Modulators of the human CCR5 receptor. Part 3: SAR of substituted 1-[3-(4-methanesulfonylphenyl)-3-phenylpropyl]-piperidinyl phenylacetamides

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 13, 2006, Pages 3533-3536

  Cumming, John G ^a   Brown, Simon J ^a   Cooper, Anne E ^a   Faull, Alan W ^a   Flynn, Anthony P ^a   Grime, Ken ^a   Oldfield, John ^a   Shaw, John S ^a   Shepherd, Emma ^a   Tucker, Howard ^a   Whittaker, David ^a  

^a ASTRAZENECA   (United Kingdom)

Author keywords

CCR5; CCR5 antagonist; CCR5 modulator; Chemokine receptor

Indexed keywords

1 [3 (4 METHANESULFONYLPHENYL) 3 PHENYLPROPYL]PIPERIDINYL PHENYLACETAMIDE; CHEMOKINE RECEPTOR CCR5; CHEMOKINE RECEPTOR CCR5 ANTAGONIST; N (1 [ 3 (3,5 DIFLUOROPHENYL) 3 [4 METHANESULFONYLPHENYL]PROPYL]PIPERIDIN 4 YL) N ETHYL 2 [4 METHANESULFONYLPHENYL]ACETAMIDE; UNCLASSIFIED DRUG;

AEROBIC METABOLISM; ANIMAL CELL; ARTICLE; CHO CELL; DRUG ACTIVITY; DRUG BINDING; DRUG BIOAVAILABILITY; DRUG HALF LIFE; DRUG IDENTIFICATION; DRUG METABOLISM; DRUG POTENCY; DRUG STRUCTURE; HUMAN; IC 50; NONHUMAN; PROTEIN BINDING;

ACETANILIDES; ANIMALS; CRYSTALLOGRAPHY, X-RAY; DOGS; HUMANS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PIPERIDINES; RATS; RECEPTORS, CCR5; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONES; TIME FACTORS;

EID: 33646918010     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.03.089     Document Type: Article

References (22)

1. For a review of CCR5 as a target for HIV-1 and small molecule CCR5 ligands, see:. Kazmierski W., Bifulco N., Yang H., Boone L., DeAnda F., Watson C., and Kenakin T. Bioorg. Med. Chem. 11 (2003) 2663 4155
2. Pipitone N., and Pitzalis C. Curr. Opin. Anti-inflamm. Immunomodul. Investig. Drugs 2 (2000) 9
3. Vierboom M.P.M., Zavodny P.J., Chou C.-C., Tagat J.R., Pugliese-Sivo C., Strizki J., Steensma R.W., McCombie S.W., Çelebi-Paul L., Remarque E., Jonker M., Narula S.K., and T'Hart B. Arthritis Rheum. 52 (2005) 627
4. Sellebjerg F., Madsen H.O., Jensen C.V., Jensen J., and Garred P. J. Neuroimmunol. 102 (2000) 98
5. Fischereder M., Luckow B., Wüthrich R.P., Rothenpieler U., Schneeberger H., Panzer U., Stahl R.A.K., Hauser I.A., Budde K., Neumayer H.-H., Krämer B.K., Land W., and Schlöndorff D. Lancet 357 (2001) 1758
6. Andres P.G., Beck P.L., Mizoguchi E., Mizoguchi A., Bhan A.K., Dawson T., Kuziel W.A., Maeda N., MacDermott R.P., Podolsky D.K., and Reinecker H.C. J. Immunol. 164 (2000) 6303
7. Kazmierski W.M., Peckham J.P., Duan M., Kenakin T.P., Jenkinson S., Gudmundsson K.S., Piscitelli S.C., and Feldman P.L. Curr. Med. Chem.: Anti-infect. Agents 4 (2005) 133 and references therein
8. Seto M., Aikawa K., Miyamoto N., Aramaki Y., Kanzaki N., Takashima K., Kuze Y., Iizawa Y., Baba M., and Shiraishi M. J. Med. Chem. 49 (2006) 2037
9. Kim D., Wang L., Hale J.J., Lynch C.L., Budhu R.J., MacCoss M., Mills S.G., Malkowitz L., Gould S.L., DeMartino J.A., Springer M.S., Hazuda D., Miller M., Kessler J., Hrin R.C., Carver G., Carella A., Henry K., Lineberger J., Schleif W.A., and Emini E.A. Bioorg. Med. Chem. Lett. 15 (2005) 2129
10. Shah S.K., Chen N., Guthikonda R.N., Mills S.G., Malkowitz L., Springer M.S., Gould S.L., DeMartino J.A., Carella A., Carver G., Holmes K., Schleif W.A., Danzeisen R., Hazuda D., Kessler J., Lineberger J., Miller M., Emini E.A., and MacCoss M. Bioorg. Med. Chem. Lett. 15 (2005) 977
11. Imamura S., Nishikawa Y., Ichikawa H., Hattori T., Matsushita Y., Hashiguchi S., Kanzaki N., Iizawa Y., Baba M., and Sugihara Y. Bioorg. Med. Chem. 13 (2004) 397
12. Seto M., Miyamoto N., Aikawa K., Aramaki Y., Kanzaki N., Iizawa Y., Baba M., and Shiraishi M. Bioorg. Med. Chem. 13 (2004) 363
13. Seto M., Aramaki Y., Imoto H., Aikawa K., Oda T., Kanzaki N., Iizawa Y., Baba M., and Shiraishi M. Chem. Pharm. Bull. 52 (2004) 818
14. Shankaran K., Donnelly K.L., Shah S.K., Caldwell C.G., Chen P., Finke P.E., Oates B., MacCoss M., Mills S.G., DeMartino J.A., Gould S.L., Malkowitz L., Siciliano S.J., Springer M.S., Kwei G., Carella A., Carver G., Danzeisen R., Hazuda D., Holmes K., Kessler J., Lineberger J., Miller M., Emini E.A., and Schleif W.A. Bioorg. Med. Chem. Lett. 14 (2004) 3589
15. Burrows J.N., Cumming J.G., Fillery S.M., Hamlin G.A., Hudson J.A., Jackson R.J., McLaughlin S., and Shaw J.S. Bioorg. Med. Chem. Lett. 15 (2005) 25
16. Cumming J.G., Cooper A.E., Grime K., Logan C.J., McLaughlin S., Oldfield J., Shaw J.S., Tucker H., Winter J., and Whittaker D. Bioorg. Med. Chem. Lett. 15 (2005) 5012
17. Burrows, J.; Cooper, A.; Cumming, J.; McInally, T.; Tucker, H. WO 01/087839, 2001; Chem. Abstr. 2002, 135, 371644.
18. Cumming, J.; Tucker, H. WO 03/042177, 2003; Chem. Abstr. 2003, 138, 385312.
19. van Heerden P.S., Bezuidenhoudt B.C.B., and Ferreira D. Tetrahedron 53 (1997) 6045
20. An explosion hazard in the preparation of 3-trifluoromethylphenylmagnesium bromide has been reported, see: Urben, P. G. Ed.; Bretherick's Handbook of Reactive Chemical Hazards; 5th ed.; Butterworth: Heinemann, 1995; p 852.
21. For experimental procedure, see Ref. 8.
22. Springthorpe, B.; Strandlund, G. WO 2005037052; Chem. Abstr. 2005, 142, 426388.