quinagolide

A very short stereoselective synthesis of enantiomerically pure (3 S , 4a S , 10a R ) - quinagolide has been developed. The key steps involved are a copper-catalyzed regioselective arylation of ( S )-epichlorohydrin with 1,6-dimethoxynaphthalene and a diastereoselective trans -reduction of a cyclic enamine intermediate. The possibility to use both enantiomers of epichlorohydrin and the diastereodivergency found in the reduction process paves the way for a general preparation also in the nonracemic form of chiral trans- fused 3-substituted octahydrobenzo[ g ]quinolines that are privileged structures in medicinal chemistry...

The stereoselective reduction of a diastereoisomeric mixture of benzo[ g ]octahydroquinolinium ion was examined in detail. A diastereoselective borohydride reduction in combination with an efficient deacylative enzymatic resolution of its β-aminoester precursor are the key steps for a stereoselective installation of the three chiral centres present in the (3 S ,4a S ,10a R )-eutomer of the medicinal drug quinagolide. The obtained data paves the way for an easy and practical attainment of chiral 3-substituted octahydrobenzo[ g ]quinolines that are privileged structures in medicinal chemistry...

Endometriosis is one of the most common benign gynecological disorders in reproductive-aged women. The major symptoms are chronic pelvic pain and infertility. Despite its profound impact on women's health and quality of life, its pathogenesis has not been fully elucidated, it cannot be cured and the long-term use of drugs yields severe side effects and hinders fertility. This review aims to present the advances in pathogenesis and the newly reported lead compounds and drugs managing endometriosis. This paper investigated Genetic changes, estrogen-dependent inflammation induction, progesterone resistance, imbalance in proliferation and apoptosis, angiogenesis, lymphangiogenesis and neurogenesis, and tissue remodeling in its pathogenesis; and explored the pharmacological mechanisms, constitutive relationships, and application prospects of each compound in the text...

BACKGROUND: Resistance to dopamine agonists is not uncommonly seen in prolactinomas. However, development of resistance to dopamine agonists after an initial period of robust treatment response is rare, and only 39 cases have been reported in the past four decades. We describe a Chinese man with this rare condition and explored the postulated mechanisms that may explain this phenomenon. We compiled similar cases that were previously reported and compared their etiology, progress, and response to treatment...

PURPOSE: Three dopamine agonists [bromocriptine, cabergoline, and quinagolide (CV)] have been used for hyperprolactinemia treatment for decades. Several studies have reviewed the efficacy and safety of bromocriptine and cabergoline. However, no systematic review or meta-analysis has discussed the efficacy and safety of CV in hyperprolactinemia and prolactinoma treatment. METHODS: Five medical databases (PubMed, Web of Science, Embase, Scopus, and Cochrane Library) were searched up to 9 May 2022 to identify studies related to CV and hyperprolactinemia...

Objective: The aim of this systematic review is to recap the data obtained from randomized controlled trials looking at new pharmacologic treatments for endometriosis published over the last decade with a focus on non-hormonal therapeutic options alleviating endometriosis-associated pelvic pain. Methods: We identified relevant original studies in the English language through a search of the MEDLINE, Scopus, and EMBASE (2012 to present) databases using the appropriate MeSH terms and applying the article type filter 'randomized controlled trials'...

Dopamine agonists (DAs) represent a mainstay of therapy for hyperprolactinemia and prolactinomas. The widespread use of DAs, including bromocriptine, cabergoline and (in some countries) quinagolide, has led to the emergence and recognition of impulse control disorders (ICDs) that may occur in association with DA therapy.Such ICDs include pathological gambling, compulsive shopping, hypersexuality and punding (the performance of repetitive tasks), among others. These manifestations can lead to substantial harms to patients and their families, if left undiagnosed and untreated...

The diastereoselective formal synthesis of (-)-quinagolide, a D2 receptor agonist, has been achieved. The synthesis started from l-pyroglutamic acid and relied on utilization of (a) a stereospecific catalytic hydrogenation and diastereoselective Horner-Emmons-Michael cascade to obtain functionalized prolinate, (b) a Lewis acid mediated Pummerer cyclization to construct a tricyclic fused ring system, and (c) a diastereoselective ring expansion via a bicyclic aziridinium intermediate to access the required 3-substituted piperidine scaffold...

WHAT IS KNOWN AND OBJECTIVE: Hyperprolactinemia is a neuroendocrine disease that is responsible for a quarter of cases of secondary amenorrhea, which can lead to infertility in women. Dopaminergic agonists (bromocriptine, cabergoline, quinagolide) can be used in the treatment. However, there is a lack of secondary studies that compare their efficacy and safety, especially through a network meta-analysis. Thus, to contribute to the decision-making, a systematic review and network meta-analyses (NMA) were performed to evaluate the efficacy and safety of dopaminergic agonists in the treatment of hyperprolactinemia...

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a potentially serious complication of ovarian stimulation in assisted reproduction technology (ART). It is characterised by enlarged ovaries and an acute fluid shift from the intravascular space to the third space, resulting in bloating, increased risk of venous thromboembolism, and decreased organ perfusion. Most cases are mild, but forms of moderate or severe OHSS appear in 3% to 8% of in vitro fertilisation (IVF) cycles. Dopamine agonists were introduced as a secondary prevention intervention for OHSS in women at high risk of OHSS undergoing ART treatment...

