Chemistry and Pharmacology of Nicotinic Ligands Based on 6‐[5‐(Azetidin‐2‐ylmethoxy)pyridin‐3‐yl]hex‐5‐yn‐1‐ol (AMOP‐H‐OH) for Possible Use in Depression

AMOP‐H‐OH (sazetidine‐A; 6‐[5‐(azetidin‐2‐ylmethoxy)pyridin‐3‐yl]hex‐5‐yn‐1‐ol) and some sulfur‐bearing analogues were tested for their activities in vitro against human α4β2‐, α4β4‐, α3β4*‐ and α1*‐nicotinic acetylcholine receptors (nAChRs). AMOP‐H‐OH was also assessed in an antidepressant efficacy model. AMOP‐H‐OH and some of its analogues have high potency and selectivity for α4β2‐nAChRs over other nAChR subtypes. Effects are manifested as partial agonism, perhaps reflecting selectivity for high sensitivity (α4)₃(β2)₂‐nAChRs. More prolonged exposure to AMOP‐H‐OH and its analogues produces inhibition of subsequent responses to acute challenges with full nicotinic agonists, again selectively for α4β2‐nAChRs over other nAChR subtypes. The inhibition is mediated either via antagonism or desensitization of nAChR function, but the degree of inhibition of α4β2‐nAChRs is limited by the partial agonist activity of the drugs. Certain aspects of the in vitro pharmacology suggest that AMOP‐H‐OH and some of its analogues have a set of binding sites on α4β2‐nAChRs that are distinct from those for full agonists. The in vitro pharmacological profile suggests that peripheral side effects of AMOP‐H‐OH or its analogues would be minimal and that their behavioral effects would be dominated by central nAChR actions. AMOP‐H‐OH also has profound and high potency antidepressant‐like effects in the forced swim test. The net action of prolonged exposure to AMOP‐H‐OH or its analogues, as for nicotine, seems to be a selective decrease in α4β2‐nAChR function. Inactivation of nAChRs may be a common neurochemical endpoint for nicotine dependence, its treatment, and some of its manifestations, including relief from depression.     

Enzymatic Methylation and Structure–Activity‐Relationship Studies on Polycarcin V,a Gilvocarcin‐Type Antitumor Agent

Polycarcin V, a polyketide natural product of Streptomyces polyformus, was chosen to study structure–activity relationships of the gilvocarcin group of antitumor antibiotics due to a similar chemical structure and comparable bioactivity with gilvocarcin V, the principle compound of this group, and the feasibility of enzymatic modifications of its sugar moiety by auxiliary O‐methyltransferases. Such enzymes were used to modify the interaction of the drug with histone H3, the biological target that interacts with the sugar moiety. Cytotoxicity assays revealed that a free 2′‐OH group of the sugar moiety is essential to maintain the bioactivity of polycarcin V, apparently an important hydrogen bond donor for the interaction with histone H3, and converting 3′‐OH into an OCH₃ group improved the bioactivity. Bis‐methylated polycarcin derivatives revealed weaker activity than the parent compound, indicating that at least two hydrogen bond donors in the sugar are necessary for optimal binding.     

Discovery of 7‐Aryl‐Substituted (1,5‐Naphthyridin‐4‐yl)ureas as Aurora Kinase Inhibitors

As part of our research projects to identify new chemical entities of biological interest, we developed a synthetic approach and the biological evaluation of (7‐aryl‐1,5‐naphthyridin‐4‐yl)ureas as a novel class of Aurora kinase inhibitors for the treatment of malignant diseases based on pathological cell proliferation. 1,5‐Naphthyridine derivatives showed excellent inhibitory activities toward Aurora kinases A and B, and the most active compound, 1‐cyclopropyl‐3‐[7‐(1‐methyl‐1H‐pyrazol‐4‐yl)‐1,5‐naphthyridin‐4‐yl]urea ( 49 ), displayed IC₅₀ values of 13 and 107 nM against Aurora kinases A and B, respectively. In addition, the selectivity toward a panel of seven cancer‐related protein kinases was highlighted. In vitro ADME properties were also determined in order to rationalize the difficulties in correlating antiproliferative activity with Aurora kinase inhibition. Finally, the good safety profile of these compounds imparts promising potential for their further development as anticancer agents.     

