- Second generation 2-pyridyl biphenyl amide inhibitors of the hedgehog pathway
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Potent and efficacious inhibitors of the hedgehog pathway for the treatment of cancer have been prepared using the 2-pyridyl biphenyl amide scaffold common to the clinical lead GDC-0449. Analogs with polar groups in the para-position of the aryl amide ring optimized potency, had minimal CYP inhibition, and possessed good exposure in rats. Compounds 9d and 14f potently inhibited hedgehog signaling as measured by Gli1 mRNA and were found to be equivalent or more potent than GDC-0449, respectively, when studied in a Ptch+/- medulloblastoma allograft model, that is, highly dependent on hedgehog signaling.
- Castanedo, Georgette M.,Wang, Shumei,Robarge, Kirk D.,Blackwood, Elizabeth,Burdick, Daniel,Chang, Christine,Dijkgraaf, Gerrit J.P.,Gould, Stephen,Gunzner, Janet,Guichert, Oivin,Halladay, Jason,Khojasteh, Cyrus,Lee, Leslie,Marsters Jr., James C.,Murray, Lesley,Peterson, David,Plise, Emile,Salphati, Laurent,De Sauvage, Frederic J.,Wong, Susan,Sutherlin, Daniel P.
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p. 6748 - 6753
(2011/01/12)
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- PYRIDYL INHIBITORS OF HEDGEHOG SIGNALLING
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The invention provides novel inhibitors of hedgehog signaling that are useful as s therapeutic agent for treating malignancies where the compounds have the general formula (I): where A, X, Y R1, R2, R3, R4, m and n are as described herein.
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Page/Page column 192-193
(2009/11/29)
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- Pyridyl inhibitors of hedgehog signalling
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The invention provides novel inhibitors of hedgehog signaling that are useful as a therapeutic agents for treating malignancies where the compounds have the general formula I: wherein A, X, Y R1, R2, R3, R4, m and n are as described herein.
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Page/Page column 125-126
(2010/10/20)
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- STEROID PRODRUGS WITH ANDROGENIC EFFECT
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The invention relates to steroid prodrugs with androgenic effect of general formula (I), in which the group Z is bonded to the steroid, pharmaceutical compositions comprising said compounds and the use thereof for the production of medicaments with androgenic effect.
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- AMINOSULPHONYL- OR AMINOSULPHONYLAMINO-SUBSTITUTED PHENYL ESTERS AS ESTRADIOL PRODRUGS
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The invention relates to estradiol prodrugs of general formula (I), in which the group Z is bonded to the steroid. The invention further relates to methods for production thereof, pharamceutical compositions comprising said compounds and use thereof for the production of medicaments with an estrogenic effect.
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Page/Page column 18
(2008/06/13)
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- Estriol and estetrol prodrugs
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This invention provides estriol and estetrol prodrugs of general formula (I), in which group Y is bonded to the steroid process for their production, pharmaceutical compositions that contain these compounds, as well as their use for the production of pharmaceutical agents with estrogenic action.
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Page/Page column 8
(2008/06/13)
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- Steroid prodrugs with androgenic action
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This invention relates to steroid prodrugs with androgenic action of general formula (I), in which group Z is bonded to the steroid, pharmaceutical compositions that contain these compounds as well as their use for the production of pharmaceutical agents with androgenic action.
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Page/Page column 9
(2008/06/13)
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- Estradiol prodrugs
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The invention relates to estradiol prodrugs of general formula (I), in which group Z is bonded to the steroid, process for their production, pharmaceutical compositions that contain these compounds, as well as their use for the production of pharmaceutica
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Page/Page column 9
(2008/06/13)
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- AMINOSULPHONYL- OR AMINOSULPHONYLAMINO-SUBSTITUTED PHENYL ESTERS AS ESTRIOL AND ESTETROL PRODRUGS
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The invention relates to estriol and estetrol prodrugs of general formula (I), in which group Y is bonded to the steroid, the method for production thereof, pharmaceutical compositions comprising said compounds and the use thereof for production of medicaments with estrogenic effect.
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Page/Page column 21-22
(2008/06/13)
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