2019-11-24 11:46:04
Satyendra Mishra,*a Sejal Patel,a,1 and Chandni G. Halpania,1
a Medicinal Chemistry Laboratory, Center for Engineering and Enterprise, University and Institute of Advanced
Research, Koba Institutional, Area Gandhinagar, Gujarat 382426, India, e-mail: [email protected]
1. Introduction
Curcumin is a natural product isolated from the roots of the plant Curcuma longa L. and has been used since centuries as a spice, dietary pigment and traditional Indian medicine for cure of miscellaneous diseases that include rheumatism, diabetic wounds, hepatic disorder, biliary disorders, blood purification, rheumatoid arthritis cough and anorexia.[1–4] Curcumin, the principal curcuminoid of turmeric has been studied extensively due to its wide range of medicinal properties[5–20] such as anticancer, antioxidant, antimicrobial, antiangiogenic, anti-inflammatory, anti-HIV, antiarthritic, antidepressant, anti-aging, antimalarial, antibacterial and antidiabetic activities.
Curcumin has three functional groups that can contribute to its biological activities, namely an aromatic o-methoxyphenolic group, α,β-unsaturated β-diketo moiety and a seven carbon linker. Their redox actions are expectedly more complex and have led to conflicting interpretations on the roles of the functional groups.[21–28] In spite of widely illustrated biological activities, the prospective activity of curcumin is restricted owing to its meager potency and bioavailability.[29] A chunk of the rationale behind this is its physical and metabolic instability which affirms its alteration. Previously, researchers attempted chemical modifications in curcumin to increase its potency. This comprises diketone and monoketone analogs of curcumin and Knoevenagel condensation of curcumin.[30,31] In earlier reports,
researchers established improved pharmacological activity of curcumin when 1,3-dicarbonyl moiety of curcumin was replaced by isosteric isoxazoles and pyrazoles.[32–33] Claramunt et al. have discussed a few biological and pharmacological properties of pyrazoles derived from curcumin, curcuminoids and hemicurcuminoids collectively.[34]
A numerous examples of pyrazole and isoxazole derivatives of curcumin have been employed as active stable curcumin analogs for various biological activities. In this context, this review aims to provide a more comprehensive introduction of pyrazole and isoxazole derivatives of curcumin, advancements in pyrazole and isoxazole derivatives of curcumin, synthetic methodologies and its applications in medicinal chemistry. Research articles published in the past 10 years are focused in this review.
2. General Synthetic Procedure for the Synthesis of Curcumin Pyrazole Derivatives
Curcumin (1.0 mmol) and different hydrazine derivatives (1.2 mmol) were added in glacial acetic acid (5 mL). The solution was refluxed; reaction monitored through TLC, and then the solvent was removed in vacuo. The residue was dissolved in ethyl acetate and washed with water. Organic portion was collected, dried over sodium sulfate, and then, evaporated in vacuo to yield crude product. The crude product was further purified by column chromatography (AcOEt/hexanes 4:6) to afford desired product (Scheme 1). Classical curcumin pyrazole, isoxazole and their derivatives are summarized in Figure 1. Some of their biological activities and applications will be conferred in the subsequent segment.
3. Biological Activities of Curcumin Pyrazole and Isoxazole Analogs
3.1. Curcumin Pyrazole and Isoxazole Analogs as Anti-Neurodegenerative Disease
Alzheimer’s disease (AD) is the most common form of dementia. In an AD patient’s brain, senile plaques and neurofibrillary tangles, the abnormal aggregates of amyloid β (Aβ) peptide and tau protein are observed as the two major hallmarks of this disease. Aggregation of amyloid-β (Aβ) and tau plays a crucial role in the commencement and development of Alzheimer’s disease (AD). Therefore, the inhibition of Aβ and tau aggregation may represent a potential therapeutic target for AD.
Curcumin has been reported for binding to the amyloid β peptide (Aβ) and also inhibits amyloid precursor protein (APP) metabolism. Replacement of the 1,3-dicarbonyl moiety of curcumin with isosteric
isoxazoles and pyrazoles restricts rotational freedom. Curcumin-derived isoxazoles and pyrazoles inhibit Aβ secretion, bind to or inhibit the formation of fibrillar Aβ42 and tau aggregates, 10–100 folds more than curcumin. Numerous curcumin pyrazole derivatives exhibited excellent inhibition of γ-secretase activity, tau aggregation, depolymerized tau protein aggregates and affinity to fibrillar Aβ42 at low micromolar concentrations (Table 1).[35]
To develop a new drug for treatment of AD, series of curcumin derivatives were synthesized and appraised for their inhibitory activities against both tau and Aβ aggregation. Compound 5 is a more potent
aggregation inhibitor (IC50: Aβ 1.2�0.2 μM and tau 0.66�0.13 μM).[36] This compound has a better pharmacokinetic profile and pharmacological efficacy in vivo than curcumin, making it suitable as a drug for AD. In other report, Okuda et al. (2017)[52] designed and synthesized novel curcumin pyrazole 3 for both Aβ and tau dual aggregation inhibitors. Compound 3 inhibited Aβ aggregation in vitro and protected cultured cells from Aβ-induced cytotoxicity. Moreover, PE859 ameliorated cognitive dysfunction and reduced the extent of aggregated Aβ and tau in brains of senescence-accelerated mouse prone (SAMP8). These results warrant consideration of compound 3 as a candidate drug for AD.
Sherin et al. (2015)[53] synthesized a number of derivatives of curcumin, which displayed antioxidant activity based on DPPH, FRAP and β-carotene bleaching assays. Some of them (azole and isoxazole) are
better antioxidants than curcumin. Broadly, EC50 values are expressed as the inhibition of 2,2-diphenyl-1-picrylhydrazyl (DPPH). EC50 for curcumin (1), 3,5-bis(4-hydroxy-3-methoxystyryl)isoxazole (2) and 3,5-bis(4-hydroxy-3-methoxystyryl)pyrazole (3) are 40�0.06, 14�0.18 and 8�0.11 μM, respectively. Moreover, these are important in studies associated to neuroprotection and Alzheimer’s disease.
Accumulated evidences suggest that deposition of neurotoxic α-synuclein aggregates in the brain during the development of neurodegenerative diseases like Parkinson’s disease can be curbed by anti-aggregation strategies that either disrupt or eliminate toxic aggregates.
Curcumin, a dietary polyphenol, shows anti-amyloid activity but the use of this polyphenol is limited due to its instability. To solve these problems, through a chemical modification in dicarbonyl group of
curcumin, two stable analogs, viz. curcumin pyrazole and curcumin isoxazole and their derivatives were synthesized. Biochemical, biophysical and cell based assays revealed that curcumin pyrazole 3 and its
derivative N-(3-nitrophenylpyrazole) curcumin 4 display incredible potency in not only arresting fibrillization and disrupting fibrils but also forestalling construction of A11 conformation in the protein that
converses toxic effects. Compounds 3 and 15 also decreased neurotoxicity associated with fast aggregating A53T mutant form of α-synuclein. These two analogs of curcumin described here may, therefore, be useful therapeutic inhibitors for the treatment of α-synuclein amyloidosis and toxicity in Parkinson’s disease and other synucleinopathies.[37] Parkinson’s disease (PD) is characterized by the progressive degeneration via apoptosis of nigrostriatal dopaminergic neurons associated with inflammation, resulting in behavioral anomalies. Therefore, an anti-apoptotic and anti-inflammatory regimen may be useful in treatment of PD (Table 2).
