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2.
Expert Opin Ther Pat ; 29(10): 817-827, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31573364

RESUMO

Introduction: Glaucoma is a group of progressive optic neuropathies in which elevated intraocular pressure (IOP) as a consequence of an increased aqueous humor (AH) outflow resistance, is the main and only clinically modifiable risk factor for its development and progression. Relaxing Trabecular meshwork (TM) tissue, Rho-Kinase (ROCK) inhibitors directly decrease resistance in the conventional AH outflow, thus resulting in a significant IOP-lowering effect. Areas covered: The progress made in the field of ROCK inhibitors for glaucoma treatment will be discussed, referring to the recent patent literature published mainly in the last 3 years. Development and last studies conducted on the recently approved ripasudil and netarsudil will be described, along with newly reported combinations with other antiglaucoma agents. New molecular entities as ROCK inhibitors will be reported as well as new biological approaches to affect the Rho/ROCK pathway. Expert opinion: With three drugs currently available on the market belonging to this class, ROCK inhibitors have been definitely validated as therapeutic agents for glaucoma treatment. The literature of the last 3 years confirmed the success of the soft-drug and bis-functional approaches in the design of ROCK inhibitors. However, few completely new molecular scaffolds have been reported.


Assuntos
Glaucoma/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Quinases Associadas a rho/antagonistas & inibidores , Animais , Progressão da Doença , Desenvolvimento de Medicamentos , Glaucoma/enzimologia , Humanos , Pressão Intraocular/efeitos dos fármacos , Patentes como Assunto , Inibidores de Proteínas Quinases/administração & dosagem , Quinases Associadas a rho/metabolismo
3.
Expert Opin Ther Pat ; 29(10): 781-792, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31596641

RESUMO

Introduction: Glaucoma affects more than 70 million people worldwide. One of the major therapeutic options for its management is based on the inhibition of the metalloenzyme carbonic anhydrases (CAs, EC 4.2.1.1). CA inhibitors (CAIs) diminish ocular hypertension in glaucomatous patients by reducing the rate of bicarbonate formation and thus, the secretion of the aqueous humor. Areas covered: This review is intended to cover the major contributions in terms of patent literature reports for the treatment of ophthalmic diseases by means of CAIs in a time frame spanning from 2013 to date. Expert opinion: The patent literature is dominated by innovative pharmaceutical formulations including a CAI alone or in combination with other therapeutic agents. Very few novelties within drug discovery are currently present and they mainly account for new CAI moieties and classical CAIs merged into scaffolds bearing additional chemical functionalities beneficial for the pharmacological treatment of the disease. It is reasonable to expect that in the near future the so-called 'old drugs' will achieve pharmacological performances in the management of ocular hypertension beyond any expectations and thus open a new era of drug repurposing merely based on material science advancements.


Assuntos
Inibidores da Anidrase Carbônica/administração & dosagem , Glaucoma/tratamento farmacológico , Hipertensão Ocular/tratamento farmacológico , Animais , Inibidores da Anidrase Carbônica/farmacologia , Anidrases Carbônicas/efeitos dos fármacos , Anidrases Carbônicas/metabolismo , Desenho de Drogas , Reposicionamento de Medicamentos , Glaucoma/enzimologia , Humanos , Hipertensão Ocular/enzimologia , Patentes como Assunto
4.
Expert Opin Ther Pat ; 29(11): 909-919, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31566022

RESUMO

Introduction: Myeloid cell leukemia-1 (MCL-1) is an anti-apoptotic member of the B-cell lymphoma-2 (BCL-2) family of proteins that regulates apoptosis. Elevated levels of MCL-1 contribute to tumorigenesis and resistance, not only to conventional chemotherapies but also to targeted therapies, including the BCL-2 selective inhibitor venetoclax. Accordingly, researchers in both the pharmaceutical industry and academia have been actively seeking MCL-1 inhibitors in the quest for new anti-cancer drugs. Areas covered: This review covers the patent literature on the discovery and development of small-molecule inhibitors of MCL-1 since 2017. Expert opinion: Pharmacologic inhibition of MCL-1's oncogenic activity has certainly come of age with the discovery of numerous inhibitors spanning a variety of chemotypes that selectively inhibit MCL-1 in the picomolar range and with on-target cell activity. Furthermore, seminal research by Servier has demonstrated for the first time that MCL-1 inhibition is tolerable in animal models of cancer, paving the way for the six Phase 1 clinical trials that are currently underway for hematological malignancies, among other cancers. After more than a decade of research, the hurdles and obstacles are mostly behind us, and uncovering the therapeutic impact of disrupting the protein-protein interactions of MCL-1 in humans is imminent.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Proteína de Sequência 1 de Leucemia de Células Mieloides/antagonistas & inibidores , Animais , Descoberta de Drogas/métodos , Humanos , Terapia de Alvo Molecular , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Patentes como Assunto
5.
Expert Opin Ther Pat ; 29(11): 871-879, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31593642

