The present invention relates to new solid phase peptide methods for synthesizing analogues that exhibit oxytocin antagonist activity, specifically Barusiban and its intermediates. Specifically, the present invention relates to a solid phase process for preparing a compound having the formula c[AA.sub.1-AA.sub.6]-AA.sub.7-ol, wherein AA.sub.1 is propionic acid, AA.sub.2 is preferably D-Trp, AA.sub.3 is Ile, AA.sub.4 is preferably AlloIle, AA.sub.5 is Asn, AA.sub.6 is hCy, and AA.sub.7 is preferably N-Me-Orn-ol, or a pharmaceutically acceptable salt or solvate thereof.

The present invention relates to new solid phase peptide methods for synthesizing analogues that exhibit oxytocin antagonist activity, specifically Barusiban and its intermediates. Specifically, the present invention relates to a solid phase process for preparing a compound having the formula c[AA.sub.1-AA.sub.6]-AA.sub.7-ol, wherein AA.sub.1 is propionic acid, AA.sub.2 is preferably D-Trp, AA.sub.3 is Ile, AA.sub.4 is preferably AlloIle, AA.sub.5 is Asn, AA.sub.6 is hCy, and AA.sub.7 is preferably N-Me-Orn-ol, or a pharmaceutically acceptable salt or solvate thereof.

Disclosed are .sup.13N-oxytocin molecules, methods of manufacture of .sup.13N-oxytocin molecules and methods of use of .sup.13N-oxytocin molecules in the determination of the distribution and kinetics of .sup.13N-oxytocin molecules after craniofacial or other application methods.

Disclosed are .sup.13N-oxytocin molecules, methods of manufacture of .sup.13N-oxytocin molecules and methods of use of .sup.13N-oxytocin molecules in the determination of the distribution and kinetics of .sup.13N-oxytocin molecules after craniofacial or other application methods.

Method of obtaining and/or verifying a binder to prepro-Vasopressin (SEQ ID NO. 1) or fragments thereof of at least 6 amino acids in length, including Copeptin (SEQ ID NO. 2), comprising at least one of the steps of: a) generating the binder using a developer comprising an amino acid sequence of at least 6 amino acids in length contained in an amino acid sequence corresponding to the C-terminal part but lacking amino acid 164 of prepro-Vasopressin (SEQ ID NO. 1); b) determining whether the binder is capable of binding to an amino acid sequence of at least 4 amino acids in length contained in an amino acid sequence corresponding to the C-terminal part but lacking amino acid 164 of prepro-Vasopressin (SEQ ID NO. 1); c) selecting and optionally isolating the binder from a plurality of binders which is capable of binding to an amino acid sequence contained in an amino acid sequence corresponding to the C-terminal part but lacking amino acid 164 of prepro-Vasopressin (SEQ ID NO. 1); d) carrying out binding assays with the binder in order to determine the ex vivo stability of prepro-Vasopressin or fragments thereof of at least 6 amino acids in length, including Copeptin, in a biological sample; e) carrying out binding assays with the binder and another binder for comparison purposes in order to determine the concentration of prepro-Vasopressin or fragments thereof of at least 6 amino acids in length, including Copeptin, in a biological sample; wherein the C-terminal part consists of amino acids 138 to 164 of prepro-Vasopressin (SEQ ID NO. 1), in order to obtain a binder or a mixture of binders capable of binding to an epitope contained in an amino acid sequence corresponding to amino acids 138 to 163 but lacking amino acid 164 of prepro-Vasopressin (SEQ ID NO. 1).

Method of obtaining and/or verifying a binder to prepro-Vasopressin (SEQ ID NO. 1) or fragments thereof of at least 6 amino acids in length, including Copeptin (SEQ ID NO. 2), comprising at least one of the steps of: a) generating the binder using a developer comprising an amino acid sequence of at least 6 amino acids in length contained in an amino acid sequence corresponding to the C-terminal part but lacking amino acid 164 of prepro-Vasopressin (SEQ ID NO. 1); b) determining whether the binder is capable of binding to an amino acid sequence of at least 4 amino acids in length contained in an amino acid sequence corresponding to the C-terminal part but lacking amino acid 164 of prepro-Vasopressin (SEQ ID NO. 1); c) selecting and optionally isolating the binder from a plurality of binders which is capable of binding to an amino acid sequence contained in an amino acid sequence corresponding to the C-terminal part but lacking amino acid 164 of prepro-Vasopressin (SEQ ID NO. 1); d) carrying out binding assays with the binder in order to determine the ex vivo stability of prepro-Vasopressin or fragments thereof of at least 6 amino acids in length, including Copeptin, in a biological sample; e) carrying out binding assays with the binder and another binder for comparison purposes in order to determine the concentration of prepro-Vasopressin or fragments thereof of at least 6 amino acids in length, including Copeptin, in a biological sample; wherein the C-terminal part consists of amino acids 138 to 164 of prepro-Vasopressin (SEQ ID NO. 1), in order to obtain a binder or a mixture of binders capable of binding to an epitope contained in an amino acid sequence corresponding to amino acids 138 to 163 but lacking amino acid 164 of prepro-Vasopressin (SEQ ID NO. 1).

The present invention relates to a method for prognosis of an outcome or assessing the risk of a patient having suffered a stroke or a transient ischemic attack, comprising the determination of the level of at least one marker peptide in said sample said marker peptide selected from the group comprising ANP, AVP, ADM, ET-1, troponin, CRP, calcitonin and hGH or fragments thereof or its precursor or fragments thereof and attributing the level of said at least one marker peptides its precursor or fragments thereof with the prognosis of an outcome or assessing the risk for said patient.

A method is provided for the preparation of an N-acyl peptide, N-acyl polypeptide or N-acyl protein comprising reacting a peptide, polypeptide or protein with an acyl halide in the presence of the biologically compatible tertiary amine nicotinamide as catalyst, thus obtaining the desired N-acyl peptide, N-acyl polypeptide or N-acyl protein.

A method is provided for the preparation of an N-acyl peptide, N-acyl polypeptide or N-acyl protein comprising reacting a peptide, polypeptide or protein with an acyl halide in the presence of the biologically compatible tertiary amine nicotinamide as catalyst, thus obtaining the desired N-acyl peptide, N-acyl polypeptide or N-acyl protein.

The present compounds compounds are oxytocin receptor agonists for the treatment of autism, stress, including post traumatic stress disorder, anxiety, including anxiety disorders and depression, schizophrenia, psychiatric disorders and memory loss, alcohol withdrawal, drug addiction and for the treatment of Prader-Willi Syndrome.