Curcumin phenylpyrazole 7 exhibited neuroprotective and memory-enhancing effects and this may be effective for the treatment of Alzheimer’s disease. Curcumin phenylpyrazole (1–10 μM) suppressed the lipopolysaccharide (LPS)-induced nitric oxide (NO) production and also masked the LPS-induced nuclear translocation of nuclear factor κB (NF-κB), and expression of inducible NO synthase (iNOS) and thus, the effectiveness of pyrazole derivatives of curcumin were better than curcumin. Results imply that pyrazole derivatives of curcumin show anti-inflammatory effects during inhibitions of NF-κB and p38 MAPK pathways in microglia, suppression of iNOS. Results suggest that curcumin phenylpyrazole may have therapeutic potential for a variety of neurodegenerative diseases related to inflammatory conditions.[38]
Curcumin phenylpyrazole in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) rodent model of PD exerts reduced tyrosine hydroxylase (TH), exacerbated oxidative stress and dopamine transporter and vesicular monoamine transporter 2 (VMAT2) expressions. This may have strong therapeutic potential for dealing of PD.[54]
Curcumin phenylpyrazole 7 and cyclohexyl bisphenol have superior biological properties compared with parent compound curcumin. MPTP model of PD was used as anti-inflammatory and anti-apoptotic mediated neuroprotection of pyrazole derivatives of curcumin. Co-treatment of MPTP with pyrazole derivatives of curcumin significantly attenuated motor impairments and pathological changes caused by MPTP administration. Together, these results demonstrate that pyrazole derivatives of curcumin are neuroprotective through its anti-inflammatory and anti-apoptotic properties. Consequently, pyrazole derivatives of curcumin have prospects to be auxiliaries as therapeutic candidates for treatment of PD.[55]
Curcumin, a potent antioxidant, has been reported to display diverse neuroprotective properties against various neurodegenerative diseases including PD. Curcumin phenylpyrazole was investigated on rotenone-induced toxicity and its possible mechanisms in neuroblastoma SK& NG SH cells. Therefore, it can be further developed as a promising drug for cure of PD.[56]
Compound 8 is the best inhibitor of iNOS and also more selective. Qualitative structure–activity analysis shows that the presence/absence of diverse substituents confirms that fluorine group enhances the biological activity (Table 3). Curcumin phenylpyrazole 7, which has neurotrophic activity, enhances memory and blocks cell death in multiple toxicity assays related to ischemic stroke. Pyrazole derivatives of curcumin were tested in a rigorous rabbit ischemic stroke model and were confirmed its in vivo activity on molecular basis. Curcumin phenylpyrazole preserves the calcium-calmodulin-dependent kinase signaling pathways associated with neurotrophic growth factors which are critical for the maintenance of neuronal function and have great potential for the treatment of ischemic stroke as well as other CNS pathologies.[57]
3.2. Curcumin Pyrazole and Isoxazole Analogs as Anticancer Agents
Curcumin exists in solution as a tautomeric mixture of keto and enol forms, and the enol form was found to be responsible for the rapid degradation of the compound. To augment the firmness of curcumin, numerous analogs were synthesized in which the diketone moiety of curcumin was replaced by isoxazole (compound 2) and pyrazole (compound 3) groups. Isoxazole and pyrazole curcumins were found to be extremely stable at physiological pH. Interestingly, compounds 2 and 3 also showed better free radical scavenging activity than curcumin (Table 4).
Ahsan et al. (2013) depicted synthesis, characterization and in vitro anticancer activity of a novel series of curcumin analogs to explore potential therapeutics for cancer. Several compounds were tested and
showed promising anticancer activity in both onedose and 5-dose assays. The studies established that compound 9 exhibited the best activity and may be potential therapeutic for cancer.[40] Numbers of click diarylpentane curcuminoids and their pyrazole derivatives have been synthesized for various cellular tubulin functional assays. This class of compounds validates as novel types of antimitotic agents, confirming structure-activity relationships and recognizing the pyrazole adduct 4k as a promising lead (Table 5).[41]
Curcumin analogs of benzyloxime and the isoxazole and pyrazole demonstrated outstanding amplification in the antitumor activity both in the parental and in the MDR MCF-7 cells. Moreover, curcumin and the isoxazole analogs, fashioned untimely reductions in the amounts of relevant gene transcripts which were diverse. Cytotoxicity and cell death induction assays evidently indicted antitumor activity of curcumin analogs, which have substantial activity in both MCF-7 and in MCF-7R.[59]
Isoxazole and pyrazole derivatives were less prone to nucleophilic benzyl mercaptan addition than curcumin. Pyrazole and isoxazole derivatives of curcumin exhibited increased cell growth inhibitory and proapoptotic effects in liver cancer HA22T/VGH cells as well as in other tumor cell types compared with curcumin. In conclusion, isoxazole and pyrazole were deficient in the capability of the parent compound to sensitize the HA22T/VGH cells to cisplatin (CIS), an effect which emerged to take place during an interaction of curcumin and CIS at the level of SH group. Therefore, the potential of interacting with cell thiols might not be stipulated for the further effective antitumor activities of new diketone modified curcumin derivatives.[60]
Since long time, curcumin is used to treat many illness. Active pharmacophore of curcumin remains unknown, apparently unselective scaffold, or Michael acceptor properties of α,β-unsaturated 1,3-diketone
moiety central to its structure. To investigate this, pyrazole and isoxazole analogs were synthesized and evaluated against two breast cancer cell lines; several of them exhibited excellent anti-proliferative activity.[61] HER2 (Human epidermal growth factor receptor 2) has an imperative function in cancer aggressiveness, poor prognosis as a drug target for cancer. In particular, to effectively treat HER2-positive cancer, small molecule inhibitors were developed to target HER2 kinase. Deliberately, curcumin has been used as spice to inhibit cancer activity. Four classes (β-diketone, monoketone, pyrazole and isoxazole) of curcumin analogs were evaluated as HER2 inhibitors using in vitro and in silico studies. The intermolecular interactions were established by molecular dynamics simulation studies.[62] Human epidermal growth factor receptor 2 (HER2) has an important role in cancer aggressiveness and poor prognosis. HER2 has been used as a drug target for cancers. Two dazzling compounds, bisdemethylcurcumin (AS-KTC006) and 3,5-bis[(E)-3,4-dimethoxystyryl)]isoxazole (AS-KTC021) reported as HER2 inhibitors in vitro and in silico studies. The curcumin analogs in this study have β-diketone, monoketone, pyrazole and isoxazole. Tetrahydrocurcumin (THC), a major metabolite of curcumin, has potential application in cancer as preventive and chemotherapeutic agent. A series of new pyrazole derivatives of THC have been synthesized by treating THC with various substituents. Many of them (1, 2, 3, 14 and 15) exhibit excellent anticancer activity against MCF-7 cell lines with good IC50 values. 4-Bromophenyl group at the pyrazole derivative of curcumin was most active and inhibits the growth of all three tested cancer cell lines with IC50 values of 8.0 μM (A549), 9.8 μM (HeLa) and 5.8 μM (MCF-7).
Curcumin-pyrazole-Mannich derivatives have been recognized as potent inhibitors of Mycobacterium tuberculosis (Table 6).[42] Pyrazole and triazole curcumin analogs were synthesized and exhibited activity in micromolar against Head and Neck cancer. Plausible molecular mechanisms, effects of these analogs in the expression of pSTAT3, pFAK, pERK1/2 and pAKT suggest inhibition of the pSTAT3 (Tyr 705) phosphorylation. Molecular docking studies discovered the promising binding type of pyrazole compound 2 in the SH2 domain of STAT3 (curcumin pyrazole and curcumin click chemistry analogs 6 and 16–18).
