Reverse-turn mimetics and compositions and methods related thereto

A method of antagonizing the binding of substance P to the neurokinin-1 receptor in a mammal, comprising administering to a mammal an effective amount of a compound having the structure:

• or a pharmaceutically acceptable salt or stereoisomer thereof,
• wherein
• A is —(CR4R4a)m— where m is 1, 2 or 3;
• R2 and R4 are, at each occurrence, the same or different and independently an amino acid side chain moiety or amino acid side chain derivative;
• R2a and R4a are, at each occurrence, the same or different and independently hydrogen, hydroxy, —COOH, —CONH2, —R5, —OR5, —COOR5, —COR5 or —CONHR5, where R5 is lower alkyl optionally substituted with halogen or hydroxy;
• and
• R1 and R3 are the same or different and independently an amino acid, an amino acid side chain moiety, an amino acid side chain derivative, a peptide, a peptide derivative, a solid support, or a protein;
• wherein said method is used to treat a condition responsive to a reduction of substance P activity in a mammal in need of such treatment;
• and
• wherein said condition is emesis, pain, migraine, oedema, rheumatoid arthritis, asthma, bronchial hyperactivity, allergic rhinitis, ulcerative colitis, Crohn's disease, proliferative vitreoretinopathy, irritable bowel syndrome, cystitis, bladder detruser hyperreflexia, anxiety, depression, dysthymic disorders, chronic obstructive airway disease, neuropathy, contact dermatitis, atopic dermatitis, urticaria or eczematoid dermatitis.