Pioglitazone

U 72107 · PINEPOLLEN · Pioglitazone · Pioglitozaone · D4-Pioglitazone · Pioglitazone (Actos) · Pioglitazone free base · Pioglitazone USP/EP/BP

https://huagongshe.com/ko/chemical/4829

식별자 및 물리적 특성

CAS No.	111025-46-8
분자식	C19H20N2O3S
평균 분자량	356.4 g/mol
단동위원소 질량	356.1194635 g/mol
SMILES	CCc1ccc(CCOc2ccc(CC3SC(=O)NC3=O)cc2)nc1
InChIKey	HYAFETHFCAUJAY-UHFFFAOYSA-N
PubChem CID	4829
ChEMBL	CHEMBL595
ChEBI	CHEBI:8228
EC No.	601-029-7
DTXSID	DTXSID3037129

화학 및 물리적 성질

XLogP	3.8
극성 표면적	93.6
수소 결합 공여자 수	1
수소 결합 수용자 수	5
회전 가능 결합 수	7
무거운 원자 수	25
형식 전하	0
복잡도	466
의약품	Pharmaceuticals
LogP(분배 계수)	2.33.39
Color/Form	Colorless needles from dimethylformamide and water
용해도	Practically insoluble4.42e-03 g/LDMSO(약간 가열됨)
Human Drugs	Breast FeedingLactationMilk, HumanHypoglycemic AgentsThiazolidinedionesEMA approved medicines: Human medicine
Decomposition	Hazardous decomposition products formed under fire conditions: Carbon oxides, Nitrogen oxides (NOx), Sulfur oxides, Hydrogen chloride gas. /Pioglitazone hydrochloride/
녹는점	193-194C183-184 °CColorless prisms from ethanol, MP: 193-194 °C. Soluble in dimethyl formamideslightly soluble in ethanolvery slightly soluble in acetone, acetonitrile. Practically insoluble in waterinsoluble in ether. /Pioglitazone hydrochloride/183 - 184 °C183-184 C
Physical Description	Solid
Stability/Shelf Life	Stable under recommended storage conditions. /Pioglitazone hydrochloride/
Dissociation Constants	5.19pKa = 5.19 (pyridine)
Collision Cross Section	178.8 Å² [M+H]+ [CCS Type: DTBuffer gas: N2Ionization: APCI+Dataset: TOXCASTSource Identifier: DTXSID3044203]176.88 Å² [M+H]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]
Other Experimental Properties	White crystalline powder. Odorless. MW: 392.90 daltons. Soluble in N,N-dimethylformamide, slightly soluble in anhdydrous ethanol, very slightly soluble in acetone, acetonitrile, practically insoluble in water, insoluble in ether /Pioglitazone hydrochloride/
끓는 점	575.4±45.0 °C(Predicted)
밀도	1.260±0.06 g/cm3(Predicted)
저장 조건	under inert gas (nitrogen or Argon) at 2-8°C
pKa(산도 계수)	6.35±0.50(Predicted)
물리적 상태	흰색 내지 회백색 고체.
색상	흰색에서 황백색까지
헨리 상수	5.8×106 mol/(m3Pa) at 25℃, HSDB (2015)
InChI	InChI=1S/C19H20N2O3S/c1-2-13-3-6-15(20-12-13)9-10-24-16-7-4-14(5-8-16)11-17-18(22)21-19(23)25-17/h3-8,12,17H,2,9-11H2,1H3,(H,21,22,23)
InChIKey	HYAFETHFCAUJAY-UHFFFAOYSA-N
SMILES	S1C(CC2=CC=C(OCCC3=NC=C(CC)C=C3)C=C2)C(=O)NC1=O

