. 2024 Oct 30. Online ahead of print. doi: 10.1039/d4md00450g

Pharmacological and some physiochemical parameters of thiophene-based USFDA-approved drugs.

S no	Drug name	Category	Biological target	Mechanism	Dosage type and route	Half-life (in h) and excretion	Phase 1 metabolism	DB ID
	(Brand name)
	(Approval year)
1.	Brinzolamide	Small molecule	Carbonic anhydrase-2 (CA-II)	Inhibition of CA-II reduces the formation of bicarbonates in the ciliary process and reduces the intraocular pressure	Solution and ophthalmic	111 days, primarily eliminated through urine	Drug metabolised to N-desethylbrinzolamide	DB01194
1.	1989	Small molecule	Carbonic anhydrase-2 (CA-II)		Solution and ophthalmic	111 days, primarily eliminated through urine	Drug metabolised to N-desethylbrinzolamide	DB01194
2.	Dorzolamide	Small molecule	Carbonic anhydrase-2 (CA-II)	Inhibition of CA-II reduces the formation of bicarbonates in the ciliary process and reduces the intraocular pressure	Solution (2.0% w/v) and ophthalmic	Half-life >4 months, excreted out primarily through urine	Drug metabolised to N-desethyldorzolamide	DB00869
2.	1995	Small molecule	Carbonic anhydrase-2 (CA-II)		Solution (2.0% w/v) and ophthalmic	Half-life >4 months, excreted out primarily through urine	Drug metabolised to N-desethyldorzolamide	DB00869
3.	Olanzapine	Small molecule	Dopamine receptor and serotonin receptors	Blocks dopamine in the mesolimbic pathway for its post-synaptic action	Tablet (15 mg) orally	Half-life is about 21 to 54 h (average 30 h), mainly excreted in the urine	Drug metabolized in the liver and most of the activity through cytochrome P450 (CYP-450)	DB00334
3.	1996	Small molecule	Dopamine receptor and serotonin receptors		Tablet (15 mg) orally			DB00334
4.	Ketotifen	Small molecule	Histamine-receptor blocker (H1R)	Non-competitive antagonist of H1 histamine receptors	Solution, syrup, tablet	Half-life is about 3 to 5 h, excreted in the urine, primarily as metabolite	Drug metabolised in the liver and form three metabolites; major one is the N-glucuronide derivative	DB00920
4.	1999	Small molecule	Histamine-receptor blocker (H1R)	Non-competitive antagonist of H1 histamine receptors	Solution, syrup, tablet			DB00920
5.	Suprofen	Small molecule	Cyclooxygenase (COX) inhibitor	The drug inhibits the prostaglandin synthesis with COX inhibition, resulting in the analgesic effect	Tablet orally	Half-life 72 h	Metabolised in the liver via CYP-450 isozyme 2C9	DB00870
5.	1998	Small molecule	Cyclooxygenase (COX) inhibitor		Tablet orally	Half-life 72 h	Metabolised in the liver via CYP-450 isozyme 2C9	DB00870
6.	Tioconazole	Small molecule	Ergosterol inhibition	Prevents the synthesis of ergosterol, which increases the cellular permeability	Ointment via topical route	NA	Metabolization via glucuronide conjugation	DB01007
6.	1983	Small molecule	Ergosterol inhibition		Ointment via topical route	NA	Metabolization via glucuronide conjugation	DB01007
7.	Duloxetine	Small molecule	Inhibition of sodium-dependent serotonin, dopamine, and noradrenaline transporters	Drug inhibits the serotonin (5-HT₂, 5-HT₃), dopamine, and norepinephrine uptake	Tablet orally	Half-life 12 h, excreted mainly in urine	Metabolised in the liver via CYP2D6 and CYP1A2	DB00476
7.	1998	Small molecule			Tablet orally	Half-life 12 h, excreted mainly in urine	Metabolised in the liver via CYP2D6 and CYP1A2	DB00476
8.	Canagliflozin	Small molecule	Sodium–glucose co-transporter 2 (SGLT-2) inhibitors	Prevents SGLT-2 cotransporters, resulting in reduction	Tablet orally	Half-life 10.6 h, mainly excreted through faeces	Metabolised via O-glucuronidation (UGT1A9 and UGT2B4)	DB0890
