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PubMed1999

Stimulation of benzyladenine-induced in vitro shoot organogenesis and endogenous proline in melon (Cucumis melo L.) by fish protein hydrolysates in combination with proline analogues.

A previous study demonstrated that proline is beneficial for improving melon in vitro shoot organogenesis. A natural source of proline and proline precursors can be obtained from fish protein hydrolysates (FPH), a byproduct of the fishery industry. Proline analogues azetidine-2-carboxylate and hydroxyproline in combination with standardized FPH were used to stimulate proline synthesis and benzyladenine-induced shoot organogenesis by exploiting the proposed proline-linked pentose phosphate pathway (PPP). In the presence of elevated levels of endogenous proline, potential stimulation of cytokinins and auxin may occur via the PPP and shikimate pathways, respectively. Treatments with FPH singly and in combination with the above proline analogues significantly increased the endogenous proline content and the extent of differentiation, suggesting that in vitro organogenesis is closely linked to proline synthesis, strengthening the hypothesis that purine metabolism via the proline-linked PPP may be important for organogenesis. Thioproline addition resulted in increased proline levels but without corresponding stimulation of organogenesis. This study also provides potential use of fishery waste for value-added application in plant micropropagation industry.

Adenine↗
PubMed1995

Structure-activity study of tripeptide thrombin inhibitors using alpha-alkyl amino acids and other conformationally constrained amino acid substitutions.

In our continuing effort to design novel thrombin inhibitors, a series of conformationally constrained amino acids (e.g. alpha-alkyl, N-alkyl cyclic, etc.) were utilized in a systematic structure-activity study of the P3, P2, and P1 positions of tripeptide arginal thrombin inhibitors. Early examples of this effort include: D-MePhe-Pro-Arg-H (15), Boc-D-Phg-Pro-Arg-H (18), D-1-Tiq-Pro-Arg-H (23, D-1-Tiq = D-1,2,3,4-tetrahydroisoquinolin-1-ylcarbonyl), and Boc-D-Phe-Pro-Arg-H (25).10a,20 The current work clarifies the contribution of each residue of the tripeptide arginals toward the potent and selective inhibition of thrombin relative to that of t-PA and plasmin. The alpha-methylarginal modification in the P1 residue resulted in analogs 30 (D-MePhe at P3) and 32 (D-1-Tiq at P3) which had lower potency toward thrombin while exhibiting improved selectivity. Analogs modified at the P2 site were found to be very sensitive to the conformational changes induced by variations in side chain ring size with the flexible pipecolinic acid 31 being 2 orders of magnitude less potent at thrombin inhibition than the conformationally constrained azetidine analog 20. Examination of the P3 binding region indicated that alpha-alkylphenylglycine residues resulted in a tendency to exhibit substantial improvements in selectivity over the nonalkylated residues. Combinations of optimal P3 and P2 changes led to compounds TFA-D-Phg(alpha Et)-Azt-Arg-H (16), TFA-D-Phg(alpha Me)-Azt-Arg-H (17), Ac-D-Phg(alpha Me)-Azt-Arg-H (21), TFA-D-Phg(alpha Me)-Pro-Arg-H (27), 30, and 32, which are clearly more selective for thrombin versus plasmin than the nonconformationally constrained compounds.

Amino Acid Sequence↗
PubMed1993

7-Azetidinylquinolones as antibacterial agents. Synthesis and structure-activity relationships.

A series of novel antibacterial quinolones and naphthyridones has been prepared which contain 7-azetidinyl substituents in place of the usual piperazine or aminopyrrolidine groups. These azetidinyl derivatives were evaluated for in vitro activity by determining minimum inhibitory concentrations against a variety of bacteria. In vivo efficacy in the mouse infection model and blood levels in the mouse were determined for several compounds. The influence on the structure-activity relationships of varying substituents in the azetidine ring and at position 8 (CH, CF, CCl, N) and N-1 (ethyl, fluoroethyl, cyclopropyl, tert-butyl, 4-fluorophenyl, and 2,4-difluorophenyl) was also studied. Compounds with outstandingly broad-spectrum activity, particularly against Gram-positive organisms, improved in vivo efficacy, and high blood levels were identified in this work. 7-Azetidinyl-8-chloroquinolones were considered as warranting further development.

