Darglitazone

Darglitazone
Legal status

Legal status	Development terminated
Identifiers
IUPAC name 5-[(4-[3-(5-Methyl-2-phenyl-1,3-oxazol-4-yl)propanoyl]phenyl)methyl]-1,3-thiazolidine-2,4-dione
CAS Number	141200-24-0^Y
PubChem (CID)	60870
ChemSpider	54854^N
UNII	AVP9C03Z3K^Y
ChEMBL	CHEMBL55624^N
Chemical and physical data
Formula	C₂₃H₂₀N₂O₄S
Molar mass	420.481 g/mol
3D model (Jmol)	Interactive image
SMILES CC1=C(N=C(O1)C2=CC=CC=C2)CCC(=O)C3=CC=C(C=C3)CC4C(=O)NC(=O)S4
InChI InChI=1S/C23H20N2O4S/c1-14-18(24-22(29-14)17-5-3-2-4-6-17)11-12-19(26)16-9-7-15(8-10-16)13-20-21(27)25-23(28)30-20/h2-10,20H,11-13H2,1H3,(H,25,27,28)^N Key:QQKNSPHAFATFNQ-UHFFFAOYSA-N^N
^NY (what is this?) (verify)

Darglitazone (previously known as CP 86325-2) is a member of the thiazolidinedione class of drugs and an agonist of peroxisome proliferator-activated receptor-γ (PPAR-γ), an orphan member of the nuclear receptor superfamily of transcription factors. It has a variety of insulin-sensitizing effects, such as improving glycemic and lipidemic control, and was researched by Pfizer as a treatment of metabolic disorders such as type 2 diabetes mellitus.^[1]

Its development was terminated on November 08, 1999.^[2]

Synthesis

Synthesis of darglitazone

References

↑ Hulin, Bernard; Clark, David A.; Goldstein, Steven W.; McDermott, Ruth E.; Dambek, Paul J.; Kappeler, Werner H.; Lamphere, Charles H.; Lewis, Diana M.; Rizzi, James P. (1992). "Novel thiazolidine-2,4-diones as potent euglycemic agents". Journal of Medicinal Chemistry. 35 (10): 1853–64. doi:10.1021/jm00088a022. PMID 1588563.
↑ "Drug Profile: Darglitazone". AdisInsight. Adis International Ltd, part of Springer Science+Business Media. Retrieved 28 November 2015.

Oral anti-diabetic drugs, insulins and insulin analogs, and other drugs used in diabetes (A10)

Insulin

Sensitizers

Biguanides	Buformin^‡ Metformin^# Phenformin^‡

TZDs/"glitazones" (PPAR)	Ciglitazone^§ Darglitazone^§ Englitazone^§ Lobeglitazone Netoglitazone^§ Pioglitazone Rivoglitazone^† Rosiglitazone Troglitazone^‡

Dual PPAR agonists	Aleglitazar^† Muraglitazar^§ Saroglitazar Tesaglitazar^§

Secretagogues

K⁺_ATP

Sulfonylureas	1st generation: Acetohexamide Carbutamide Chlorpropamide Glycyclamide Metahexamide Tolazamide Tolbutamide 2nd generation: Glibenclamide (glyburide)^# Glibornuride Glicaramide Gliclazide Glimepiride Glipizide Gliquidone Glisoxepide Glyclopyramide

Meglitinides/"glinides"	Mitiglinide Nateglinide Repaglinide

GLP-1 agonists

DPP-4 inhibitors/"gliptins"

Free fatty acid receptor 1 (GPR40)

Fasiglifam^†

Analogs/other insulins

fast-acting (Insulin aspart
Insulin glulisine
Insulin lispro)
short-acting (Regular insulin)
long-acting (Insulin detemir
Insulin glargine
NPH insulin)
ultra-long-acting (Insulin degludec)
inhalable (Exubera^‡
Afrezza)

Other

Aldose reductase inhibitors	Epalrestat Fidarestat^§ Ranirestat^† Tolrestat^‡ Zenarestat^§

Alpha-glucosidase inhibitors	Acarbose Miglitol Voglibose

Amylin analog	Pramlintide

Sodium glucose transporter (SGLT2) inhibitors/"gliflozins"	Canagliflozin Dapagliflozin Empagliflozin Ipragliflozin Remogliflozin^§ Sergliflozin^§ Tofogliflozin^†

