Vernalis &r&d) Ltd.

H. Lundbeck A/s

Les Laboratoires Servier

Vernalis Limited

Simon Bedford

Allan Michael Jordan

Karine Poullennec

Ian Yule

Klenke Burkhard

I-Jen Chen

Martin James Drysdale

Paul Webb

Stephen Stokes

Nicolas Foloppe

Andrea Fiumana

Guillaume De Nanteuil

Arnaud Le Tiran

Olivier Geneste

James Brooke Murray

James Edward Paul Davidson

Patrick Casara

Thierry Le Diguarher

Jean-Michel Henlin

Christopher John Graham

Douglas Stewart Williamson

Daniel Maddox

Yikang Wang

Jérôme-Benoît Starck

András Kotschy

Maïa Chanrion

Attila Paczal

Claire Walmsley

Stuart Christopher Ray

Ana Leticia Maragno

Jérôme-Benoit Starck

Jéröme-Benoit Starck

Frédéric Colland

Emma Sanders

András Herner

Jerome-Benoit Starck

James Edward Davidson

Mark Philip Dodsworth

Mátyás Pál TIMÁRI

Allan Jordan

Karinne Poullennec

Compounds of formula (I) are Areceptor antagonists: Wherein Ris optionally substituted aryl or an optionally substituted 5- or 6-membered heteroaryl ring; Rand Rare independently selected from hydrogen, C-Calkyl, C-Ccycloalkyl, C-Ccycloalkyl-(C-C)-alkyl, aryl-(C-C)-alkyl optionally substituted in the ring part thereof, a 5- or 6-membered monocyclic heterocyclic group optionally linked via a C-Calkylene chain and optionally substituted in the ring part thereof, benzimidazol-2-yl-methyl, pyrid-3-yl-carbonyl, or (1-methyl-piperidin-4-yl)-carbonyl-methyl; or Rand Rtaken together with the nitrogen atom to which they are attached form an optionally substituted 5- or 6-membered ring; Ris C-Calkyl, C-Calkenyl, &#x2014;N(&#x2014;R)&#x2014;R, or optionally substituted heteroarylmethylamino; and Rand Rare independently selected from hydrogen or C-Calkyl; or Rand Rtaken together with the nitrogen atom to which they are attached form an optionally substituted 4- to 6-membered saturated ring.

Thienopyrimidine compounds

A method of treating a mammal suffering from a cancer responsive to inhibition of protein kinase activity, by administering to the mammal an amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof, effective to inhibit protein kinase activity, wherein the compound of formula (I) is: 

Indolyl-pyridone derivatives having checkpoint kinase 1 inhibitory activity

Compounds of formula (I): wherein R, R, R, R, R, R, R, A, A, T and W are as defined in the description. Medicinal products containing the same which are useful in treating conditions requiring a pro-apoptotic agent.

Indole and pyrrole compounds, a process for their preparation and pharmaceutical compositions containing them

Compounds of formula (I): wherein R, R, R, R, R, R, R, A, A, T and W are as defined in the description. Medicinal products containing the same which are useful in treating pathologies involving a deficit in apoptosis, such as cancer, auto-immune diseases, and diseases of the immune system.

The present invention is directed to arylpyrrolopyridine derivatives of Formula A:  The compounds are considered useful for the treatment of diseases associated with LRRK2 such as Lewy body dementia, Parkinson's disease or cancer.

Arylpyrrolopyridine derived compounds as LRRK2 inhibitors

Compounds of formula (I) are Areceptor antagonists:  Wherein Ris optionally substituted aryl or an optionally substituted 5- or 6-membered heteroaryl ring; Rand Rare independently selected from hydrogen, C-Calkyl, C-Ccycloalkyl, C-Ccycloalkyl-(C-C)-alkyl, aryl-(C-C)-alkyl optionally substituted in the ring part thereof, a 5- or 6-membered monocyclic heterocyclic group optionally linked via a C-Calkylene chain and optionally substituted in the ring part thereof, benzimidazol-2-yl-methyl, pyrid-3-yl-carbonyl, or (1-methyl-piperidin-4-yl)-carbonyl-methyl; or Rand Rtaken together with the nitrogen atom to which they are attached form an optionally substituted 5- or 6-membered ring; Ris C-Calkyl, C-Calkenyl, &#x2014;(&#x2014;R)&#x2014;R, or optionally substituted heteroarylmethylamino; and Rand Rare independently selected from hydrogen or C-Calkyl; or Rand Rtaken together with the nitrogen atom to which they are attached form an optionally substituted 4- to 6-membered saturated ring.

