Spirodiketopiperazine-based CCR5 antagonists: Lead optimization from biologically active metabolite

Bioorganic and Medicinal Chemistry Letters

Volumn 17, Issue 3, 2007, Pages 727-731

  Nishizawa, Rena ^a   Nishiyama, Toshihiko ^a   Hisaichi, Katsuya ^a   Matsunaga, Naoki ^a   Minamoto, Chiaki ^a   Habashita, Hiromu ^a   Takaoka, Yoshikazu ^a   Toda, Masaaki ^a   Shibayama, Shiro ^a   Tada, Hideaki ^a   Sagawa, Kenji ^a   Fukushima, Daikichi ^a   Maeda, Kenji ^b   Mitsuya, Hiroaki ^b,c  

^a ONO PHARMACEUTICAL CO   (Japan)

^b KUMAMOTO UNIV SCHOOL OF MEDICINE   (Japan)

^c NATIONAL INSTITUTES OF HEALTH   (United States)

Author keywords

Active metabolite; CCR5; HIV 1

Indexed keywords

CHEMOKINE RECEPTOR CCR5 ANTAGONIST; LEAD; MACROPHAGE INFLAMMATORY PROTEIN 1ALPHA; PIPERAZINE DERIVATIVE; SERINE; SPIRODIKETOPIPERAZINE; UNCLASSIFIED DRUG;

ARTICLE; DRUG DESIGN; DRUG INHIBITION; DRUG PROTEIN BINDING; DRUG SYNTHESIS; HUMAN; HUMAN CELL; ISOMER;

ANIMALS; ANTI-HIV AGENTS; CHO CELLS; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; COMBINATORIAL CHEMISTRY TECHNIQUES; CRICETINAE; CRICETULUS; DRUG DESIGN; HUMANS; HYDROXYLATION; INDICATORS AND REAGENTS; ISOMERISM; MACROPHAGE INFLAMMATORY PROTEIN-1; MAGNETIC RESONANCE SPECTROSCOPY; MICROSOMES, LIVER; OXIDATION-REDUCTION; PROTEIN BINDING; RATS; RECEPTORS, CCR5;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 33846354589     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.10.084     Document Type: Article

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25. 50, compound 13 did not show any significant inhibition at 30 μM. Furthermore, compound 13 showed an improved aqueous solubility (pH 6.8) compared to compound 12 (12, <0.2 μg/ml; 13, 2.7 μg/ml).