Topadur Pharma Ag

Novartis Ag

Sandoz Gmbh

Reto Naef

Hermann Tenor

Robin Alec Fairhurst

Stephen Paul Collingwood

David Andrew Sandham

Gurdip Bhalay

Peter C Hiestand

Trevor G Payne

Klaus Hasspacher

Lukas Oberer

Rene Hersperger

Hans-Ulrich Naegeli

Sylvie Felicite Gomez

Marcel Karl Eberle

Johann Jakob Boelsterli

Hans-Jorg Roth

The present invention relates to compounds of formula (I) or pharmaceutically acceptable salt, solvate or hydrate thereof, wherein Ris C-Calkyl optionally substituted with F, C-Ccycloalkyl, C-Calkoxy; X represents a bond or C-Calkylene optionally substituted with OH, ONO, ONO; Ris H, OH, ONO, ONO, C(O)OH, C(O)OC-Calkyl, CHO, CN, C-Calkoxy, OC(O)H, OC(O)—C-Calkyl, C(O)N(R)OR, OC-Calkylene-C(O)OH, OC-Calkylene-C(O)OC-Calkyl, OC-Calkylene-C(O)N(R)OR, S(O)C-Calkyl, CR═N—OR, CR═N—NRR, CR═NRor CR═N—ONO; Ris C-Calkyl optionally substituted with F, OH, ONO, ONO, C-Calkoxy, C-Ccycloalkyl; C-Ccycloalkyl, C-Calkenyl, C-Calkynyl; Ris C-Calkyl optionally substituted with C-Ccycloalkyl, C-Calkoxy, F, ONO, ONO; C-Calkenyl, C-Calkynyl, C-Ccycloalkyl; Ris H, SON—RR, NHSONRR; Ris H or C-Calkyl; Ris H, C-Calkyl, C-Calkoxy, C-Calkyl substituted with phenyl, benzyl or a heterocyclic ring, wherein said phenyl, benzyl or said heterocyclic ring are independently optionally substituted by C-Calkyl, F; Ris H, CHor CH; R: H, C-Calkyl optionally substituted with OH, ONO, ONO, CN, COOH, COOC-Calkyl, C-Calkoxy, OC(O)H, OC(O)—C-Calkyl, C(O)N(R)OR, OC-Calkylene-C(O)OH, OC-Calkylene-C(O)OC-Calkyl, OC-Calkylene-C(O)N(R)OR, S(O)C-Calkyl; Rand Rare each independently H, C-Calkyl optionally substituted with OH, ONO, ONO, CN, COOH, COOC-C, C-Calkoxy, OC(O)H, OC(O)—C-Calkyl, C(O)N(R)OR, OC-Calkylene-C(O)OH, OC-Calkylene-C(O)OC-Calkyl, OC-Calkylene-C(O)N(R)OR, S(O)C-Calkyl; i or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein preferably said heterocyclic ring is selected from aziridine, azetidine, pyrolidine, piperidine, morpholine, piperazine and homopiperazine, wherein said heterocyclic ring is optionally substituted with C-Calkyl; Ris C-Calkyl optionally substituted with OH, ONO, ONO, CN, COOH, COOC-Calkyl, C-Calkoxy, OC(O)H, OC(O)—C-Calkyl, C(O)N(R)OR, OC-Calkylene-C(O)OH, OC-Calkylene-C(O)OC-Calkyl, OC-Calkylene-C(O)N(R)OR, S(O)C-Calkyl; Rand Rare each independently H or C-Calkyl optionally substituted with F, OH, ONO, ONO, COOH, C-Calkoxy, C-CCycloalkyl; or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein preferably said heterocyclic ring is selected from aziridine, azetidine, pyrolidine, piperidine, morpholine, piperazine, homopiperazine, 2,5-diazabicyclo[2,2,1]heptane and 3,7-diazabicyclo[3,3,0]octane, wherein said heterocyclic ring is optionally substituted with R; Ris C-Calkyl optionally substituted with halogen, OH, ONO, ONO, C-Calkoxy, C-Chaloalkoxy, COOR, NRR, C═NR, or with a tetrazole group which is optionally substituted with C-Calkyl; or a heteroaryl ring which is optionally substituted with F, wherein the at least one heteroatom of said heteroaryl ring is nitrogen; Ris H, or C-Calkyl optionally substituted with F, OH, ONO, ONO, NRR, or with a heteroaryl ring, wherein the at least one heteroatom of said heteroaryl ring is nitrogen, and wherein preferably said heteroaryl ring is selected from pyrrolidine, piperidine, piperazine, morpholine, pyrrole, and imidazole, wherein nitrogen atom is directly bound to C-Calkyl; Rand Rare each independently H or C-Calkyl optionally substituted with ONO, ONO; Ris C-Calkyl optionally substituted with F, ONO, ONO; C-CCycloalkyl; and their use in methods of treating or preventing a disease alleviated by inhibition of PDE-5 in a human or in a non-human mammal.