Among them, compounds 17 and 18 demonstrated potent cytotoxic activity against HNSCC cell lines. Amusingly, derivatives 16 and 17 have important effect on pSTAT3 phosphorylation. Disruption of pFAK and pAKT phosphorylation signaling is shown with compound 18. Compound 17 is the first reported click-chemistry curcumin analog showing good cytotoxic activity. A number of pyrazole derivatives of penta-1,4-dien-3-one compounds containing a substituted pyrazole subunit were designed, synthesized and characterized.
Some of synthesized compounds showed significant antiproliferative activity against HepG2 cell lines. Especially, those compounds were active against HepG2 cells with IC50 values of 0.10–5.05 μM, which
were superior to that of the contrast sorafenib (IC50=16.20 μM). Isoxazole analogs of curcumin exhibit in MCF-7R antiproliferative and cell death effects comparable to those achieved in MCF-7 and cause minor changes in NF-κB or STAT3 activation.[65] 4,4’-(1E,1’E)-2,2’-(1-(3-chlorophenyl)-1H-pyrazole-3,5-diyl)bis(ethene-2,1-diyl) bis(2-methoxyphenol) exhibited a high degree of cytotoxicity and cell proliferation inhibition against cancer cells can be selected for further in vitro and in vivo investigations.[66] Isoxazole analogs of curcumin exhibited significantly improved in vitro drug-like properties including solubility, metabolic stability, cell permeability and lack of nonspecific cytotoxicity when compared with curcumin.[67]
3.3. Curcumin Pyrazole and Isoxazole Analogs as Antibacterial and Antifungal Agents
A novel, synthetic procedure for benzothiazole, pyrazole and benzylidene derivatives of curcumin has been reported. These analogs were screened for their antibacterial activity against Gram-positive and Gramnegative bacteria, viz. Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella typhi, Escherichia coli, Bacillus cereus and Providencia rettgeri, and antifungal activity against fungi, viz. Aspergillus niger, Aspergillus fumigates and Aspergillus flavus. Mechanism of inhibition was also discussed (Table 7).
4-Phenylaminomethyl curcumin, arylidene curcumin and pyrazole curcumin derivatives were synthesized and their anti-inflammatory, antioxidant and antibacterial activities were carried out in vitro study.
Some of the synthesized dimethylamino curcuminoid derivatives have shown potent anti-inflammatory properties than parent curcumin. A molecular docking interaction of synthesized derivative was also
studied.[45] Curcumin exhibits antioxidant activity at 52.51 μg/mL and anti-inflammatory activity at 129.85 μg/mL. Curcumin pyrazole displays better antioxidant activity (23: 74.03 μg/mL and 24: 46.05 μg/mL) and anti-inflammatory activity (23: 216.32 μg/mL and 24: 29.44 μg/mL).
3.4. Curcumin Pyrazole and Isoxazole Analogs as Antimalarial Agents
Earlier studies have shown that curcumin inhibits chloroquine-sensitive (CQJ S) and chloroquine-resistant (CQJR) Plasmodium falciparum growth in culture with IC50 of approximately 3.25 μM (MIC=13.2 μM) and 4.21 μM (MIC=14.4 μM), respectively. In order to improve its potential, a number of pyrazoles derivatives have been synthesized and evaluated for their inhibition activity against P. falciparum growth in
culture. Amongst synthesized compounds, pyrazole derivative of curcumin, 3-nitrophenylphenyl curcumin pyrazole and benzylidene derivative of curcumin exhibited inhibitory for CQJS P. falciparum at IC50 of 0.48, 0.87 and 0.92 μM and CQJR P. falciparum at IC50 of 0.45, 0.89 and 0.75 μM, respectively. Pyrazole analog of curcumin exhibited excellent seven-fold higher antimalarial potency against CQJS and nine-fold higher antimalarial potency against CQJR. Curcumin pyrazole analogs illustrated here may be promising candidates for the design of novel antimalarial agents (Table 8).[33]
3.5. Curcumin Pyrazole and Isoxazole Analogs as Antioxidant and Anti-Inflammatory Agents
Pyrazole and isoxazole analogs of curcumin were prepared and evaluated for antioxidant, COX-1/COX-2 inhibitory and anti-inflammatory activities. Replacement of β-diketo group with isosteric pyrazole, isoxazole analogs of curcumin exhibited higher antioxidant activity than trolox and curcumin (Table 9).
Curcumin pyrazole and isoxazole derivative exhibited anti-inflammatory activity of 68.8 2.9 and 60.3 2.9%, respectively, and inhibition on carrageenan induced rat paw edema assay at 75 mg/kg. The pyrazole derivatives of curcumin have been reported to have superior anti-inflammatory activity than curcumin. These activities are partly mediated by pyrazole curcumin based on inhibition of the JNK signaling pathway and reinforce the utility of it as an anti-inflammatory agent in macrophages (Table 10).
Asymmetrical pyrazole curcumin analogs were prepared by using polyethylene glycol (PEG-400) as eco-friendly medium. These analogs demonstrated good in vivo analgesic activity as compared to the standard ibuprofen, in vitro antioxidant activity, and exhibited good hydrogen peroxide scavenging activity as compared to the standard butylated hydroxy toluene (BHT) and in vitro anti-inflammatory activities as compared to standard diclofenac sodium (Table 11).
A series of pyrazole, pyridopyrazoltriazine, pyrazolotriazine, isoxazole and pyridine-containing products were prepared as a new class of antioxidant agents starting with curcumin and appropriate chemical reagents. Reaction of curcumin with diazonium salts affords the corresponding 4-arylazo derivatives. Also, pyrazole and isoxazole derivatives were obtained upon treatment of curcumin with hydrazines or
hydroxylamine hydrochloride. The newly synthesized compounds were evaluated as antioxidant agents.
Most of the compounds exhibited good activities, compounds 32 and 33 exhibited high protection against DNA damage induced by the bleomycine-iron complex as compared with curcumin (percentage of antioxidant activity: 32, 95.96% and 33, 93.75%).[48] Antioxidant activity and redox behavior of curcumin and its structurally modified synthetic analogs were studied. Alteration of 1,3-dicarbonyl moiety of
curcumin to an isosteric heterocycle as in pyrazole curcumin, which restricts its rotational freedom, leads to an enhancement of its redox properties as well as its antioxidant activity. Cyclic voltammetric studies demonstrate that H-atom transfer from CH2 group at the center active methylene group also plays a significant role in the antioxidant properties of curcumin. The pyrazole curcumin shows better antioxidant properties (viz. lower oxidation potential) than curcumin due to the absence of keto-enol tautomerism. Thus, the central methylene group in curcumin also plays a role along with the hydroxy group in the antioxidant activity of curcumin (Table 12).
Curcumin derived isoxazoles, pyrazoles and pyrimidines were screened for anti-inflammatory and antinociceptive activities.
3.6. Curcumin Pyrazole and Isoxazole Analogs and Their Other Various Activities Jha et. al[70] synthesized a number of analogs of curcumin and studied the effects of substituents and chemical nature of the interaction of curcumin to Gquadruplex. Curcumin stabilized the quadruplex structure of telomeric DNA sequence while curcumin pyrazole and 3-nitrophenyl curcumin pyrazole analogs were reported for its conformation. To advance the control of airway epithelial cell function and asthma, new derivatives of curcumin were investigated to see the effects on pharmacological properties. Pyrazole derivatives of curcumin, extensively obscured IL-6, TNF-α and GM-CSF production by NHBE cells, down regulated the level of active serine peptidase inhibitor. Curcumin derivatives, pyrazole derivatives of curcumin, can be promising candidates to treat asthma associated with neutrophilic airway inflammation and remodeling.
