How Many Drugs Are Catecholics, by Da-Peng Yang, Hong-Fang Ji, Guang-Yan Tang, Wei Ren, Hong-Yu Zhang*, Molecules, 2007, 12, 878-884

Supplementary Material for - How Many Drugs Are Catecholics, by Da-Peng Yang, Hong-Fang Ji, Guang-Yan Tang, Wei Ren, Hong-Yu Zhang*, Molecules, 2007, 12, 878-884

Table S1. Catecholics identified from CMC.

No CMC Number Name Structure Activity

O H HO N 1 MCMC00000595 adrenalone CH3 adrenergic

HO HO OH Chiral

HO O OH antiviral; 2 MCMC00009836 aphloiol O OH HO antiinflammatory

HO O OH Chiral

N CH H 3 3 MCMC00000177 apomorphine HO emetic

HO OH diagnostic aid; 4 MCMC00006456 arbutamine N OH cardiotonic H OH

HO O antioxidant; 5 MCMC00010715 baicalein analgesic; HO OH O antiallergic

OH O Chiral HO

O O antiasthmatic; 6 MCMC00010411 baicalin OH O antiallergic HO OH O OH

OH HO OH O H enzyme inhibitor 7 MCMC00000976 benserazide H2N N N (decarboxylase) H OH OH OH

caffeic acid phenethyl antiviral; 8 MCMC00006778 ester enzyme inhibitor

O O

Molecules, 2007, 12, Molecules, 2007, 12, 878-884 2 Table S1. Cont.

O OH enzyme inhibitor 9 MCMC00010571 carbidopa CH H N 3 (decarboxylase) HO NH2 OH

HO OChiral

O O N S N S antibiotic; 10 MCMC00006131 cefetecol H H H2N N N H antibacterial O O HO OH H HO O Chiral HO O 11 MCMC00010530 chf-1301 antiparkinsonian NH CH HO 2 3

OH Chiral HO antiviral; 12 MCMC00000898 cianidol HO O OH antineoplastic HO OH O O OH O O HO phagocyte stimulant; 13 MCMC00007713 cichoric acid O O OH HO antineoplastic HO

HO O

O HO 14 MCMC00009461 citromycetin O antibiotic HOO

CH3

HO OH

antispasmodic; 15 MCMC00004237 clofeverine O Cl anticholinergic N H

H3C CH3

CH3 16 MCMC00003077 colterol N bronchodilator HO H OH HO

HOHO

O O 17 MCMC00001729 cynarine O choleretic HO O OH

HO OH O OH

Molecules, 2007, 12, Molecules, 2007, 12, 878-884 3

Table S1. Cont.

O HO OH O

18 MCMC00006608 digalloyl trioleate HO ultraviolet screen O

HO HO OH

HO CH3 CH 3 antitussive; 19 MCMC00001167 dioxethedrin HO N adrenergic OH H

HO CH3

20 MCMC00002622 dioxifedrine CH3 bronchodilator HO N OH H

H C 21 MCMC00009077 dl-methyldopa 3 antihypertensive OH H2N O

HO CH3

22 MCMC00003673 dobutamine HO N cardiotonic H OH H HO N 23 MCMC00003884 dopamantine O antiparkinsonian HO

HNHO 2 24 MCMC00000060 dopamine adrenergic HO

N N H 25 MCMC00005460 dopexamine H cardioprotective

HO OH Chiral OH H O HO 26 MCMC00003277 droxidopa OH antiparkinsonian H NH2 HO

OH O O OH

27 MCMC00001113 ellagic acid hemostatic

HO O O OH

Molecules, 2007, 12, Molecules, 2007, 12, 878-884 4

Table S1. Cont.

O O + enzyme inhibitor N O N CH 3 (catechol-O-methyl- 28 MCMC00006466 entacapone HO H C transferase); N 3 OH antiparkinsonian Chiral HO bronchodilator; 29 MCMC00006922 epinephrine N adrenergic HO H OH OH OH

HO O 30 MCMC00007320 eriodictyol bioflavanoid

OH O O Chiral

N OH

O O OH O OH 31 MCMC00003555 ethoxazorutoside OH O antihemorrhagic O OH O O H3C OH OH HO OH HO OH

HCHO 3 32 MCMC00001273 ethylnorepinephrine bronchodilator

H2N

O Chiral

O CH3 33 MCMC00010602 etilevodopa NH antiparkinsonian HO 2 OH

OH HO OH

34 MCMC00004116 exifone HO OH antiparkinsonian OH O

H dopamine receptor N antagonist;

35 MCMC00004827 fenoldopam OH dopamine receptor Cl agonist;

HO OH antihypertensive 18F Chiral NH 2 diagnostic aid (brain O 36 MCMC00007665 fluorodopa f 18 imaging); H HO OH diagnostic aid OH

Molecules, 2007, 12, Molecules, 2007, 12, 878-884 5

Table S1. Cont.

