Rm, p.0.)
1 POC13, HNO,
CH3 OACH , POCI,
b 1
2-one 2-methyl-5-nitro- 5-omino-2-methyl-
Trang 61376 M Mupirocin
0 N, CH,
+ CH3-ONa
J H CI
0 CH3
5-(1 -ocetyl-2-imidozolin-
2-ylamino)pyrirnidine (I)
Reference(s):
DOS 2 849 537 (Beiersdorf; appl 15.1 1.1978)
DOS 2 937 023 (Beiersdorf; appl 13.9.1979)
synthesis of 5 amino-2-methyl-4,6-dichloropyrimidine:
Huber, W.; Holscher, H.A.: Chem Ber (CHBEAM) 71B, 87 (1938)
Ochiai, E.; Kashida, Y.: Yakugaku Zasshi (YKKZAJ) 62,97 (1942)
medical use for promoting growth:
DOS 3 904 795 (Beiersdorf; appl 17.2.1989)
combination with hydrochlorothiazide, triamterene:
EP 317 855 (Beiersdorf; appl 12.1 1.1988; D-prior 24.1 1.1987)
Formularion(s): f c tabl 0.2 mg, 0.3 mg, 0.4 mg
Trade Name(s):
D: Cynt (Beiersdorf-Lillyl Physiotens (Solvay F: Physiotens (Solvay
GB: Physiotens (Solvay)
Mupirocin
(Pseudomonic acid)
ATC: D06AX09; ROI AX06 Use: antibiotic
RN: 12650-69-0 MF: C,6H,0, MW: 500.63
LD,,: 1638 mgkg (M, i.v.); 5 g/kg (M, p.0.);
1310 mglkg (R, i.v.); 5 glkg (R, p.0.)
CN: [2S-[2u(E),3~,4~,5a[2R*,3R*(IR*,2R*)]]]r9-[[3-methyl-I-oxo-4-[tetrahydro-3,4-dihydroxy-5-[[3-(2-
hydroxy- l-methylpropyl)oxiranyl]methyl]-2H-pyran-2-yl]-2-butenyl]oxy]nonanoic acid
Fermentation of Pseurlomonas~uorescens NCIB 10586
Reference(s):
DE 2 227 739 (Beecham; GB-prior 12.6.1971)
US 3 977 943 (Beecham; 31.8.1976; appl 7.7.1975; prior 27.3.1974)
US 4 071 536 (Beecham; 31.1.1978; prior 12.6.1971)
Fuller, A.T et al.: Nature (London) (NATUAS) 234,416 (1971)
structure:
Chain, E.B et al.: J Chem Soc., Chem Commun (JCCCAT) 20,847 (1974)
Trang 7Muzolimine M 1377
Formulation(s): cream 20 mglg; ointment 2 % (as calcium salt)
Trade Name(s):
D: Turixin (SmithKline GB: Bactroban (SmithKline J: Bactroban (SmithKline
F: Bactroban (SmithKline I: Bactroban (SmithKline USA: Bactroban (SmithKline
Muzolimine ATC: C O ~ C D O I
Use: diuretic RN: 55294-15-0 MF: C,,H,,CI,N,O MW: 272.14 EINECS: 259-573-2
CN: 5-amino-2-[1-(3,4-dichlorophenyl)ethyl]-2,4-dihydro-3H-pyrazol-3-one
H
2 HZ, Ni-kieselguhr
3 HCI
0
3',4'-dichloro-
acetophenone
ethyl 8-amino-8-
ethoxyocrylate
ethylhydrazine (I)
H3cgz:
O - 3
N"2 Muzolimine
DE 2 366 559 (Bayer; pripr 17.4.1973)
DOS 2 363 139 (Bayer; appl 19.12.1973)
Moller, E.; Horstmann, H.; Meng, K.: Pharmatherapeutica (PHARDW) 1,540 (1977)
US 3 957 814 (Bayer; 18.5.1976; appl 15.4.1974; D-prior 17.3.1973)
synthesis of 1-(3,4-dichloropheny1)ethylhydrazine:
DE 1 003 215 (Hoechst; appl 1954)
Houben-Weyl 10/2,47
Formulation(s): tabl 20.7 mg, 31 mg, 248 mg
Trade Narne(s):
D: Edrul (ZymaIBayer; 1985); I: Edrul (Bayropharm; 1983);
Trang 81378 M Mycophenolate mofetil
Mycophenolate mofetil
(ME-MPA; RS-61443)
ATC: L04AA06 Use: anti-inflammatory, immunosuppressive RN: 128794-94-5 MF: C,,H,,NO, MW: 433.50
CN: (E)-6-(1,3-dihydro-4-hydroxy-6-methoxy-7-methy1-3-0x0-5-is0benz0furanyl)-4-methyl-4-hexen0ic acid 2-(4-morpho1inyl)ethyl ester
hydrochloride
RN: 116680-01-4 MF,
(E)-6-(1.3-dihydro-4-hydroxy-
6-methoxy-7-methyl-5-oxo-
