Ojima I. (ed.) Fluorine in Medicinal Chemistry and Chemical Biology
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Fluorine-containing Drugs for Human Use Approved by FDA in the United States 533
Formula Pharmaceutical action Dosage form CAS No. Approval date/
drug sponsor
C
18
H
14
N
2
O
4
F
4
S
Androgen antagonist
Antineoplastic agent
Oral tablet 90357 - 06 - 5
Oct. 1995/
Astrazeneca
C
21
H
23
BrFNO
2
Antipsychotic agent 10457 - 90 - 6
Janssen
Organon
Cilag - Chemi
C
15
H
22
FN
3
O
6
Antineoplastic agent Oral tablet 154361 - 50 - 9
April 1998/
HLR
C
17
H
14
F
3
N
3
O
2
S
Anti - infl ammatory
Nonsteroidal
cyclooxygenase
inhibitor
Oral capsule 169590 - 42 - 5
Dec. 1998/
GD Searle
C
26
H
33
FNO
5
Na
Hydroxymethylglutaryl -
CoA reductase
inhibitor
Oral tablet 143201 - 11 - 0
June 1997/
Bayer Pharms
C
22
H
22
F
3
N ⋅ HCl
Calcimimetic agent Oral tablet 226256 - 56 - 0
March 2004/
Amgen
534 Fluorine in Medicinal Chemistry and Chemical Biology
Active ingredient/
trade name
Chemical name Structure
Ciprofl oxacin
Hydrochloride/
Ciloxan
Cipro
Proquin XR
monohydrochloride
monohydrate salt of
1 - cyclopropyl - 6 - fl uoro - 1,
4 - dihydro - 4 - oxo - 7 - (1 -
piperazinyl) - 3 -
quinolinecarboxylic acid
HN
N
F
COOH
O
·HCl·H
2
O
N
Ciprofl oxacin/
Cipro
1 - cyclopropyl - 6 - fl uoro - 1,4 -
dihydro - 4 - oxo - 7 - (1 -
piperazinyl) - 3 -
quinolinecarboxylic acid
HN
N
N
F
COOH
O
Cisapride Monohydrate
∆
/
Propulsid
4 - amino - 5 - chloro - N - [1 - [3 -
(4 - fl uorophenoxy)propyl] -
3 - methoxypiperidin - 4 - yl] -
2 - methoxybenzamide
hydrate
O
NH
2
Cl
NH
N
O
O
F
O
H
2
O
Fluorine-containing Drugs for Human Use Approved by FDA in the United States 535
Formula Pharmaceutical action Dosage form CAS No. Approval date/
drug sponsor
C
17
H
18
FN
3
O
3
·
HCl · H
2
O
Antibacterial agent
Ophthalmic
ointment and
drops
Oral tablet
86393 - 32 - 0
Oct. 1987/
Alcon,
Bausch and Lomb
Hitech Pharma
Novex
Bayer Pharms
Barr
Carlsbad
Cobalt
Dr Reddys Labs
Ltd
Genpharm
Hikma
IVAX Pharms
Martec USA
LLC
Mylan
Pliva
Ranbaxy
Sandoz
Taro
Teva
Torpharm
Unique Pharm
Labs
Esprit Pharma
C
17
H
18
FN
3
O
3
Antimicrobial agent
Oral suspension
Injectable
Ophthalmic drops
85721 - 33 - 1
Oct. 1987/
Bayer Pharms
Abraxis Pharm
Bedford Labs
Hospira
Sicor Pharms
Nexus Pharms
C
23
H
31
ClFN
3
O
5
Anti - ulcer agent
Gastrointestinal agent
Serotonin agonist
Oral suspension
and tablet
81098 - 60 - 4
July 1993/
Janssen Pharma
536 Fluorine in Medicinal Chemistry and Chemical Biology
Active ingredient/
trade name
Chemical name Structure
Citalopram Hydrobromide/
Celexa
1 - [3 - (dimethylamino) -
propyl] - ) - 1 - (p -
fl uorophenyl) - 5 -
phthalancarbonitrile
monohydrobromide
O
NC
F
N
CH
3
CH
3
HB
r
Clobetasol Propionate/
Olux
Temovate
Embeline
Cormax
Clobex
(11 β , 16 β ) - 21 - chloro - 9 -
fl uoro - 11 - hydroxy - 16 -
methyl - 17 - (1 - oxopropoxy) -
pregna - 1,4 - diene - 3,20 - dione
O
CH
3
F H
OCOCH
2
CH
3
H
H
H
3
C
HO
O
Cl
CH
3
Clocortolone Pivalate/
Cloderm
9 - chloro - 6 α - fl uoro - 11 β , 21 -
dihydroxy - 16 α -
methylpregna - 1,4 - diene -
3,20 - dione - 21 - pivalate
O
H
3
C
HO
CH
3
CH
3
Cl
F
O
O
O