HO O O

HO 37 MCMC00002916 folescutol capillary protectant N O

O Chiral H H O O H OH O N O N CH3 N N CH antibiotic; H S 3 38 MCMC00005667 fomidacillin O N H N antibacterial O H3C HO OH O OH

39 MCMC00006710 gallic acid astringent HOHO OH

H3C CH3

O H C OH OH3 spermaticide; HO insecticide; 40 MCMC00010223 gossypol OH OH antimalarial; HO CH3 O antioxidant H C CH 3 3 OH HO

N HO H

41 MCMC00001935 hexoprenaline bronchodilator H N HO

HO OH OH Chiral HO

OH CH O O 3 OH 42 MCMC00006852 huangqioside-e O O sweetener

O O OH HO OH OH HO OH HO OH HO 43 MCMC00001257 isoetharine bronchodilator

H N CH3

CH3 CH3

Molecules, 2007, 12, Molecules, 2007, 12, 878-884 6

Table S1. Cont.

OH H HO N CH 44 MCMC00002560 isoproterenol 3 adrenergic

CH3 HO OH

HO O OH 45 MCMC00001123 leucocianidol capillary protectant OH OH OH

OH Chiral HO

46 MCMC00006244 levdobutamine cardiotonic H HO N

CH3 H

OH H Chiral N CH bronchodilator; 47 MCMC00000050 levisoprenaline HO 3 antiasthmatic CH3 HO O Chiral

OH NH 2 48 MCMC00006962 levodopa HO antiparkinsonian OH

Chiral NH2 HO CH3 vasoconstrictor; 49 MCMC00007083 levonordefrin adrenergic OH OH

CH3 CH3 H H HO OH 50 MCMC00005851 masoprocol antineoplastic HO OH

OHChiral

H HO O OH antispasmodic; 51 MCMC00004738 meciadanol O CH3 H anticholinergic OH

HO OH Chiral

52 MCMC00007071 methyldopa CH3 antihypertensive OH H2N O

Molecules, 2007, 12, Molecules, 2007, 12, 878-884 7

Table S1. Cont.

Chiral HO NH2 O CH 53 MCMC00001852 methyldopate 3 antihypertensive H C O HO 3

OH Chiral OH OH

O O

O CH O 3 54 MCMC00003289 monoxerutin O O antidote OH O OH

OH HO OH OH OH

O CH3 HO N CH 55 MCMC00002973 n-methyladrenalone 3 antineoplastic HO

O + O N

HO O 56 MCMC00006082 nitecapone antineoplastic

HO H3C CH3 O

57 MCMC00002903 norbudrine N bronchodilator HO H

HO OH

CH3

NH 2 58 MCMC00002427 nordefrin HO vasoconstrictor OH

OH Chiral HO

59 MCMC00000052 norepinephrine NH adrenergic HO 2

OH O Chiral

HO CH O 3 O O O coronary HO O O OH vasodilator; CH 60 MCMC00010143 oleuropein 3 antispasmodic; antihypertensive OH OH

HO NH2

61 MCMC00001601 oxidopamine adrenergic HO OH

Molecules, 2007, 12, Molecules, 2007, 12, 878-884 8

Table S1. Cont.

N HO vascular disorders 62 MCMC00001354 papaveroline (therapeutic) OH OH HO O HO

63 MCMC00003471 phenisonone CH3 bronchodilator H N

CH3 H3C HO

N HO 64 MCMC00002868 pipratecol N vasodilator HO H3C O

HO O 65 MCMC00000711 propyl gallate HO antioxidant O

HO CH3

O O OH 66 MCMC00000809 protokylol HO adrenergic

N HO H

CH3 OH HO

O HO 67 MCMC00009540 quercetin antihemorrhagic OH HO O

HO H3C H N 68 MCMC00005810 racepinephrine bronchodilator HO OH

OH H

69 MCMC00003621 rimiterol bronchodilator N H HO OH OH Chiral OH CH HO O 3 OH O 70 MCMC00000892 rutin O O capillary protectant O OH OH O OH HO OH OH

Molecules, 2007, 12, Molecules, 2007, 12, 878-884 9

Table S1. Cont.

