BRL-50481: Difference between revisions

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			{{Short description\|Chemical compound}}
	{{Drugbox		{{Drugbox
			\| Verifiedfields = changed
⚫	\| IUPAC_name = N,N,2-Trimethyl-5-~~nitro-benzenesulfonamide~~
			\| Watchedfields = changed
	\| image = BRL50481_structure.png
			\| verifiedrevid = 424658335
⚫	\| CAS_number = 433695-36-4
		⚫	\| IUPAC_name = ''N'',''N'',2-Trimethyl-5-nitrobenzenesulfonamide
⚫	\| ATC_prefix =
			\| image = BRL-50,481.svg
⚫	\| ATC_suffix =
			\| width = 150
⚫	\| PubChem = 2921148
⚫	\| DrugBank =
⚫	\| C=9\|H=12\|N=2\|O=4\|S=1
	\| molecular_weight = 244.267 g/mol
⚫	\| smiles = Cc1ccc(N(=O)=O)cc1S(=O)(=O)N(C)C
⚫	\| bioavailability =
⚫	\| protein_bound =
⚫	\| metabolism =
⚫	\| elimination_half-life =
⚫	\| excretion =
⚫	\| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
⚫	\| pregnancy_US = <!-- A / B / C / D / X -->
⚫	\| pregnancy_category=
⚫	\| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
⚫	\| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->
⚫	\| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C -->
⚫	\| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
⚫	\| legal_status =
⚫	\| routes_of_administration =
⚫	}}

			<!--Clinical data-->
⚫	'''BRL-50481''' is a drug developed by ] which is the first compound that acts as a ] selective for the ~~PDE<sub>7</sub>~~ ~~subtype~~.<ref>Smith SJ, Cieslinski LB, Newton R, Donnelly LE, Fenwick PS, Nicholson AG, Barnes PJ, Barnette MS, Giembycz MA. Discovery of BRL 50481 , a selective inhibitor of phosphodiesterase 7: in vitro studies in human monocytes, lung macrophages, and CD8+ T-lymphocytes. ''Molecular Pharmacology~~''.~~ ~~2004~~ ~~Dec;~~66(6):1679-89. ~~PMID~~ ~~15371556~~</ref> It has been shown to increase mineralisation activity in ]s, suggesting a potential role for ]s in the treatment of ].<ref>Pekkinen M, Ahlström ME, Riehle U, Huttunen MM, Lamberg-Allardt CJ. Effects of phosphodiesterase 7 inhibition by RNA interference on the gene expression and differentiation of human mesenchymal stem cell-derived osteoblasts. ''Bone~~''.~~ ~~2008~~ ~~Jul;~~43(1~~):84-91.~~ ~~PMID~~ 18420479</ref>
			\| tradename =
		⚫	\| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
		⚫	\| pregnancy_US = <!-- A / B / C / D / X -->
		⚫	\| pregnancy_category =
		⚫	\| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
		⚫	\| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->
		⚫	\| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C -->
		⚫	\| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
		⚫	\| legal_status =
		⚫	\| routes_of_administration =

			<!--Pharmacokinetic data-->
		⚫	\| bioavailability =
		⚫	\| protein_bound =
		⚫	\| metabolism =
		⚫	\| elimination_half-life =
		⚫	\| excretion =

			<!--Identifiers-->
			\| IUPHAR_ligand = 5154
			\| CAS_number_Ref = {{cascite\|correct\|??}}
		⚫	\| CAS_number = 433695-36-4
			\| UNII_Ref = {{fdacite\|correct\|FDA}}
			\| UNII = 03G869PR3P
		⚫	\| ATC_prefix = None
		⚫	\| ATC_suffix =
		⚫	\| PubChem = 2921148
			\| DrugBank_Ref = {{drugbankcite\|correct\|drugbank}}
		⚫	\| DrugBank =
			\| ChEBI = 93472
			\| ChEMBL_Ref = {{ebicite\|changed\|EBI}}
			\| ChEMBL = 484928
			\| ChemSpiderID_Ref = {{chemspidercite\|changed\|chemspider}}
			\| ChemSpiderID = 2194720