Other	Benfluorex^‡ Bromocriptine

^#WHO-EM
^‡Withdrawn from market
Clinical trials:
- ^†Phase III
- ^§Never to phase III

Nuclear receptor modulators

CAR

Agonists	5β-Dihydroprogesterone 6,7-Dimethylesculetin Amiodarone Artemisinin Benfuracarb Carbamazepine Carvedilol Chlorpromazine Chrysin CITCO Clotrimazole Cyclophosphamide Cypermethrin DHEA Efavirenz Ellagic acid Griseofulvin Methoxychlor Mifepristone Nefazodone Nevirapine Nicardipine Octicizer Permethrin Phenobarbital Phenytoin Reserpine TCPOBOP Telmisartan Tolnaftate Troglitazone Valproic acid

Antagonists	3,17β-Estradiol 3α-Androstanol 3α-Androstenol 3β-Androstanol 17-Androstanol AITC Ethinyl estradiol Meclizine Nigramide J Okadaic acid PK-11195 S-07662 T-0901317

ERR

ERRα

Agonists	6,3′,4′-Trihydroxyflavone Biochanin A Cholesterol Daidzein Genistein

Antagonists	Diethylstilbestrol XCT-790

ERRβ

Agonists	DY-131 (GSK-9089) GSK-4716 (GW-4716)

Antagonists	4-Hydroxytamoxifen (afimoxifene) Diethylstilbestrol

ERRγ

Agonists	Bisphenol A DY-131 (GSK-9089) GSK-4716 (GW-4716)

Antagonists	4-Hydroxytamoxifen (afimoxifene) Diethylstilbestrol

FXR

Agonists	Bile acids Cafestol Chenodeoxycholic acid Fexaramine GW-4064 Obeticholic acid

Antagonists	Guggulsterone

LXR

Agonists	22R-Hydroxycholesterol 24S-Hydroxycholesterol 27-Hydroxycholesterol Cholestenoic acid DMHCA GW-3965 Hypocholamide T-0901317

Antagonists	Efavirenz

PPAR

PPARα

Agonists	15-HETE 15-HpETE Aleglitazar Aluminium clofibrate Arachidonic acid Bezafibrate Clofibrate CP-775146 Daidzein DHEA Elafibranor Etomoxir Fenofibrate Genistein Gemfibrozil GW-7647 Leukotriene B₄ LG-101506 LG-100754 Lobeglitazone Muraglitazar Oleylethanolamide Palmitoylethanolamide Pemafibrate Perfluorononanoic acid Perfluorooctanoic acid Pioglitazone Saroglitazar Sodelglitazar Tesaglitazar Tetradecylthioacetic acid Troglitazone WY-14643

Antagonists	GW-6471 MK-886

PPARδ

Agonists	15-HETE 15-HpETE Arachidonic acid Bezafibrate Daidzein Elafibranor Fonadelpar Genistein GW-0742 GW-501516 L-165,041 LG-101506 MBX-8025 Sodelglitazar Tetradecylthioacetic acid

Antagonists	FH-535 GSK-0660 GSK-3787

PPARγ

Agonists	5-Oxo-ETE 5-Oxo-15-hydroxy-ETE 15-Deoxy-Δ^12,14-prostaglandin J₂ 15-HETE 15-HpETE Aleglitazar Arachidonic acid Balaglitazone Berberine Bezafibrate Cevoglitazar Ciglitazone Daidzein Darglitazone Edaglitazone Efatutazone Englitazone Etalocib Farglitazar Genistein GW-1929 Ibuprofen Imiglitazar Indeglitazar LG-100268 LG-100754 LG-101506 Lobeglitazone Muraglitazar (muroglitazar) nTZDpa Naveglitazar Netoglitazone Oxeglitazar Peliglitazar Pemaglitazar Perfluorononanoic acid Pioglitazone Prostaglandin J₂ Ragaglitazar Reglitazar Rivoglitazone Rosiglitazone RS5444 Saroglitazar Sipoglitazar Sodelglitazar Telmisartan Tesaglitazar Troglitazone

SPPARMs	BADGE EPI-001 INT-131 MK-0533 S26948

Antagonists	FH-535 GW-9662 SR-202 T-0070907

Unknown	SR-1664

Unselective

Agonists	Ciprofibrate Clinofibrate Clofibride Englitazone Etofibrate Farglitazar Netoglitazone Ronifibrate Rivoglitazone Simfibrate

