Medivir Ab

Quiapeg Pharmaceuticals Ab

Wallac Oy

Christian Sund

Marek Kwiatkowski

Christer Sahlberg

Veli-Matti Mukkala

Dmitry Antonov

Stefan Lindstrom

Hans Kristian Wallberg

Xiao-Xiong Zhou

Horst Wahling

Ilkka Hemmila

Stefan Lindström

Nils Gunnar Johansson

Katarina Jansson

Lourdes Salvador

Nathalie Roue

Jyrki Ylikoski

The present application provides compounds of Formula (I): or pharmaceutically acceptable salts thereof, wherein D is a residue of a GLP-polypeptide or an analog thereof, which underdo hydrolysis under physiological conditions to release the GLP-polypeptide or analog thereof and which are useful in the treatment of disorders that could be beneficially treated with the GLP-polypeptide or analog thereof.

Releasable GLP-1 conjugates

The present application provides compounds of Formula (B): or pharmaceutically acceptable salts thereof, wherein D is a residue of a biologically active drug, which underdo hydrolysis under physiological conditions to release the biologically active drug and which are useful in the treatment of disorders that could be beneficially treated with the drug.

Releasable conjugates

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

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

Prodrugs

Bifuncitonal chelating pyridine compound and its use for conferring chelating properties on organic compounds. The pyridine compound has the structure ##STR1## where (i) n is an integer 1 or 2, (ii) R.sub.1, R.sub.2 and R.sub.3 represent groups that have no electrons capable of significantly delocalizing or resonating with the pyridine ring, such as hydrogen, alkyl or aralkyl having an aliphatic carbon atom next to the pyridine ring; at least two of R.sub.1, R.sub.2 and R.sub.3 being hydrogen, iii) Z an Z' represent identical or different structures, each of which comprises at least one heteroatom having a free pair of electrons as that the said at least one heteroatom together with the nitrogen atom of the pyridine ring is capable of chelating a metal ion, iv) - - - - specifies that the group X-Y is a substituent replacing a hydrogen anywhere in the parent pyridine compound, and v) X-Y represents an organic group which is inert to said chelation, and in which iX is an inert and stable bridge and Y is a functional group or a residue of an organic compounbd that has properties conferred on the compound of formula II; said group X-Y being linked to the pyridine ring of formula II via an aliphatic carbon atom attached to and acid ester, salt and chelate forms thereof involving at least one of said chelating heteroatoms.

Metal-chelating 2,6-disubstituted pyridine compounds and their use

A chelate formed between Eu.sup.3+, Tb.sup.3+, Dy.sup.3+ and Sm.sup.3+ and a compound having the formula ##STR1## where A.sub.1-6 are single carbon or nitrogen atoms; n=1 or 2; R.sub.1-6 is nothing when A is a nitrogen, and hydrogen or an organic group when A is a carbon; Z and Z' are selected among --N(CH.sub.2 CH.sub.2 COO.sup.-).sub.2, --N(CH.sub.2 COO.sup.-).sub.2, --N(CH.sub.2 OPO.sub.3.sup.2-).sub.2 and --N(CH.sub.2 PO.sub.3.sup.2-).sub.2 ;--species that --X--Y is a substituent replacing a hydrogen anywhere in the parent compound; and --X--Y represents an organic group containing no chelating heteroatom closer than four atoms from a chelating heteroatom in the parent compound and X is a stable bridge containing certain groups and Y is selected from (a) specified relative groups allowing coupling to other compounds and (b) residues of compounds participating in biospecific affinity reactions.

Spectrofluorometric method and compounds that are of value for the method

Growing community of inventors

Varby, Sweden

Christian Sund