			<!--Chemical data-->
		⚫	\| C=9 \| H=12 \| N=2 \| O=4 \| S=1
		⚫	\| smiles = Cc1ccc(N(=O)=O)cc1S(=O)(=O)N(C)C
			\| StdInChI_Ref = {{stdinchicite\|changed\|chemspider}}
			\| StdInChI = 1S/C9H12N2O4S/c1-7-4-5-8(11(12)13)6-9(7)16(14,15)10(2)3/h4-6H,1-3H3
			\| StdInChIKey_Ref = {{stdinchicite\|changed\|chemspider}}
			\| StdInChIKey = IFIUFCJFLGCQPH-UHFFFAOYSA-N
		⚫	}}

		⚫	'''BRL-50481''' is a drug developed by ] which is the first compound that acts as a ] selective for the ] family.<ref>{{cite journal \| vauthors = Smith SJ, Cieslinski LB, Newton R, Donnelly LE, Fenwick PS, Nicholson AG, Barnes PJ, Barnette MS, Giembycz MA \| display-authors = 6 \| title = Discovery of BRL 50481 , a selective inhibitor of phosphodiesterase 7: in vitro studies in human monocytes, lung macrophages, and CD8+ T-lymphocytes \| journal = Molecular Pharmacology \| volume = 66 \| issue = 6 \| pages = 1679–89 \| date = December 2004 \| pmid = 15371556 \| doi = 10.1124/mol.104.002246 \| s2cid = 9491524 \| url = http://molpharm.aspetjournals.org/content/molpharm/66/6/1679.full.pdf }}</ref> PDE7 activity is encoded by two genes, ] and ]. BRL-50481 actually shows about an 80-fold preference for the ] subtype, for which it was developed, over ].<ref>{{cite journal \| vauthors = Alaamery MA, Wyman AR, Ivey FD, Allain C, Demirbas D, Wang L, Ceyhan O, Hoffman CS \| display-authors = 6 \| title = New classes of PDE7 inhibitors identified by a fission yeast-based HTS \| journal = Journal of Biomolecular Screening \| volume = 15 \| issue = 4 \| pages = 359–67 \| date = April 2010 \| pmid = 20228279 \| pmc = 2854023 \| doi = 10.1177/1087057110362100 }}</ref> BRL-50481 has been shown to increase mineralisation activity in ]s, suggesting a potential role for ]s in the treatment of ].<ref>{{cite journal \| vauthors = Pekkinen M, Ahlström ME, Riehle U, Huttunen MM, Lamberg-Allardt CJ \| title = Effects of phosphodiesterase 7 inhibition by RNA interference on the gene expression and differentiation of human mesenchymal stem cell-derived osteoblasts \| journal = Bone \| volume = 43 \| issue = 1 \| pages = 84–91 \| date = July 2008 \| pmid = 18420479 \| doi = 10.1016/j.bone.2008.02.021 }}</ref>

	==References==		== References ==
			{{reflist}}
	<references/>

	{{Phosphodiesterase inhibitors}}		{{Phosphodiesterase inhibitors}}

	]		]
	]		]
	]		]
			]
			]

Latest revision as of 10:52, 7 November 2024

Chemical compound Pharmaceutical compound

BRL-50481
Clinical data

ATC code	None
Identifiers
IUPAC name N,N,2-Trimethyl-5-nitrobenzenesulfonamide
CAS Number	433695-36-4
PubChem CID	2921148
IUPHAR/BPS	5154
ChemSpider	2194720
UNII	03G869PR3P
ChEBI	CHEBI:93472
ChEMBL	ChEMBL484928
CompTox Dashboard (EPA)	DTXSID30195832
Chemical and physical data
Formula	C₉H₁₂N₂O₄S
Molar mass	244.27 g·mol
3D model (JSmol)	Interactive image
SMILES Cc1ccc(N(=O)=O)cc1S(=O)(=O)N(C)C
InChI InChI=1S/C9H12N2O4S/c1-7-4-5-8(11(12)13)6-9(7)16(14,15)10(2)3/h4-6H,1-3H3 Key:IFIUFCJFLGCQPH-UHFFFAOYSA-N
(what is this?) (verify)

BRL-50481 is a drug developed by GlaxoSmithKline which is the first compound that acts as a phosphodiesterase inhibitor selective for the PDE7 family. PDE7 activity is encoded by two genes, PDE7A and PDE7B. BRL-50481 actually shows about an 80-fold preference for the PDE7A subtype, for which it was developed, over PDE7B. BRL-50481 has been shown to increase mineralisation activity in osteoblasts, suggesting a potential role for PDE7 inhibitors in the treatment of osteoporosis.

