D2 dopamine agonists

Deca/octahydro 6-alkyloxazolo /-fused quinolines 17 were prepared and evaluated as dopaminergics (87EUP1). A series of linearly annelated 8-alkyl-deca/ octahydrooxazoloquinolines 18 and their salts were prepared for use as dopamine D2-agonists and hypertensive agents. The rran.s-( )-l-propyl-6-oxodecahydro-quinoline was brominated, then treated with urea in methanol to give the 2-amino... 

Hillefors-Berglund M, Liu Y, von Euler G Persistent, specific and dose-dependent effects of toluene exposure on dopamine D2 agonist binding in the rat caudate-putamen. Toxicology 77 223-232, 1993... 

The dopamine D2 agonist SAR area has been reviewed by Hacksell and coworkers from the perspective of stereochemistry and pharmacological profiles of the enantiomers of the compounds synthesized by that research group during a period of 10 years. The structural classes surveyed were 3-phenylpiperidines, 2-aminotetralins and their ring-methylated analogues and octahydrobenzo[/]quinolines (OHB[f]Qs) [60]. 

I 72 CPCR-specific Combinational Libraries Based on the Concept of Privileged Substructures Tab. 12.4 Some privileged structural motifs of Dopamine D2 agonists... 

Fig. 12.5 Dopamine D2 agonists having a distinct N-arylpiperazine privileged motif and structurally different peripheral fragments.

Dopamine D2 agonists, Tachykinin NKl antagonists, al Adrenoceptor antagonists, PGE2 antagonists,... 

The dopamine D2 agonists bromocriptine and cabergoline (pp. 114, 188) inhibit prolactin-releasing AH cells (indications suppression of lactation, prolactin-producing tumors). Excessive, but not normal, growth hormone release can also be inhibited (indication acromegaly) (3). 

Maj J, Rogoz Z, Skuza G, et al Antidepressants given repeatedly increase the behavioural effect of dopamine D2 agonist. J Neural Transm 78 1-8, 1989 Maj J, Rogoz Z, Skuza G The effect of combined treatment with MK-801 and antidepressant drugs in the forced swimming test in rats. Polish Journal of Pharmacology and Pharmacy 44 217-226, 1992... 

Several of the compound types in this chapter have useful biological activities. This is not unexpected since many of those compounds which are effective in the modification of responses to bioamines are themselves organic bases. Quinelorane (114) which is a potent dopamine (D2) agonist has been patented as an antihypertensive and antiparkinsonism agent <85USP4501890>. 

Bowyer JF, Weiner N (1987) Modulation of the Ca++-evoked release of [3H]dopamine from striatal synaptosomes by dopamine (D2) agonists and antagonists. J Pharmacol Exp Ther 247 27-33. 

Von Euler G, Meister B, Hokfelt T, Eneroth P, Fuxe K (1990) Intraventricular injection of neurotensin reduces dopamine D2 agonist binding in rat forebrain and intermediate lobe of the pituitary gland. Relationship to serum hormone levels and nerve terminal coexistence. Brain Res 537 253-262. 

Kapoon R, Pirtosek Z, Frankel JP, Stern GM, Lees AJ, Bottomley JM, Haran NS. Treatment of Parkinson s disease with novel dopamine D2 agonist SK F 101468. Lancet 1989 l(8652) 1445-6. 

PJ Swart, WEM Oelen, AP Bruins, PG Tepper, RA de Zeeuw. Determination of the dopamine D2 agonist N-0923 and its major metabolites in perfused rat livers by HPLC-UV-atmospheric pressure ionization mass spectrometry. J Anal Toxicol 18 71, 1994. 

Fluorodediazoniation via thermal decomposition of arenediazonium hexafluorophosphateshas been used as an intermediate step in the preparation of interesting fluoroaromatics with biological activity, such as 4-(luororesoreinol (24),73 the dopamine D2 agonist 25.80 and naph-thyridinc 26, an immediate precursor of the antibacterial agent enoxacine.81... 

Inhibition of Forskolln-Stimulated Activation of Adenylate Cyclase -Inhibition of forskolin-stlmulated adenylate cyclase in membranes and cells has been observed with a2 80 l8ts In platelets, and adipocytes 36,64 muscarinic-cholinergic agonists In cardiac cells Aj -adenoslne agonists and insulin in rat adipocytes 35 somatostatin in S49 lymphoma cells29,66,67 pituitary and dopamine D2-agonists in pituitary.68 The Inhibition varies between 50 and 75%. 

The dopamine D2-agonist pramipexole 27 (Mirapex) contains a fused bicyclic tetrahydroben-zothiazole design, which is also easy to obtain by a Hantzsch-t)rpe condensation reaction between a a-brominated protected form of 4-aminocyclohexanone and thiourea [81]. 

Importantly, with REPLACE one can add new groups onto an atom. For example, if a particular type of carbon is identified as an attachment point for a Br, one would identify the carbon atom with GCL and replace the identified carbon atom with a carbon atom with an attached bromine REPLACE C(Br). The combination of MODHIT and REPLACE allows one to transform a hit atom in a molecule into the particular atom t3 e in a molecule to be suggested for synthesis. In the dopamine D2 agonist case, the identified aromatic atom would be transformed into into a carbon bearing an OH and the identified aliphatic atom an... 

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