2-phenyl-3,4-dihydropyrrolo[2,1-f] [1,2,4]triazinone derivatives as phosphodiesterase inhibitors and uses thereof

The present invention relates to compounds of formula I or pharmaceutically acceptable salt, solvate or hydrate thereof and their use in methods of treating or preventing a disease alleviated by inhibition of PDE5 in a human or in a non-human mammal.

Dual mode of action soluble guanylate cyclase activators and phosphodiesterase inhibitors and uses thereof

The present invention relates to compounds of formula I

2-phenyl-3,4-dihydropyrrolo[2,1 -f] [1,2,4]triazinone derivatives as phosphodiesterase inhibitors and uses thereof

The present invention relates to compounds of formula I or pharmaceutically acceptable salt, solvate or hydrate thereof, wherein

2-phenyl-3,4-dihydropyrrolo[2,1-Ff] [1,2,4]triazinone derivatives as phosphodiesterase inhibitors and uses thereof

The present invention relates to compounds of formula I or pharmaceutically acceptable salt, solvate or hydrate thereof, whereinRis C-Calkyl optionally substituted with F, C-Ccycloalkyl, C-Calkoxy;X represents a bond or C-Calkylene optionally substituted with OH, ONO, ONO;Ris H, OH, ONO, ONO, C(O)OH, C(O)OC-Calkyl, CHO, CN, C-Calkoxy, OC(O)H, OC(O)&#x2014;C-Calkyl, C(O)N(R)OR, OC-Calkylene-C(O)OH, OC-Calkylene-C(O)OC-Calkyl, OC-Calkylene-C(O)N(R)OR, S(O)C-Calkyl, CR&#x2550;N&#x2014;OR, CR&#x2550;N&#x2014;NRR, CR&#x2550;NRor CR&#x2550;N&#x2014;ONO;Ris C-Calkyl optionally substituted with F, OH, ONO, ONO, C-Calkoxy, C-Ccycloalkyl; C-Ccycloalkyl, C-Calkenyl, C-Calkynyl;Ris C-Calkyl optionally substituted with C-Ccycloalkyl, C-Calkoxy, F, ONO, ONO; C-Calkenyl, C-Calkynyl, C-Ccycloalkyl;Ris H, SONRR, NHSONRR;Ris H or C-Calkyl;Ris H, C-Calkyl, C-Calkoxy, C-Calkyl substituted with phenyl, benzyl or a heterocyclic ring, wherein said phenyl, benzyl or said heterocyclic ring are independently optionally substituted by C-Calkyl, F;Ris H, CHor CH;R: H, C-Calkyl optionally substituted with OH, ONO, ONO, CN, COOH, COOC-Calkyl, C-Calkoxy, OC(O)H, OC(O)&#x2014;C-Calkyl, C(O)N(R)OR, OC-Calkylene-C(O)OH, OC-Calkylene-C(O)OC-Calkyl, OC-Calkylene-C(O)N(R)OR, S(O)C-Calkyl;Rand Rare each independently H, C-Calkyl optionally substituted with OH, ONO, ONO, CN, COOH, COOC-C, C-Calkoxy, OC(O)H, OC(O)&#x2014;C-Calkyl, C(O)N(R)OR, OC-Calkylene-C(O)OH, OC-Calkylene-C(O)OC-Calkyl, OC-Calkylene-C(O)N(R)OR, S(O)C-Calkyl; or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein preferably said heterocyclic ring is selected from aziridine, azetidine, pyrollidine, piperidine, morpholine, piperazine and homopiperazine, wherein said heterocyclic ring is optionally substituted with C-Calkyl;Ris C-Calkyl optionally substituted with OH, ONO, ONO, CN, COOH, COOC-Calkyl, C-Calkoxy, OC(O)H, OC(O)&#x2014;C-Calkyl, C(O)N(R)OR, OC-Calkylene-C(O)OH, OC-Calkylene-C(O)OC-Calkyl, OC-Calkylene-C(O)N(R)OR, S(O)C-Calkyl;Rand Rare each independently H or C-Calkyl optionally substituted with F, OH, ONO, ONO, COOH, C-Calkoxy, C-Ccycloalkyl; or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein preferably said heterocyclic ring is selected from aziridine, azetidine, pyrollidine, piperidine, morpholine, piperazine, homopiperazine, 2,5-diazabicyclo[2,2,1]heptane and 3,7-diazabicyclo[3,3,0]octane, wherein said heterocyclic ring is optionally substituted with R;Ris C-Calkyl optionally substituted with halogen, OH, ONO, ONO, C-Calkoxy, C-Chaloalkoxy, COOR, NRR, C&#x2550;NR, or with a tetrazole group which is optionally substituted with C-Calkyl; or a heteroaryl ring which is optionally substituted with F, wherein the at least one heteroatom of said heteroaryl ring is nitrogen;Ris H, or C-Calkyl optionally substituted with F, OH, ONO, ONO, NRR, or with a heteroaryl ring, wherein the at least one heteroatom of said heteroaryl ring is nitrogen, and wherein preferably said heteroaryl ring is selected from pyrrolidine, piperidine, piperazine, morpholine, pyrrole, and imidazole, wherein nitrogen atom is directly bound to C-Calkyl;Rand Rare each independently H or C-Calkyl optionally substituted with ONO, ONO; Ris C-Calkyl optionally substituted with F, ONO, ONO; C-Ccycloalkyl;and their use in methods of treating or preventing a disease alleviated by inhibition of PDE-5 in a human or in a non-human mammal.