8.	2013	Small molecule	Sodium–glucose co-transporter 2 (SGLT-2) inhibitors	Prevents SGLT-2 cotransporters, resulting in reduction	Tablet orally	Half-life 10.6 h, mainly excreted through faeces	Metabolised via O-glucuronidation (UGT1A9 and UGT2B4)	DB0890
9.	Rotigotine	Small molecule	Dopamine receptor agonist	Drugs mimic the dopamine receptor and activate neurotransmitter	Patch via transdermal route	Half-life 5 to 7 h, route of elimination is urine (71%), fecal (23%)	Metabolised via CYP isoenzyme, sulfotransferase	DB05271
9.	2007	Small molecule	Dopamine receptor agonist		Patch via transdermal route		Metabolised via CYP isoenzyme, sulfotransferase	DB05271
10.	Ticlopidine	Small molecule	Adenosine diphosphate inhibitor	Inhibition activation of platelet and aggregation (P2Y12 ADP receptors)	Tablet orally	Half-life 7.9 h, mostly in the urine	Metabolised by the liver	DB00208
10.	1991	Small molecule	Adenosine diphosphate inhibitor		Tablet orally	Half-life 7.9 h, mostly in the urine	Metabolised by the liver	DB00208
11.	Clopidogrel	Small molecule	Adenosine diphosphate inhibitor	Inhibition activation of platelet and aggregation (P2Y12 ADP receptors)	Tablet orally	Half-life 6 h, excreted 50% in the urine and 46% in the feces	Metabolised by cytochromes enzymes (CYP1A2, CYP2C9, CYP2B6)	DB00758
11.	1997	Small molecule	Adenosine diphosphate inhibitor		Tablet orally		Metabolised by cytochromes enzymes (CYP1A2, CYP2C9, CYP2B6)	DB00758
12.	Prasugrel	Small molecule	Adenosine diphosphate inhibitor	Inhibition activation of platelet and aggregation (P2Y12 ADP receptors)	Tablet orally	Half-life 7.4 h, mainly excreted in urine	Metabolised by CYP-450 enzymes	DB06209
12.	2009	Small molecule	Adenosine diphosphate inhibitor		Tablet orally	Half-life 7.4 h, mainly excreted in urine	Metabolised by CYP-450 enzymes	DB06209
13.	Eprosartan	Small molecule	Angiotensin II receptor antagonist (AT1 inhibitor)	The drug inhibits the AT1 receptor, which results in vasodilation	Tablet orally	Half-life 5–9 h, NA	Metabolised by CYP-450 enzymes	DB00876
13.	1997	Small molecule	Angiotensin II receptor antagonist (AT1 inhibitor)		Tablet orally	Half-life 5–9 h, NA	Metabolised by CYP-450 enzymes	DB00876
14.	Icatibant	Small molecule	Bradykinin B2 receptor (BB2 receptor) inhibitor	Selective BB2 receptor inhibitor reduces the incidence of hereditary angioedema	Solution via parenteral route	Half-life 1.4 h, primarily excreted in the urine	Metabolised by CYP-450 enzymes	DB06196
14.	2011	Small molecule	Bradykinin B2 receptor (BB2 receptor) inhibitor		Solution via parenteral route	Half-life 1.4 h, primarily excreted in the urine	Metabolised by CYP-450 enzymes	DB06196
15.	Rivaroxaban	Small molecule	Inhibits the coagulation factor	The drug inhibits the free and clot-bound factor Xa	Tablet orally	Half-life 5–9 h, excreted into urine	Metabolised by cytochrome enzymes	DB06228
15.	2011	Small molecule	Inhibits the coagulation factor	The drug inhibits the free and clot-bound factor Xa	Tablet orally	Half-life 5–9 h, excreted into urine	Metabolised by cytochrome enzymes	DB06228
16.	Raltitrexed	Small molecule	Thymidylate synthase (TS) inhibition	The drug is a folic acid antagonist via inhibiting TS, which results in cell death	Solution via parenteral route	Half-life 192 h, NA	Metabolised into folyl polyglutamate synthetase	DB00293
