Scaffold hopping of fused piperidine-type NK3 receptor antagonists to reduce environmental impact

被引：1

作者：

Yamamoto, Koki ^{[1
]}

Inuki, Shinsuke ^{[1
]}

Ohno, Hiroaki ^{[1
]}

Oishi, Shinya ^{[1
]}

机构：

[1] Kyoto Univ, Grad Sch Pharmaceut Sci, Sakyo Ku, Kyoto 6068501, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2019年 / 27卷 / 10期

关键词：

Environmental impact; Fezolinetant; GnRH; NK3; receptor; Scaffold hopping; WATER TREATMENT-PLANT; HUMAN NEUROKININ-3 RECEPTOR; PHARMACEUTICALS; KISSPEPTIN; SECRETION; HORMONES; FATE; GNRH; PHOTODEGRADATION; IDENTIFICATION;

D O I：

10.1016/j.bmc.2019.03.059

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Neurokinin-3 receptor (NK3R) plays a pivotal role in the release of gonadotropin-releasing hormone in the hypothalamus-pituitary-gonadal (HPG) axis. To develop novel NK3R antagonists with less environmental toxicity, a series of heterocyclic scaffolds for the triazolopiperazine substructure in an NK3R antagonist fezoli-netant were designed and synthesized. An isoxazolo[3,4-c]piperidine derivative exhibited moderate NK3R antagonistic activity and favorable properties that were decomposable under environmental conditions.

引用

页码：2019 / 2026

页数：8

共 45 条

[21] Virtual Screening to Identify Novel Antagonists for the G Protein-Coupled NK3 Receptor
Geldenhuys, Werner J.
Kuzenko, Stephanie R.
Simmons, Mark A.
JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (22) : 8080 - 8088
[22] Cardiovascular and behavioural effects of intracerebroventricularly administered tachykinin NK3 receptor antagonists in the conscious rat
Cellier, E
Barbot, L
Regoli, D
Couture, R
BRITISH JOURNAL OF PHARMACOLOGY, 1997, 122 (04) : 643 - 654
[23] Intraventricular injections of tachykinin NK3 receptor agonist reduce the gain of the baroreflex in unrestrained rats
Flynn, FW
EXPERIMENTAL NEUROLOGY, 2005, 193 (01) : 118 - 124
[24] Senktide-induced gerbil foot tapping behaviour is blocked by selective NK1 and NK3 receptor antagonists
Sundqvist, M.
Kristensson, E.
Adolfsson, R.
Leffler, A.
Ahlstedt, I.
Sigfridsson, K.
Jussila, R.
de Verdier, J.
Noven, A.
Johansson, A.
Pahlman, I.
von Mentzer, B.
Lindstrom, E.
NEUROPEPTIDES, 2008, 42 (04) : 479 - 480
[25] Senktide-induced gerbil foot tapping behaviour is blocked by selective tachykinin NK1 and NK3 receptor antagonists
Sundqvist, Monika
Kristensson, Elin
Adolfsson, Rebecka
Leffler, Agnes
Ahlstedt, Ingela
Engberg, Susanna
Drmota, Tomas
Sigfridsson, Kalle
Jussila, Rainer
De Verdier, Jennie
Noven, Anna
Johansson, Anders
Pahlman, Ingrid
von Mentzer, Bengt
Lindstrom, Erik
EUROPEAN JOURNAL OF PHARMACOLOGY, 2007, 577 (1-3) : 78 - 86
[26] NONPEPTIDE ANGIOTENSIN RECEPTOR ANTAGONISTS BIND TO TACHYKININ NK3 RECEPTORS OF RAT AND GUINEA-PIG BRAIN
CHRETIEN, L
GUILLEMETTE, G
REGOLI, D
EUROPEAN JOURNAL OF PHARMACOLOGY, 1994, 256 (01) : 73 - 78
[27] ASSESSMENT OF NEONATAL VENTRAL HIPPOCAMPAL LESIONED GERBILS AS A METHOD TO EVALUATE THE THERAPEUTIC POTENTIAL OF NK3 RECEPTOR ANTAGONISTS
Durkin, S.
Jacquet, A.
Risterucci, C.
Pouzet, B.
Ballard, T. M.
Spooren, W.
JOURNAL OF PSYCHOPHARMACOLOGY, 2010, 24 : A46 - A46
[28] Use of a dipeptide chemical library in the development of non-peptide tachykinin NK3 receptor selective antagonists
Boden, P
Eden, JM
Hodgson, J
Horwell, DC
Hughes, J
McKnight, AT
Lewthwaite, RA
Pritchard, MC
Raphy, J
Meecham, K
Ratcliffe, GS
SumanChauhan, N
Woodruff, GN
JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (08) : 1664 - 1675
[29] Preclinical investigation of the antipsychotic-like effect of NK3 receptor antagonists versus marketed antipsychotics in gerbils
Pouzet, B
Moller, NS
JOURNAL OF PSYCHOPHARMACOLOGY, 2003, 17 (03) : A46 - A46
[30] Comparison of selective neurokinin receptor antagonists (NK1, NK2, NK3) and mixed profile antagonists (NK1/2, NK1/2/3) in a model of visceral hypersensitivity in rats
Reiche, Dania
Jasserand, Daniel
Sann, Holger
Preuschoff, Ulf
Antel, Jochen
GASTROENTEROLOGY, 2006, 130 (04) : A338 - A338

← 1 2 3 4 5 →