Synthesis of the orally active spiroindoline-based growth hormone secretagogue, MK-677

被引：52

作者：

Maligres, PE ^{[1
]}

Houpis, I ^{[1
]}

Rossen, K ^{[1
]}

Molina, A ^{[1
]}

Sager, J ^{[1
]}

Upadhyay, V ^{[1
]}

Wells, KM ^{[1
]}

Reamer, RA ^{[1
]}

Lynch, JE ^{[1
]}

Askin, D ^{[1
]}

Volante, RP ^{[1
]}

Reider, PJ ^{[1
]}

Houghton, P ^{[1
]}

机构：

[1] MERCK & CO INC,MERCK RES LABS,DEVLAB,HODDESDON EN11 9BU,HERTS,ENGLAND

来源：

TETRAHEDRON | 1997年 / 53卷 / 32期

关键词：

Fischer indole; growth hormone secretagogue; MK-677; Rosenmund; spiroindoline;

D O I：

10.1016/S0040-4020(97)00359-1

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

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. (C) 1997 Elsevier Science Ltd.

引用

页码：10983 / 10992

页数：10

共 28 条

[1] NEUROENDOCRINE RESPONSES TO A NOVEL GROWTH-HORMONE SECRETAGOGUE, L-692,429, IN HEALTHY OLDER SUBJECTS [J].

ALOI, JA ;

GERTZ, BJ ;

HARTMAN, ML ;

HUHN, WC ;

PEZZOLI, SS ;

WITTREICH, JM ;

KRUPA, DA ;

THORNER, MO .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1994, 79 (04) :943-949

[2] SYNTHESIS OF 1-CARBETHOXY-4-CYANO-4-PHENYLPIPERIDINE [J].

BERCZ, CV ;

ICE, RD .

JOURNAL OF PHARMACEUTICAL SCIENCES, 1972, 61 (08) :1316-&

[3]

CHEN ST, 1989, SYNTHESIS-STUTTGART, P36

[4]

GANESAN A, 1993, TETRAHEDRON LETT, V34, P439

[5] GROWTH-HORMONE RESPONSE IN MAN TO L-692,429, A NOVEL NONPEPTIDE MIMIC OF GROWTH HORMONE-RELEASING PEPTIDE-6 [J].

GERTZ, BJ ;

BARRETT, JS ;

EISENHANDLER, R ;

KRUPA, DA ;

WITTREICH, JM ;

SEIBOLD, JR ;

SCHNEIDER, SH .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1993, 77 (05) :1393-1397

[6] L-692,429, A NONPEPTIDE GROWTH-HORMONE (GH) SECRETAGOGUE, REVERSES GLUCOCORTICOID SUPPRESSION OF GH SECRETION [J].

GERTZ, BJ ;

SCIBERRAS, DG ;

YOGENDRAN, L ;

CHRISTIE, K ;

BADOR, K ;

KRUPA, D ;

WITTREICH, JM ;

JAMES, I .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1994, 79 (03) :745-749

[7]

GRIBBLE GW, 1994, CONTEMP ORG SYNTH, P145

[8] SYNTHESIS OF SOME PEPTIDES RELATED TO ACTIVE SITE OF ENZYMES [J].

HAYAKAWA, T ;

HARADA, K ;

FOX, SW .

BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, 1966, 39 (02) :391-+

[9]

Heacock R.A., 1969, ADV HETEROCYCL CHEM, V10, P43

[10] O-BENZYL-N-TERT-BUTYLOXYCARBONYL-L-SERINE [J].

HRUBY, VJ ;

EHLER, KW .

JOURNAL OF ORGANIC CHEMISTRY, 1970, 35 (05) :1690-&

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