Contraceptive progestagens

Petrow,

doi:10.1021/cr60268a004

Cited by 22 publications

(4 citation statements)

References 5 publications

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“…Ethinylestradiol, the first orally active synthetic steroidal estrogen, is one of the most commonly used medications in humans. It was synthesized in 1938 at Schering AG in Berlin by Hans Herloff Inhoffen and Walter Hohlweg [31]. In addition to oral contraception, EE2 is used for the treatment of menopausal and post-menopausal symptoms.…”

Section: Potential Explanations For the Increase In Asd Prevalencementioning

confidence: 99%

The link between oral contraceptive use and prevalence in autism spectrum disorder

Strifert

2014

Medical Hypotheses

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Autism spectrum disorder (ASD) is a group of developmental disabilities that include full syndrome autism, Asperger's syndrome, and other pervasive developmental disorders. The identified prevalence of ASD has increased in a short time period across multiple studies causing some to conclude that it has reached epidemic proportions in the U.S. Many possible explanations for the rise in numbers of individuals diagnosed with ASD have been offered and yet, causes and contributing factors for ASD are inadequately understood. Current evidence suggests that both genetics and environment play a part in causing ASD. One possible risk factor for the increase in prevalence has been profoundly overlooked in the existing biomedical and epidemiologic literature. As the prevalence of ASD has risen in the last sixty years, so has the prevalence of the usage of the oral contraceptives and other modern hormonal delivery methods. In 1960 about one million American women were using oral contraceptives, today close to 11 million women in the U.S. use oral contraceptives. Eighty-two percent of sexually active women in the U.S. have used oral contraceptives at some point during their reproductive years. Thus, the growth in use of progesterone/estrogen-based contraceptives in the United State has reached near-ubiquitous levels among women in the child-bearing age range. The suppression of ovulation produced by estrogen-progesterone is an indisputable abnormality. It is logical to consider the outcome of the ovum that would have been normally released from the ovary during ovulation. To date there is no comprehensive research into the potential neurodevelopmental effects of oral contraceptive use on progeny. The issue has been only sparsely considered in the biomedical literature. This article hypothesizes that the compounds, estrogen and progesterone, used in oral contraceptives modify the condition of the oocyte and give rise to a potent risk factor that helps explain the recent increase in the prevalence of ASD's. This hypothesis does not propose to delineate the cause of autism. Rather, it attempts to explain the recent dramatic increase in prevalence and point the way for further study that will lead to causal examination.

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Section: Potential Explanations For the Increase In Asd Prevalencementioning

confidence: 99%

The link between oral contraceptive use and prevalence in autism spectrum disorder

Strifert

2014

Medical Hypotheses

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“…Yellow crystals; yield: 0.47g (74%); mp 140-143 °C (dec) (CH 2 (14), 69 (41), 54 (10), no other peaks >10%.…”