Compounds of formula (I) have checkpoint kinase 1 (CHK1) inhibitory activity: wherein R, R, Rand Rare independently selected from hydrogen, hydroxy, methyl, trifluoromethyl, hydroxymethyl, methoxy, trifluoromethoxy, methylamino and dimethylamino; R, and Rare independently selected from hydrogen, hydroxy, C-Calkyl, fluoro-(C-C)-alkyl, hydroxy-(C-C)-alkyl, C-Calkoxy, fluoro-(C-C)-alkoxy, hydroxy-(C-C)-alkoxy, &#x2014;N(R)&#x2014;R, -Alk-N(R)&#x2014;R, &#x2014;O-Alk-N(R)&#x2014;R, &#x2014;C(&#x2550;O)OH, carboxy-(C-C)-alkyl, or &#x2014;C(&#x2550;O)&#x2014;NH&#x2014;R; Alk is a straight or branched chain divalent C-Calkylene radical; Rand Rare independently selected from hydrogen, hydroxy, or C-Calkoxy; X is a straight chain divalent C-Calkylene radical, optionally substituted on one or more carbons by Rand/or R; W is selected from &#x2014;C(&#x2550;O)&#x2014;N(&#x2014;R)&#x2014; or &#x2014;N(&#x2014;R)&#x2014;C(&#x2550;O)&#x2014;; Y is hydrogen, C-Calkyl, C-Calkoxy, or halo; and Q is selected from optionally substituted phenyl, optionally substituted cyclohexyl, or an optionally substituted 6-membered monocyclic heteroaryl ring.

The present invention is directed to arylpyrrolopyridine derivatives of formula (A) (A). The compounds are considered useful for the treatment of diseases associated with LRRK2 such as Lewy body dementia, Parkinson's disease cancer. 

Compounds of formula (I) are Areceptor antagonists, wherein Ris optionally substituted aryl or an optionally substituted 5- or 6-membered heteroaryl ring; Rand Rare independently selected from hydrogen, C-Calkyl, C-Ccycloalkyl, C-Ccycloalkyl-(C-C)-alkyl, aryl-(C-C)-alkyl optionally substituted in the ring part thereof, a 5- or 6-membered monocyclic heterocyclic group optionally linked via a C-Calkylene chain and optionally substituted in the ring part thereof, benzimidazol-2-yl-methyl, pyrid-3-yl-carbonyl, or (1-methyl-piperidin-4-yl)-carbonyl-methyl; or Rand Rtaken together with the nitrogen atom to which they are attached form an optionally substituted 5- or 6-membered ring; Ris C-Calkyl, C-Calkenyl, &#x2014;N(&#x2014;R)&#x2014;R, or optionally substituted heteroarylmethylamino; and Rand Rare independently selected from hydrogen or C-Calkyl; or Rand Rtaken together with the nitrogen atom to which they are attached form an optionally substituted 4- to 6-membered saturated ring. 

Compounds of formula (I) have checkpoint kinase 1 (CHK1) inhibitory activity: wherein R, R, Rand Rare independently selected from hydrogen, hydroxy, methyl, trifluoromethyl, hydroxymethyl, methoxy, trifluoromethoxy, methylamino and dimethylamino; R, and Rare independently selected from hydrogen, hydroxy, C-Calkyl, fluoro-(C-C)-alkyl, hydroxy-(CC)-alkyl, C-Calkoxy, fluoro-(C-C)-alkoxy, hydroxy-(C-C)-alkoxy, -AIk-N(R)&#x2014;R, -0-AIk-N(R)&#x2014;R, &#x2014;C(&#x2550;O)OH, carboxy-(C-C)-alkyl, or &#x2014;C(&#x2550;O)&#x2014;NH&#x2014;R; AIk is a straight or branched chain divalent C-Calkylene radical; Rand Rare independently selected from hydrogen, hydroxy, or C-Calkoxy; X is a straight chain divalent C-Calkylene radical, optionally substituted on one or more carbons by Rand/or R; W is selected from &#x2014;C(&#x2550;O)&#x2014;N(&#x2014;R)&#x2014; or &#x2014;N(&#x2014;R)&#x2014;C(&#x2550;O)&#x2014;; Y is hydrogen, C-Calkyl, C-Calkoxy, or halo; and Q is selected from optionally substituted phenyl, optionally substituted cyclohexyl, or an optionally substituted 6-membered monocyclic heteroaryl ring. 

Compounds of formula (I) are Awherein R1 and R2 are independently selected from hydrogen, or optionally substituted CrC6 alkyl, C-Calkoxy-(C-C)-alkyl, C-Ccycloalkyl, aryl, heteroaryl, aryl-(C-C)-alkyl, or heteroaryl-(C-C)-alkyl; or Rand Rtaken together with the nitrogen atom to which they are attached form an optionally substituted 5- or 6-membered ring; Rand Rare independently selected from hydrogen, or optionally substituted C-Calkyl, C-Calkoxy-(C-C)-alkyl, C-Ccycloalkyl, aryl, heteroaryl, aryl-(C-C)-alkyl, or heteroaryl-C-C)-alkyl; or Rand Rtaken together with the nitrogen atom to which they are attached form an optionally substituted 5- or 6-membered ring; Rand Rare independently selected from hydrogen, C-Calkyl, aryl, aryl-(C-C)-alkyl, &#x2014;NHR&#x2014;N(&#x2014;R)&#x2014;R, &#x2014;NH&#x2014;(C&#x2550;O)&#x2014;R, &#x2014;(C&#x2550;O)&#x2014;NH&#x2014;R, &#x2014;(C&#x2550;O)&#x2014;O&#x2014;R, or halo; and R, R, R, R, R, and Rare independently selected from C-Calkyl, aryl, aryl-(C-C)-alkyl and heteroaryl. 

Thienopyrimidine compounds and compositions

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Simon Bedford