OH Chiral

OH CH3 enzyme inhibitor 71 MCMC00007657 tetracyclic catechols1 (cholesteryl ester CH3 transfer protein) CH CH 3 H3C 3

OHChiral

CH3 OH enzyme inhibitor H CH 72 MCMC00007656 tetracyclic catechols2 3 (cholesteryl ester transfer protein) CHH H3C 3

H N OH N N CNS stimulant; 73 MCMC00002703 theodrenaline H3C N antihypertensive O N O CH3 HO OH O O + N O enzyme inhibitor 74 MCMC00006484 tolcapone (catechol-O-methyl- HO CH3 OH transferase)

CH3 O CH3 O bronchodilator; 75 MCMC00003539 tretoquinol O antiallergic HO H CH3 N

Cl Chiral HO Vasodilator; N H HO dopamine receptor 76 MCMC00010810 (r)-(+)-fenoldopam agonist; antihypertensive

HO H Chiral N CH 77 MCMC00010809 (r)-isoproterenol HO 3 antiasthmatic

CH3 HO

1-(p-hydroxybenzyl)- N enzyme inhibitor HO H 78 MCMC00008199 6,7-dihydroxy-1,2,3,4- (dihydropteridine tetrahydroisoquin reductase enzyme )

Molecules, 2007, 12, Molecules, 2007, 12, 878-884 10 Table S2. Catecholic drugs recorded in US FDA database.

Catecholic Drug name (usage/strength) Marketing status apomorphine (1) apokyn (injectable; subcutaneous/10MG/ML) prescription arbutamine (1) genesa (injectable; injection/0.05MG/ML) discontinued carbidopa (1) carbidopa and levodopa (tablet; oral/Multiple Strengths); discontinued (2) carbilev (tablet, for suspension; oral/10MG; 25MG; 100MG; 250MG); prescription (3) lodosyn (tablet; oral/25MG); prescription (4) parcopa (tablet, orally disintegrating; oral/10MG; 25MG; 100MG; prescription 250MG); (5) sinemet (tablet; oral/10MG; 25MG; 100MG; 250MG); prescription (6) sinemet cr (tablet, extended release; oral/25MG; 50MG; 100MG; prescription 200MG); (7) stalevo 100 (tablet; oral/25MG; 200MG; 100MG); prescription (8) stalevo 150 (tablet; oral/37.5MG; 200MG; 150MG); prescription (9) stalevo 50 (tablet; oral/12.5MG; 200MG; 50MG) prescription dobutamine (1) dobutamine hydrochloride (injectable; injection/EQ 12.5MG prescription BASE/ML; EQ 1.25GM BASE/100ML); (2) dobutamine hydrochloride in dextrose 5% (injectable; injection/EQ prescription 50MG BASE/100ML; EQ 100MG BASE/100ML; EQ 200MG BASE/200ML); (3) dobutamine hydrochloride in dextrose 5% in plastic container prescription (injectable; injection/Multiple Strengths); (4) dobutrex (injectable; injection/EQ 12.5MG BASE/ML) discontinued dopamine (1) dopamine hydrochloride (injectable; injection/Multiple Strengths); prescription (2) dopamine hydrochloride and dextrose 5%(injectable; prescription injection/40MG/100ML; 80MG/100ML; 160MG/100ML; 320MG/100ML); (3) dopamine hydrochloride and dextrose 5% in plastic container prescription (injectable; injection/40MG/100ML; 80MG/100ML; 160MG/100ML; 320MG/100ML); (4) dopamine hydrochloride in dextrose 5% (injectable; discontinued injection/1.6MG/ML); (5) dopamine hydrochloride in dextrose 5% in plastic container prescription (injectable; injection/Multiple Strengths); (6) intropin (injectable; injection/40MG/ML; 80MG/ML; 160MG/ML) discontinued entacapone (1) comtan (tablet; oral/200MG); prescription (2) stalevo 100 (tablet; oral/25MG; 200MG; 100MG); prescription (3) stalevo 150 (tablet; oral/37.5MG; 200MG; 150MG); prescription (4) stalevo 50 (tablet; oral/12.5MG; 200MG; 50MG) prescription epinephrine (1) alphacaine hydrochloride w/ epinephrine (injectable; discontinued injection/0.01MG/ML; 0.02MG/ML; 2%); (2) bronitin mist (aerosol, metered; inhalation/0.3MG/INH; 0.2MG/INH); over-the-counter (3) bronkaid mist (aerosol, metered; inhalation/0.25MG/INH); discontinued (4) bupivacaine hydrochloride and epinephrine (injectable; injection/ prescription 0.005MG/ML; 0.0091MG/ML; 0.25%; 0.5%; 0.75%); (5) bupivacaine hydrochloride w/epinephrine (injectable; prescription injection/0.0091MG/ML; 0.5%); (6) citanest forte (injectable; injection/0.005MG/ML; 4%); prescription (7) duranest (injectable; injection/Multiple Strengths); discontinued (8) epi e z pen jr (injectable; intramuscular/0.15MG/DELIVERY; discontinued 0.3MG/DELIVERY); (9) epinephrine ( aerosol, metered; inhalation/0.2MG/INH); over-the-counter (10) epipen (injectable; injection/0.15MG/DELIVERY; prescription 0.3MG/DELIVERY); (11) epipen e z pen (injectable; intramuscular/0.15MG/DELIVERY; discontinued 0.3MG/DELIVERY); (12) epipen jr. (injectable; intramuscular/0.3MG/DELIVERY; prescription 0.15MG/DELIVERY); (13) iontocaine (solution; intophoresis/0.01MG/ML; 2%) discontinued