Design,Synthesis, and Evaluation of 2‐Amino‐6‐nitrobenzothiazole‐Derived Hydrazones as MAO Inhibitors: Role of the Methylene Spacer Group

A series of 2‐amino‐6‐nitrobenzothiazole‐derived extended hydrazones were designed, synthesized, and investigated for their ability to inhibit monoamine oxidase A and B (MAO‐A/MAO‐B). The compounds were found to exhibit inhibitory activities in the nanomolar to micromolar range. Some of the compounds showed excellent potency and selectivity against the MAO‐B isoform. N′‐(5‐Chloro‐2‐oxoindolin‐3‐ylidene)‐2‐(6‐nitrobenzothiazol‐2‐ylamino)acetohydrazide (compound 31 ) showed the highest MAO‐B inhibitory activity (IC₅₀=1.8±0.3 nm , selectivity index [SI]=766.67), whereas compound 6 [N′‐(1‐(4‐bromophenyl)ethylidene)‐2‐(6‐nitrobenzothiazol‐2‐ylamino)acetohydrazide] was found to be the most active MAO‐A inhibitor (IC₅₀=0.42±0.003 μm ). Kinetic studies revealed that compounds 6 and 31 exhibit competitive‐type reversible inhibition against both MAO‐A and MAO‐B, respectively. Structure–activity relationship (SAR) studies disclosed several structural aspects significant for potency and the contribution of the methylene spacer toward MAO‐B inhibitory potency, with minimal or no neurotoxicity. Molecular modeling studies yielded a good correlation between experimental and theoretical inhibitory data. Binding pose analysis revealed the significance of cumulative effects of π–π stacking and hydrogen bond interactions for effective stabilization of virtual ligand–protein complexes. Further optimization studies of compound 31 , including co‐crystallization of inhibitor–MAO‐B complexes, are essential to develop these compounds as potential therapeutic agents for MAO‐B‐associated neurodegenerative diseases.     

β‐Aminopeptidase‐Catalyzed Biotransformations of β2‐Dipeptides: Kinetic Resolution and Enzymatic Coupling

We have previously shown that the β‐aminopeptidases BapA from Sphingosinicella xenopeptidilytica and DmpA from Ochrobactrum anthropi can catalyze reactions with non‐natural β³‐peptides and β³‐amino acid amides. Here we report that these exceptional enzymes are also able to utilize synthetic dipeptides with N‐terminal β²‐amino acid residues as substrates under aqueous conditions. The suitability of a β²‐peptide as a substrate for BapA or DmpA was strongly dependent on the size of the C_α substituent of the N‐terminal β²‐amino acid. BapA was shown to convert a diastereomeric mixture of the β²‐peptide H‐β²hPhe‐β²hAla‐OH, but did not act on diastereomerically pure β²,β³‐dipeptides containing an N‐terminal β²‐homoalanine. In contrast, DmpA was only active with the latter dipeptides as substrates. BapA‐catalyzed transformation of the diastereomeric mixture of H‐β²hPhe‐β²hAla‐OH proceeded along two highly S‐enantioselective reaction routes, one leading to substrate hydrolysis and the other to the synthesis of coupling products. The synthetic route predominated even at neutral pH. A rise in pH of three log units shifted the synthesis‐to‐hydrolysis ratio (v_S/v_H) further towards peptide formation. Because the equilibrium of the reaction lies on the side of hydrolysis, prolonged incubation resulted in the cleavage of all peptides that carried an N‐terminal β‐amino acid of S configuration. After completion of the enzymatic reaction, only the S enantiomer of β²‐homophenylalanine was detected (ee>99 % for H‐(S)‐β²‐hPhe‐OH, E>500); this confirmed the high enantioselectivity of the reaction. Our findings suggest interesting new applications of the enzymes BapA and DmpA for the production of enantiopure β²‐amino acids and the enantioselective coupling of N‐terminal β²‐amino acids to peptides.     

