Medivir Ab

Christer Sahlberg

Hans Kristian Wallberg

Xiao-Xiong Zhou

Christian Sund

Dmitry Antonov

Genaidy Kalyanov

Stefan Lindstrom

Lotta Naeslund

Stefan Lindström

Lourdes Salvador Oden

Rolf Noreen

Per Engelhardt

Horst Wahling

Marita Hogberg

Rolf Nor&eacute;en

Lourdes Salvador Odén

Nils Gunnar Johansson

Nathalie Roue

Katarina Jansson

Stefan Lindstr&ouml;m

Lourdes Salvador Od&eacute;n

Lourdes Salvador

Novel bicyclic tetrahydrofuran compounds and derivatives, and pharmaceutically acceptable salts thereof, according to the formula:  These compounds have utility in the treatment of retroviruses such as HIV, especially reverse transcriptase mutant which allow an obligate chain terminating nucleoside- or nucleotide-phosphate to be excised from the nascent DNA strand by ATP or pyrophosphate-mediated excision.

1-[2', 3&#x2032; -dideoxy-3&#x2032; C- (hydroxymethyl)&#x2014;beta-D-erythro-pentofuranosyl] cytosine derivatives as HIV inhibitors

Compounds of the formula Z: where; A is CH or N; Ris a substituent to a carbon atom in the ring containing A selected from &#x2014;S(&#x2550;O)Ra, where Ra is &#x2014;C-Calkyl, &#x2014;ORx, &#x2014;NRxRx, &#x2014;NHNRxRx, &#x2014;NHNHC(&#x2550;O)ORx, &#x2014;NRxOH; &#x2014;C(&#x2550;O)&#x2014;Rb, where Rb is &#x2014;CT-C4-alkyl, ORx, &#x2014;NRxRx, &#x2014;NHNRxRx, &#x2014;NHC-C-alkyl-C(&#x2550;O)Orx &#x2014;NRxRc, where Rc is H, C-Calkyl, &#x2014;NRxRx; &#x2014;C(=0)Rd, &#x2014;CN, S(&#x2550;O)pRx, where Rd is Rd is C1-C4-alkyl, &#x2014;ORx, &#x2014;NRxRx C-C-alkyl-O&#x2014;C1-C3-alkylC(&#x2550;O)ORx, &#x2014;C-C-alkyl-COORx; &#x2014;C-Calkyl-OH or C-Calkyl ethers or esters thereof (O&#x2014;C-Calkyl)q-O&#x2014;Rx a 5 or 6 membered aromatic ring having 1-3 hetero atoms p is 1 or 2; Rx is independently selected from H, C-Calkyl or acetyl; or a pair of Rx can together with the adjacent N atom form a ring; L is -0-, &#x2014;S(&#x2550;O)&#x2014;, or &#x2014;CH&#x2014;, where r is 0, 1 or 2; R-Rare substituents as defined in the specification; X is &#x2014;(CRR')n-D-(CRR&#x2032;)m-; D is a bond, &#x2014;NR&#x2014;, -0-, &#x2014;S&#x2014;, &#x2014;S(=0)- or &#x2014;S(=0)-; and pharmaceutically acceptable salts and prodrugs thereof, have utility as HIV antivirals. 

Non-nucleotide reverse transcriptase inhibitors

Compounds of the formula (I) wherein: Ris independently H&#x2014;OR, &#x2014;NHR; C-Calkyl; or, when n is 2, adjacent Rtogether define an olefinic bond; Ris H; or when the gem Ris C-Calkyl, that Rmay also be C-Calkyl; or when the gem Ris &#x2014;OR, that Rmay also be &#x2014;C(&#x2550;O)OH or a pharmaceutically acceptable ester thereof; Ris independently H, or a pharmaceutically acceptable ester thereof; Ris independently H or a pharmaceutically acceptable amide thereof; Rand R6 are H or an amine prodrug moiety n is 1, 2 or 3; and pharmaceutically acceptable salts thereof; have utility in the treatment or prophylaxis of HIV, especially reverse transcriptase mutants which allow an obligate chain terminating nucleoside- or nucleotide phosphate to be excised from the nascent DNA strand by ATP- or pyrophosphate-mediated excision.

1-[2',3&#x2032; -dideoxy-3&#x2032; C-(hydroxymethyl)&#x2014;beta-D-erythro-pentofuranosyl] cytosine derivatives as HIV

A compound of the formula (Y): where; Ris O, S; Ris a nitrogen-containing heterocycle; Ris H, C-Calkyl; X is &#x2014;(CRR')-D-(CRR&#x2032;)&#x2014;; D is a bond, &#x2014;NR&#x2014;, &#x2014;O&#x2014;, &#x2014;S&#x2014;, &#x2014;S(&#x2550;O)&#x2014; or &#x2014;S(&#x2550;O)&#x2014;; n and m are independently 0, 1 or 2, Rand R&#x2032; are independently H, C-Calkyl, haloC-Calkyl, hydroxy, or Rand R&#x2032; together with their adjacent C atom is &#x2014;C(&#x2550;O)&#x2014;; Ris independently H, C-Calkyl; E is CH&#x2014;, &#x2014;CHOH&#x2014;, &#x2014;C(&#x2550;O)&#x2014;, &#x2014;NR&#x2014;, &#x2014;O&#x2014;, &#x2014;S&#x2014;, &#x2014;S(&#x2550;O)&#x2014;; n and m are independently 0, 1 or 2; p and q are independently 0, 1 or 2, where p+q&#x2266;2; Ris an optionally substituted carbocycle or heterocycle; Ris independently H, C-Calkyl, halo substituted C-Calkyl, hydroxy; have utility as HIV antivirals.

Non-nucleoside reverse transcriptase inhibitors

This invention relates to non-nucleoside reverse transcriptase inhibitors active against HIV-1 and having an improved resistance and pharmacokinetic profile. The invention further relates to novel intermediates in the synthesis of such compounds and the use of the compounds in antiviral methods and compositions.

Antivirals

Intermediate compounds of non-nucleoside reverse transcriptase inhibitors

Prodrugs

Growing community of inventors

Hagersten, Sweden

Christer Sahlberg