5-isobenzofuronyl)-4-methyl-
4-hexenoic acid
2-morphalino
ethanol (11)
C,,H,,NO, HCI MW: 469.96
CH2C12 DMF
mycophenolic acid chloride (I)
CH3
Mycophenolote mofetil
Reference(s):
US 4 727 069 (Syntex; appl 30.1.1987; USA-prior 30.1.1987)
preparation by azeotmpic water removal from I and II:
US 5 247 083 (Syntex; appl 10.7.1992; USA-prior 10.7.1992)
treatment of allograft rejection:
US 4 786 637 (Syntex; appl 22.1.1988; USA-prior.30.1.1987,4.9.1987, 22.1.1988, 17.8.1988)
immunoassays,for mycophenolic acid derivatives:
WO 9 602 004 (Behringwerke AG; appl 29.6.1995; USA-prior 7.7.1994)
high dose oral suspension:
WO 9 509 626 (Syntex; appl 27.9.1994; USA-prior 1.10.1993)
high-dosage unit formulation obtained by hot-meltjlling:
WO 9 426 266 (Syntex; appl 10.5.1994; USA-prior 13.5.1993)
intravenous fornzulation using crystalline anhydrous mycophenolate mofetil:
WO 9 507 902 (Syntex; appl 12.9.1994; USA-prior 15.9.1993)
combination of immunosuppressives:
WO 9 202 229 (SmithKline Beecham Corp.; appl 7.8.1991; USA-prior 10.8.1990, 5.12.1990)
WO 9 1 19 498 (Du Pont Merck; appl 5.6.1991; USA-prior 6.1 1.1990)
Formulation(s): cps 250 mg; tabl 500 mg
Trade Name(s):
D: CellCept (Roche) GB: CellCept (Roche) USA: CellCept (Roche)
F: CellCept (Produits Roche) I: CellCept (Roche)
Trang 9Mycophenolic acid M 1379
Mycophenolic acid ATC: L04AA06
Use: antibiotic, antineoplastic, antiviral RN: 24280-93-1 MF: CI7H2,O6 MW: 320.34 EINECS: 246-119-3
LD,,: 1 glkg (M, p.0.);
450 mglkg (R, i.v.); 352 mgikg (R, p.0.)
CN: (E)-6-(l,3-dihydro-4-hydroxy-6-methoxy-~-methyl-3-oxo-~-isobenzofuranyl)-4-methyl-4-hexenoic acid
I Mycophenolic acid I
By fermentation of Penicillium stoloniferum
Reference(s):
BE 862 618 (Lilly; appl 4.1.1978; USA-prior 21.3.1977)
GB 1 157 099 (ICI; valid from 31.7.1967; prior 27.9.1966, 13.6.1967)
structure:
Logan, W.R.; Newbold, G.T.: J Chem Soc (JCSOA9) 1957 1946
use as immunosuppressive and anticancer agent:
Williams, R.H.: J Antibiot (JANTAJ) 21,463 (1968)
Suzuki, S et al.: J Antibiot (JANTAJ) 22, 297 (1969)
GB 1 157 100 (ICI; valid from 2.8.1967; prior 27.9.1966)
antiviral activily:
Ando, K et al.: J Antibiot (JANTAJ) 21,649 (1968)
total synthesis:
Birch, A.J.: J Chem Soc., Chem Commun (JCCCAT) 1969, 788
Canonica, L et al.: Tetrahedron Lett (TELEAY) 1971, 2691
review:
Carter, S.B et al.: Nature (London) (NATUAS) 223, 848 (1969)
Trade Narne(s):
USA: Melbex (Lilly); wfm
Myrtecaine
(Nopoxamine)
ATC: NOlB Use: local anesthetic, antispasmodic
RN: 7712-50-7 MF: C1,H3,NO MW: 265.44 EINECS: 231-735-7
LDS,: 48 mglkg (M, i.v.)
CN: 2-[2-(6,6-dimethylbicyclo[3.l.l]hept-2-en-2-yl)ethoxy]-N,N-diethylethanamine
lauryl sulfate
RN: 76157-55-6 MF: C17H3,N0 C12H2,04S MW: 531.84
Trang 101380 M Myrtecaine t
I
1 NoNH2, toluene
chloride
Reference(s):
GB 861 900 (0 P Gaudin; appl 1959)
Trade Name(s):
D: Acidrine (Solvay Pharma)- Algesalona (Solvay AlgCsal SuractivC (Solvay
Algesal (Solvay Pharma)- F: Acidrine (Solvay Pharma)- I: Acidrine (Solvay Pharma)- 1