Fluorine-containing Drugs for Human Use Approved by FDA in the United States 537
Formula Pharmaceutical action Dosage form CAS No. Approval date/
drug sponsor
C
20
H
21
FN
2
O · HBr
Antidepressant
Serotonin uptake
inhibitor
Oral tablet and
solution
59729 - 32 - 7
July 1998/
Alphapharm
Apotex Inc
Aurobindo
Pharma Ltd
Forest Labs
Actavis
Elizabeth
Akyma Pharms
Apotex Inc
Caraco
Cobalt
Corepharma
Dr Reddys
Labs Ltd
Interpharm
Invagen
IVAS Pharms
Kali Labs
Mylan
Pliva
Sandoz
Taro
Teva Pharms
Torrent Pharms
Watson Labs
Biovail Labs
Intl
C
25
H
32
ClFO
5
Anti - infl ammatory
Glucocorticoid
Topical foam,
cream, gel,
ointment, spray,
and solution
25122 - 46 - 7
Dec. 1985/
Connetics
Actavis Mid
Atlantic
Altana
Fougera
Healthpoint
Stiefel
Taro
Teva Pharms
Perrigo
Galderma Labs
LP
DPT
Tolmar
Morton Grove
C
27
H
36
ClFO
5
Glucocorticoid Topical 34097 - 16 - 0
Aug. 1977/
Healthpoint
538 Fluorine in Medicinal Chemistry and Chemical Biology
Active ingredient/
trade name
Chemical name Structure
Clofarabine
2 - chloro - 9 - (2 - deoxy - 2 - fl uoro -
β -
D - arabinofuranosyl) - 9
H - purin - 6 - amine
O
F
OH
N
HO
N
N
N
Cl
NH
2
Desfl urane
( ± )1,2,2,2 - tetrafl uoroethyl
difl uoromethyl ether
F
3
C O
CF
2
H
F
Desoximetasone/
Topicort
pregna - 1, 4 - diene - 3, 20 - dione,
9 - fl uoro - 11, 21 - dihydroxy -
16 - methyl - , (11 β , 16 α ) -
O
H
3
C
HO
CH
3
H
F H
CH
3
O
OH
H
Dexamethasone Acetate
∆
V
/
Decadron - LA
[(8 S ,9 R ,10 S ,11 S ,13 S ,14 S ,16 R ,17 R ) -
9 - fl uoro - 11 - hydroxy - 17 - (2 -
hydroxyacetyl) - 10,13,16 -
trimethyl - 3 - oxo - 6,7,8,11,12,
14,15,16 - octahydrocyclopen
ta[a]phenanthren - 17 - yl]
acetate hydrate
O
HO
H
F
H
O
OH
O
O
H
2
O
Dexamethasone Sodium
Phosphate
V
sodium [2 - [(8 S ,9 R ,10 S ,11 S ,
13 S ,14 S ,16 R ,17 R ) - 9 - fl uoro -
11,17 - dihydroxy - 10,13,16 -
trimethyl - 3 - oxo - 6,7,8,
11,12,14,15,16 -
octahydrocyclopenta[ a ]
phenanthren - 17 - yl] - 2 -
oxoethyl] phosphate
O
HO
H
F
H
OH
O
O
P
O
O
O
Na
Dexamethasone
V
Mymethasone
9 - fl uoro - 11 β ,17,21 -
trihydroxy - 16 α -
methylpregna - 1,4 - diene -
3,20 - dione
O
H
3
C
HO
CH
3
F
CH
3
O
OH
OH
Fluorine-containing Drugs for Human Use Approved by FDA in the United States 539
Formula Pharmaceutical action Dosage form CAS No. Approval date/
drug sponsor
C
10
H
11
ClFN
5
O
3
Anti - metabolite Injectable 123318 - 82 - 1
Dec. 2004/
Genzyme
C
3
H
2
F
6
O Anesthetic Inhalation 57041 - 67 - 5
Sept. 1992/
Baxter Hlthcare
Corp
C
22
H
29
FO
4
Anti - infl ammatory
Anti - pruritic agent
Topical cream,
gel and
ointment
382 - 67 - 2
March 1982/
Taro Pharms
North
Perrigo New York
Taro
C
24
H
33
FO
7
Synthetic
adrenocortical
steroid
Injectable 55812 - 90 - 3
Sept. 1973/
Watson Labs
Merck
C
22
H
28
FNaO
8
P
Antiasthmatic
Glucocorticoid
Ophthalmic drops
Injectable
50 - 02 - 2
Sept. 1959/
Merck
∆
Abraxis Pharn
Baxter Hlthcare
Luitpold
Teva Parenteral
Alcon Universal
Baush and Lomb
C
22
H
29
FO
5
Synthetic
adrenocortical
steroid
Oral tablet, elixir,
and solution
Ophthalmic drops
50 - 02 - 2
Dec.1960/
Organon USA
Inc
∆
Morton Grove
Roxane
Par Pharm
540 Fluorine in Medicinal Chemistry and Chemical Biology
Active ingredient/
trade name
