Ojima I. (ed.) Fluorine in Medicinal Chemistry and Chemical Biology

Fluorine-containing Drugs for Human Use Approved by FDA in the United States 573

Formula Pharmaceutical action Dosage form CAS No. Approval date/

drug sponsor

C

11

H

13

ClF

3

N

3

O

4

S

3

Antihypertensive agent

Diuretic

Sodium chloride

symporter inhibitor

Oral tablet 346 - 18 - 9

Sept. 1961/

Pﬁ zer

C

37

H

42

F

2

N

8

O

4

Antibiotic

Antifungal

Trypanocidal agent

Oral suspension 171228 - 49 - 2

Sept. 2006/

Schering

C

17

H

11

ClF

4

N

2

S

Hypnotic

Sedative

Oral tablet 36735 - 22 - 5

Dec. 1985/

Questcor Pharms

C

8

H

5

F

3

N

2

OS

Anesthetics

Anticonvulsant

Excitatory amino acid

antagonist

Neuroprotective agent

Oral tablet 1744 - 22 - 5

Dec. 1995/

Sanoﬁ Aventis

Impax Labs

574 Fluorine in Medicinal Chemistry and Chemical Biology

Active ingredient/

trade name

Chemical name Structure

Risperidone/

Risperdal

Consta

3 - [2 - [4 - (6 - ﬂ uoro - 1,2 -

benzoxazol - 3 - yl)piperidin -

1 - yl]ethyl] - 2 - methyl - 6,7,8,9 -

tetrahydropyrido[2,1 - b ]

pyrimidin - 4 - one

O

N

F

N

O

Rosuvastatin Calcium/

Crestor

calcium ( E ,3 R ,5 R ) - 7 - [4 - (4 -

ﬂ uorophenyl) - 2 - (methyl -

methylsulfonyl - amino) - 6 -

propan - 2 - yl - pyrimidin - 5 - yl] -

3,5 - dihydroxy - hept - 6 - enoate

NN

F

N

S

O

2

OH

CO

2

-

OH

Ca

2+

2

Sevoﬂ uran * /

Ultane

Sojourn

1,1,1,3,3,3 - hexaﬂ uoro - 2 -

(ﬂ uoromethoxy)propane

F

3

C

O

CF

3

F

Sitagliptin Phospate/

Januvia

Janumet

7 - [(3 R ) - 3 - amino - 1 - oxo - 4 -

(2,4,5 - triﬂ uorophenyl)butyl] -

5,6,7,8 - tetrahydro - 3 -

(triﬂ uoromethyl) - 1,2,4 -

triazolo[4,3 - a ]pyrazine

phosphate (1 : 1)

monohydrate

F

N

O

N

CF

3

H

2

N

H

• H

3

PO

4

• H

2

O

Sodium Fluoride, Triclosan/

Colgate Total

Sodium Fluroide, F - 18

Sodium

Monoﬂ uorophosphate/

Extra Strength AIM

disodium ﬂ uoro - dioxido -

oxophosphorane

Fluorine-containing Drugs for Human Use Approved by FDA in the United States 575

Formula Pharmaceutical action Dosage form CAS No. Approval date/

drug sponsor

C

23

H

27

FN

4

O

2

Serotonin antagonist

Antipsychotic agent

Dopamine antagonist

Injectable

Oral solution and

tablet

106266 - 06 - 2

Dec. 1993/

Janssen Pharma

C

44

H

54

CaF

2

N

6

O

12

S

2

Hydroxymethylglutaryl -

CoA reductase

inhibitor

Oral tablet 147098 - 20 - 2

Aug. 2003/

Astrazeneca

C

4

H

3

F

7

O

Platelet aggregation

inhibitor

Anesthetic

Inhalation 28523 - 86 - 6

June 1995/

Abbott

Baxter Hlthcare

Minrad

C

16

H

15

F

6

N

5

O ⋅

H

3

PO

4

⋅ H

2

O

DPP - 4 inhibitor for

type 2 diabetes

Oral tablet 654671 - 77 - 9

Oct. 2006/

Merck Co Inc.