RESUMO

Introduction: Human urate transporter 1 (URAT1), which is an influx transporter protein, is located at the apical surface of renal tubular cells and presumed to be the major transporter responsible for the reabsorption of urate from blood. About 90% of patients develop hyperuricemia due to insufficient urate excretion; thus, it is important to develop URAT1 inhibitors that could enhance renal urate excretion by blocking the reabsorption of urate anion. Areas covered: In this review, the authors addressed the patent applications (2016-2019) about URAT1 inhibitors and some medicinal chemistry strategies employed in these patents. Expert opinion: Substituent decorating, bioisosterism, and scaffold hopping are three common medicinal chemistry strategies used in the discovery of URAT1 inhibitors. Meanwhile, the introduction of sulfonyl group into small molecules has become one of the important strategies for structural optimization of URAT1 inhibitors. Furthermore, developing drug candidates targeting both URAT1 and xanthine oxidase (XOD) has attracted lots of interest and attention.


Assuntos
Desenvolvimento de Medicamentos/métodos , Hiperuricemia/tratamento farmacológico , Transportadores de Ânions Orgânicos/antagonistas & inibidores , Proteínas de Transporte de Cátions Orgânicos/antagonistas & inibidores , Animais , Humanos , Hiperuricemia/fisiopatologia , Patentes como Assunto , Ácido Úrico/metabolismo , Xantina Oxidase/antagonistas & inibidores
6.
Expert Opin Ther Pat ; 29(11): 891-907, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31603360

RESUMO

Introduction: Pharmacotherapy is limited by the inefficient drug targeting of non-healthy cells/tissues. In this pharmacological landscape, liposomes are contributing to the impulse given by Nanotechnology to optimize drug therapy. Areas covered: The analysis of the state-of-the-art in liposomal formulations for drug delivery purposes have underlined that lately published patents (since 2014) are exploring alternative compositions and ways to optimize the stability and drug loading content/release profile. These improvements are complemented by improved long-circulating structures and further liposome functionalizations, which have definitively opened the road for the (co-)delivery of therapeutics to the site of action. Liposomes are also contributing to new drug delivery approaches involving the generation of extracellular vesicles by targeted cells, while opening new ways to combine disease diagnosis and therapy (theranosis). Expert opinion: Patent publications on liposomal formulations have expanded new ways in drug delivery. New lipid compositions and strategies to optimize stability and drug vehiculization capabilities have settle solid pillars in liposome fabrication. Despite, their architecture has been satisfactorily adapted for combining passive and active drug targeting concepts, new inputs of liposomes into the disease arena should answer for: a simple/scalable/cost-effective formulation; a safe/stable/controllable formulation meeting quality control regulations; and, a confirmed therapeutic efficiency in clinical investigations.


Assuntos
Química Farmacêutica/métodos , Sistemas de Liberação de Medicamentos , Lipídeos/química , Animais , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Humanos , Lipossomos , Nanotecnologia/métodos , Patentes como Assunto
7.
BMJ ; 367: l5766, 2019 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-31645328

RESUMO

OBJECTIVE: To determine the extent to which late stage development of new drugs relies on support from public funding. DESIGN: Cohort study. SETTING: All new drugs containing one or more new molecular entities approved by the US Food and Drug Administration (FDA) between January 2008 and December 2017 via the new drug application pathway. MAIN OUTCOME MEASURES: Patents or drug development histories documenting late stage research contributions by a public sector research institution or a spin-off company, as well as each drug's regulatory approval pathway and first-in-class designation. RESULTS: Over the 10 year study period, the FDA approved 248 drugs containing one or more new molecular entities. Of these drugs, 48 (19%) had origins in publicly supported research and development and 14 (6%) originated in companies spun off from a publicly supported research program. Drugs in these groups were more likely to receive expedited FDA approval (68% v 47%, P=0.005) or be designated first in class (45% v 26%, P=0.007), indicating therapeutic importance. CONCLUSIONS: A review of the patents associated with new drugs approved over the past decade indicates that publicly supported research had a major role in the late stage development of at least one in four new drugs, either through direct funding of late stage research or through spin-off companies created from public sector research institutions. These findings could have implications for policy makers in determining fair prices and revenue flows for these products.