Curcumin inhibits microfilament formation, which is similar to its role in inhibiting microtubule formation. A series of stable curcumin analogs were synthesized to evaluate their affinity for actin and their
ability to inhibit actin self-assembly using isothermal titration calorimetry. Benzylidene derivative is more effective actin self-assembly than curcumin, whereas oxazole, pyrazole and acetyl derivatives are less
effective than curcumin. Disorganization of the actin network in the presence of curcumin leads to destabilization of filaments. Curcumin is softly fluorescent in aqueous solution which binds to actin and augments fluorescence several fold with a large blue shift in the emission maximum (Table 13).
A comparative structure-activity study revealed three modifications, namely i) enolized dicarbonyl moiety and/or replacement by pyrazole, ii) hydrogenation of the interaryl linker, and iii) (dihydro) prenylation scrutinize mPGES-1/5-LO inhibition. Calcium/calmodulin dependent protein kinase II (CaMKII) plays an important role in pathological glutamate signaling and brain functions such as learning and memory are activated by calcium influx through the N-methyl-d-aspartate type glutamate receptor (NMDAR). Pyrazole curcumin, synthesized by using microwave, was found to be more potent inhibitor of CaMKII than curcumin. Curcumin pyrazole exhibits better CaMKII autophosphorylation (IC50 6.5�3.38 μM) than curcumin (IC50 33�9.0 μM), isoxazole curcumin (IC50 18.01�1.61 μM) and phenyl curcumin pyrazole (IC50 111�11.49 μM). Thus, acute inhibition of CaMKII may be a potential strategy for providing neuroprotection as shown by two independent groups using the CaMKII inhibitor tat-CN21 peptide.[73]
Curcumin modulates PKC activity and binds to the activator binding site. Several isoxazole and pyrazole derivatives of curcumin were synthesized for exploration of the utility of the carbonyl and hydroxy groups of curcumin in PKC binding. Molecular docking revealed that hydroxy, carbonyl and pyrazole ring of curcumin, pyrazole and isoxazole derivatives form hydrogen bonds with the protein residues (Table 14).
Numerous semicarbazone and pyrazole derivatives of curcumin have been synthesized as potential mitigation agents to cure acute radiation syndrome (ARS). Oxidation potentials and radical scavenging
properties of semicarbazone and pyrazole curcumin derivatives were examined and exhibited low dose modifying factors (DMF).[74] Pyrazole curcumin derivatives demonstrated bioactivity and brain absorption to re-establish membrane integrity. It also endorses membrane homeostasis subsequent TBI, which can promote a modern line of non-invasive curative treatment for TBI patients by endogenous up-regulation of molecules imperative for neural refurbish and flexibility.[75]
Adipocyte dysfunction, obesity and related metabolic turmoils are of foremost healthcare apprehension worldwide. Amongst existing medications, natural products and motivated molecules clutch 40% space in clinically approved medicines. Novel curcumin derivative (curcumin 3,4-dichlorophenylpyrazole), having potent activity and efficacy over curcumin as antiadipogenic agent, executed its activity by blocking mitotic clonal expansion along with inhibition of AKT/mTOR pathway.
CDPP (Curcumin-3,4-dichlorophenylpyrazole 40) is a curcumin derived chemical entity which is more effective and overcomes the pharmacokinetic limitation of curcumin. CDPP were reported as potential
drug candidates against adipogenesis and dyslipidemia with enhanced gastrointestinal stability and bioavailability. CDPP was found to be a potent inhibitor of adipogenesis in vitro. CDPP demonstrated
manifest enhancement in gastrointestinal firmness and bioavailability in vivo as compared to curcumin.[51]
Isoxazole analogs are the most active group, with mono-O-methylcurcumin isoxazole being the most active compound (MIC 0.09 mg/mL) against Mycobacterium tuberculosis. It was 1131-fold more active than curcumin (1), the parent compound, and was approximately 18- and 2-fold more active than the standard drugs kanamycin and isoniazid, respectively.[76] Pyrazole and isoxazole derivatives of fluorinated curcuminoid were performed for computational/docking and in vitro bioassay against leukemia cell lines by cell viability assay.[77] Water-soluble pyrazole curcumin derivative (PyCurOAc) was found to inhibit formation of advanced glycation end products (AGEs) better than curcumin. Additionally, the AGE inhibition activity was substantiated in vivo using C. elegans as an animal model.
4. Conclusions
The focal point of this review is discussing various pharmacological activities of the curcumin pyrazole and isoxazole derivatives reported in the past decade. It also endows with an insight on latest advances of curcumin pyrazole and isoxazole derivatives encompassing diverse biological activities like antimalarial, anti-neurodegenerative, antimicrobial, anticancer and other activities. Some of pyrazole and isoxazole derivatives exhibited inhibitions of Aβ42 secretion, α-synuclein amyloidosis and iNOS which are associated with Alzheimer’s and anti-neurodegenerative disease, anti-proliferative activity, antioxidant activity, inhibitory activity for CQJS P. falciparum and CQJR P. falciparum, antioxidant activity, anti-inflammatory activity and stabilization of G-quadruplex. These are highlighted in the present review which may be considered in further development. This review might be useful for other working researchers and chemists in design and development of additional noteworthy molecules having curcumin pyrazole and isoxazole entity for the cure of different lethal diseases in future.
Author’s Contribution Statement
S. M. conducted a comprehensive literature review and wrote the article along with S. P. and C. G. H.
Acknowledgments
This work is generously supported by the Department of Science and Technology (DST-SERB/ECR/2015/000363) India, and GUJCOST (MRP/2015-2016/2276), Gujarat India to S. M.