NaF

Prevention of dental

caries

Dental paste 7681 - 49 - 4

July 1997/

Colgate Palmolive

Feb. 1972/

GE Healthcare

Na

2

FO

3

P

Prevention of dental

caries

Dental gel and

paste

10163 - 15 - 2

Aug. 1986/

Chesebrough

Brands

∆

576 Fluorine in Medicinal Chemistry and Chemical Biology

Active ingredient/

trade name

Chemical name Structure

Sorafenbin Tosylate/

Nexavar

4 - [4 - [[4 - chloro - 3 - (triﬂ uorometh

yl)phenyl]carbamoylamino]

phenoxy] - N - methylpyridine -

2 - carboxamide

4 - methylbenzenesulfonate

Cl

F

3

C

NH

O

HN

O

N

O

HN

SO

2

HO

Sparﬂ oxacin/

Zagam

∆

5 - amino - 1 - cyclopropyl -

7 - [(3 S ,5 R ) - 3,5 -

dimethylpiperazin - 1 - yl] - 6,8 -

diﬂ uoro - 4 - oxoquinoline - 3 -

carboxylic acid

N

F

N

FH

2

N

O

HO

2

C

NH

Sulindac/

Clinoril

2 - [(3 Z ) - 6 - ﬂ uoro - 2 - methyl -

3 - [(4 - methylsulﬁ nylphenyl)

methylidene]inden - 1 -

yl]acetic acid

HO

F

O

S

O

Sunitinib Malate/

Sutent

N - (2 - diethylaminoethyl) - 5 - [( Z ) -

(5 - ﬂ uoro - 2 - oxo - 1 H - indol - 3 -

ylidene)methyl] - 2,4 - dimethyl - 1 H -

pyrrole - 3 - carboxamide;

(2 S ) - 2 - hydroxybutanedioic

acid

NH

O

NH

F

O

NH

CO

2

H

CO

2

H

HO

N

Fluorine-containing Drugs for Human Use Approved by FDA in the United States 577

Formula Pharmaceutical action Dosage form CAS No. Approval date/

drug sponsor

C

21

H

16

ClF

3

N

4

O

3

⋅

C

7

H

8

O

3

S

Antineoplastic agent

Protein kinase inhibitor

Oral tablet 475207 - 59 - 1

Dec. 2005/

Bayer Pharms

C

19

H

22

F

2

N

4

O

3

Antibacterial agent Oral tablet 110871 - 86 - 8

Dec. 1996/

Mylan

C

20

H

17

FO

3

S

Nonsteroidal anti -

inﬂ ammatory agent

Antineoplastic agent

Cyclooxygenase

inhibitor

Oral tablet 38194 - 50 - 2

Sept. 1978/

Merck

Mutual Pharm

Mylan

Sandoz

Teva

∆

Watson Labs

C

26

H

33

FN

4

O

7

Antineoplastic agent

Angiogenesis inhibitor

Oral capsule 341031 - 54 - 7

Jan. 2006/

CPPI CV

578 Fluorine in Medicinal Chemistry and Chemical Biology

Active ingredient/

trade name

Chemical name Structure

Tipranavir/

Aptivus

N - [3 - [(1 R ) - 1 - [(6 R ) - 6 - (2 -

cyclohexylethyl) - 2 - hydroxy -

4 - oxo - 6 - propyl - 5 H - pyran - 3 - yl]

propyl]phenyl] - 5 -

(triﬂ uoromethyl)pyridine - 2 -

sulfonamide

N

HN

CF

3

O O

HO

O

2

S

Travoprost/

Travatan

Travatan Z

propan - 2 - yl ( Z ) - 7 -

[(1 R ,2 R ,3 R ,5 S ) - 3,5 -

dihydroxy - 2 - [( E ,3 R ) - 3 - hydroxy -

4 - [3 - (triﬂ uoromethyl)phenoxy]

but - 1 - enyl]cyclopentyl]

hept - 5 - enoate

O

F

3

C

OH

O

OH

HO

Triamcinolone Acetonide *

1

/

Azmacort

Kenalog

Triacet

Triderm

Oracort

Oralone

Mykacet

(11 β ,16 α ) - 9 - ﬂ uoro - 11,21 -

dihydroxy - 16,17 - [(1 -

methylethylidene)bis(oxy)] -

pregna - 1,4 - diene - 3,20 - dione

O

HO

H

F

H

O

HO

Fluorine-containing Drugs for Human Use Approved by FDA in the United States 579

Formula Pharmaceutical action Dosage form CAS No. Approval date/

drug sponsor

C

31

H

33

F

3

N

2

O

5

S

Anti - HIV agent

Antiviral protease

inhibitor

Oral capsule 174484 - 41 - 4

June 2005/

Boehringer

Ingelheim

C

26

H

35

F

3

O

6

Antihypertensive agent

Antiglaucoma

Ophthalmic drops 157283 - 68 - 6

March 2001/

Alcon

C

24

H

31

FO

6

Glucocorticoid

Anti - inﬂ ammatory

agent

Immunosuppressive

agent

Inhalation (aersol)