Assuntos
Ensaios Clínicos como Assunto/economia , Aprovação de Drogas/economia , Setor Público/economia , Pesquisa Médica Translacional/economia , Ensaios Clínicos como Assunto/estatística & dados numéricos , Estudos de Coortes , Aprovação de Drogas/legislação & jurisprudência , Aprovação de Drogas/estatística & dados numéricos , Humanos , Patentes como Assunto/estatística & dados numéricos , Setor Público/estatística & dados numéricos , Pesquisa Médica Translacional/estatística & dados numéricos , Estados Unidos , United States Food and Drug Administration/legislação & jurisprudência , United States Food and Drug Administration/estatística & dados numéricos
9.
Expert Opin Ther Pat ; 29(10): 805-815, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31486689

RESUMO

Introduction: Glaucoma is a neurodegenerative disease of the eye characterized by selective retinal ganglion cell loss that provokes progressive defects in the visual field. Elevated intraocular pressure (IOP) is an important contributor for the progression of glaucoma. The current therapeutic arsenal for reducing IOP includes prostaglandin analogs, ß-blockers, carbonic anhydrase inhibitors, α-adrenergic agonist, miotics, rho-kinase inhibitors and combinations thereof, generally administered as eye drops. Areas covered: This manuscript reviews the state of art on adrenergic modulators for treating glaucoma. Both monotherapy and fixed-drugs combinations including α2-adrenergic agonists and ß-blockers are discussed as well as drug delivery systems where these classes of drugs are used. The review then covers the patent literature involving adrenoceptors modulators over the period 2013-2019. Expert opinion: While the scientific community is moving forward novel targets and related modulators for treating glaucoma and ocular hypertension, adrenergic modulators held a prominent position in the therapy of glaucoma and related disorders. Indeed, though not embodying anymore the first-choice monotherapy, they are widely marketed worldwide ordinarily in combination with other drugs, are subjects of many studies for identifying new drug compositions and have been assessed as active ingredients in several innovative ocular drug delivery systems.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Antagonistas Adrenérgicos beta/administração & dosagem , Glaucoma/tratamento farmacológico , Antagonistas Adrenérgicos beta/farmacologia , Animais , Combinação de Medicamentos , Sistemas de Liberação de Medicamentos , Desenho de Drogas , Glaucoma/fisiopatologia , Humanos , Pressão Intraocular/efeitos dos fármacos , Hipertensão Ocular/tratamento farmacológico , Patentes como Assunto
10.
Expert Opin Ther Pat ; 29(10): 829-839, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31510806

RESUMO

Introduction: Glaucoma, a leading cause of irreversible blindness worldwide, is commonly diagnosed solely in advanced stages of the disease when important and irreversible losses of visual field have already occurred. The identification of effective biomarkers and methods for diagnostic purposes are main interests of the scientific community. Areas covered: This review presents an overview of the current diagnostic methods used for glaucoma and introduces the areas where new efforts are being done for the identification of more sensitive and specific biomarkers. The review then covers the patent literature of the period 2013-2019 regarding diagnostic approaches and biomarkers of glaucoma and the claimed methods for their qualitative and/or quantitative analysis. Expert opinion: In the absence of treatment, glaucoma can cause blindness in a few years. Early diagnostic tools are urgently needed, as this disease incidence is deemed to rapidly increase in the next decades. The current diagnosis of glaucoma, which is based on specific signs of the disease, such as high intraocular pressure, specific optic nerve head changes and visual field loss, is not enough anymore. Molecular genetics represents the area where most efforts are currently made to improve the early detection and monitoring of the disease progression.


