The discovery of novel cyclohexylamide CCR2 antagonists.

Lanter, James C; Markotan, Thomas P; Zhang, Xuqing; Subasinghe, Nalin; Kang, Fu-An; Hou, Cuifen; Singer, Monica; Opas, Evan; McKenney, Sandra; Crysler, Carl; Johnson, Dana; Molloy, Christopher J; Sui, Zhihua

Lanter, James C; Markotan, Thomas P; Zhang, Xuqing; Subasinghe, Nalin; Kang, Fu-An; Hou, Cuifen; Singer, Monica; Opas, Evan; McKenney, Sandra; Crysler, Carl; Johnson, Dana; Molloy, Christopher J; Sui, Zhihua.

Lanter JC; Johnson & Johnson Pharmaceutical Research and Development, Welsh & McKean Roads, Spring House, PA 19002, USA. jlanter@its.jnj.com

Bioorg Med Chem Lett ; 21(24): 7496-501, 2011 Dec 15.

Article en En | MEDLINE | ID: mdl-22061641

ABSTRACT

ABSTRACT

As a result of further SAR studies on a piperidinyl piperidine scaffold, we report the discovery of compound 44, a potent, orally bioavailable CCR2 antagonist. While having some in vitro hERG activity, this molecule was clean in an in vivo model of QT prolongation. In addition, it showed excellent efficacy when dosed orally in a transgenic murine model of acute inflammation.

Asunto(s)

Amidas/química; Antiinflamatorios/química; Receptores CCR2/antagonistas & inhibidores; Enfermedad Aguda; Administración Oral; Amidas/farmacología; Amidas/uso terapéutico; Animales; Antiinflamatorios/farmacocinética; Antiinflamatorios/farmacología; Antiinflamatorios/uso terapéutico; Evaluación Preclínica de Medicamentos; Humanos; Inflamación/tratamiento farmacológico; Ratones; Ratones Transgénicos; Ratas; Receptores CCR2/metabolismo; Relación Estructura-Actividad

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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Receptores CCR2 / Amidas / Antiinflamatorios Límite: Animals / Humans Idioma: En Año: 2011 Tipo del documento: Article

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