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Lund, Sweden

Mahmutovic-Persson I.,Lund University | Johansson M.,Respiratorius AB | Brandelius A.,Lund University | Calven J.,Lund University | And 3 more authors.
International Immunopharmacology | Year: 2012

Thymic stromal lymphopoietin (TSLP), an immunomodulating potentially disease-inducing cytokine, is overproduced in TLR3-stimulated bronchial epithelial cells from asthmatic donors whereas production of antiviral IFNβ is deficient. It is of therapeutic interest that capsazepine inhibits epithelial TSLP and relaxes human small airways with similar potencies. However, it is not known if other capsazepine-like compounds share such dual actions. This study explores epithelial anti-TSLP and anti-IFNβ effects of capsazepine and novel capsazepine-like bronchorelaxants. We used primary bronchial epithelial cells from asthmatic and chronic obstructive pulmonary disease (COPD) donors, and human small airways dissected from surgically removed lungs. Seven novel capsazepinoids were about 10 times, and one compound (RES187) > 30 times, more potent than capsazepine as relaxants of LTD 4-contracted small airways. TLR3-induced TSLP, TNFα, CXCL8, and IFNβ mRNA and protein levels were dose-dependently and non-selectively inhibited by capsazepine, equally in cells from asthmatic and COPD donors. The novel compounds, except RES187, reduced TSLP and IFNβ but none are more potent than capsazepine. Only capsazepine consistently inhibited TNFα and CXCL8 production and attenuated TLR3-induced epithelial NF-κB signalling. Hence, the present compounds did not separate between inhibition of TLR3-induced epithelial TSLP and IFNβ, but all compounds, except capsazepine, did separate between the bronchorelaxant and the epithelial immune effects. We conclude that similar mechanisms may be involved in capsazepine-like inhibition of TLR3-induced epithelial TSLP and IFNβ and that these are distinct from mechanisms involved in relaxation of small airways by these compounds. © 2012 Elsevier B.V. All rights reserved.


Patent
Respiratorius Ab | Date: 2015-12-17

Compounds and a method for imaging myocardial perfusion, including administering to a patient a compound linked to an imaging moiety, wherein the compound binds MC-1, and scanning the patient using diagnostic imaging. Kits including the compound or precursor compounds linked or not linked to an imaging moiety are also described.


Patent
Respiratorius Ab | Date: 2010-02-24

The invention relates to novel compounds having the general formula (I), and which compounds are useful to treat a disorder or disease characterized by bronchoconstriction, e.g. COPD and asthma.


Patent
Respiratorius Ab | Date: 2012-12-18

Compounds and a method for imaging myocardial perfusion, including administering to a patient a compound linked to an imaging moiety, wherein the compound binds MC-1, and scanning the patient using diagnostic imaging. Kits including the compound or precursor compounds linked or not linked to an imaging moiety are also described.


Dalence-Guzman M.F.,Respiratorius AB | Toftered J.,Respiratorius AB | Oltner V.T.,Respiratorius AB | Wensbo D.,Respiratorius AB | Johansson M.H.,Respiratorius AB
Bioorganic and Medicinal Chemistry Letters | Year: 2010

The synthesis and bronchorelaxing effects of a series of novel tetrahydroisoquinoline amides are described. The compounds were evaluated for their ability to relax LTD4 contracted isolated human small airways ex-vivo. Several compounds demonstrated highly efficacious bronchorelaxing properties. Cinnamide 71 was selected for further studies and constitutes a promising candidate as a novel bronchorelaxing agent for the treatment of pulmonary disorders. © 2010 Elsevier Ltd. All rights reserved.

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