Molecules, 2007, 12, Molecules, 2007, 12, 878-884 11

Table S2. Cont.

(14) lidocaine hydrochloride and epinephrine (solution; intophoresis; prescription topical/Multiple Strengths); (15) lidocaine hydrochloride w/ epinephrine (injectable; injection/Multiple prescription Strengths); (16) lidocaton (injectable; injection/0.02MG/ML; 0.01MG/ML; 2%); prescription (17) lidosite topical system kit (patch; iontophoresis; prescription topical/1.05MG/PATCH; 100MG/PATCH); (18) lignospan forte (injectable; injection/EQ 0.02MG BASE/ML; 2%); prescription (19) lignospan standard (injectable; injection/EQ 0.01MG BASE/ML; prescription 2%); (20) marcaine hydrochloride w/ epinephrine (injectable; prescription injection/0.0091MG/ML; 0.25%; 0.5%; 0.75%)； (21) marcaine hydrochloride w/ epinephrine preservative free (injectable; prescription injection/0.0091MG/ML; 0.25%; 0.5%; 0.75%)； (22) medihaler-epi (aerosol, metered; inhalation/0.3MG/INH); discontinued (23) octocaine (injectable; injection/0.01MG/ML; 0.02MG/ML; 2%); prescription (24) primatene mist (aerosol, metered; inhalation/0.3MG/INH; over-the-counter 0.2MG/INH); (25) procaine hydrochloride w/ epinephrine (injectable; discontinued injection/0.02MG/ML; 1%; 2%); (26) sensorcaine (injectable; injection/Multiple Strengths); prescription (27) septocaine (injectable; injection/EQ 0.017MG BASE/1.7ML; EQ prescription 0.01MG BASE/1.7ML; EQ 0.0085MG BASE/1.7ML; EQ 0.005MG BASE/1.7ML; 4%); (28) sus-phrine sulfite-free (injectable; injection/5MG/ML; 1.5MG/AMP); discontinued (29) twinject (injectable; im-sc/EQ 0.15MG/DELIVERY; EQ prescription 0.3MG/DELIVERY); (30) twinject 0.3 (injectable; im-sc/EQ 0.15MG/DELIVERY; EQ prescription 0.3MG/DELIVERY) (31) xylocaine w/ epinephrine (injectable; injection/Multiple Strengths) prescription fenoldopam (1) corlopam (injectable; injection/EQ 10MG BASE/ML); prescription (2) fenoldopam mesylate (injectable; injection/EQ 10MG BASE/ML) prescription isoetharine (1) beta-2 (solution; inhalation/1%) prescription (2) bronkometer (aerosol; metered; solution; inhalation/0.34MG/INH; 1%; discontinued 0.25%); (3) bronkosol (aerosol; metered; solution; inhalation/0.34MG/INH; 1%; discontinued 0.25%); (4) isoetharine hydrochloride (solution; inhalation/Multiple Strengths); discontinued (5) isoetharine hydrochloride s/f (solution; inhalation/1%; 0.08%; 0.17% discontinued 0.25%); (6) isoetharine mesylate (aerosol, metered; inhalation/0.34MG/INH) discontinued isoproterenol (1) aerolone (solution; inhalation/0.25%); discontinued (2) duo-medihaler (aerosol; metered; inhalation/0.16MG/INH; discontinued 0.24MG/INH); (3) isoproterenol hydrochloride (aerosol; metered; inhalation; injectable; prescription injection; solution/0.12MG/INH; 0.02MG/ML; 0.2MG/ML; 0.5%; 0.25%); (4) isuprel (solution; inhalation; tablet; rectal; sublingual; injectable; prescription injection; aerosol, metered/Multiple Strengths); (5) medihaler-iso (aerosol; metered; inhalation/0.12MG/INH; discontinued 0.08MG/INH); (6) mucomyst w/ isoprotereno (solution; inhalation/10%; 0.5%); discontinued (7) norisodrine (powder; inhalation/25%; 10%); discontinued (8) norisodrine aerotrol (disc; inhalation/0.25%); discontinued (9) vapo-iso (solution; inhalation/0.5%) discontinued

