1516-32-1Relevant articles and documents
Potent gonadotropin releasing hormone antagonists with low histamine- releasing activity
Nestor Jr.,Tahilramani,Ho,Goodpasture,Vickery,Ferrandon
, p. 3942 - 3948 (1992)
The incorporation of Arg residues into position 6 of gonadotropin releasing hormone antagonists had resulted in compounds with increased in vivo potency but also made these analogues potent mast cell degranulators. We have focused on the substitution of position 8 by hArg(R)2 (N(G)-N(G)'- dialkylhomoarginine) substitutions, based on the hypotheses that the Arg-Pro sequence is of major importance for this side effect and that shielding of the charge may be an effective way to block degranulation. Analogues in four series were evaluated: (A) [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal- (3)3,6,Arg5,hArg(R)28,D-Ala10]GnRH, (B) [N-Ac-D-Nal(2)1,D-pCl- Phe2,D-Pal(3)3,6,hArg(R)25,8,D-Ala10]-GnRH, (C) [N-Ac-D-Nal(2)1,D- pCl-Phe2,D-Pal(3)3,6,hArg(R)28,D-Ala10]GnRH, (D) [N-Ac-D-Nal(2)1,D- pCl-Phe2,D-Pal(3)3,D-hArg(R)26,hArg(R)28,D-Ala10]GnRH. Although substitution by hArg(Et)2, hArg(Bu), hArg(CH2)3, and hArg(CH2CF3)2 was tested, in each series the hArg(Et)2 residue was superior. Two compounds were considered for clinical evaluation: [N-Ac-D-Nal(2)1,D-pCl-Phe2,D- Pal(3)3,6,hArg(Et)28,D-Ala10]GnRH and [N-Ac-D-Nal(2)1,D-pCl-Phe2,D- Pal(3)3,D-hArg(Et)26,hARg-(Et)28,D-Ala10]GnRH (ganirelix acetate). These compounds had high potency for ovulation suppression and low histamine- releasing potency in vitro (ED50 = 0.6, 0.29 μg/rat and EC50 = 196, 13 μg/mL, respectively). Ganirelix is currently in Phase II clinical trials and appears to be the most potent GnRH antagonist tested in humans (based upon ED50 for 24-h suppression of testosterone levels).
Cobalt-promoted one-pot reaction of isothiocyanates toward the synthesis of aryl/alkylcyanamides and substituted tetrazoles
Seelam, Mohan,Kammela, Prasada Rao,Shaikh, Bajivali,Tamminana, Ramana,Bogiri, Sujatha
, p. 535 - 544 (2018/07/05)
[Figure not available: see fulltext.] The synthesis of cyanamides and tetrazoles from isothiocyanates through tandem reaction using cobalt catalyst has been demonstrated. In the case of tetrazole preparation, the reaction involved addition/desulfurization/nucleophilic addition/electrocyclization, whereas aromatic cyanamides were constructed from isothiocyanates through addition/desulfurization. Cheap cobalt sulfate was used for the synthesis of various cyanamides and tetrazoles. In addition, cobalt catalyst was found to be desulfurization reagent that has not been previously reported. The final products have been obtained from starting precursors in good to high yield.
An efficient methodology for the synthesis of thioureas from amine mediated by a cobalt source
Seelam, Mohan,Shaikh, Baji Vali,Tamminana, Ramana,Kammela, Prasada Rao
supporting information, p. 5297 - 5300 (2016/11/11)
The cheap, readily available and air stable cobalt catalyst was used as the desulfurization agent for the conversion of aniline to thioureas in one pot three step reaction under mild reaction conditions. The reactions are rapid and facile and accomplished at room temperature.