안전 및 규제

GHS 분류	WarningH302+H312+H332 (16.7%): Harmful if swallowed, in contact with skin or if inhaled [Warning Acute toxicity, oralacute toxicity, dermalacute toxicity, inhalation]P203, P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P317, P318, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 6 reports by companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
규제 정보	Hazard Traits - CarcinogenicityStatus: Active Update: 08-11-2019 https://echa.europa.eu/registration-dossier/-/registered-dossier/30090
FDA 요건	The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including pioglitazone hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Pioglitazone hydrochloride/
History and Incidents	Rosiglitazone was approved by the U.S. Food and Drug Administration (FDA) for type 2 diabetes in 1999. The unique mechanism of action and low risk of hypoglycemia contributed to rapid market uptake of rosiglitazone, but safety concerns became more prominent in 2007. There were 5 major events on 4 calendar days in 2007 regarding safety concerns related to rosiglitazone in certain patients: (1) the May 21, 2007, online release of the rosiglitazone meta-analysis performed by Nissen and Wolski and the FDA safety warning on the same day(2) the July 30, 2007, conclusion of an FDA advisory committee meeting that rosiglitazone increased cardiac ischemic risk(3) the August 14, 2007, update of thiazolidinedione (TZD) labels with a black-box warning for heart failureand (4) the November 14, 2007, update to the warnings and precautions section of the rosiglitazone label for coadministration of nitrate or insulin. /The purpose of this paper was/ to (1) describe TZD (rosiglitazone and pioglitazone) utilization trends from January 1, 2007, continuing through May 2008 amid public announcements of safety concerns and (2) determine the percentage of TZD users who had medical claims indicating increased cardiovascular (CV) risk before and after release (May 21, 2007) of the FDA safety warning and online release of the meta-analysis performed by Nissen and Wolski. A retrospective analysis of pharmacy claims was performed from 9 commercial plans with a combined 9 million eligible members, including a 1.4 million-member cohort from 1 of the plans for which medical claims data were available. We evaluated trends in TZD use for each month for the 17-month period from January 1, 2007, through May 31, 2008, including the percentage of TZD users at increased CV risk. In the trend analysis, for each calendar month of 2007, we calculated mean pharmacy claim counts per day per million members for each of the 2 TZD drugs and for a comparison drug, sitagliptin, a new oral hypoglycemic agent in a different class (dipeptidyl-peptidase-IV inhibitors). For the CV risk analysis, we used the database of integrated medical and pharmacy claims for the 1.4 million-member cohort to identify patients with a current days supply of a TZD on May 20, 2007, December 7, 2007, or May 20, 2008. The medical claims for all identified patients were queried back 2 years from May 20, 2007, December 7, 2007, or May 20, 2008, respectively. Rosiglitazone users at increased CV rsk were defined as those with a medical claim with a primary diagnosis for congestive heart failure (CHF

용도

개요

Pioglitazone is an agonist of the peroxisome proliferator-activated receptor γ (PPARγ; EC50 = ~500-600 nM for both human and murine PPARγ). It is selective for PPARγ over PPARα, exhibiting low level activation of PPARα at 1 μM and 5.4-fold activation at a concentration of 10 μM. Pioglitazone inhibits pyruvate oxidation and glucose production in hepatocytes when used at a concentration of 10 μM. In vivo, pioglitazone (0.3-3 mg/kg per day) reduces hyperglycemia, hyperlipidemia, and hyperinsulinemia in a dose-dependent manner in male Wistar fatty rats. It reduces the number of lesions in a transgenic rat adenocarcinoma of prostate (TRAP) model. Pioglitazone (2.5 mg/kg) also decreases production of neuroinflammatory cytokines and reduces immobility in the forced swim and tail suspension tests in a mouse model of chronic mild stress, indicating antidepressant-like activity that can be reversed by the PPARγ antagonist GW9662 .

용도

Pioglitazone shows antidiabetic activity in patients with type 2 diabetes mellitus.

일반 설명

Pioglitazone, (±)-5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2,4-thiazolidinedione (Actos),is an odorless, white, crystalline powder that must be convertedto a salt such as its hydrochloride before it will haveany water solubility. Although the molecule contains one chiralcenter, the compound is used as the racemic mixture. Thisis primarily a result of the in vivo interconversion of the twoenantiomers. Thus, there are no differences in the pharmacologicalactivity of the two enantiomers.