Sandoz Gmbh

Novartis Ag

Wilfried Bauer

Janos Pless

Rainer Albert

Ian Lewis

Gisbert Weckbecker

Christian Bruns

Bernhard Wietfeld

David Bodmer

Mark Meisenbach

Heribert Hellstern

Ivo Felner

Edmond Sandrin

Francois Cardinaux

Rene Huguenin

Sylvain Cottens

Ulrich Hommel

J&ouml;rg Kallen

Claus Ehrhardt

Josef Gottfried Meingassner

Rolf Baenteli

Gabriele Weitz-Schmidt

Monika Mergler

Dieter Geyl

Francedillaois Cardinaux

Walter Prikoszovich

Gabriele Weitz Schmidt

Fran&ccedil;ois Nuninger

Nagarajan Chandramouli

The invention provides cyclo[{4-(NH&#x2014;CH&#x2014;NH&#x2014;CO&#x2014;O&#x2014;)Pro}-Phg-DTrp-Lys-Tyr(4-Benzyl)-Phe], optionally in protected form, or a pharmaceutically acceptable salt or complex thereof, which has interesting pharmaceutical properties.

Somatostatin analogues

The invention provides cyclo[{4-(NH&#x2014;CH&#x2014;NH&#x2014;CO&#x2014;O-)Pro}-Phg-DTrp-Lys-Tyr(4-Benzyl)-Phe], optionally in protected form, or a pharmaceutically acceptable salt or complex thereof, which has interesting pharmaceutical properties.

Mevinolin derivatives wherein the lactone ring is modified have interesting pharmaceutical properties, particularly in preventing or treating disorders or diseases mediated by LFA-1/ICAM-1 interactions.

Melvinolin derivatives

Mevinolin compounds for use in the treatment or prevention of autoimmune diseases, inflammation, ischemia/reperfusion injury and graft rejection. Such compounds bind to the LFA-1 I-domain and thereby inhibit LFA-1/ICAM-1 or LFA-1/ICAM-3 interactions.

Lymphocyte function antigen-1 antagonists

Somatostain analogues comprising the amino acid sequence of the formula (I): -(D/L)Trp-Lys-X,-X,, wherein X,is a substituted Thr, Ser, Tyr, Glu or Cys residue and X,is an &agr;-amino acid having an aromatic residue on the C,side chain, or an amino acid unit selected from Dab, Dpr, Dpm, His (Bzl)HyPro, thienyl-Ala, cyclohexyl-Ala and t.-butyl-Ala, the residue Lys of said sequence corresponding to the residue Lys,of the native somatostatin-14, in free form, in salt form or complexed with a detectable element have interesting pharmacological properties.

Somatostatin peptides

A biologically active peptide selected from growth factors, peptide hormones, interferons and cytokines and analogues and derivatives thereof, and bearing at least one chelating group linked to an amino group of said peptide, the chelating group being capable of complexing a detectable element and such amino group having no significant binding affinity to target receptors, are complexed with a detectable element and are useful as a pharmaceutical, e.g. a radiopharmaceutical for in vivo imaging of target tissues or for therapy.

Polypeptide derivatives

The present invention provides a sugar derivative of a biologically active peptide, which derivative has a prolonged duration of action when compared to the non-sugar modified peptide, and contains at least on one of the amino acid units a sugar residue which is attached to an amino group thereof by a coupling other than a direct N-glycosidic bond, and additionally, when it is a condensation product of a carboxyl group containing sugar and a peptide with less than 8 amino acid units, by a coupling other than a direct amide bond.

Peptide derivatives

Peptide derivatives selected from (i) a calcitonin peptide and a LHRH antagonist peptide modified by at least one sugar residue and/or at least one short polyhydroxy compound or derivative, and (ii) a calcitonin peptide modified by at least one formyl and/or at least C.sub.3-5 alkyl attached to an amino group other than a N-terminal amino group, and (iii) a calcitonin peptide modified by a combination of said substituents, with the provisos that

Calcitonin derivatives

Somatostatine derivatives of the general formula ##STR1## wherein either (a)

Somatostatine derivatives

Straight-chain or mono-cyclicpolypeptides comprising a heptapeptide moiety, said moiety having in the 1-position (N-terminal) an .alpha.-N-phenylalkylated, optionally ring-substituted phenylalanine residue, in the 2-position a cysteine residue, in the 3-position an optionally ring-substituted phenylalanine residue, in the 4-position an optionally benzene-ring-substituted tryptophan residue, in the 5-position an optionally .epsilon.-N-alkylated lysine residue and in the 7-position (C-terminal) a cysteine or cysteinol residue the S-atoms of the cysteine residue at the 2-position and the cysteine or cysteinol residue at the 7-position being linked together in the case of the mono-cyclic polypeptides to form an -S-S-bridge, whereby the residues at the 1-, 2-, 4-, 6-, and 7-positions of said heptapeptide moiety may each be in the (L)- or (D)-configuration and the residues at the 4-, 5- and 6-positions of said heptapeptide moiety may each be optionally .alpha.-N-alkylated, said polypeptides being in free or protected form, as well as salt forms and complexes thereof. Subject compounds are useful as pharmaceuticals, e.g. as GH-secretion inhibitors.

Polypeptides, processes for their production, pharmaceutical

The invention provides polypeptides of formula I,

Organic compounds

N-Acyl-polypeptides comprising the basic sequence ##STR1## wherein 'Acyl' is the acyl residue of an organic or inorganic acid; A is H or alkyl; &gt;N--CH(Z)--CO-- and E are the residues of natural .alpha.-amino acids or corresponding (D)-amino acids; C is --Trp-- or --(D)Trp--; F is a terminal grouping; and Y.sub.1 and Y.sub.2 are each H or together are a direct bond; as well as their salt forms and complexes.

N-Acyl-polypeptides and processes for the production thereof

Straight-chain and mono-cyclic polypeptides containing the basic sequence ##STR1## wherein X is an amino acid residue, the residues in the 1- and 6-positions being linked by an --S--S-- bridge when the polypeptide is monocyclic, have pharmacological, in particular GH--, gastric- and pancreatic-secretion inhibiting activity.

Growing community of inventors

Lampenberg, Switzerland

Wilfried Bauer