Unsorted

Agonists	Seladelpar

PXR

Agonists	5α-Dihydroprogesterone 5β-Dihydroprogesterone 17α-Hydroxypregnenolone 17α-Hydroxyprogesterone Δ⁴-Androstenedione Δ⁵-Androstenediol Δ⁵-Androstenedione AA-861 Allopregnanolone Alpha-Lipoic acid Ambrisentan AMI-193 Amlodipine besylate Antimycotics Artemisinin Aurothioglucose Bile acids Bithionol Bosentan Bumecaine Cafestol Cephaloridine Cephradine Chlorpromazine Ciglitazone Clindamycin Clofenvinfos Chloroxine Clotrimazole Colforsin Corticosterone Cyclophosphamide Cyproterone acetate Demecolcine Dexamethasone DHEA DHEA-S Dibunate sodium Diclazuril Dicloxacillin Dimercaprol Dinaline Docetaxel Docusate calcium Dodecylbenzenesulfonic acid Dronabinol Droxidopa Eburnamonine Ecopipam Enzacamene Epothilone B Erythromycin Famprofazone Febantel Felodipine Fenbendazole Fentanyl Flucloxacillin Fluorometholone Griseofulvin Guggulsterone Haloprogin Hetacillin potassium Hyperforin Hypericum perforatum (St John's wort) Indinavir sulfate Lasalocid sodium Levothyroxine Linolenic acid LOE-908 Loratadine Lovastatin Meclizine Methacycline Methylprednisolone Metyrapone Mevastatin Mifepristone Nafcillin Nicardipine Nicotine Nifedipine Nilvadipine Nisoldipine Norelgestromin Omeprazole Orlistat Oxatomide Paclitaxel Phenobarbital Piperine Plicamycin Prednisolone Pregnanolone Pregnenolone Pregnenolone 16α-carbonitrile Proadifen Progesterone Quingestrone Reserpine Reverse triiodothyronine Rifampicin Rifaximin Rimexolone Riodipine Ritonavir Simvastatin Sirolimus Spironolactone Spiroxatrine SR-12813 Suberoylanilide Sulfisoxazole Suramin Tacrolimus Tenylidone Terconazole Testosterone isocaproate Tetracycline Thiamylal sodium Thiothixene Thonzonium bromide Tianeptine Troglitazone Troleandomycin Tropanyl 3,5-dimethulbenzoate Zafirlukast Zearalanol

Antagonists	Ketoconazole Sesamin

RAR

Agonists	9CDHRA 9-cis-Retinoic acid (alitretinoin) AC-261066 AC-55649 Acitretin Adapalene all-trans-Retinoic acid (tretinoin) AM-580 BMS-493 BMS-753 BMS-961 CD-1530 CD-2314 CD-437 Ch-55 EC 23 Etretinate Fenretinide Isotretinoin Palovarotene Retinoic acid Retinol (vitamin A) Tamibarotene Tazarotene Tazarotenic acid TTNPB

Antagonists	BMS-195614 BMS-493 CD-2665 ER-50891 LE-135 MM-11253

Others	Retinoic acid metabolism inhibitors: Liarozole

RXR

Agonists	9CDHRA 9-cis-Retinoic acid (alitretinoin) all-trans-Retinoic acid (tretinoin) Bexarotene CD 3254 Docosahexaenoic acid Fluorobexarotene Isotretinoin LG-100268 LG-101506 LG-100754 Retinoic acid Retinol (vitamin A) SR-11237

Antagonists	HX-531 HX-630 LG-100754 PA-452 UVI-3003

SHR

See here instead.

VDR

Agonists	7-Dehydrocholesterol 22-Oxacalcitriol 25-Hydroxyergocalciferol Alfacalcidol Calcifediol Calciferol Calcipotriol Calcitriol Cholecalciferol (vitamin D₃) Dihydrotachysterol Doxercalciferol EB-1089 Eldecalcitol Ercalcidiol Ercalcitriol Ergocalciferol (vitamin D₂) Lithocholic acid Paricalcitol Tacalcitol

Agonists	Dextrothyroxine DITPA Eprotirome (KB-2115) KB-2611 KB-130015 Levothyroxine Liothyronine MB-07811 MGL-3196 (VIA-3196) Sobetirome (GC-1, GRX-431) Thyroxine Tiratricol Triiodothyronine VK-0214 VK-2809 ZYT1

Others	Carrier proteins: Albumin Thyroxine-binding globulin Transthyretin

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