4-Quinolones↗
PubMed1993

Synthesis and biological activities of angiotensin II, Sarilesin, and Sarmesin analogues containing Aze or Pip at position 7.

Analogues of [Sar1]angiotensin II, Sarilesin (type I antagonist), and Sarmesin (type II antagonist) with L-azetidine-2-carboxylic acid (Aze) and L-pipecolic acid (Pip) at position 7 have been prepared by the solid-phase method, purified by reverse-phase HPLC, and bioassayed in the rat uterus. Analogues of the superagonist [Sar1]ANGII with Aze or Pip at position 7 and sarcosine (Sar) or aminoisobutyric acid (Aib) at position 1 had high intrinsic activity in the rat isolated uterus assay (34-184%). Analogues of Sarilesin ([Sar1,Ile8]ANGII) with Aze or Pip at position 7 and Sar or Aib at position 1 retained high antagonist activity (pA2 = 7.1-8.3). Analogues of Sarmesin ([Sar1,Tyr-(OMe)4]ANGII) with Aze and Pip at position 7 had pA2 values of 7.4 and 6.5, respectively. [Aze7]-ANGII and [Pip7]ANGII had low activities (12% and 1%, respectively), and deletion of Sar at position 1 of Sarmesin analogues abolished binding (or affinity) as judged from pA2 values. Nuclear Overhauser effect (NOE) spectroscopy studies of [Sar1,Aze7]ANGII in DMSO-d6 have indicated a clustering of the three aromatic rings (Tyr, His, Phe) and proximity of Sar C alpha and Arg C delta protons to the Tyr/Phe ring protons. These data emphasize that replacement of Pro with the lower and higher homologs Aze and Pip does not greatly alter the structural requirements necessary for expression of agonist or antagonist activity, when sarcosine occupies position 1, but not when Asp occupies position 1, suggesting that there is an intimate relationship between the N-terminal and penultimate residues of the molecule in the biologically active conformation of the molecule.

Angiotensin II↗
PubMed1993

Comparison of 5-HT1A and dopamine D2 pharmacophores. X-ray structures and affinities of conformationally constrained ligands.

Conformational and molecular mechanics studies of a new series of tricyclic ligands with affinity for either the dopamine D2 receptor or the 5-HT1A receptor, or both, has enabled us to elaborate considerably on previous pharmacophore models for these receptors. The new tricyclic ligands are either angular, 2,3,3a,4,5,9b-hexahydro-1H-benz[e]indole derivatives, or linear, 2,3,3a,4,5,9a-hexahydro-1H-benz[f]indole derivatives; they have either cis or trans ring junctions, and many of the ligands are resolved. In order to have X-ray crystal coordinates for every structural type, two additional crystal structures were determined: 14a, the trans-(+-)-6-hydroxy-3-(n-propyl) angular derivative as the hydrochloride, and (+-)-1,2,2a,3,4,8b-hexahydro-8-methoxy-2-(2-propenyl)-naphth[2,1- b]azetidine hydrochloride (16d). Several recently reported imidazoquinolinones with dopaminergic and serotonergic activities were also used in developing the models as were other known ligands which are conformationally constrained. A new method for determining intrinsic activity at the D2 receptor made consistent and reliable estimates of dopamine agonist, partial agonist, and antagonist activities available. The models explain these activities in terms of the 3-dimensional structural features of the ligands and their probable orientations at the D2 receptor site. They also explain why allyl and propyl analogs of some structures have very different affinities while affinities are quite similar for allyl and propyl analogs of other structures; at both receptors a particular orientation of the amine substituent in the binding site correlates with preference for allyl over propyl derivatives. Suggestions are made for enhancing selectivity at the 5-HT1A receptor or at the dopamine D2 receptor. An angular, cis, (3aR,9bS), 2-propyl, 9-hydroxy, 3-(n-propyl) analog should be selective for the 5-HT1A receptor. A linear, trans, (3aR,9aS), 7-hydroxy, 1-(2-propenyl) analog should be selective for the dopamine D2 receptor, and would be predicted to be an antagonist.