Endometriosis requires medical management during a woman's reproductive years. Most treatments aim to create a hypoestrogenic milieu, but for patients wishing to conceive, drugs that allow normal ovarian function are needed. Targeting angiogenesis, a hallmark of the disease, using dopamine agonists (DAs) is a promising strategy for endometriosis treatment. Herein, we review experimental and clinical data that investigate this concept. In experimental models of endometriosis, DAs (bromocriptine, cabergoline, quinagolide) downregulate proangiogenic and upregulate antiangiogenic pathways in inflammatory, endothelial and endometrial cells, blocking cellular proliferation and reducing lesion size...

Unprotected, primary 2-azidoamines are versatile precursors to vicinal diamines, which are among the most common motifs in biologically active compounds. Herein, we report their operationally simple synthesis through an iron-catalyzed difunctionalization of alkenes. A wide array of alkene substrates are tolerated, including complex drug-like molecules and a tripeptide. Facile derivatizations of the azidoamine group demonstrate the versatility of this masked diamine motif in chemoselective, orthogonal transformations...

OBJECTIVE: Endometriosis is a common gynecologic disease that frequently leading to chronic pelvic pain, severe dysmenorrhea, and subfertility. As first-line hormonal treatment can interfere with ovulation and may cause recurrent pelvic pain, exploration of new non-hormonal therapeutic approaches becomes increasingly necessary. This review aimed to evaluate the pre-clinical and clinical efficacy and safety of non-hormonal treatment for endometriosis DATA SOURCES:: Databases including PubMed, Embase, Cochrane Library, SINOMED, ClinicalTrials...

BACKGROUND: The negative symptoms of schizophrenia pose a heavy burden on patients and relatives and represent an unmet therapeutic need. The observed association of negative symptoms with impaired reward system function has stimulated research on prodopaminergic agents as potential adjunctive treatments. METHODS: We conducted a systematic review and meta-analysis of published randomized controlled trials of amphetamine, methylphenidate, modafinil, armodafinil, lisdexamphetamine, L-dopa, levodopa, bromocriptine, cabergoline, quinagolide, lisuride, pergolide, apomorphine, ropinirole, pramipexole, piribedil, and rotigotine augmentation in schizophrenia and schizoaffective disorder...

The enantioselective formal total synthesis of (-)-quinagolide has been accomplished in a linear sequence of 8 purification steps from pyridine. The key steps are (a) organocatalyzed Diels-Alder reaction for fixing all three stereocenters on piperidine ring; (b) protecting group enabled deoxygenation of isoquinuclidine skeleton under Birch reduction condition; (c) Lewis acid (TiCl4 ) catalyzed intramolecular Friedel-Crafts cyclization of dicarboxylic acid; and (d) one-pot diastereoselective ketone reduction-intramolecular cyclization to form oxazolidinone which enables trans -geometry installation...

A potent dopamine (D2 ) receptor agonist (±)-quinagolide, which is used for the treatment of hyperprolactinemia, was synthesized using the ring closing metathesis (RCM) approach from meta -hydroxybenzaldehyde as the starting material. The key features of this synthesis are pyrolytic elimination, late-stage expedient synthesis of functionalized trans-fused tetrahydropyridine-3-carboxylates from olefin 6 , via conjugate addition-elimination upon acetate 11 , followed by RCM and phenyliodine bis(trifluoroacetate) (PIFA)-mediated Hofmann rearrangement of piperidine-3-carboxamide, which enables the synthesis of 3-aminopiperidine skeleton of quinagolide...

Accumulating evidence supports that the hormone prolactin (PRL) is galactopoietic in dairy ruminants. Accordingly, the inhibition of PRL secretion by the dopamine agonists quinagolide and cabergoline causes a sharp decline in milk production and could be useful in several critical periods. First, PRL inhibition may reduce the incidence during the periparturient period of metabolic disorders caused by the abrupt increase in energy demand for milk production. Metabolic disturbances can be lessened by reducing milk output by milking once a day or incompletely in the first few days of lactation...

Background: The aim of the current study is to compare quinagolide with cabergoline in prevention of ovarian hyperstimulation syndrome (OHSS) among high risk women undergoing intracytoplasmic sperm injection (ICSI). MATERIALS AND METHODS: This randomized clinical trial study was performed from March 2015 to February 2017. One hundred and twenty six women undergoing ICSI who were at high risk of developing OHSS (having over 20 follicles of >12 mm), were randomized into two groups...

The objective of this study was to determine whether the responsiveness of the mammary gland to prolactin (PRL) is affected by the concentration of the hormone. After 1 pre-experimental week (d -7 to -1), 18 Holstein cows in mid to late lactation were injected intramuscularly twice daily with either 0.5 mg of quinagolide (QN) or 2 mL of water (control) for 2 wk (d 1 to 14; treatment period). After the treatment period, all cows received daily subcutaneous injections of 300 mg of domperidone (DOMP) for 3 wk (d 15 to 35; DOMP period)...

The purpose of this review is to analyze current medical strategies in the prevention of ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation for in vitro fertilization. Owing to contemporary preventive measures of OHSS, the incidence of moderate and severe forms of the syndrome varies between 0.18% and 1.40%. Although none of medical strategies is completely effective, there is high-quality evidence that replacing human chorionic gonadotropin (hCG) by gonadotropin-releasing hormone (GnRH) agonists after GnRH antagonists and moderate- quality evidence that GnRH antagonist protocols, dopamine agonists and mild protocols reduce the occurrence of OHSS...