Recent trends in neuropathic pain patents.

INTRODUCTION: Neuropathic pain (NP) is one of the most important health problems faced nowadays. NP is a chronic disease that cannot be treated like other pain conditions because it is developed from a nerve injury that evolves into a permanent dysfunction of the central and/or peripheral nervous system. Therefore, it involves the participation of several systems and should be viewed as a multi-factorial disease that needs a whole new pharmacological strategy in order to achieve the desired pain relief. Areas covered: The Espacenet site was used as the main source in order to perform the patent research for NP treatment. This review covers the patents with relevant approaches for NP treatment from 2014 until today. Expert opinion: Our patent research has shown that there is not a consensus approach to treat NP in any of its forms. In our opinion, the approach regarding NP needs to be like cancer's approach. As there are different types of cancer and different ways to treat them, the same needs to be done for NP. Currently, there are several promising targets, which corroborates that this is a wide-open research area. For these reasons, neuropathic pain is a therapeutic field full of potential for innovation.

Acylhydrazone derivatives: a patent review.

INTRODUCTION: The N-acylhydrazone (NAH) moiety has been characterized as a privileged structure, capable of providing ligands points for more than one type of bioreceptor. Modifications of the subunits bonded to its acyl and imine functions resulted in several derivatives, which modulate a great diversity of molecular targets. In this context, this patent review reflects the use of the NAH moiety in different compounds. AREAS COVERED: In this review, the authors perform an analysis of the therapeutic profile of NAH compounds together with their perspective of its usability. The Espacenet and Delphion databases were used as main sources of search, and 'N-acylhydrazone,', 'Acylhydrazone' and 'hydrazone' were used as keywords. From a total of 117 patents retrieved, 22 presented pharmacological activities described in the document, thus being chosen for this review. EXPERT OPINION: In the last century, only six patents disclosing NAH derivatives for therapeutic purposes were published, and only in 2010, this subunit started receiving some real attention regarding its therapeutic potential. In this review, the Brazilian and Chinese Universities were identified as the major patent applicants, especially for drug candidates for the treatment of chronic pain, inflammatory disorders and cancer. The NAH subunit is very versatile both from synthetic and medicinal chemistry point of view. This feature is a direct result from the conformational diversity that this framework presents, achievable by subtle and simple chemical changes. Therefore, our opinion is that this moiety suits a lot more drug discovery projects than it seems to at first glance. In conclusion, we strongly support and encourage a raise in the use of this unique subunit.

N-acylhydrazone improves exercise intolerance in rats submitted to myocardial infarction by the recovery of calcium homeostasis in skeletal muscle.

AIMS: This work investigated the effects of 3,4-methylenedioxybenzoyl-2-thienylhydrazone (LASSBio-294) treatment on the contractile response of soleus (SOL) muscle from rats submitted to myocardial infarction (MI). MAIN METHODS: Following coronary artery ligation, LASSBio-294 (2mg/kg, i.p.) or vehicle was administrated once daily for 4 weeks. KEY FINDINGS: The run time to fatigue for sham rats was 17.9 ±2.6 min, and it was reduced to 3.3 ± 0.8 min (P<0.05) in MI rats. In MI rats treated with LASSBio-294, the time to fatigue was 15.1 ± 3.6 min. During the contractile test, SOL muscles from sham rats showed a response of 7.12 ± 0.54N/cm(2) at 60 Hz, which was decreased to 5.45 ± 0.49 N/cm(2) (P<0.05) in MI rats. The contractility of SOL muscles from the MI-LASSBio-294 group was increased to 9.01 ± 0.65N/cm(2). At 16 mM caffeine, the contractility was reduced from 2.31 ± 0.33 to 1.60 ± 0.21 N/cm(2) (P<0.05) in the MI group. In SOL muscles from MI-LASSBio-294 rats, the caffeine response was increased to 2.62 ± 0.33 N/cm(2). Moreover, SERCA2a expression in SOL muscles was decreased by 0.31-fold (31%) in the MI group compared to the Sham group (P<0.05). In the MI-LASSBio-294 group, it was increased by 1.53-fold (153%) compared to the MI group (P<0.05). Meanwhile, the nuclear density in SOL muscles was increased in the MI group compared to the Sham group. Treatment with LASSBio-294 prevented this enhancement of cellular infiltrate. SIGNIFICANCE: LASSBio-294 treatment prevented the development of muscular fatigue and improved exercise intolerance in rats submitted to MI.

Phenylpiperazine derivatives: a patent review (2006 - present).

INTRODUCTION: The N-phenylpiperazine subunit represents one of the most versatile scaffolds used in the medicinal chemistry field. Recently, some N-phenylpiperazine derivatives have reached late stage clinical trials for the treatment of CNS disorders, thus, this is clearly a molecular template that already has proven its "druglikeness," However, this scaffold is still strictly seen as a "CNS structure" by great part of the scientific community. The aim of this review is to draw a contemporary profile of the patents regarding N-phenylpiperazine derivatives and, them, suggest new research fields to be explored. AREAS COVERED: The site of the World Intellectual Property Organization (WIPO) was used as the main source in order to perform the research of the patents containing N-phenylpiperazine compounds with therapeutic uses. This review highlights some examples to show that this heterocyclic moiety can successfully yield new classes of hits and prototypes for many other therapeutic fields through appropriate substitution of the molecular skeleton. EXPERT OPINION: The patent research concerning N-phenylpiperazine derivatives indicated for therapeutic uses from 2006 to present date resulted in thirty three documents. It is a low number if one considers the several compounds bearing the N-phenylpiperazine nucleus that reached the market and/or clinical trials. Therefore, this subunit seems to be much underrated at the moment. The adequate use of the N-phenylpiperazine moiety, through modulation of its basicity and substitution pattern of the aromatic ring, can yield pharmacokinetic and pharmacodynamic improvements that are certainly useful in several therapeutic areas, thus, being able to diversify the application and utility of this scaffold. We expect and strongly suggest the growth of this diversification.