Assuntos
Biomarcadores/metabolismo , Glaucoma/diagnóstico , Biologia Molecular/métodos , Animais , Progressão da Doença , Diagnóstico Precoce , Glaucoma/fisiopatologia , Humanos , Pressão Intraocular/fisiologia , Patentes como Assunto , Testes de Campo Visual
11.
Expert Opin Ther Pat ; 29(10): 761-767, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31540558

RESUMO

Introduction: Macular degeneration (MD) and macular edema (ME) are ophthalmologic diseases affecting an increasing number of the aging population. Until recently, there were few therapeutic options for both conditions but the last two decades saw important advances. Areas covered: This review summarizes the agents used for the treatment of age-related MD (AMD), which include verteporfin, for photodynamic therapy, and anti-VEGF agents, the aptamer pegaptanib, the monoclonal antibodies (MAbs) ranibizumab (Lucentis®) and bevacizumab (Avastin®) and the fusion protein aflibercept (Eylea®). All these drugs are effective only for the wet form of AMD, whereas for the dry form there is no treatment available. ME is, on the other hand, treated with nonsteroidal anti-inflammatory drugs and carbonic anhydrase (CA) inhibitors. Recently, MAbs such as ranibizumab and bevacizumab were also shown to be effective for the management of the cystoid and diabetic ME. Expert opinion: There are important advances made in the field in the last years but longer-acting anti-VEGF agents or drugs with less ocular side effects are needed. Many such agents are in clinical development.


Assuntos
Desenvolvimento de Medicamentos , Degeneração Macular/tratamento farmacológico , Edema Macular/tratamento farmacológico , Idoso , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/farmacologia , Animais , Humanos , Degeneração Macular/fisiopatologia , Degeneração Macular/prevenção & controle , Edema Macular/fisiopatologia , Edema Macular/prevenção & controle , Patentes como Assunto , Fotoquimioterapia/métodos
13.
Expert Opin Ther Pat ; 29(11): 881-889, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31530116

RESUMO

Introduction: A multitude of cellular and physiological functions have been attributed to the biological activity of PTEN (Phosphatase and tensin homolog) such as inhibiting angiogenesis, promoting apoptosis, preventing cell proliferation, and maintaining cellular homeostasis. Based on whether cell growth is needed to be initiated or to be inhibited, enhancing PTEN expression or seeking to inhibit it was pursued. Areas covered: Here the authors provide recent updates to their previous publication on 'PTEN modulators: A patent review', and discuss on new specificities that affirm the therapeutic potential of PTEN in promoting neuro-regeneration, stem cell regeneration, autophagy, bone and cartilage regeneration. Also, targeting PTEN appears to be effective in developing new treatment strategies for Parkinson's disease, Alzheimer's disease, macular degeneration, immune disorders, asthma, arthritis, lupus, Crohn's disease, and several cancer types. Expert opinion: PTEN mainly inhibits the PI3k/Akt pathway. However, the PI3k/Akt pathway can be activated by other signaling proteins. Thus, novel treatment strategies that can regulate PTEN alone, or combinational treatment approaches that can induce PTEN and simultaneously affect downstream mediators in the PI3K/Akt pathway, are needed, which were not investigated in detail. Commercial interests associated with molecules that regulate PTEN are discussed here, along with limitations and new possibilities to improve them.


Assuntos
Desenvolvimento de Medicamentos/métodos , PTEN Fosfo-Hidrolase/efeitos dos fármacos , Animais , Humanos , PTEN Fosfo-Hidrolase/metabolismo , Patentes como Assunto , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
14.
Expert Opin Ther Pat ; 29(11): 841-870, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31560232

RESUMO

Introduction: Benzofuran is a fundamental unit in numerous bioactive heterocycles. They have attracted chemists and medical researchers due to their broad range of biological activity, where some of them possess unique anticancer, antitubercular, antidiabetic, anti-Alzheimer and anti-inflammatory properties. The benzofuran nucleus is present in a huge number of bioactive natural and synthetic compounds. Benzofuran derivatives have potent applications in pharmaceuticals, agriculture, and polymers. The recent developments considering the biological activities of benzofuran compounds are reported. They have a vital role as pronounced inhibitors against a number of diseases, viruses, fungus, microbes, and enzymes. Areas covered: This review covers the recent developments of biological activities of benzofurans during the period 2014-2019. The covered areas here comprised antimicrobial, anti-inflammatory, antitumor, antitubercular, antidiabetic, anti-Alzheimer, antioxidant, antiviral, vasorelaxant, anti-osteoporotic and enzyme inhibitory activities. Expert opinion: In addition to the already commercialized 34 benzofurans-based drugs in the market, this chapter outlines several potent benzofuran derivatives that may be useful as potential pro-drugs. It is also focused on providing details of SAR and the effect of certain functional groups on the activity of the benzofuran compounds. The presence of -OH, -OMe, sulfonamide, or halogen contributed greatly to increasing the therapeutic activities comparing with reference drugs.