Binding Sites↗
PubMed1993

Synthesis and evaluation of the antitumor activity of 4,5-diamino-substituted 1,2-benzoquinones.

A series of 4,5-diamino-substituted-1,2-benzoquinones were prepared from catechol and the corresponding secondary amines in high yield in a single step using copper complex formation to stabilize the intermediate. The cytotoxicity of the products under various conditions was evaluated using the EMT-6 mammary carcinoma cell line, and antitumor activity was tested in the L1210 murine leukemia. The 4,5-diaziridinyl-1,2-benzoquinone was a more potent cytotoxic agent than diaziquone (AZQ) and was very effective against the L1210 leukemia. The azetidine, pyrrolidine, and diethylamine derivatives were not effective antitumor agents.

Animals↗
PubMed1992

Beta-proline analogues as agonists at the strychnine-sensitive glycine receptor.

3-Carboxy-3,4-dehydropyrrolidine was found to bind with affinity equal to that of glycine in a [3H]strychnine binding assay. Simple substitution of the 1-, 2-, 4-, or 5-position resulted in marked loss of affinity. A decline in affinity was also found upon enlargement, contraction, or saturation of the 5-membered ring. However, beta-proline and azetidine-3-carboxylic acid retained significant binding affinity. Despite its good affinity in [3H]strychnine binding, 3-carboxy-3,4-dehydropyrrolidine showed only weak agonist activity in intracellular recordings of cultured murine spinal cord neurons. This apparent lack of correlation between binding and functional results is discussed in light of the current models of the strychnine-sensitive glycine receptor.

Animals↗
PubMed1992

Synthesis and in vitro characterization of novel amino terminally modified oxotremorine derivatives for brain muscarinic receptors.

A series of novel 2-substituted acetylenic pyrrolidines and piperidines related to oxotremorine (1) were prepared and evaluated in vitro as muscarinic cholinergic agents at brain M1 and M2 receptors. One analogue, 3-(2-oxo-1-pyrrolidinyl)-1-[2(R)-pyrrolidinyl]-1-propyne hydrogen oxalate (6a), was found to be a partial agonist producing a PI hydrolysis response at cortical M1 receptors approximately 3-fold larger than that produced by 1. The intrinsic activity profile of 6a at brain muscarinic receptors is similar to those of azetidine oxo analogue 2 and dimethylamino oxo analogue. All three compounds are partial M1 agonists and full M2 agonists; however, the profile of 6a in binding studies is significantly different. While 2 and 3 exhibit large M2 selectivities ranging between 8-fold to several hundred-fold, the binding profile of 6a shows almost no subtype selectivity.

Animals↗
PubMed1991

Muscarinic receptor binding and activation of second messengers by substituted N-methyl-N-[4-(1-azacycloalkyl)-2-butynyl]acetamides.

A series of substituted azacycloalkyl analogues of the muscarinic agonist UH 5 (N-methyl-N-[4-(1-pyrrolidinyl)-2-butynyl]acetamide, 1a) were synthesized and evaluated pharmacologically. These compounds were developed as intermediates for further derivatization leading to functionalized congeners of 1a. The compounds were synthesized by using a Mannich-type condensation of N-acetyl-N-methylpropargylamine to various substituted saturated azaheterocycles. The compounds were screened at a single concentration in competitive binding assays in rat cerebral cortical membranes against either [3H]N-methylscopolamine (at 100 microM) or [3H]oxotremorine-M (at 1 microM) labels. Candidates were then selected for further evaluation of their effect on phosphoinositide (PI) turnover in membranes from A9L cells transfected with cDNA of either m1-muscarinic cholinergic receptors (m1AChRs) or m3AChRs. The analogues were also tested for the inhibition of adenylate cyclase in NG108-15 cells expressing m4AChRs. The azetidine analogue of 1a had a Ki value of 12 nM for the inhibition of [3H]oxotremorine-M binding in rat brain and had an agonist potency at m1-,m3-, and m4AChRs comparable to 1a. The substituted 5- and 6-member ring analogues generally had lower binding affinities and were less potent than 1a in stimulating PI turnover. Several compounds were moderately effective in inhibiting cyclic AMP production in NG108-15 cells.