Synthesis,Pharmacological Evaluation,and Docking Studies of Novel Pyridazinone‐Based Cannabinoid Receptor Type 2 Ligands

In recent years, cannabinoid type 2 receptors (CB₂R) have emerged as promising therapeutic targets in a wide variety of diseases. Selective ligands of CB₂R are devoid of the psychoactive effects typically observed for CB₁R ligands. Based on our recent studies on a class of pyridazinone 4‐carboxamides, further structural modifications of the pyridazinone core were made to better investigate the structure–activity relationships for this promising scaffold with the aim to develop potent CB₂R ligands. In binding assays, two of the new synthesized compounds [6‐(3,4‐dichlorophenyl)‐2‐(4‐fluorobenzyl)‐cis‐N‐(4‐methylcyclohexyl)‐3‐oxo‐2,3‐dihydropyridazine‐4‐carboxamide ( 2 ) and 6‐(4‐chloro‐3‐methylphenyl)‐cis‐N‐(4‐methylcyclohexyl)‐3‐oxo‐2‐pentyl‐2,3‐dihydropyridazine‐4‐carboxamide ( 22 )] showed high CB₂R affinity, with K_i values of 2.1 and 1.6 nm , respectively. In addition, functional assays of these compounds and other new active related derivatives revealed their pharmacological profiles as CB₂R inverse agonists. Compound 22 displayed the highest CB₂R selectivity and potency, presenting a favorable in silico pharmacokinetic profile. Furthermore, a molecular modeling study revealed how 22 produces inverse agonism through blocking the movement of the toggle‐switch residue, W6.48.     

Palladium‐Catalyzed Selective Aryl Ring C–H Activation of N‐Acyl‐2‐aminobiaryls: Efficient Access to Multiaryl‐Substituted Naphthalenes

Palladium‐catalyzed cycloaromatization of N‐acyl‐2‐aminobiaryls, through a sequence of ortho C−H bond activation/alkyne insertion/meta C−H bond activation/alkyne insertion, was developed. An efficient synthesis of multiaryl‐substituted naphthalenes, N‐[2‐(5,6,7,8‐tetraarylnaphthalen‐1‐yl)aryl]acetamides, was demonstrated using molecular oxygen as the sole oxidant. Furthermore, through Buchwald's synthetic protocol, two compounds were converted into corresponding fluorescent carbazoles in 30–40% yield by intramolecular C−N bond formation.

     

Synthesis and characterization of polyhydroxylated polybutadiene binding 2,2′‐thiobis(4‐methyl‐6‐tert‐butylphenol) with isophorone diisocyanate

A macromolecular hindered phenol antioxidant, polyhydroxylated polybutadiene containing thioether binding 2,2′‐thiobis(4‐methyl‐6‐tert‐butylphenol) (PHPBT‐b‐TPH), was synthesized via a two‐step nucleophilic addition reaction using isophorone diisocyanate (IPDI) as linkage. First, the ? OH groups of PHPBT reacted with secondary ? NCO groups of IPDI to form the adduct PHPBT‐NCO, then the PHPBT‐b‐TPH was obtained by one phenolic ? OH of 2,2′‐thiobis(4‐methyl‐6‐tert‐butylphenol) (TPH) reacting with the PHPBT‐NCO. The PHPBT‐b‐TPH was characterized by Fourier transform infrared spectroscopy, ¹H nuclear magnetic resonance (¹H‐NMR), ¹³C‐NMR, and thermogravimetric analysis, and its antioxidant activity in natural rubber was studied by an accelerated aging test. Influences of reaction conditions on the two nucleophilic reactions between ? OH group and ? NCO group were investigated. In addition, catalytic mechanism for the reaction between PHPBT‐NCO and TPH was discussed. The results showed that the adduct PHPBT‐NCO could be obtained by using dibutyltin dilaurate (DBTDL) as catalyst, and the suitable temperature and DBTDL amount were 35°C and 3 wt %, respectively. However, triethylamine (TEA) was more efficient than DBTDL to catalyze the reaction between PHPBT‐NCO and TPH because of steric hindrance effect. In addition, it was found that the thermal stability and antioxidant activity of PHPBT‐b‐TPH were higher than those of the low molecular weight antioxidant TPH. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40942.     