Assuntos
Benzofuranos/farmacologia , Desenho de Drogas , Animais , Benzofuranos/química , Humanos , Patentes como Assunto , Pró-Fármacos , Relação Estrutura-Atividade
16.
Expert Opin Ther Pat ; 29(10): 769-780, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31385719

RESUMO

Introduction: Glaucoma is one of the main leading causes of irreversible blindness in the world. The treatment of this disease relies on the use of drugs able to reduce/control the intraocular pressure (IOP), one of the main risk factors for glaucoma. Current therapies are based on the use of compounds belonging to well-established categories (prostaglandin analogs, ß-adrenergic blockers, α-adrenergic agonists, carbonic anhydrase inhibitors, Rho kinase inhibitors, and cholinergic agonists). However, even if they are effective in reducing IOP, important side effects impair patient compliance, accounting for the necessity of novel therapy approaches. Therefore, new targets are emerging as alternative and more complete routes to fight glaucoma disease. Areas covered: This review provides a comprehensive update on the development state of innovative strategies against glaucoma describing results, administration routes, pharmaceutical compositions, structures, and SARs as well as the related shortcomings within the 2013-2019 range. Expert opinion: New innovative pharmacological targets have been explored in the last six years, allowing a broader therapeutic arsenal against glaucoma and IOP-related pathologies. The endocannabinoid system and FAAH inhibitors were the most investigated from a medicinal chemistry point of view.


Assuntos
Desenvolvimento de Medicamentos , Glaucoma/tratamento farmacológico , Pressão Intraocular/efeitos dos fármacos , Animais , Glaucoma/fisiopatologia , Humanos , Adesão à Medicação , Patentes como Assunto , Fatores de Risco , Relação Estrutura-Atividade
17.
Expert Opin Ther Pat ; 29(10): 753-759, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31438732

RESUMO

Introduction: Glaucoma refers to a heterogeneous group of optic neuropathies characterized by an enhanced intraocular pressure (IOP). To date, there are six available different drug classes for the treatment of glaucoma and ocular hypertension: ß-adrenergic antagonists, prostaglandins, carbonic anhydrase inhibitors, α2-selective adrenergic, muscarinic agonists and rho kinase inhibitors, which act by reducing the production or increasing the drainage of aqueous humor. Areas covered: This manuscript reviews patent US2018244666A1, that describes the synthesis of novel potential rho kinase and monoamine transporters inhibitors with a benzamide or isoquinoline amide scaffolds, and patent US2018256595A1 that investigates the long-term treatment of glaucoma or ocular hypertension with ripasudil, a rho kinase inhibitor. Expert opinion: A variety of netarsudil congeners were synthesized as rho kinases inhibitors in patent US2018244666A1. Results of patent US2018256595A1 showed that ripasudil is among the best candidates for glaucoma long-term treatment, as IOP continuously dropped over the course of the treatment.


Assuntos
Glaucoma/tratamento farmacológico , Hipertensão Ocular/tratamento farmacológico , Quinases Associadas a rho/antagonistas & inibidores , Benzoatos/administração & dosagem , Benzoatos/farmacologia , Glaucoma/patologia , Humanos , Pressão Intraocular/efeitos dos fármacos , Isoquinolinas/administração & dosagem , Isoquinolinas/farmacologia , Hipertensão Ocular/patologia , Patentes como Assunto , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacologia , Sulfonamidas/administração & dosagem , Sulfonamidas/farmacologia , beta-Alanina/administração & dosagem , beta-Alanina/análogos & derivados , beta-Alanina/farmacologia , Quinases Associadas a rho/metabolismo
18.
Expert Opin Ther Pat ; 29(10): 749-752, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31456444