3,6-Thioxanthenediamine-10,10-dioxideCatalog No.:AA0006OP CAS No.:10215-25-5 MDL No.:MFCD00041841 MF:C13H12N2O2S MW:260.3116 |
3-Chloro-4-methoxybenzonitrileCatalog No.:AA0006OF CAS No.:102151-33-7 MDL No.:MFCD03093073 MF:C8H6ClNO MW:167.5923 |
2-Bromo-3-iodonaphthaleneCatalog No.:AA0006O9 CAS No.:102153-44-6 MDL No.:MFCD06656515 MF:C10H6BrI MW:332.9631 |
2-Chloronaphthalene-1-sulfonyl chlorideCatalog No.:AA0006P5 CAS No.:102154-19-8 MDL No.:MFCD22196559 MF:C10H6Cl2O2S MW:261.1244 |
6-Chloro-2-naphthylsulfonylchlorideCatalog No.:AA0006O5 CAS No.:102153-63-9 MDL No.:MFCD04037080 MF:C10H6Cl2O2S MW:261.1244 |
6-Bromo-1-nitronaphthaleneCatalog No.:AA0006O8 CAS No.:102153-48-0 MDL No.:MFCD01464122 MF:C10H6BrNO2 MW:252.0641 |
3-Amino-5-iodobenzoic acidCatalog No.:AA0006PA CAS No.:102153-73-1 MDL No.:MFCD00068822 MF:C7H6INO2 MW:263.0325 |
2-Iodo-3-nitronaphthaleneCatalog No.:AA0006PB CAS No.:102153-71-9 MDL No.:MFCD06656539 MF:C10H6INO2 MW:299.0646 |
5-(Chlorosulfonyl)thiophene-2-carboxylic acidCatalog No.:AA0006PE CAS No.:10216-12-3 MDL No.:MFCD10485859 MF:C5H3ClO4S2 MW:226.6579 |
2-Bromo-4-methyl-5-nitroanilineCatalog No.:AA0006PO CAS No.:102169-99-3 MDL No.:MFCD01239994 MF:C7H7BrN2O2 MW:231.0467 |
2-(Hydrazinecarbonyl)benzenesulfonamideCatalog No.:AA0006PU CAS No.:102169-52-8 MDL No.:MFCD03986492 MF:C7H9N3O3S MW:215.2297 |
5-Hexyn-1-amine, hydrochlorideCatalog No.:AA0006PT CAS No.:102169-54-0 MDL No.:MFCD09923614 MF:C6H12ClN MW:133.6192 |
Sodium 5-bromo-4-chloro-1H-indol-3-yl phosphateCatalog No.:AA0006Q5 CAS No.:102185-33-1 MDL No.:MFCD00150468 MF:C8H4BrClNNa2O4P MW:370.4320 |
methyl 3-(4-bromophenyl)butanoateCatalog No.:AA0006Q4 CAS No.:1021735-42-1 MDL No.:MFCD16330770 MF:C11H13BrO2 MW:257.1237 |
Ethanaminium,2-[[(4-aminophenoxy)hydroxyphosphinyl]oxy]-N,N,N-trimethyl-, inner saltCatalog No.:AA0006Q6 CAS No.:102185-28-4 MDL No.:MFCD00063476 MF:C11H19N2O4P MW:274.2533 |
4-Bromo-5-methylbenzene-1,2-diamineCatalog No.:AA0006PV CAS No.:102169-44-8 MDL No.:MFCD16987757 MF:C7H9BrN2 MW:201.0638 |
(2-(7-Oxabicyclo[4.1.0]heptan-3-yl)ethyl)triethoxysilaneCatalog No.:AA0006Q2 CAS No.:10217-34-2 MDL No.:MFCD00069159 MF:C14H28O4Si MW:288.4552 |
2-Bromo-5-chloro-4-methylanilineCatalog No.:AA0006QM CAS No.:102170-52-5 MDL No.:MFCD00806533 MF:C7H7BrClN MW:220.4942 |
2-Bromo-6-methyl-4-nitroanilineCatalog No.:AA0006QK CAS No.:102170-56-9 MDL No.:MFCD00053089 MF:C7H7BrN2O2 MW:231.0467 |
6-Bromo-1-methyl-1H-indazole-3-carboxylic acidCatalog No.:AA0006R1 CAS No.:1021859-29-9 MDL No.:MFCD15071436 MF:C9H7BrN2O2 MW:255.0681 |
3-(Benzyl(isopropyl)amino)-1-(naphthalen-2-yl)propan-1-one hydrochlorideCatalog No.:AA0006QU CAS No.:1021868-92-7 MDL No.:MFCD04974534 MF:C23H26ClNO MW:367.9116 |
ethyl 8-bromo-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylateCatalog No.:AA0006R0 CAS No.:1021859-84-6 MDL No.:MFCD27992132 MF:C11H12BrNO3 MW:286.1219 |
5-Quinolineboronic Acid Pinacol EsterCatalog No.:AA0006QW CAS No.:1021868-08-5 MDL No.:MFCD22418302 MF:C15H18BNO2 MW:255.1199 |
N-(2-Fluorophenyl)-1H-imidazole-5-carboxamideCatalog No.:AA0006R4 CAS No.:102186-93-6 MDL No.:MFCD21648536 MF:C10H8FN3O MW:205.1884 |
4-Bromo-5-chloro-2-methoxyanilineCatalog No.:AA0006QL CAS No.:102170-53-6 MDL No.:MFCD09878150 MF:C7H7BrClNO MW:236.4936 |
4-Methyl-2-(trifluoromethyl)phenylboronic acidCatalog No.:AA0006QX CAS No.:1021860-94-5 MDL No.:MFCD11616521 MF:C8H8BF3O2 MW:203.9541 |
Bromochlorophenol blue sodium saltCatalog No.:AA0006R7 CAS No.:102185-52-4 MDL No.:MFCD00001612 MF:C19H9Br2Cl2NaO5S MW:603.0405 |
Bromophenol red sodium saltCatalog No.:AA0006R8 CAS No.:102185-50-2 MDL No.:MFCD00037160 MF:C19H11Br2NaO5S MW:534.1504 |
Boc-D-N-Me-Phe DCHACatalog No.:AA0006RC CAS No.:102185-45-5 MDL No.:MFCD00058079 MF:C27H44N2O4 MW:460.6493 |
Boc-Phe(4-No2)-OH DCHACatalog No.:AA0006RE CAS No.:102185-42-2 MDL No.:MFCD00069882 MF:C26H41N3O6 MW:491.6202 |
Boc-Arg(Mtr)-OHCatalog No.:AA0006RF CAS No.:102185-38-6 MDL No.:MFCD00043097 MF:C21H34N4O7S MW:486.5823 |
4-((4-(Diethylamino)-2-methylphenyl)imino)-1-oxo-N-phenyl-1,4-dihydronaphthalene-2-carboxamideCatalog No.:AA0006RY CAS No.:102187-19-9 MDL No.:MFCD00191571 MF:C28H27N3O2 MW:437.5329 |
trans-4-(Aminomethyl)cyclohexanol HydrochlorideCatalog No.:AA0006RI CAS No.:1021919-08-3 MDL No.:MFCD27956893 MF:C7H16ClNO MW:165.6610 |
Boc-D-Pro-OSuCatalog No.:AA0006RH CAS No.:102185-34-2 MDL No.:MFCD00069687 MF:C14H20N2O6 MW:312.3184 |
tert-Butyl 4-bromo-3-methyl-1H-pyrazole-1-carboxylateCatalog No.:AA0006SH CAS No.:1021919-24-3 MDL No.:MFCD18434446 MF:C9H13BrN2O2 MW:261.1157 |
tert-Butyl ((trans-4-hydroxycyclohexyl)methyl)carbamateCatalog No.:AA0006SF CAS No.:1021919-45-8 MDL No.:MFCD07369858 MF:C12H23NO3 MW:229.3159 |
(S)-tert-Butyl 2-(methoxycarbonyl)-4-oxopyrrolidine-1-carboxylateCatalog No.:AA0006SO CAS No.:102195-80-2 MDL No.:MFCD01861778 MF:C11H17NO5 MW:243.2564 |