Molecules, 2007, 12, Molecules, 2007, 12, 878-884 12

Table S2. Cont.

levodopa (1) bendopa (capsule; oral/250MG; 500MG; 100MG); discontinued (2) carbidopa and levodopa (tablet; oral; extended release/Multiple prescription Strengths); (3) carbilev (tablet, for suspension; oral/10MG; 100MG; 25MG; 250MG); prescription (4) dopar (capsule; oral; tablet/250MG; 500MG; 100MG); discontinued (5) larodopa (capsule; oral; tablet/250MG; 500MG; 100MG) discontinued (6) parcopa (tablet; orally disintegrating; oral/10MG; 100MG; 25MG; prescription 250MG); (7) sinemet (tablet; oral/10MG; 100MG; 25MG; 250MG); prescription (8)stalevo 100 (tablet; oral/25MG; 200MG; 100MG; 37.5MG; 150MG; prescription 12.5MG; 50MG); (9) stalevo 150 (tablet; oral/25MG; 200MG; 100MG; 37.5MG; 150MG; prescription 12.5MG; 50MG); (10) stalevo 50 (tablet; oral/25MG; 200MG; 100MG; 37.5MG; 150MG; prescription 12.5MG; 50MG) levonordefrin (1) arestocaine hydrochloride w/ levonordefrin (injectable; discontinued injection/0.05MG/ML; 2%); (2) carbocaine w/ neo-cobefrin (injectable; injection/3%; 0.05MG/ML; prescription 2%); (3) isocaine hydrochloride w/ levonordefrin (injectable; prescription injection/0.05MG/ML; 2%); (4) mepivacaine hydrochloride w/ levonordefrin (injectable; prescription injection/0.05MG/ML; 2%); (5) polocaine w/ levonordefrin (injectable; injection/0.05MG/ML; 2%); prescription (6) ravocaine and novocain w/ neo-cobefrin (injectable; injection/EQ discontinued 0.033MG BASE/ML; 0.05MG/ML; 2%; 0.4%); (7) scandonest l (injectable; injection/0.05MG/ML; 2%) prescription masoprocol (1) actinex (cream, topical/10%); discontinued

methyldopa (1) aldoclor-150 (tablet; oral/150MG; 250MG); discontinued (2) aldoclor-250 (tablet; oral/150MG; 250MG); discontinued (3) aldoril 15 (tablet; oral/15MG; 250MG; 30MG; 500MG); discontinued (4) aldoril 25 (tablet; oral/15MG; 250MG; 30MG; 500MG); discontinued (5) aldoril d30 (tablet; oral/15MG; 250MG; 30MG; 500MG; 50MG); discontinued (6) aldoril d50 (tablet; oral/15MG; 250MG; 30MG; 500MG; 50MG); discontinued (7) methyldopa (tablet; oral/Multiple Strengths); prescription (8) methyldopa and chlorothiazide (tablet; oral/250MG; 150MG); discontinued (9) methyldopa and hydrochlorothiazide (tablet; oral/15MG; 250MG; prescription 30MG; 500MG; 50MG); methyldopate (1) aldomet (tablet; oral; injectable; injection; suspension/Multiple discontinued Strengths); (2) methyldopate hcl (injectable; injection/50MG/ML); discontinued (3) methyldopate hydrochloride (injectable; injection/50MG/ML) prescription norepinephrine (1) levophed (injectable; injection/EQ 1MG BASE/ML); prescription (2) norepinephrine bitartrate (injectable; injection/EQ 1MG BASE/ML); prescription (3) ravocaine and novocain w/ levophed (injectable; injection/EQ discontinued 0.033MG BASE/ML; 0.05MG/ML; 2%; 0.4%) protokylol (1) ventaire (tablet; oral/2MG) discontinued

tolcapone (1) tasmar (tablet; oral/100MG; 200MG) prescription

(r)-(+)-fenoldopam (1) corlopam (injectable; injection/EQ 10MG BASE/ML); prescription (2) fenoldopam mesylate (injectable; injection/EQ 10MG BASE/ML) prescription