PCO371
- CAS No.
- 1613373-33-3
- Chemical Name:
- PCO371
- Synonyms
- PCO371;CPD2050;PCO371,PCO 371,inhibit,Inhibitor,THR,PCO-371,Thyroid Hormone Receptor;1-[3,5-Dimethyl-4-[2-[[4-oxo-2-[4-(trifluoromethoxy)phenyl]-1,3,8-triazaspiro[4.5]dec-1-en-8-yl]sulfonyl]ethyl]phenyl]-5,5-dimethylimidazolidine-2,4-dione;1-[3,5-Dimethyl-4-[2-[[4-oxo-2-[4-(trifluoromethoxy)phenyl]-1,3,8-triazaspiro[4.5]dec-1-en-8-yl]sulfonyl]ethyl]phenyl]-5,5-dimethyl-2,4-imidazolidinedione;2,4-Imidazolidinedione, 1-[3,5-dimethyl-4-[2-[[4-oxo-2-[4-(trifluoromethoxy)phenyl]-1,3,8-triazaspiro[4.5]dec-1-en-8-yl]sulfonyl]ethyl]phenyl]-5,5-dimethyl-
- CBNumber:
- CB03355936
- Molecular Formula:
- C29H32F3N5O6S
- Molecular Weight:
- 635.65
- MDL Number:
- MOL File:
- 1613373-33-3.mol
| Density | 1.47±0.1 g/cm3(Predicted) |
|---|---|
| storage temp. | Store at -20°C |
| solubility | DMSO: 125 mg/mL (196.65 mM) |
| form | Solid |
| pka | 8.39±0.10(Predicted) |
| color | White to off-white |
| InChIKey | LDZJFVOUPUFOHX-UHFFFAOYSA-N |
| SMILES | C1(=O)N(C2=CC(C)=C(CCS(N3CCC4(N=C(C5=CC=C(OC(F)(F)F)C=C5)NC4=O)CC3)(=O)=O)C(C)=C2)C(C)(C)C(=O)N1 |
| FDA UNII | TE53TU0WSQ |
PCO371 Chemical Properties,Uses,Production
Description
PCO371 is a novel, orally active small molecule that acts as a full agonist of PTHR1. PCO371 does not affect the PTH type 2 receptor (PTHR2), and analysis using PTHR1-PTHR2 chimeric receptors indicated that Proline 415 of PTHR1 is critical for PCO371-mediated PTHR1 activation[1].
Uses
PCO371 is a non-peptide chemical parathyroid hormone receptor 1 (PTHR1) agonist that exhibits PTH-mimetic activity in vivo via oral administration. PTH1R is a class B1 G protein-coupled receptor (GPCR) and a major regulator of mineral ion homeostasis and bone metabolism. PTH1R responds to ligands for parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP) and activates Gs, Gq and β-arrestins. Natural and modified forms of these ligands induce substantial anabolic bone formation and are used in the clinical treatment of osteoporosis. PCO371 is used in the treatment of patients with hypoparathyroidism.
Biological Activity
PCO371 selectively induces cAMP production in COS-7 cells expressing human PTH1R (EC50 = 2.4 μM) over COS-7 cells expressing human PTH2R (EC50 = > 100 μM). PCO371 (1 and 3 μM) induces calcium release from isolated fetal rat long bones. It increases lumbar spine and proximal femur bone mineral density (BMD), lumbar spine bone strength, serum levels of osteocalcin, and bone formation in the lumbar spine without affecting serum calcium levels in an ovariectomized (OVX) rat model of osteopenia when administered at a dose of 10 mg/kg per day. PCO371 (9 mg/kg) increases serum, but not urinary, calcium levels in a hypocalcemic thyroparathyroidectomized (TPTX) rat model of hypothyroidism.
Synthesis
PCO371 is obtained by the Heck reaction of vinylsulfonamide intermediate 6b with aryl bromide followed by hydrogenation[1].
References
[1] YOSHIKAZU NISHIMURA*. Lead Optimization and Avoidance of Reactive Metabolite Leading to PCO371, a Potent, Selective, and Orally Available Human Parathyroid Hormone Receptor 1 (hPTHR1) Agonist[J]. Journal of Medicinal Chemistry, 2020, 63 10: 5089-5099. DOI:10.1021/acs.jmedchem.9b01743.
PCO371 Preparation Products And Raw materials
Raw materials
Preparation Products
PCO371 Suppliers
| Supplier | Tel | Country | ProdList | Advantage | |
|---|---|---|---|---|---|
| Wuhan Jingkang en Biomedical Technology Co., Ltd | +8613720134139 | orders@jknbiochem.com | China | 5225 | 58 |
| TargetMol Chemicals Inc. | +1-781-999-5354 +1-00000000000 | marketing@targetmol.com | United States | 19892 | 58 |
| HANGZHOU CLAP TECHNOLOGY CO.,LTD | 86-571-88216897,88216896 13588875226 | sales@hzclap.com | CHINA | 6313 | 58 |
| Nantong HI-FUTURE Biology Co., Ltd. | +undefined18051384581 | sales@chemhifuture.com | China | 3136 | 58 |
| Wuhan Topule Biopharmaceutical Co., Ltd | +8618327326525 | masar@topule.com | China | 8474 | 58 |
| LEAPCHEM CO., LTD. | +86-852-30606658 | market18@leapchem.com | China | 43348 | 58 |
| Wuhan Jingkangen Biomedical Technology Co., Ltd | 13720134139 13720134139 | orders@jknbiochem.com | China | 5731 | 58 |
| ShangHai Caerulum Pharma Discovery Co., Ltd. | 18149758185 | sales-cpd@caerulumpharma.com | China | 3466 | 58 |
| Shanghai Rechem science Co., Ltd. | 21-31433387 15618786686 | sales@rechemscience.com | China | 2988 | 58 |
| Shenzhen SUNGENING Bio-Medical Co., Ltd. | 0755-28967200 13631290199 | wxf@sungening.com | China | 9592 | 60 |