Design,Synthesis, and Structure–Activity Relationships of 3,4,5‐Trisubstituted 4,5‐Dihydro‐1,2,4‐oxadiazoles as TGR5 Agonists

Given its role in the mediation of energy and glucose homeostasis, the G‐protein‐coupled bile acid receptor 1 (TGR5) is considered a potential target for the treatment of type 2 diabetes mellitus and other metabolic disorders. By thorough analysis of diverse structures of published TGR5 agonists, a hypothetical ligand‐based pharmacophore model was built, and a new class of potent TGR5 agonists, based on the novel 3,4,5‐trisubstituted 4,5‐dihydro‐1,2,4‐oxadiazole core, was discovered by rational design. Three distinct synthetic methods for constructing 4,5‐dihydro‐1,2,4‐oxadiazoles and extensive structure–activity relationship studies are reported herein. Compound (R)‐ 54 n , the structure of which was determined by single‐crystal X‐ray diffraction and quantum chemical solid‐state TDDFT‐ECD calculations, showed the best potency, with an EC₅₀ value of 1.4 nM toward hTGR5. Its favorable properties in vitro warrant further investigation.     

Functionalized multiarm poly(ϵ‐caprolactone)s: Synthesis,structure analysis,and network formation

The purpose of this research was to synthesize and characterize a novel class of four‐arm, star‐shape biodegradable polymers having double‐bond functionality as a precursor for free‐radical polymerization, with unsaturated monomers or macromers or photocrosslinking for network formation. The synthesis involved two basic steps. First, hydroxyl‐functionalized four‐arm poly(?‐caprolactone)s (PPCL‐OH) were synthesized by the ring‐opening polymerization of ?‐caprolactone in the presence of pentaerythritol and stannous octoate. Second, double‐bond–functionalized four‐arm poly(?‐caprolactone)s (PPCL‐Ma) were synthesized by reacting PPCL‐OH with maleic anhydride in the melt at 130°C. Quantitative conversion of hydroxyl functionality in PPCL‐OH to double‐bond functionality was achieved for low molecular weight PPCL‐OH. Both the PPCL‐OH and the PPCL‐Ma were characterized by FTIR, ¹H‐NMR, ¹³C‐NMR, SEC, and DSC. The capability of the double‐bond–functionalized four‐arm poly(?‐caprolactone)s (PPCL‐Ma) to form network structures was preliminarily shown by photocrosslinking PPCL‐Ma. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 2296–2306, 2002     

Indium‐Catalyzed Formal N‐Arylation and N‐Alkylation of Pyrroles with Amines

Under indium Lewis acid catalysis, a nitrogen atom of N‐unsubstituted pyrroles was replaced with a nitrogen atom of primary amines, thereby producing N‐aryl‐ and N‐alkylpyrroles. This system formally introducing such carbon frameworks to the pyrrole nitrogen atom shows unique selectivity: only the H−N(pyrrolyl) unit undergoes the N‐arylation and N‐alkylation even in the coexistence of a similar H−N(indolyl) part; and an aryl–halogen bond remains intact. These are clearly different from the typical method depending on the C−N(pyrrolyl) bond‐forming reaction with organic halides as substrates. From a viewpoint of pyrrole N‐protection–deprotection chemistry, worth noting is that a methyl group on the pyrrole nitrogen atom can be removed, albeit in a formal way.

     

Synthesis of Methylene‐Bridge Polyarenes through Palladium‐Catalyzed Activation of Benzylic Carbon‐Hydrogen Bond

In the presence of palladium(II) acetate [Pd(OAc)₂] and an N‐heterocyclic carbene (NHC) ligand, fluorene derivatives can be generated in good to excellent yields from 2‐halo‐2′‐methylbiaryls through the benzylic C H bond activation (14 examples; 81–97% yields). The scope and limitations of this protocol have been examined. A wide range of functional groups, such as alkyl, alkoxy, ester, nitrile, and others, is able to tolerate the reaction conditions herein. The cyclization of an isotope‐labelled biphenyl gave the corresponding product with a primary kinetic isotope effect (k_H/k_D=4.8:1), which indicates that the rate‐determining step of this reaction is the activation of the benzylic C H bond. Moreover, indenofluorenes were also accessed in excellent results from terphenyls (3 examples; 91–92% yields). The cascade reaction of 2,6‐dichloro‐2′‐methylbiphenyl with diphenylacetylene produced 8,9‐diphenyl‐4H‐cyclopenta[def]phenanthrene in 60% yield through the activation of an aryl and a benzylic C H bond.     

