- Domino Aryne Annulation via a Nucleophilic-Ene Process
-
1,2-Benzdiyne equivalents possess the unique property that they can react with two arynophiles through iteratively generated 1,2- and 2,3-aryne intermediates. Upon rational modification on the second leaving group of these aryne precursors, a domino aryne annulation approach was developed through a nucleophilic-ene reaction sequence. Various benzo-fused N-heterocyclic frameworks were achievable under transition metal-free conditions with a broad substrate scope.
- Xu, Hai,He, Jia,Shi, Jiarong,Tan, Liang,Qiu, Dachuan,Luo, Xiaohua,Li, Yang
-
p. 3555 - 3559
(2018/03/21)
-
- A facile synthesis of the spiroindoline-based growth hormone secretagogue, MK-677
-
A facile and improved route for the synthesis of the orally active spiroindoline-based growth hormone secretagogue, MK-677 was described. The key step adopted the Fischer indole/reduction strategy. The preparation of the key intermediates N-protected piperidine carboxaldehyde 5 and the N-Boc-O-benzyl-d-serine (2) are also optimized.
- Qi, Xian Liang,Yang, Er Qun,Zhang, Jun Tao,Wang, Tao,Cao, Xiao Ping
-
p. 661 - 664
(2012/07/03)
-
- Polymorphic forms of a growth hormone secretagogue
-
This invention is concerned with polymorphic forms of the compound N-?1(R)-?(1,2-dihydro-1-methanesulfonylspiro?3H-indole-3,4'-piperdin!-1'-yl)carbonyl!-2-(phenylmethyloxy)ethyl!-2-amino-2-methylpropanamide methanesulfonate which is a growth hormone secretagogue that is useful in food animals to promote their growth thereby rendering the production of edible meat products more efficient, and in humans, to treat physiological or medical conditions characterized by a deficiency in growth hormone secretion, and to treat medical conditions which are improved by the anabolic effects of growth hormone. The instant polymorphic forms have advantages over the other known forms of N-?1(R)-?(1,2-dihydro-1-methanesulfonylspiro?3H-indole-3,4'-piperdin!-1'-yl)carbonyl!-2-(phenylmethyloxy)-ethyl!-2-amino-2-methylpropanamide methanesulfonate in terms of thermodynamic stability and suitability for inclusion in pharmaceutical formulations. The present invention is also concerned with processes for preparing these polymorphic forms, pharmaceutical formulations comprising these polymorphic forms as active ingredients and the use of the polymorphic form of the compound and their formulations in the treatment of certain disorders.
- -
-
-
- Synthesis of the orally active spiroindoline-based Growth Hormone Secretagogue, MK-677
-
The preparation of the Merck Growth Hormone Secretagogue; MK-677 is described. A Fischer indole/reduction based strategy provides the novel spiroindoline nucleus of this potent compound. This optimized sequence necessitates the isolation of only one intermediate 10 and provides MK-677 in 48% overall yield from isonipecotic acid 3.
- Maligres, Peter E.,Houpis, Ioannis,Rossen, Kai,Molina, Audrey,Sager, Jess,Upadhyay, Veena,Wells, Kenneth M.,Reamer, Robert A.,Lynch, Joseph E.,Askin, David,Volante,Reider, Paul J.,Houghton, Peter
-
p. 10983 - 10992
(2007/10/03)
-
- Spiro piperidines and homologs which promote release of growth hormone
-
There are disclosed certain novel compounds identified as spiro piperidines and homologs which promote the release of growth hormone in humans and animals. This property can be utilized to promote the growth of food animals to render the production of edible meat products more efficient, and in humans, to treat physiological or medical conditions characterized by a deficiency in growth hormone secretion, such as short stature in growth hormone deficient children, and to treat medical conditions which are improved by the anabolic effects of growth hormone. Growth hormone releasing compositions containing such spiro compounds as the active ingredient thereof are also disclosed.
- -
-
-