16.	1998	Small molecule	Thymidylate synthase (TS) inhibition		Solution via parenteral route	Half-life 192 h, NA	Metabolised into folyl polyglutamate synthetase	DB00293
17.	Tenoxicam	Small molecule	Cyclooxygenase (COX) inhibitor	The drug inhibits prostaglandin synthesis with COX inhibition, resulting in the analgesic effect	Tablet orally	Half-life 72 h, NA	Metabolised in the liver to 5-hydroxy tenoxicam	DB00469
17.	2000	Small molecule	Cyclooxygenase (COX) inhibitor		Tablet orally	Half-life 72 h, NA	Metabolised in the liver to 5-hydroxy tenoxicam	DB00469
18.	Tiagabine	Small molecule	Gamma-aminobutyric acid (GABA) inhibition	Drugs block the sodium and chloride-dependent GABA transporter	Tablet orally	Half-life 7–9 h, mainly through faeces	Drug excreted in the urine (25%) and faeces (63%) and other remaining unchanged	DB00906
18.	1997	Small molecule	Gamma-aminobutyric acid (GABA) inhibition		Tablet orally	Half-life 7–9 h, mainly through faeces		DB00906
19.	Aclidinium	Small molecule	Muscarinic acetylcholine receptor	The drug inhibits the M3 receptor located in the lungs, resulting in the relaxation of smooth muscles	Capsule for respiratory inhalation; oral	Half-life 24–44 h, excreted in urine	74% of drugs excreted in urine, and others cleaved into dithienylglycolic acid and inactive metabolite N-methylscopine	DB08897
19.	2012	Small molecule	Muscarinic acetylcholine receptor		Capsule for respiratory inhalation; oral	Half-life 24–44 h, excreted in urine		DB08897
20.	Tiotropium	Small molecule	Muscarinic acetylcholine receptor	The drug inhibits the M3 receptor located in the lungs, resulting in the relaxation of smooth muscles	Capsule for respiratory inhalation; oral	Half-life 24 h (chronic obstructive pulmonary disease) COPD and 44 h in asthma, excreted unchanged in urine	74% of drugs excreted in the urine, and others cleaved into dithienylglycolic acid and inactive metabolite N-methylscopine	DB01409
20.	2004	Small molecule	Muscarinic acetylcholine receptor		Capsule for respiratory inhalation; oral			DB01409
21.	Cefoxitin	Small molecule	Cell wall inhibition	d-Alanyl-d-alanine carboxypeptidase DacC inhibition	Solution with intravenous and intramuscular injection	Half-life is 41 to 59 minutes, excreted in urine	Most of the drugs excreted from the kidney unchanged	DB01331
21.	1973	Small molecule	Cell wall inhibition	d-Alanyl-d-alanine carboxypeptidase DacC inhibition	Solution with intravenous and intramuscular injection	Half-life is 41 to 59 minutes, excreted in urine	Most of the drugs excreted from the kidney unchanged	DB01331
22.	Lotilaner	Small molecule	Gamma-aminobutyric acid (GABA)-gated chloride channel	Non-competitive inhibition of GABA-gated chloride channel	Ophthalmic solution	Half-life 11 days, NA	Metabolised by cytochrome enzyme	DB17992
23.	Oliceridine	Small molecule	μ-Opioid receptor agonist	Activate the μ-opioid receptor	Intravenous injection	Half-life is 1.3 to 3 h, mainly through urine	Metabolised by CYP3A4 and CYP2D6 to oxy-oliceridine	DB14881
24.	Relugolix	Small molecule	Gonadotropin-releasing hormone (GnRH) receptor agonist	GnRH receptor reduces the release of luteinising hormone	Tablet orally	Half-life 25 h, mainly through faeces	Metabolised by CYP3A	DB11853
25.	Avatrombopag	Small molecule	Agonist thrombopoietin (TPO) receptor	TPO stimulates the production of platelets	Tablet orally	Half-life 19 h, mainly faecal excretion	Metabolised by CYP3A and CYP2C9	DB11995
26.	Tiaprofenic acid	Small molecule	COX and LOX inhibitor	Inhibit prostaglandin synthesis	Capsule, tablet orally	1.5–2.5 hours, NA	Hepatic	DB01600