Natriuretic compounds, conjugates, and uses thereof

Details Natriuretic compounds, conjugates, and uses thereof Natriuretic compounds, conjugates, and uses thereof

C - Chemistry, Metallurgy

07

K

C07K 14/575 (2006.01) A61K 38/22 (2006.01) A61K 47/48 (2006.01) C07C 53/128 (2006.01) C07C 233/18 (2006.01) C07D 207/46 (2006.01) C08G 65/329 (2006.01) C07K 14/72 (2006.01)

Patent

CA 2504287

Modified natriuretic compounds and conjugates thereof are disclosed in the present invention. In particular, conjugated forms of hBNP are provided that include at least one modifying moiety attached thereto. The modified natriuretic compound conjugates retain activity for stimulating cGMP production, binding to NPR-A receptor, and in some embodiments an improved half-life in circulation as compared to unmodified counterpart natriuretic compounds. Oral, parenteral, subcutaneous, and intravenous forms to of the compounds and conjugates may be prepared as treatments and/or therapies for heart conditions particularly congestive heart failure. Modifying moieties comprising oligomeric structures having a variety of lengths and configurations are also disclosed. Analogs of the natriuretic compound are also disclosed, having an amino acid sequence that is other than the native sequence.

L'invention concerne des composés natriurétiques modifiés, leurs conjugués et leur utilisation. Elle concerne notamment des formes conjuguées de hBNP auxquelles est attaché au moins un groupe fonctionnel de modification. Les conjugués des composés natriurétiques modifiés gardent l'activité de stimulation de la production de cGMP et de liaison au récepteur NPR-A, et ont dans certains modes de réalisation une demi-vie plus longue en circulation par rapport à leurs homologues natriurétiques non modifiés. On peut préparer des formes orales, parentérales, sous-cutanées ou intraveineuses, utilisées comme agents de traitement et/ou thérapeutiques lors des maladies cardiaques, notamment en cas d'insuffisance cardiaque globale. L'invention porte aussi sur des groupes fonctionnels de modification qui comprennent des structures oligomères ayant des longueurs et des configurations diverses. Elle concerne aussi des analogues du composé natriurétique, qui ont une séquence d'acides aminés différente de la séquence native.

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