Topical cream,

spray, and

ointment

Injectable

Dental paste

Nasal (spray)

76 - 25 - 5

March 1959/

Abbott

Apothecon

Teva

Actavis Mid

Atlantic

Altana

G and W Labs

Ranbaxy

Perrigo New York

Taro

Vintage

Del Ray Labs

Morton Grove

Carolina Medcl

Sanoﬁ Aventis

580 Fluorine in Medicinal Chemistry and Chemical Biology

Active ingredient/

trade name

Chemical name Structure

Triamcinolone

Hexacetonide/

Aristospan

(11 β ,16 α ) - 21 - (3,3 - dimethyl - 1 -

oxobutoxy) - 9 - ﬂ uoro - 11 -

hydroxy - 16,17 - [(1 -

methylethylidene)bis(oxy)] -

pregna - 1,4 - diene - 3,20 - dione

O

HO

H

F

H

O

Triﬂ uoperazine

Hydrochloride/

Stelazine

10 - [3 - (4 - methylpiperazin - 1 -

yl)propyl] - 2 - (triﬂ uoromethyl)

phenothiazine

dihydrochloride

2HCl

S

N

CF

3

Triﬂ upromazine

2

/

Vesprin

∆

N,N - dimethyl - 3 - [2 -

(triﬂ uoromethyl)phenothiazin -

10 - yl]propan - 1 - amine

S

N

CF

3

N

Triﬂ uridine/

Viroptic

1 - [4 - hydroxy - 5 -

(hydroxymethyl)oxolan - 2 - yl] -

5 - (triﬂ uoromethyl)pyrimidine -

2,4 - dione

HN

N

CF

3

O

HO

OH

Trovaﬂ oxacin Mesylate/

Trovan

∆

7 - [(1 S ,5 R ) - 6 - amino - 3 -

azabicyclo[3.1.0]hexan - 3 -

yl] - 1 - (2,4 - diﬂ uorophenyl) -

6 - ﬂ uoro - 4 - oxo - 1,8 -

naphthyridine - 3 -

carboxylic acid;

methanesulfonic acid

N

N O

N

F

H

2

N

CO

2

H

S

OO

OH

Fluorine-containing Drugs for Human Use Approved by FDA in the United States 581

Formula Pharmaceutical action Dosage form CAS No. Approval date/

drug sponsor

C

30

H

41

FO

7

Anti - inﬂ ammatory

agent

Injectable 5611 - 51 - 8

July 1969/

Sandoz

C

21

H

26

Cl

2

F

3

N

3

S

Antiemetic

Antipsychotic agent

Dopamine antagonist

Oral concentrate

and tablet

440 - 17 - 5

April 1959/

GlaxoSmithKline

Mylan

Sandoz

C

18

H

19

F

3

N

2

S

Antiemetic

Antipsychotic agent

Dopamine antagonist

Oral suspension

and tablet

Injectable

146 - 54 - 3

Sept. 1957/

Apothecon

C

10

H

11

F

3

N

2

O

5

Antiviral agent

Antimetabolite

Ophthalmic drops 70 - 00 - 8

April 1980/

Monarch Pharms

Alcon

C

21

H

19

F

3

N

4

O

6

S Anti - infective agent Oral tablet 147059 - 75 - 4

Dec. 1997/

Pﬁ zer

582 Fluorine in Medicinal Chemistry and Chemical Biology

Active ingredient/

trade name

Chemical name Structure

Valrubicin/

Valstar

[2 - oxo - 2 - [(2 S ,4 S ) - 2,5,12 -

trihydroxy - 4 - [5 - hydroxy - 6 -

methyl - 4 - [(2,2,2 -

triﬂ uoroacetyl)amino]oxan - 2 -

yl]oxy - 7 - methoxy - 6,11 - dioxo -

3,4 - dihydro - 1 H - tetracen - 2 - yl]

ethyl] pentanoate

O

OH

NH

O

CF

3

O

HO

OH

Voriconazole/

Vfend

(2 R ,3 S ) - 2 - (2,4 - diﬂ uorophenyl) -

3 - (5 - ﬂ uoropyrimidin - 4 - yl) - 1 -

(1,2,4 - triazol - 1 - yl)butan - 2 - ol

N N

F

N

OH

∆

Discontinued from the market.

V

See the veterinary drug list (Section 2).

1

Triamcinolone and Triamcinolone Diacetate are discontinued from the market.

2

Triﬂ upromazine and Triﬂ upromazine Hydrochloride are discontinued from the market.

3

Not approved.

Ojima I. (ed.) Fluorine in Medicinal Chemistry and Chemical Biology

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