Octadecyl 2-mercaptoacetateCatalog No.:AA0006SZ CAS No.:10220-46-9 MDL No.:MFCD00022084 MF:C20H40O2S MW:344.5954 |
(2S,4S)-1-tert-Butyl 2-methyl 4-hydroxypyrrolidine-1,2-dicarboxylateCatalog No.:AA0006SP CAS No.:102195-79-9 MDL No.:MFCD00237541 MF:C11H19NO5 MW:245.2723 |
1-(4-Nitrophenyl)pyrrolidineCatalog No.:AA0006T4 CAS No.:10220-22-1 MDL No.:MFCD00020819 MF:C10H12N2O2 MW:192.2145 |
(5-Chloro-2-(methylamino)phenyl)(phenyl)methanoneCatalog No.:AA0006TH CAS No.:1022-13-5 MDL No.:MFCD00008284 MF:C14H12ClNO MW:245.7042 |
(tert-Butyldimethylsilyloxy)acetaldehydeCatalog No.:AA0006RW CAS No.:102191-92-4 MDL No.:MFCD01321229 MF:C8H18O2Si MW:174.3128 |
Ethyl 1-Boc-4-isopropyl-4-piperidinecarboxylateCatalog No.:AA0006V6 CAS No.:1022128-75-1 MDL No.:MFCD10565656 MF:C16H29NO4 MW:299.4058 |
2-Phenyl-4H-benzo[d][1,3]oxazin-4-oneCatalog No.:AA0006TB CAS No.:1022-46-4 MDL No.:MFCD00043598 MF:C14H9NO2 MW:223.2268 |
N-FormylkynurenineCatalog No.:AA0006TE CAS No.:1022-31-7 MDL No.:MFCD16294964 MF:C11H12N2O4 MW:236.2240 |
2-(7-Fluoroquinolin-6-yl)acetic acidCatalog No.:AA0006UE CAS No.:1022091-54-8 MDL No.:MFCD17011786 MF:C11H8FNO2 MW:205.1851 |
6-Bromo-5,7-difluoroquinolineCatalog No.:AA0006UF CAS No.:1022091-49-1 MDL No.:MFCD12828677 MF:C9H4BrF2N MW:244.0356 |
4-Amino-5-bromo-1-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2(1H)-oneCatalog No.:AA0006T7 CAS No.:1022-79-3 MDL No.:MFCD00047496 MF:C9H12BrN3O4 MW:306.1133 |
1-(3-Aminophenyl)piperazin-2-oneCatalog No.:AA0006V4 CAS No.:1022128-80-8 MDL No.:MFCD10568158 MF:C10H13N3O MW:191.2297 |
(R)-tert-Butyl 3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylateCatalog No.:AA0006UY CAS No.:1022150-11-3 MDL No.:MFCD28167899 MF:C27H30N6O3 MW:486.5655 |
4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-propanenitrileCatalog No.:AA0006U9 CAS No.:1022092-33-6 MDL No.:MFCD16660233 MF:C12H18BN3O2 MW:247.1012 |
2-Bromo-6-iodobenzoic acidCatalog No.:AA0006V2 CAS No.:1022128-96-6 MDL No.:MFCD11036149 MF:C7H4BrIO2 MW:326.9139 |
5-(1-(2,3-Dimethylphenyl)vinyl)-1H-imidazoleCatalog No.:AA0006S7 CAS No.:1021949-47-2 MDL No.:MFCD13180466 MF:C13H14N2 MW:198.2637 |
Methyl 2-(3-bromoquinolin-6-yl)acetateCatalog No.:AA0006UD CAS No.:1022091-89-9 MDL No.:MFCD26398873 MF:C12H10BrNO2 MW:280.1173 |
2-(3-Bromoquinolin-6-yl)acetic acidCatalog No.:AA0006UC CAS No.:1022091-93-5 MDL No.:MFCD17215805 MF:C11H8BrNO2 MW:266.0907 |
tert-Butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazole-1-carboxylateCatalog No.:AA0006RJ CAS No.:1021918-86-4 MDL No.:MFCD24038762 MF:C18H25BN2O4 MW:344.2131 |
3-(5-Bromopyridin-3-yl)propanoic acidCatalog No.:AA0006V1 CAS No.:1022128-98-8 MDL No.:MFCD11042449 MF:C8H8BrNO2 MW:230.0586 |
(S)-N-Boc-3-MethylmorpholineCatalog No.:AA0006VB CAS No.:1022094-01-4 MDL No.:MFCD12964052 MF:C10H19NO3 MW:201.2628 |
(S)-3-Methylmorpholine hydrochlorideCatalog No.:AA0006VA CAS No.:1022094-03-6 MDL No.:MFCD18382512 MF:C5H12ClNO MW:137.6079 |
3-Chloro-5-(hydroxymethyl)benzonitrileCatalog No.:AA0006RT CAS No.:1021871-35-1 MDL No.:MFCD18392447 MF:C8H6ClNO MW:167.5923 |
2-(3-(Aminomethyl)phenyl)propan-2-olCatalog No.:AA0006RQ CAS No.:1021871-68-0 MDL No.:MFCD30721612 MF:C10H15NO MW:165.2322 |
N-(4-Bromophenyl)-N-methylthiocarbamoyl chlorideCatalog No.:AA0006S6 CAS No.:10219-03-1 MDL No.:MFCD03093776 MF:C8H7BrClNS MW:264.5699 |
3-Bromoquinolin-6-yl acetateCatalog No.:AA0006VR CAS No.:1022151-47-8 MDL No.:MFCD19687231 MF:C11H8BrNO2 MW:266.0907 |
6-Bromo-5-fluorobenzo[d]thiazol-2-amineCatalog No.:AA0006VS CAS No.:1022151-32-1 MDL No.:MFCD23705697 MF:C7H4BrFN2S MW:247.0875 |
(R)-N-Boc-3-MethylmorpholineCatalog No.:AA0006VC CAS No.:1022093-98-6 MDL No.:MFCD16038029 MF:C10H19NO3 MW:201.2628 |
DMT-dC(bz)PhosphoramiditeCatalog No.:AA0006VE CAS No.:102212-98-6 MDL No.:MFCD00036315 MF:C46H52N5O8P MW:833.9075 |
4-BroMo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazoleCatalog No.:AA0006VP CAS No.:1022158-35-5 MDL No.:MFCD22380249 MF:C12H13BrN2O MW:281.1484 |
((1R,2S)-2-(Aminomethyl)cyclopropyl)methanolCatalog No.:AA0006VU CAS No.:102225-89-8 MDL No.:MFCD18632668 MF:C5H11NO MW:101.1469 |
(R)-3-(4-Phenoxyphenyl)-1-(piperidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amineCatalog No.:AA0006VT CAS No.:1022150-12-4 MDL No.:MFCD09972163 MF:C22H22N6O MW:386.4497 |
(S)-(-)-STERICOLCatalog No.:AA0006VV CAS No.:102225-88-7 MDL No.:MFCD09836213 MF:C17H28O MW:248.4036 |
2-Methoxyquinoline-4-carboxylic acidCatalog No.:AA0006W5 CAS No.:10222-62-5 MDL No.:MFCD01550057 MF:C11H9NO3 MW:203.1941 |
2-Butoxyquinoline-4-carboxylic acidCatalog No.:AA0006W6 CAS No.:10222-61-4 MDL No.:MFCD11527607 MF:C14H15NO3 MW:245.2738 |
3-(pyridin-4-yl)-4,5-dihydro-1,2,4-oxadiazol-5-oneCatalog No.:AA0006WP CAS No.:102227-52-1 MDL No.:MFCD12774152 MF:C7H5N3O2 MW:163.1335 |