RESUMO

Introduction: Age-related macular degeneration (AMD) is the leading cause of central vision loss in developed countries. Effective therapy for AMD is currently limited to the treatment of the patient with intravitreal injections of anti-VEGF drugs. Areas covered: A method for the management of age-related macular degeneration (AMD) is claimed. It consists of the administration of pure botulinum-toxin or a serogroup of recombinant botulinum-toxins or their peptide fragments or neurotoxin associated with accessory proteins in extra-ocular regions of the eye. The toxin modifies the retinal pigment epithelium, maintaining its structure and function, and delaying the various stages of the macular degeneration. Expert opinion: The botulinum-toxin (BT) is administrated as extra-ocular infusions avoiding the risk of direct intraocular injection and the complications associated with the patients. The possibility to administer BT with accessory proteins (hemagglutinin, monoclonal antibody (anti-VEGF)), makes the novel system interesting for developing combined approaches for AMD treatment. The use of BT (alone or conjugated to other agents) as a method for treating or preventing AMD requires necessarily a patient case report study, as well as the in vitro or in vivo data, for supporting all the claims of the present patent.


Assuntos
Toxinas Botulínicas/administração & dosagem , Degeneração Macular/tratamento farmacológico , Epitélio Pigmentado da Retina/efeitos dos fármacos , Humanos , Degeneração Macular/fisiopatologia , Patentes como Assunto , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
19.
Expert Opin Ther Pat ; 29(10): 793-803, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31462124

RESUMO

Introduction: Elevated intraocular pressure (IOP) is the most prevalent risk factor for glaucoma. Prostaglandin analogs are a first-line therapy for glaucoma due to their ability to reduce IOP, once-daily dosing, efficacy, and minimal side-effect profile. Many compounds targeting different PG receptors have been developed in the last years, some of them being in clinical use. Latanoprost, Bimatoprost, Travoprost, and Tafluprost are clinically used as antiglaucoma drugs and act as agonists of the PGF2α receptor. The inability to fully understand the mechanism of action of clinically used PGF2α analogs is thus a strong driver for additional research into the mechanism of action of ocular hypotensive drugs belonging to this class of pharmacological agents. Areas covered: This review explores the last 5 years (2013-2018), where many patents describing new compounds acting on different prostaglandin receptors, and mainly targeting EP1-4 and FP receptors, were released. Expert opinion: To date, there has been a growing awareness over recent years of the therapeutic use of novel derivatives as new antiglaucoma pharmaceutical products. Patents involved in discovering new approaches and new molecules for the treatment of glaucoma diseases encouraged the scientific community to increase the variety of drugs available for the treatment of ocular diseases.


Assuntos
Glaucoma/tratamento farmacológico , Prostaglandinas Sintéticas/farmacologia , Receptores de Prostaglandina/agonistas , Animais , Anti-Hipertensivos/farmacologia , Desenvolvimento de Medicamentos , Glaucoma/patologia , Humanos , Pressão Intraocular/efeitos dos fármacos , Patentes como Assunto , Fatores de Risco
20.
Expert Opin Ther Pat ; 29(9): 703-731, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31369715

RESUMO

Introduction: Combretastatins represent a potent class of phenolic-stilbene natural products that function as colchicine binding site inhibitors of tubulin polymerization and have been advanced as promising anticancer lead compounds. Among them, combretastatin A-4 is the most potent lead molecule due to its broad spectrum cytotoxicity against a variety of tumors. However, low water solubility due to its high lipophilic nature and inter-conversion of olefinic double bond from more active cis to less active trans-conformation poses limitations to its clinical utility. However, different approaches including prodrugs, salt formations, structural modifications, prevention of inter-conversion of the olefinic bond and changes to the substitution pattern on the rings of combretastatin A-4 were investigated and successfully resulted in different combretastatin-based molecules that demonstrated varying levels of potency against different types of tumors during their in-vitro and in-vivo studies. Areas covered: This review covers the patents over a period of 2008-2018. Expert opinion: Molecular hybridization and prodrug designing imparted multi-targeted actions to combretastatin derivatives. Currently, various combretastatin derivatives are under clinical trials. These derivatives could be used to treat disorders other than cancer, due to their vascular disrupting action.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Bibenzilas/farmacologia , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/química , Bibenzilas/química , Desenho de Drogas , Humanos , Patentes como Assunto , Solubilidade , Relação Estrutura-Atividade , Moduladores de Tubulina/química , Moduladores de Tubulina/farmacologia
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