1. A process for the synthesis of 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine of formula (I)
which comprises the steps of:
(a) transforming 2,3-dichlorobenzoyl cyanide of formula (II)
with 1-2 mol equivalent of an aminoguanidine salt in 3-6 mol equivalent of methanesulfonic acid to obtain an adduct of the Formula (IV)
and,
(b) then transforming the obtained adduct of formula (IV) without isolation with magnesium oxide, to obtain the compound of the Formula (I).
2. The process defined in claim 1 further comprising the step of recrystallizing the obtained compound of the Formula (I) using an organic solvent.
3. The process defined in claim 1, wherein according to step (a) the aminoguanidine salt is the dimesylate salt of the formula (III)
4. The process defined in claim 3, wherein according to step (a) 1.3 mol equivalent of aminoguanidine dimesylate of formula (III) are used per equivalent of the compound of the Formula (II).
5. The process defined in claim 1, wherein according to step (a) 4.2 mol equivalent of methanesulfonic acid are employed per equivalent of the compound of the Formula (II).
6. The process defined in claim 1, wherein according to step (b) the cyclization is carried out in the presence of 2-4 mol equivalent of magnesium oxide.
7. The process according to claim 6, wherein the cyclization is carried out by using 3.75 mol equivalent of magnesium oxide.
8. The process according to claim 2, wherein acetone is the organic solvent used for the recrystallization.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A method for directly identifying a non-endogenous compound as a compound having inverse agonist, agonist, or partial agonist activity to a non-endogenous, constitutively activated version of a known G protein-coupled receptor, wherein said non-endogenous, constitutively activated version comprises the amino acid sequence of SEQ.ID.No.:471, said method comprising:
(a) contacting a non-endogenous candidate compound with said non-endogenous, constitutively activated version of the known GPCR comprising the amino acid sequence of SEQ.ID.No.:471; and
(b) measuring the compound efficacy at said contacted receptor, and identifying whether said non-endogenous compound has inverse agonist activity, agonist activity, or partial agonist activity at said contacted receptor.
2. The method of claim 1 further comprising the following step:
assessing, by using an endogenous ligand based assay, the effect of the non-endogenous compound identified as having inverse agonist, agonist, or partial agonist activity on the binding of an endogenous ligand to said known GPCR.
3. The method of claim 2 wherein said non-endogenous compound is an allosteric modulator of said known GPCR.