Leo Pharmaceutical Products Ltd. A/s

Topotarget A/s

Leo Pharmaceutical Products, Ltd.

Mette Knak Christensen

Fredrik Bjorkling

Lars Kristian Albert Bl&aelig;hr

Morten Dahl S&oslash;rensen

The present application discloses novel squaric acid derivatives of the formula A: from &#x2014;C(&#x2550;O)&#x2014;, &#x2014;S(&#x2550;O)&#x2014;, &#x2014;C(&#x2550;S)&#x2014; and &#x2014;P(&#x2550;O)(R)&#x2014;; B: -, &#x2014;O&#x2014;, &#x2014;NR&#x2014; and &#x2014;C(&#x2550;O)&#x2014;NR&#x2014;; D: -, &#x2014;O&#x2014;, &#x2014;CRR&#x2014; and &#x2014;NR; m=0-12; n=0-12; m+n=1-20; p=0-2; R: heteroaryl, aryl; R: H, C-alkyl, C-cycloalkyl, &#x2014;[CHCHO]&#x2014;(C-alkyl), C-alkenyl, aryl, heterocyclyl, heteroaryl; R: C-alkyl, C-cycloalkyl, &#x2014;[CHCHO]&#x2014;(C-alkyl), C-alkenyl, aryl, heterocyclyl, heteroaryl; or Rand R: N-containing heterocyclic/heteroaromatic ring; Rand R*: H, C-alkyl, C-alkenyl; and pharmaceutically acceptable salts and prodrugs thereof, and their use in the treatment of diseases/conditions caused by an elevated level of NAMPRT (inflammatory and tissue repair disorders, particularly rheumatoid arthritis, inflammatory bowel disease, asthma and CPOD, osteoarthritis, osteoporosis and fibrotic diseases; dermatosis; autoimmune diseases including systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spondylitis, tissue and organ rejection, Alzheimer's disease, stroke, atherosclerosis, restenosis, diabetes, glomerulonephritis, cancer, cachexia, inflammation associated with infection and viral infections, adult respiratory distress syndrome, ataxia telengiectasia).

Squaric acid derivatives as inhibitors of the nicotinamide

The present application discloses compounds of formula (I) wherein X is &#x2550;O, &#x2550;S, &#x2550;NH, &#x2550;NOH and &#x2550;NO-Me; A is &#x2014;C(&#x2550;O)&#x2014;, &#x2014;S(&#x2550;O)&#x2014;, &#x2014;C(&#x2550;S)&#x2014; and P(&#x2550;O)(R)&#x2014;; B is, &#x2014;O&#x2014;, &#x2014;(CH)&#x2014;, and O&#x2014;(CH)&#x2014;; D is, &#x2014;O&#x2014;, &#x2014;CRR&#x2014; and &#x2014;NR; m is 0-12, n is 0-12, m+n is 1-20; p is 0-4; Ris opt. sub. heteroaryl; and pharmaceutically acceptable salts thereof, and prodrugs thereof. The application also discloses the compound for use as a medicament for the treatment of a disease or a condition caused by an elevated level of nicotinamide phosphoribosyltransferase (NAMPRT), e.g. inflammatory and tissue repair disorders; dermatosis; autoimmune diseases, Alzheimer's disease, stroke, athersclerosis, restenosis, diabetes, glomerulonephritis, cancer, cachexia, inflammation associated with infection and certain viral infections, including Acquired Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome, ataxia telengiectasia. 

Urea and thiourea derivatives

MMP inhibitors

Matrix metalloproteinase inhibitors

Growing community of inventors

Holte, Denmark

Mette Knak Christensen