2,2-Dibromo-2-cyanoacetamideCatalog No.:AA0006WB CAS No.:10222-01-2 MDL No.:MFCD00129791 MF:C3H2Br2N2O MW:241.8688 |
4-(2-Hydroxyethyl)-3-methyl-1-phenyl-2-pyrazolin-5-oneCatalog No.:AA0006WZ CAS No.:10223-33-3 MDL No.:MFCD00067790 MF:C12H14N2O2 MW:218.2518 |
2H-Pyrido[4,3-b][1,4]oxazin-3(4H)-oneCatalog No.:AA0006WR CAS No.:102226-40-4 MDL No.:MFCD08062755 MF:C7H6N2O2 MW:150.1347 |
2-[[(1,1-Dimethylethyl)dimethylsilyl]oxy]ethanolCatalog No.:AA0006WO CAS No.:102229-10-7 MDL No.:MFCD09261150 MF:C8H20O2Si MW:176.3287 |
2-((tert-Butoxycarbonyl)amino)-3,3-dimethylbutanoic acidCatalog No.:AA0037YQ CAS No.:102185-35-3 MDL No.:MFCD00057782 MF:C11H21NO4 MW:231.2887 |
4,4'-DDMUCatalog No.:AA007G3G CAS No.:1022-22-6 MDL No.:MFCD00055275 MF:C14H9Cl3 MW:283.5803 |
Lorglumide (sodium salt)Catalog No.:AA008S23 CAS No.:1021868-76-7 MDL No.:MFCD00083183 MF:C22H31Cl2N2NaO4 MW:481.3883 |
1-methoxypiperidin-4-oneCatalog No.:AA008SDR CAS No.:102170-24-1 MDL No.:MFCD16619223 MF:C6H11NO2 MW:129.1570 |
Z-Tyr(3,5-i2)-oetCatalog No.:AA008T4F CAS No.:102202-92-6 MDL No.:MFCD00191084 MF:C19H19I2NO5 MW:595.1668 |
2-PMAPCatalog No.:AA008TAQ CAS No.:102212-26-0 MDL No.:MFCD24550644 MF:C12H12N2O MW:200.2365 |
SGX-523Catalog No.:AA008TGP CAS No.:1022150-57-7 MDL No.:MFCD16660190 MF:C18H13N7S MW:359.4077 |
CabozantinibCatalog No.:AA008THM CAS No.:1021950-26-4 MDL No.:MFCD17010276 MF:C31H31FN6O5 MW:586.6134 |
MK-5046Catalog No.:AA008TJT CAS No.:1022152-70-0 MDL No.:MFCD18782708 MF:C20H18F6N4O MW:444.3735 |
(4-(2-Methoxyethoxy)phenyl)methanamineCatalog No.:AA008V86 CAS No.:102196-20-3 MDL No.:MFCD09816053 MF:C10H15NO2 MW:181.2316 |
5-(5,5-Dimethyl-1,3,2-dioxaborinan-2-yl)-2-methoxypyridineCatalog No.:AA008VHF CAS No.:1022094-44-5 MDL No.:MFCD06801680 MF:C11H16BNO3 MW:221.0606 |
2-Chloro-5-[(methylthio)methyl]pyridineCatalog No.:AA008VKA CAS No.:1021870-94-9 MDL No.:MFCD12823579 MF:C7H8ClNS MW:173.6631 |
28-Oxo Ivermectin B1a (Impurity)Catalog No.:AA008W5Z CAS No.:102190-55-6 MDL No.:MFCD20486793 MF:C48H72O15 MW:889.0763 |
7-Bromo-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridineCatalog No.:AA008X2N CAS No.:1021923-54-5 MDL No.:MFCD15144602 MF:C7H3BrF3N3 MW:266.0180 |
6-Bromo-2-methyl-2H-indazole-3-carboxylic acidCatalog No.:AA008X92 CAS No.:1021859-33-5 MDL No.:MFCD11655613 MF:C9H7BrN2O2 MW:255.0681 |
3-Bromo-1-nitronaphthaleneCatalog No.:AA008XUP CAS No.:102153-47-9 MDL No.:MFCD01464123 MF:C10H6BrNO2 MW:252.0641 |
PPNDS (tetrasodium)Catalog No.:AA008Y17 CAS No.:1021868-77-8 MDL No.:MFCD03093192 MF:C18H11N4Na4O14PS2 MW:694.3612 |
3,4-Dihydro-2H-pyrido[4,3-b]-1,4-oxazineCatalog No.:AA0092DY CAS No.:102226-41-5 MDL No.:MFCD08062756 MF:C7H8N2O MW:136.1512 |
5-Bromo-4-chloro-2-methoxyanilineCatalog No.:AA00947G CAS No.:102169-94-8 MDL No.:MFCD22192351 MF:C7H7BrClNO MW:236.4936 |
2-methyl-6-(tetramethyl-1,3,2-dioxaborolan-2-yl)quinolineCatalog No.:AA0096CC CAS No.:1022090-86-3 MDL No.:MFCD13182085 MF:C16H20BNO2 MW:269.1465 |
3-Bromo-2-(2,5-dimethyl-1H-pyrrol-1-yl)pyridineCatalog No.:AA0096EX CAS No.:1021910-58-6 MDL No.:MFCD21296836 MF:C11H11BrN2 MW:251.1224 |
rac,trans-Methyl 4-(4-(trifluoromethyl)phenyl)pyrrolidine-3-carboxylateCatalog No.:AA0098ZY CAS No.:1022224-85-6 MDL No.:MFCD01862549 MF:C13H14F3NO2 MW:273.2510 |
2-(3,4-Dichlorophenyl)-2-phenylethylamine, HClCatalog No.:AA0098Y9 CAS No.:1021871-57-7 MDL No.:MFCD02089462 MF:C14H14Cl3N MW:302.6267 |
3-(Bromomethyl)-5-chlorobenzonitrileCatalog No.:AA009LU0 CAS No.:1021871-36-2 MDL No.:MFCD18392462 MF:C8H5BrClN MW:230.4890 |
Methyl 5-formylfuran-3-carboxylateCatalog No.:AA009S1K CAS No.:102169-71-1 MDL No.:MFCD22069937 MF:C7H6O4 MW:154.1201 |
2-(3,5-Dichlorophenyl)-2-phenylethylamine, HClCatalog No.:AA00H9OL CAS No.:1021871-56-6 MDL No.:MFCD01862523 MF:C14H14Cl3N MW:302.6267 |
Tert-butyl (6-bromoquinolin-3-yl)carbamateCatalog No.:AA00H9ON CAS No.:1022151-52-5 MDL No.:MFCD27665107 MF:C14H15BrN2O2 MW:323.1851 |
1-(Tetrahydro-2H-pyran-2-yl)-1H-indazole-4-carbaldehydeCatalog No.:AA00H9OP CAS No.:1022158-36-6 MDL No.:MFCD22380290 MF:C13H14N2O2 MW:230.2625 |
1-[(1-Aminopropan-2-yl)oxy]-2-chlorobenzene, HClCatalog No.:AA00H9OM CAS No.:1021871-58-8 MDL No.:MFCD02684120 MF:C9H13Cl2NO MW:222.1116 |
1,1-bis(4-chlorophenyl)-2-(isopropylamino)-1-ethanolCatalog No.:AA00INUM CAS No.:102201-72-9 MDL No.:MFCD00215306 MF:C17H19Cl2NO MW:324.2449 |
ethyl 3-{[(2,5-dimethoxyphenyl)carbamoyl]amino}propanoateCatalog No.:AA00ITDH CAS No.:1022286-64-1 MDL No.:MFCD00955136 MF:C14H20N2O5 MW:296.319 |
N-(4-{2-[(4-cyanophenyl)amino]-1,3-thiazol-4-yl}phenyl)acetamideCatalog No.:AA00IV6O CAS No.:1021996-57-5 MDL No.:MFCD00245853 MF:C18H14N4OS MW:334.395 |
2,2-dimethyl-5-({4-[5-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}methylidene)-1,3-dioxane-4,6-dioneCatalog No.:AA00IX7P CAS No.:1022052-14-7 MDL No.:MFCD00245527 MF:C17H18F3N3O4 MW:385.3377 |