Section: -Chloro-4-hydroxy-2-oxo-n-(3-phenylprop-2-ynoyl)-2h-pyran-3mentioning

confidence: 99%

Preparation of Arylpropynamides and Their Reaction with Malonyl Acid Derivatives

2013

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Synthesis of arylpropynamides and their reactions with different malonic acid derivatives is described. Treatment of arylpropynamides with unsubstituted malonyl chloride furnished N-(3-arylprop-2-ynoyl)-6-chloro-4-hydroxy-2-oxo-2H-pyran-3-carboxamides; monosubstituted malonyl chlorides or their derivatives, (chlorocarbonyl)ethylketenes, reacted with arylpropynamides to give 4-hydroxy-2-(phenylethynyl)-6H-1,3-oxazin-6-ones; and the reaction of arylpropynamides with disubstituted malonyl chlorides furnished open-chain arylpropenamides exclusively.In medicinal chemistry the alkyne group deserves particular interest because of its bioisosteric relationship to an aromatic system. In addition, the alkyne group can affect the pharmacological and pharmacokinetic properties of a drug molecule. 1 As an example, the acetylenic pharmacophore has been realized within steroids, 2 the antimycotic Terbinafin, 3 the non-nucleoside reverse transcriptase inhibitor Evafirenz and its derivatives, 4 and the MAO-inhibitors Selegeline and Rasagiline. 5 Furthermore, naturally occurring (poly)acetylenes were found to display interesting biological activity. 6 In recent years enediyne antibiotics, characterized by either nineand ten-membered rings containing two triple bonds separated by a double bond, have attracted considerable interest as novel antitumor agents. 7 The present work is aimed at the synthesis of novel and potentially bioactive alkyne-substituted 1,3-oxazines by the reaction of arylpropynamides 1 with malonyl chlorides or (chlorocarbonyl)ketenes. Cyclization of carboxamides with malonyl chlorides or (chlorocarbonyl)ketenes to 4-hydroxy-6H-1,3-oxazin-6-ones with different substituents at the 2-and 5-positions is a well-known reaction. 8 A single 4-hydroxy-5-phenyl-2-(phenylethynyl)-6H-1,3-oxazin-6-one (8e) was prepared by Komarov et al. from 3-phenylprop-2-ynamide and phenylmalonyl chloride in refluxing 1,2-dichloroethane. 8cHerein we describe the results from our studies directed to the reaction of arylpropynamides 1 with unsubstituted malonyl chloride, monosubstituted malonyl chlorides or (chlorocarbonyl)ketenes, and a disubstituted malonyl chloride.3-Phenylprop-2-ynamide (1a) was prepared in high yield according to literature procedures by the reaction of 3-phenylprop-2-ynoic acid ester with aqueous ammonia solution. 9 Following this procedure, the corresponding arylpropynamides 1b-e were obtained in good yields by ammonolysis of the crude arylpropynoic ethyl esters, which in turn resulted from esterification of the corresponding arylpropynoic acids with ethanol (Table 1). Unexpectedly, treatment of 1a-d with unsubstituted malonyl chloride 2 in diethyl ether or tetrahydrofuran under ice cooling did not deliver 4-hydroxy-2-(phenylethynyl)-6H-1,3-oxazin-6-ones of type 8 but N-(3-arylprop-2-ynoyl)-6-chloro-4-hydroxy-2-oxo-2H-pyran-3-carboxamides 5a-d, the formation of which can be explained according to Scheme 1: elimination of hydrogen chloride from malonyl chloride affords (chlorocarbonyl)ketene 3 that undergoes [4+2] cyc...

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“…This strategy can be observed in the development of sexual hormones with long-acting release during contraceptive therapy, hormonal replacement therapy or pregnancy (Petrow, 1970;Ghiselli, Jardim, 2007). The use of prodrug steroid hormones in therapy may also be applied to compounds that can be administered orally, thus increasing the absorption of the hormones.…”

Section: Steroid Hormonesmentioning

confidence: 99%

Prodrugs available on the Brazilian pharmaceutical market and their corresponding bioactivation pathways

Parise-Filho

Polli

Barberato‐Filho

et al. 2010

Braz. J. Pharm. Sci.

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The aim of this paper was to emphasize the importance of prodrug design to therapy, by examining examples available on the Brazilian pharmaceutical market. The principles of prodrug design are briefly discussed herein. Examples of prodrugs from many important therapeutic classes are shown and their advantages relative to the drugs they are derived from are also discussed. Considering the importance of these therapeutic classes, from both therapy and economic standpoints, prodrug design is a very valuable aspect in the research of new drugs and for the pharmaceutical industry as a whole.Uniterms: Prodrug design. Molecular modification. Drug development.O objetivo do trabalho foi ressaltar a importância do planejamento de pró-fármacos para a terapia, por meio de exemplos disponíveis no mercado farmacêutico brasileiro. Os princípios da latenciação são sucintamente discutidos. Apresentam-se exemplos de pró-fármacos de muitas classes terapêuticas importantes e as vantagens relativas aos fármacos dos quais derivam são, também, discutidas. Considerando-se a importância dessas classes terapêuticas, tanto do aspecto terapêutico quanto do econômico, o planejamento de pró-fármacos representa aspecto de grande valor na busca de novos fármacos e na indústria farmacêutica como um todo.Uniterms: Pró-fármacos/planejamento Fármacos/latenciação. Modificação molecular. Fármacos/ desenvolvimento.

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Contraceptive progestagens

Cited by 22 publications

References 5 publications

The link between oral contraceptive use and prevalence in autism spectrum disorder

The link between oral contraceptive use and prevalence in autism spectrum disorder

Preparation of Arylpropynamides and Their Reaction with Malonyl Acid Derivatives

Prodrugs available on the Brazilian pharmaceutical market and their corresponding bioactivation pathways

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