Competitive hydrogen bonding mechanisms underlying phase behavior of triple poly(N‐vinyl pyrrolidone)–poly(ethylene glycol)–poly(methacrylic acid‐co‐ethylacrylate) blends

Differential scanning calorimetry (DSC) of triple blends of high molecular weight poly(N‐vinyl pyrrolidone) (PVP) with oligomeric poly(ethylene glycol) (PEG) of molecular weight 400 g/mol and copolymer of methacrylic acid with ethylacrylate (PMAA‐co‐EA) demonstrates partial miscibility of polymer components, which is due to formation of interpolymer hydrogen bonds (reversible crosslinking). Because both PVP and PMAA‐co‐EA are amorphous polymers and PEG exhibits crystalline phase, the DSC examination is informative on the phase state of PEG in the triple blends and reveals a strong competition between PEG and PMAA‐co‐EA for interaction with PVP. The hydrogen bonding in the triple PVP–PEG–PMAA‐co‐EA blends has been established with FTIR Spectroscopy. To evaluate the relative strengths of hydrogen bonded complexes in PVP–PEG–PMAA‐co‐EA blends, quantum‐chemical calculations were performed. According to this analysis, the energy of H‐bonding has been found to diminish in the order: PVP–PMAA‐co‐EA–PEG(OH) > PVP–(OH)PEG(OH)–PVP > PVP–H₂O > PVP–PEG(OH) > PMAA‐co‐EA–PEG(? O? ) > PVP–PMAA‐co‐EA > PMAA‐co‐EA–PEG(OH). Thus, most stable complexes are the triple PVP–PMAA‐co‐EA–PEG(OH) complex and the complex wherein comparatively short PEG chains form simultaneously two hydrogen bonds to PVP carbonyl groups through both terminal OH‐groups, acting as H‐bonding crosslinks between longer PVP backbones. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Biosynthetic Gene Cluster of a d‐Tryptophan‐Containing Lasso Peptide,MS‐271

MS‐271, produced by Streptomyces sp. M‐271, is a lasso peptide natural product comprising 21 amino acid residues with a d ‐tryptophan at its C terminus. Because lasso peptides are ribosomal peptides, the biosynthesis of MS‐271, especially the mechanism of d ‐Trp introduction, is of great interest. The MS‐271 biosynthetic gene cluster was identified by draft genome sequencing of the MS‐271 producer, and it was revealed that the precursor peptide contains all 21 amino acid residues including the C‐terminal tryptophan. This suggested that the d ‐Trp residue is introduced by epimerization. Genes for modification enzymes such as a macrolactam synthetase (mslC), precursor peptide recognition element (mslB1), cysteine protease (mslB2), disulfide oxidoreductases (mslE, mslF), and a protein of unknown function (mslH) were found in the flanking region of the precursor peptide gene. Although obvious epimerase genes were absent in the cluster, heterologous expression of the putative MS‐271 cluster in Streptomyces lividans showed that it contains all the necessary genes for MS‐271 production including a gene for a new peptide epimerase. Furthermore, a gene‐deletion experiment indicated that MslB1, ‐B2, ‐C and ‐H were indispensable for MS‐271 production and that some interactions of the biosynthetic enzymes were essential for the biosynthesis of MS‐271.     

Synthetic Ni‐talc as filler for producing polyurethane nanocomposites

New synthetic Ni‐talc was used as filler in the synthesis of polyurethane (PU) nanocomposites by in situ polymerization and to emphasize the contribution of the new material compared with natural talc. Good dispersion of Ni‐talc was supported by homogeneous green coloration observed in the polymer matrix. X‐ray diffraction (XRD) analyses indicate the intercalation of polymeric matrix into the filler layers by the increase in d₀₀₁‐spacing value of the Ni‐talc for the nanocomposites when compared to the pristine filler. The nanocomposites obtained with synthetic talc showed an improvement in the crystallization temperature and in thermal stability when compared to pure PU and the composite obtained with natural talc. The young modulus of PU/talc materials containing both Ni‐talc and natural talc were slight higher than pure PU. As shown by scanning electron microscope (SEM), Ni‐talc fillers were well dispersed into the polymeric matrix probably due to the good compatibility of both phases filler/polymer mainly achieved by the filler OH interaction with the urethane group of the polymeric chain. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41854.     

