261735-05-1Relevant articles and documents
Potent and selective nonpeptidic inhibitors of procollagen C-proteinase
Fish, Paul V.,Allan, Gillian A.,Bailey, Simon,Blagg, Julian,Butt, Richard,Collis, Michael G.,Greiling, Doris,James, Kim,Kendall, Jackie,McElroy, Andrew,McCleverty, Dawn,Reed, Charlotte,Webster, Robert,Whitlock, Gavin A.
, p. 3442 - 3456 (2008/02/11)
6-Cyclohexyl-N-hydroxy-3-(1,2,4-oxadiazol-5-yl)hexanamides were previously disclosed as inhibitors of procollagen C-proteinase (PCP) culminating in the identification of amide 1. Our objective was to discover a second inhibitor that would have improved affinity for PCP and to optimize properties for transepidermal delivery (TED) to intact skin. Further investigation of this template identified a number of potent PCP inhibitors (IC50 values of 2-6 nM) with improved TED flux. Sulfonamide 56 had excellent PCP enzyme activity when measured with a peptide substrate (Ki 8.7 nM) or with the endogenous substrate procollagen (IC50 3.4 nM) and demonstrates excellent selectivity over MMPs involved in wound healing (>10 000-fold). In the fibroplasia model, 56 inhibited deposition of insoluble collagen by 76 ± 2% at 10 μM and was very effective at penetrating human skin in vitro with a TED flux of 1.5 μg/cm2/h, which compares favorably with values for agents that are known to penetrate skin well in vivo. Based on this profile, 56 (UK-421,045) was selected as a candidate for further preclinical evaluation as a topically applied, dermal anti-scarring agent.
CCR5 ANTAGONISTS AS THERAPEUTIC AGENTS
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Page 209, (2010/02/07)
The present invention relates to compounds of formula (I) or pharmaceutically acceptable derivatives thereof, useful in the treatment or prophylaxis of CCR5-related diseases and disorders, for example, in the inhibition of HIV replication, the prevention or treatment of an HIV infection, and in the treatment of the resulting acquired immune deficiency syndrome (AIDS).
Aryl and heteroaryl alkoxynaphthalene derivatives
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, (2008/06/13)
Compounds of the formula wherein R1, R2, R4, R23, R24, R25 and R26 are defined as in the specification. These compounds are useful psychotherapeutics and are potent serotonin (5-HT1) agonists and antagonists.
Synthesis of 4,5-dihydro 1,2,4-oxadiazoles from N-unsubstituted amidoximes
Lessel,Herfs
, p. 22 - 26 (2007/10/03)
4,5-Dihydro 1,2,4-oxadiazoles can be synthesized from aromatic and araliphatic amidoximes by cyclocondensation with aldehydes and ketones. Resulting heterocycles differ in substitution at C-3 and C-5 showing the scope of the simple reaction.
Use of naphthalene derivatives in treating lung carcinoma
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, (2008/06/13)
A method of inhibiting cell growth in human small cell lung carcinoma comprising administering to a mammal in need of such treatment a cell growth inhibitory amount of a compound of the formula STR1
Use of naphthalene derivatives in treating lung carcinoma
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, (2008/06/13)
The use of a compound of the formula or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for inhibiting cell growth in human small cell lung carcinoma through inhibition of the 5HT1D receptor.