2-phenyl-3,4-dihydropyrrolo[2,1 -F] [1,2,4]triazinone derivatives as phosphodiesterase inhibitors and uses thereof

A compound of formula (I):Ris hydrogen or alkyl optionally substituted by hydroxy, alkoxy, or alkylthio, Ris hydrogen, alkyl, hydroxyalkyl, alkylcarbonyloxyalkyl, alkoxyalkyl, alkylthioalkyl, alkenyl, cycloalkylalkyl, heterocyclylalkyl, aralkyl in which the aryl ring thereof is optionally fused to a 5-membered heterocyclic group or is optionally substituted by one or more substituents selected from alkoxy, amino, alkylamino, dialkylamino, acylamino, halogen, hydroxy, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, alkylsulfonylamino or dialkylaminosulfonylamino, Ris hydrogen or alkyl optionally substituted by hydroxy, alkoxy, or alkylthio, Ris hydrogen or alkyl, Ris a quinolinyl, isoquinolinyl or oxodihydroisoquinolinyl group optionally fused to a 5-membered heterocyclic group and optionally substituted by one or more substituents selected from halogen, cyano, hydroxy, alkyl, hydroxyalkyl, alkoxyalkyl, alkylthioalkyl, alkoxy, alkylthio, alkenyl, alkoxycarbonyl, alkynyl, carboxyl, acyl, a group of formula &#x2014;N(R)R, aryl optionally substituted by one or more substituents selected from halogen or alkoxy, or heteroaryl having 5 or 6 ring atoms attached through a ring carbon atom to the indicated carbon atom, and Rand Rare each independently hydrogen or alkyl optionally substituted by hydroxy or alkoxy or one of Rand Ris hydrogen and the other is acyl, or Rand Rtogether with the nitrogen atom to which they are attached denote a 5- or 6-membered heterocyclyl group.

8-quinolinxanthine and 8-isoquinolinxanthine derivatives as PDE 5 inhibitors

Ascomycins

Tetracyclic triterpenes

Compounds of formula I ##STR1## their physiologically-hydrolyzable and -acceptable esters and salts thereof. Said compounds, esters and pharmaceutically acceptable acid addition salts are useful as pharmaceuticals, e.g. for asthma therapy.

Isoquinoline compounds, compositions containing them and their

A cyclosporin of the formula ##STR1## wherein A is a residue of the formula ##STR2## wherein R is hydrogen, C.sub.1-3 alkyl, C.sub.1-3 alkoxy or C.sub.1-3 alkylthio; halo-substituted-C.sub.1-3 alkyl, -C.sub.1-3 alkoxy or -C.sub.1-3 alkylthio; hydroxy-substituted-C.sub.1-3 alkyl, -C.sub.2-3 alkoxy or -C.sub.2-3 alkylthio; or amino or mono- or di-(C.sub.1-2 alkyl)-amino,

O-acylated cyclosporins

6,7-Di(C.sub.1-4 alkoxy)-1-[3,5-di(C.sub.1-4 alkoxy)phenyl]-3,4-dihydro-3-hydroxy-methyl-isoquinolines, their physiologically hydrolyzable and -acceptable esters and acid addition salts thereof are novel. The said compounds and esters and pharmaceutically acceptable acid addition salts thereof are useful as pharmaceuticals, e.g. in the treatment of asthma.

Dihydro-isoquinoline derivatives, processes for their production,

Compounds of formula I ##STR1## wherein R.sub.1 is hydrogen or C.sub.1-4 alkyl; R.sub.2 is hydrogen and R.sub.3 is hydrogen or C.sub.1-4 alkyl, or R.sub.2 and R.sub.3 together represent an additional bond as indicated by the dotted line; R.sub.4 is hydrogen, C.sub.1-4 alkyl or phenyl; R.sub.5 is methoxy or ethoxy; R.sub.6 is hydrogen, hydroxy, C.sub.1-4 alkoxy, hydroxy-(C.sub.2-4 alkoxy) or (C.sub.1-4 alkoxy)-(C.sub.2-4 alkoxy); R.sub.7 and R.sub.8 are each independently C.sub.1-4 alkoxy or (C.sub.1-4 alkoxy)-(C.sub.2-4 alkoxy); and R.sub.9 is hydrogen or halogen, in free form or pharmaceutically acceptable salt form, have pharmaceutical utility, in particular as bronchodilators, eosinophil accumulation and/or activation inhibiting agents and in the treatment of prophylactic treatment of obstructive or inflammatory airways diseases.

Growing community of inventors

Rheinfelden, Switzerland

Reto Naef