Structural Exploration of (3S,6S)‐6‐Benzhydryl‐N‐benzyltetrahydro‐2H‐pyran‐3‐amine Analogues: Identification of Potent Triple Monoamine Reuptake Inhibitors as Potential Antidepressants

To further explore the basic structural motifs (3S,6S)‐6‐benzhydryl‐N‐benzyltetrahydro‐2H‐pyran‐3‐amine and (2S,4R,5R)‐2‐benzhydryl‐5‐(benzylamino)tetrahydro‐2H‐pyran‐4‐ol, developed by our research group, for monoamine transport inhibition, we designed and synthesized various structurally altered analogues. The new compounds were tested for their affinities for the dopamine transporter (DAT), the serotonin transporter (SERT), and the norepinephrine transporter (NET) in rat brain by measuring their capacity to inhibit the uptake of [³H]DA, [³H]5‐HT, and [³H]NE, respectively. Our results point to novel compounds with a TUI, DNRI, SNRI, or SSRI profile. Among the TUIs, compound 2 g exhibited a balanced potency for all three monoamine transporters (K_i: 60, 79, and 70.3 nM for DAT, SERT, and NET, respectively). In the rat forced swim test, compound 2 g produced a significant decrease in immobility in drug‐treated rats relative to vehicle, indicating a potential antidepressant property.     

Chemistry,Properties, and in Vitro and in Vivo Applications of 2′‐O‐Methoxyethyl‐4′‐thioRNA,a Novel Hybrid Type of Chemically Modified RNA

We report the synthesis, properties, and in vitro and in vivo applications of 2′‐O‐methoxyethyl‐4′‐thioRNA (MOE‐SRNA), a novel type of hybrid chemically modified RNA. In its hybridization with complementary RNA, MOE‐SRNA showed a moderate improvement of T_m value (+3.4 °C relative to an RNA:RNA duplex). However, the results of a comprehensive comparison of the nuclease stability of MOE‐SRNA relative to 2′‐O‐methoxyethylRNA (MOERNA), 2′‐O‐methyl‐4′‐thioRNA (Me‐SRNA), 2′‐O‐methylRNA (MeRNA), 4′‐thioRNA (SRNA), and natural RNA revealed that MOE‐SRNA had the highest stability (t_1/2>48 h in human plasma). Because of the favorable properties of MOE‐SRNA, we evaluated its in vitro and in vivo potencies as an anti‐microRNA oligonucleotide against miR‐21. Although the in vitro potency of MOE‐SRNA was moderate, its in vivo potency was significant for the suppression of tumor growth (similar to that of MOERNA).     

Fueling Open‐Source Drug Discovery: 177 Small‐Molecule Leads against Tuberculosis

With the aim of fuelling open‐source, translational, early‐stage drug discovery activities, the results of the recently completed antimycobacterial phenotypic screening campaign against Mycobacterium bovis BCG with hit confirmation in M. tuberculosis H37Rv were made publicly accessible. A set of 177 potent non‐cytotoxic H37Rv hits was identified and will be made available to maximize the potential impact of the compounds toward a chemical genetics/proteomics exercise, while at the same time providing a plethora of potential starting points for new synthetic lead‐generation activities. Two additional drug‐discovery‐relevant datasets are included: a) a drug‐like property analysis reflecting the latest lead‐like guidelines and b) an early lead‐generation package of the most promising hits within the clusters identified.     

Design and synthesis of biodegradable copolyester poly(ε‐caprolactone‐co‐d,l‐lactide) with four pendent functional groups

A novel biodegradable copolyester poly(ε‐caprolactone‐co‐d ,l ‐lactide) with four pendent functional groups was designed and synthesized. The synthetic route includes the following three steps: (1) synthesis of OH‐terminated PCLA (PCLA‐OH) by the ring‐opening copolymerization of ε‐caprolactone and d ,l ‐lactide; (2) end‐group functionalization of PCLA‐OH through the esterification with lysine; and (3) synthesis of tetra‐amino‐terminated PCLA (PCLA‐NH₂) by removing the protecting groups. The composition, structure, and thermal property of these copolyesters were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, and modulated differential scanning calorimetry. Results revealed that the molecular weight and glass transition temperature of PCLA‐NH₂ can be tailored by the careful selection of synthesis parameters. Moreover, polyester elastomers based on PCLA‐NH₂ were synthesized and characterized. These polyester elastomers are stabilized in their rubbery state in room temperature and exhibit tunable physiochemical and mechanical properties. POLYM. ENG. SCI., 54:2170–2176, 2014. © 2013 Society of Plastics Engineers