N-(2,4-difluorophenyl)-1-{7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl}methanesulfonamideCatalog No.:AA00IX8M CAS No.:1022105-84-5 MDL No.:MFCD07777024 MF:C16H19F2NO3S MW:343.3888 |
4-methoxy-3-[2-(phenylamino)-1,3-thiazol-4-yl]phenolCatalog No.:AA00IZXY CAS No.:1022104-58-0 MDL No.:MFCD00171152 MF:C16H14N2O2S MW:298.3596 |
2-{[4-(2-fluorophenyl)piperazin-1-yl]methylidene}-2,3-dihydro-1H-indene-1,3-dioneCatalog No.:AA00IZYF CAS No.:1022101-16-1 MDL No.:MFCD00245175 MF:C20H17FN2O2 MW:336.3596 |
1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-4-methanesulfonyl-1,4-diazepaneCatalog No.:AA00J00F CAS No.:1022094-80-9 MDL No.:MFCD00246008 MF:C12H15ClF3N3O2S MW:357.7796 |
ethyl 3-{[4-(2-fluorophenyl)piperazine-1-carbothioyl]amino}propanoateCatalog No.:AA00J00M CAS No.:1022235-03-5 MDL No.:MFCD00955137 MF:C16H22FN3O2S MW:339.4282 |
3,3-Difluoro-2,2-dimethylpropanoic AcidCatalog No.:AA00RY9A CAS No.:1022154-50-2 MDL No.:MFCD19231629 MF:C5H8F2O2 MW:138.1126 |
7-methyl-[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxylic acidCatalog No.:AA019M6K CAS No.:102170-06-9 MDL No.:MFCD09439035 MF:C7H6N4O2 MW:178.1481 |
3-(4-bromo-3-chlorophenyl)prop-2-enoic acidCatalog No.:AA019NJ1 CAS No.:1022081-97-5 MDL No.:MFCD06358688 MF:C9H6BrClO2 MW:261.4997 |
2-(3-chlorophenoxy)propan-1-amine hydrochlorideCatalog No.:AA019S28 CAS No.:1021871-66-8 MDL No.:MFCD20441772 MF:C9H13Cl2NO MW:222.1116 |
[2-(2-methoxyethoxy)phenyl]methanamineCatalog No.:AA019WIP CAS No.:102197-21-7 MDL No.:MFCD09810092 MF:C10H15NO2 MW:181.2316 |
dimethyl[2-(4-methyl-1,3-thiazol-2-yl)ethyl]amineCatalog No.:AA019ZS4 CAS No.:102158-55-4 MDL No.:MFCD22375350 MF:C8H14N2S MW:170.2752 |
7-chloronaphthalene-1-sulfonyl chlorideCatalog No.:AA01A007 CAS No.:102153-62-8 MDL No.:MFCD01365823 MF:C10H6Cl2O2S MW:261.1244 |
4-(1H-indazol-3-yl)butan-2-oneCatalog No.:AA01A5ZH CAS No.:1021910-43-9 MDL No.:MFCD11100679 MF:C11H12N2O MW:188.2258 |
4-hydroxy-1-benzothiophene-6-carbaldehydeCatalog No.:AA01ABP5 CAS No.:1021916-91-5 MDL No.:MFCD22065776 MF:C9H6O2S MW:178.2077 |
3-Cyclopropyl-3-methylbutanoyl chlorideCatalog No.:AA01ALDV CAS No.:1021939-07-0 MDL No.:MFCD29033831 MF:C8H13ClO MW:160.6412 |
2-benzamido-1,3-thiazole-4-carboxylic acidCatalog No.:AA01ARG7 CAS No.:1022011-51-3 MDL No.:MFCD11564865 MF:C11H8N2O3S MW:248.2578 |
(4-Acetyl-2-fluorophenyl)boronic acidCatalog No.:AA01B15W CAS No.:1022154-78-4 MDL No.:MFCD22570911 MF:C8H8BFO3 MW:181.9567 |
3-Cyclopropyl-3-methylbutanoic acidCatalog No.:AA01BAQA CAS No.:1021939-05-8 MDL No.:MFCD19231813 MF:C8H14O2 MW:142.1956 |
1-(1-Methyl-1H-1,2,3-triazol-4-yl)ethan-1-olCatalog No.:AA01C4QZ CAS No.:1022093-96-4 MDL No.:MFCD24109419 MF:C5H9N3O MW:127.1445 |
Methyl 2-(4-bromophenyl)-2,2-difluoroacetateCatalog No.:AA01C53P CAS No.:1022155-94-7 MDL No.:MFCD21728862 MF:C9H7BrF2O2 MW:265.0515 |
2-(3,4-Dimethoxyphenyl)-2-isopropylpentanedinitrileCatalog No.:AA01DO3D CAS No.:102201-30-9 MDL No.:MFCD16885715 MF:C16H20N2O2 MW:272.3422 |
2-(6-Methylpiperidin-2-yl)ethanolCatalog No.:AA01DSRI CAS No.:10222-77-2 MDL No.:MFCD06637464 MF:C8H17NO MW:143.2267 |
4-Chloro-2-[(dimethylamino)methyl]anilineCatalog No.:AA01DUUG CAS No.:1022251-72-4 MDL No.:MFCD20702874 MF:C9H13ClN2 MW:184.6659 |
1-(2-Bromopropyl)-4-fluorobenzeneCatalog No.:AA01DX4E CAS No.:1021927-53-6 MDL No.:MFCD17274151 MF:C9H10BrF MW:217.0781 |
ARL67156 (trisodium)Catalog No.:AA01DZA5 CAS No.:1021868-83-6 MDL No.:MFCD08544552 MF:C15H21Br2N5Na3O12P3 MW:785.0521 |
AGN 192403 hydrochlorideCatalog No.:AA01DZA6 CAS No.:1021868-90-5 MDL No.:MFCD20486793 MF:C10H20ClN MW:189.7255 |
2,7-dimethyl-7H-purin-6-amineCatalog No.:AA01EI3K CAS No.:102153-93-5 MDL No.:MFCD20704224 MF:C7H9N5 MW:163.1799 |
3-(2,4-dichlorophenyl)oxolane-2,5-dioneCatalog No.:AA01EICA CAS No.:102154-20-1 MDL No.:MFCD19371722 MF:C10H6Cl2O3 MW:245.0588 |
(2E)-3-(3-chloro-4,5-dimethoxyphenyl)prop-2-enoic acidCatalog No.:AA01EM3H CAS No.:1022080-99-4 MDL No.:MFCD02256337 MF:C11H11ClO4 MW:242.6556 |
TC-G 1003Catalog No.:AA01ENK6 CAS No.:1021912-42-4 MDL No.:MFCD30182254 MF:C26H25ClN2O2 MW:432.9419 |
4,5-Dibromo-2-methylanilineCatalog No.:AA01FF9L CAS No.:102170-00-3 MDL No.:MFCD11845874 MF:C7H7Br2N MW:264.9452 |
3-Aminocarbonyl-5-nitrophenylboronic acidCatalog No.:AA0006PG CAS No.:102170-51-4 MDL No.:MFCD07783870 MF:C7H7BN2O5 MW:209.9519 |
6-Chloroisoquinolin-1-amineCatalog No.:AA008YC3 CAS No.:102200-00-0 MDL No.:MFCD07374396 MF:C9H7ClN2 MW:178.6183 |
3-Bromo-7-chloro-6-iodoquinolin-4-olCatalog No.:AA0006RK CAS No.:1021913-04-1 MDL No.:MFCD15527297 MF:C9H4BrClINO MW:384.3956 |
Potassium bis(1,2-benzenediolato)(1,3-butadien-2-yl)silicateCatalog No.:AA008VK0 CAS No.:1021940-25-9 MDL No.:MFCD12545945 MF:C16H13KO4Si MW:336.4558 |
2-Methyl-2-(quinolin-6-yl)propanoic acidCatalog No.:AA00H9OT CAS No.:1022283-51-7 MDL No.:MFCD18260330 MF:C13H13NO2 MW:215.2478 |