65 results about "C5a receptor" patented technology

The present invention is directed to humanized antibodies which bind the human C5a receptor and their use as therapeutic and diagnostic agents. The present invention is further directed toward nucleic acid sequences which encode said humanized antibodies, and their expression in recombinant host cells. In particular, the present invention is directed towards humanized antibodies derived from murine antibody 7F3 which specifically binds to the human C5a receptor.

This invention relates to methods of treatment of inflammatory bowel disease, and especially to treatment of this condition with cyclic peptidic and peptidomimetic compounds which have the ability to modulate the activity of G protein-coupled receptors. The compounds preferably act as antagonists of the C5a receptor, and are active against C5a receptors on polymorphonuclear leukocytes and macrophages. Particularly preferred compounds for use in the methods of the invention are disclosed.

The present invention provides a compound of formula I:(I)a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

The invention relates to novel cyclic compounds which have the ability to modulate the activity of G protein-coupled receptors. The compounds preferably act as antagonists. In preferred embodiments, the invention provides cyclic peptidic and peptidomimetic antagonists of C5a receptors, which are active against C5a receptors on polymorphonuclear leukocytes and macrophages. The compounds of the invention are both potent and selective, and are useful in the treatment of a variety of inflammatory conditions.

The present invention provides novel compounds of Formula I which are antagonists of the C5a receptor. Compounds of the present invention are useful for the treatment of various C5a-mediated diseases and disorders; accordingly the present invention provides a method for the treatment of C5a-mediated diseases using the novel compounds described herein, as well as pharmaceutical compositions containing them.

Compounds are provided that are modulators of the C5a receptor. The compounds are substituted piperidines and are useful in pharmaceutical compositions, methods for the treatment of diseases and disorders involving the pathologic activation of C5a receptors.

PL37 (RAARISLGPRCIKAFTE [SEQ ID NO: 2]) is an Antisense Homology Box peptide composed of amino acids 37 to 53 of C5a-anaphylatoxin. Complementary peptides, ASGAPAPGPAGPLRPMF (Pep-A [SEQ ID NO: 1]) and ASTAPARAGLPRLPKFF (Pep-B [SEQ ID NO: 3]) were designed and characterized. Pep-A bound to PL37 and to C5a with very slow dissociation, whereas Pep-B failed to bind at all. C5a was inactivated by 7 nM or more of Pep-A and this concentration of Pep-A inhibited induction of intracellular Ca++ influx in neutrophils. Patch clamp studies also showed the effectiveness of Pep-A in C5a-receptor-expressing neuroblastoma cells. Pep-A administration prevented rats from C5a-mediated rapid lethal shock. A-Pep-A (Pep-A acetylated with alanine at the amino-terminus) was more stable in vivo and showed stronger inhibition of inflammatory reactions in mice and rats. Chemical modification of Pep-A (e.g., acetylation, or single or multiple amino acid replacement, insertion, or deletion within the native Pep-A sequence) will yield effective inhibitors, and will often improve inhibitory function on C5a anaphylatoxin. In such modified constructs it will often be desired to conserve some or all 5 prolines found in Pep-A to preserve inhibitory function on C5a.

The invention relates to a C5a receptor antagonist of structure (I), wherein X1 is a radical having a mass of about 1-300 and stands for R5-, R5-CO—, R5-N(R6)-CO—, R5-O—CO—, R5-SO2—, R5-N(R6)-SO2—, R5-N(R6)-, R5-N(R6)-CS—, R5-N(R6)-C(NH)—, R5-CS—, R5-P(O)OH—, R5-B(OH)— or R5-CH═N—O—CH2—CO—, wherein R5 / R6 represent H, F, hydroxy, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, arylalkyl, substituted arylalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyl, substituted acyl, alkoxy, alkoxyalkyl, substituted alkoxyalkyl, aryloxyalkyl or substituted aryloxyalkyl; X2=radical (biological bonding properties of a mimicrying phenylalanine unit); X3 / X4=spacer (amino acids, amino-acid analogs and amino-acid derivatives); X5=radical (biological bonding properties of a mimicrying cyclohexylalanine or homoleucine unit); X6=radical (biological bonding properties of a mimicrying tryptophan unit); X7=radical (biological bonding properties of a mimicrying norleucine or phenylalanine unit), a chemical bond being formed between X3 and X7.

A preservation solution for organs waiting to be transplanted is disclosed; the method of using the solution in a transplantation procedure is also disclosed. The preservation solutions comprise a balanced isotonic aqueous solution comprising sodium, potassium, calcium, magnesium and bicarbonate ions in a physiologically acceptable amount, together with an effective amount of a mutein of the C5a anaphylatoxin which is a C5a receptor antagonist wherein the amino acid residue naturally occurring at sequence position 69 is mutated.

This invention relates to methods of treatment of osteoarthritis, and especially to treatment of this condition with cyclic peptidic and peptidomimetic compounds which have the ability to modulate the activity of G protein-coupled receptors. The compounds preferably act as antagonists of the C5a receptor, and are active against C5a receptors on polymorphonuclear leukocytes and macrophages. Particularly preferred compounds for use in the invention are disclosed.

The present invention relates to fused piperidinyl bicyclic, meta-substituted piperidinyl and their related compounds that modulate activities of mammalian C5a receptor by directly binding to the C5a receptor. The invention also relates to pharmaceutical compositions containing such compounds and their use in the treatment of a disease or a disorder involving pathogenic activation of C5a receptors.

The present invention relates to a urea derivative of the formula (1) wherein each symbol is as described in the specification, a pharmaceutically acceptable salt thereof and pharmaceutical use thereof. The compound of the present invention has a C5a receptor antagonistic action and is useful as an agent for the prophylaxis or treatment of diseases or syndromes due to inflammation caused by C5a [e.g., autoimmune diseases such as rheumatism, systemic lupus erythematosus and the like, sepsis, adult respiratory distress syndrome, chronic obstructive pulmonary disease, allergic diseases such as asthma and the like, atherosclerosis, cardiac infarction, brain infarction, psoriasis, Alzheimer's disease and serious organ injury (e.g., pneumonia, nephritis, hepatitis, pancreatitis and the like) due to activation of leukocytes caused by ischemia, trauma, burn, surgical invasion and the like]. In addition, it is useful as an agent for the prophylaxis or treatment of infectious diseases caused by bacteria or virus that invades via a C5a receptor.