References

Smith SJ, Cieslinski LB, Newton R, Donnelly LE, Fenwick PS, Nicholson AG, et al. (December 2004). "Discovery of BRL 50481 [3-(N,N-dimethylsulfonamido)-4-methyl-nitrobenzene], a selective inhibitor of phosphodiesterase 7: in vitro studies in human monocytes, lung macrophages, and CD8+ T-lymphocytes" (PDF). Molecular Pharmacology. 66 (6): 1679–89. doi:10.1124/mol.104.002246. PMID 15371556. S2CID 9491524.
Alaamery MA, Wyman AR, Ivey FD, Allain C, Demirbas D, Wang L, et al. (April 2010). "New classes of PDE7 inhibitors identified by a fission yeast-based HTS". Journal of Biomolecular Screening. 15 (4): 359–67. doi:10.1177/1087057110362100. PMC 2854023. PMID 20228279.
Pekkinen M, Ahlström ME, Riehle U, Huttunen MM, Lamberg-Allardt CJ (July 2008). "Effects of phosphodiesterase 7 inhibition by RNA interference on the gene expression and differentiation of human mesenchymal stem cell-derived osteoblasts". Bone. 43 (1): 84–91. doi:10.1016/j.bone.2008.02.021. PMID 18420479.

v t e Phosphodiesterase inhibitors
PDE1	MMPX SCH-51866 Vinpocetine
PDE2	BAY 60-7550 Carbazeran EHNA Oxindole PDP
PDE3	Adibendan Amrinone (inamrinone) Anagrelide Benafentrine Bucladesine Carbazeran Cilostamide Cilostazol Enoximone Ensifentrine Imazodan KMUP-1 Meribendan Milrinone Olprinone Parogrelil Pimobendan Pumafentrine Quazinone RPL-554 Siguazodan Trequinsin Vesnarinone Zardaverine
PDE4	Apremilast Arofylline Atizoram Benafentrine Catramilast CC-1088 CDP-840 CGH-2466 Cilomilast Cipamfylline Crisaborole Denbutylline Difamilast Drotaverine Ensifentrine Etazolate Filaminast Glaucine HT-0712 ICI-63197 Indimilast Irsogladine Lavamilast Lirimilast Lotamilast Luteolin Mesembrenone Mesembrine Mesopram Oglemilast Piclamilast Pumafentrine Revamilast Ro 20-1724 Roflumilast Rolipram Ronomilast RPL-554 RS-25344 Tetomilast Tofimilast YM-976 Zardaverine
PDE5	Acetildenafil Aildenafil Avanafil Beminafil Benzamidenafil Dasantafil Icariin Gisadenafil Homosildenafil Lodenafil Mirodenafil MY-5445 Nitrosoprodenafil Norcarbodenafil SCH-51866 Sildenafil Sulfoaildenafil T-0156 Tadalafil Udenafil Vardenafil
PDE7	BRL-50481
PDE9	BAY 73-6691 PF-04447943 Paraxanthine
PDE10	Balipodect Mardepodect MK-8189 Papaverine TC-E 5005 Tofisopam
PDE11	BC11-38
Non-selective	Aminophylline Caffeine Choline theophyllinate CPX Dipyridamole Doxofylline Enprofylline Ibudilast IBMX Luteolin Pentoxifylline Propentofylline Theobromine Theophylline Zaprinast
Unsorted	Diazepam Diprophylline DPCPX Furafylline Lisofylline MDL-12330A Moxaverine Oxagrelate Pentifylline Proxyphylline Quercetin Satigrel Tolafentrine Trapidil
See also: Receptor/signaling modulators

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