Chemical name Structure
Difl orasone Diacetate/
Psorcon
Florone
∆
6 α ,9 - difl uoro - 11 β ,17,21 -
trihydroxy - 16 β -
methylpregna - 1,4 - diene -
3,20 - dione 17,21 -
diacetate
O
H
3
C
HO
CH
3
F
CH
3
O
OCOCH
3
OCOCH
3
F
H
H
H
Difl unisal/
Dolobid
∆
5 - (2,4 - difl uorophenyl) - 2 -
hydroxy - benzoic acid
F F
COOH
OH
Droperidol
V
/
Inaspine
3 - [1 - [4 - (4 - fluorophenyl) - 4 - oxobutyl] -
3,6 - dihydro - 2 H - pyridin - 4 - yl] -
1 H - benzimidazol - 2 - one
N
H
N
O
N
O
F
Dutasteride/
Avodart
(5 α ,17 β ) - N - {2,5 bis
(trifl uoromethyl)phenyl} -
3 - oxo - 4 - azaandrost - 1 -
ene - 17 - carboxamide
N
H
O
H
H H
H
3
C
CH
3
H
N
O
H
CF
3
CF
3
Efavirenz/
Sustiva
( S ) - 6 - chloro - 4 -
(cyclopropylethynyl) - 1,4 -
dihydro - 4 - (trifl uoromethyl) -
2 H - 3,1 - benzoxazin - 2 - one
N
H
O
Cl
O
F
3
C
Efl ornithine Hydrochloride/
Vaniqa
(+) - 2 - (difl uoromethyl) ornithine
monohydrochloride
monohydrate
H
2
N
H
2
N
F
2
HC
OH
O
Fluorine-containing Drugs for Human Use Approved by FDA in the United States 541
Formula Pharmaceutical action Dosage form CAS No. Approval date/
drug sponsor
C
26
H
32
F
2
O
7
Anti - infl ammatory
Glucocorticoid
Topical ointment
and cream
1869 - 92 - 7
March 1978/
Sanofi Aventis US
Altana
Taro
Pharmacia and
Upjohn
∆
C
13
H
8
F
2
O
3
Analgesic
Anti - Infl ammatory
Nonsteroidal
cyclooxygenase
inhibitor
Oral tablet 22494 - 42 - 4
April 1982/
TEVA
Watson Labs
Sandoz
Merck
∆
C
22
H
22
FN
3
O
2
Anesthetic
Antiemetic
Antipsychotic agent
Dopamine antagonist
Injectable 548 - 73 - 2
June 1970/
Akorn
Hospira
Luitpold
C
27
H
30
F
6
N
2
O
2
Enzyme inhibitor
Anti - prostatic
hypertrophy
Oral capsule 164656 - 23 - 9
Nov. 2001/
GlaxoSmithKline
C
14
H
9
ClF
3
NO
2
Reverse transcriptase
inhibitor
Anti - HIV agent
Oral capsule and
tablet
154598 - 52 - 4
Sept. 1998/
Bristol Myers
Squibb
C
6
H
12
F
2
N
2
O
2
⋅
HCl ⋅ H
2
O
Antineoplastic agent
Enzyme inhibitors
Trypanocidal agent
Topical cream
Injectable
∆
96020 - 91 - 6
Nov. 1990/
Skinmedica
Sanofi Aventis
US
∆
542 Fluorine in Medicinal Chemistry and Chemical Biology
Active ingredient/
trade name
Chemical name Structure
Emtricitabine/
Atripla
Emtriva
Truvada
5 - fl uoro - 1 - (2 R ,5 S ) - [2 -
(hydroxymethyl) - 1,3 -
oxathiolan - 5 - yl]cytosine
(( − ) enantiomer)
HCl
H
2
O
N
N
H
2
N
F
O
S
O
OH
Enfl urane/
Entrane
2 - chloro - 1,1,2 - trifl uoroethyl
difl uoromethyl ether
O
F
F
F
F
Cl
F
Enoxacin
∆
/
Penetrex
1 - ethyl - 6 - fl uoro - 4 - oxo - 7 -
piperazin - 1 - yl - 1,8 -
naphthyridine - 3 - carboxylic
acid
N
N
O
N
NH
HO
O
F
Escitalopram Oxalate/
Lexapro
S - (+) - 1 - [3 - (dimethylamino)propyl] -
1 - ( p - fl uorophenyl) - 5 -
phthalancarbonitrile oxalate
O
NC
F
N
CH
3
CH
3
C
2
H
2
O
4
Ezetimibe/
Zetia
Vytorin
1 - (4 - fl uorophenyl) - 3( R ) - [3 -
(4 - fl uorophenyl) - 3( S ) -
hydroxypropyl] - 4( S ) - (4 -
hydroxyphenyl) - 2 -
azetidinone
N
O
OH
OH
F
F
Flecainide Acetate/
Tambocor
N - (2 - piperidylmethyl) - 2,5 -
bis(2,2,2 - trifl uoroethoxy)
benzamide
O
O
CF
3
F
3
C
NHO
HN
OH
O
Floxuridine/
Fudr
5 - fl uoro - 1 - [4 - hydroxy - 5 -
(hydroxymethyl)
tetrahydrofuran - 2 - yl] - 1 H -
pyrimidine - 2,4 - dione
O
HO
N
NH
O
O
HO
F