Acetamides↗
PubMed1991

A new class of analogues of the bifunctional radiosensitizer alpha-(1-aziridinylmethyl)-2-nitro-1H-imidazole-1-ethanol (RSU 1069): the cycloalkylaziridines.

A series of compounds related to alpha-(1-aziridinylmethyl)-2-nitro-1H-imidazole-1-ethanol (RSU 1069, 1) were synthesized and evaluated as selective hypoxic cell cytotoxic agents and as radiosensitizers. The aziridine moiety was replaced with a number of other potential alkylating groups including cycloalkylaziridines and azetidines. The data indicated that modification of the aziridine of 1 resulted in a substantial decrease in the ability of the compounds to selectively kill hypoxic cells. However, these modifications did not affect the compounds' in vitro radiosensitizing activity since many of the derivatives were as potent as 1. All of the compounds that were evaluated in vivo were less toxic than 1, and several members of this series had significant activity. The best compound was trans-alpha-[[(4-bromotetrahydro-2H-pyran-3-yl) amino]methyl]-2-nitro-1H-imidazole-1-ethanol (18), which, due to its activity and log P value, is a candidate for additional in vivo studies.

Animals↗
PubMed1989

Stereoelectronic study of zetidoline, a dopamine D2 receptor antagonist.

A combination of experimental and theoretical methods were used to investigate the stereoelectronic structure of zetidoline, a dopamine D2 receptor antagonist showing Na+-dependent binding. The solid-state conformation of zetidoline is characterized by synplanarity (coplanarity of the two rings with the chloro substituent and the carbonyl group on the same side). The side chain in the crystal adopts a folded conformation which places the azetidine nitrogen atom at about 8 A from the center of the aromatic ring. Quantum mechanical calculations indicate the synperiplanar and antiperiplanar conformations of the ring system to be of approximately equal energies. The molecular electrostatic potential of zetidoline in a nearly extended conformation shows a remarkable similarity with that of orthopramides (e.g. metoclopramide) and indolones (e.g. piquindone), i.e. two groups of drugs displaying the same D2 selectivity and Na+-dependent binding. We postulate that the close stereoelectronic similarity between zetidoline, orthopramides, and indolones accounts for their identical mechanism of action in the molecular level.

Chemical Phenomena↗
PubMed1986

Dopamine receptor modulation by Pro-Leu-Gly-NH2 analogues possessing cyclic amino acid residues at the C-terminal position.

The synthesis of several analogues of L-prolyl-L-leucylglycinamide (PLG) was carried out in which the glycinamide residue was replaced with the following cyclic amino acid residues: L- and D-prolinamide, (+)- and (-)-thiazolidine-2-carboxamide, L- and D-3,4-dehydroprolinamide, L-azetidine-2-carboxamide, L-piperidine-2-carboxamide, and L-thiazolidine-4-carboxamide to give PLG analogues 2-10, respectively. The ability of these analogues to enhance the binding of the dopamine agonist ADTN (2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene) to dopamine receptors was determined by using bovine brain tissue. All of the PLG analogues synthesized in this study enhanced the binding of ADTN to central dopamine receptors. The percent enhancement of ADTN binding produced by analogues 2,3, and 7-10 at various concentrations was comparable to the percent enhancement produced by PLG. The PLG analogues Pro-Leu-(+)-thiazolidine-2-carboxamide (4), Pro-Leu-(-)-thiazolidine-2-carboxamide (5), and Pro-Leu-L-3,4-dehydroprolinamide (6), however, produced significantly greater enhancement (2-3-fold) in ADTN binding than did PLG.

Animals↗
PubMed1985

Synthesis and beta-lactamase inhibitory properties of 2 beta-[(acyloxy)methyl]-2-methylpenam-3 alpha-carboxylic acid 1,1-dioxides.

p-Nitrobenzyl 2 beta-[(benzoyloxy)methyl]-2 alpha-methylpenam-3 alpha-carboxylate was prepared by reaction of p-nitrobenzyl 2-[2-oxo-3 alpha-bromo-4-(benzothiazol-2-yldithio)azetidin-1-yl] -2-isopropenylacetate with silver benzoate in the presence of iodine. The resulting diester was oxidized to the sulfone with potassium permanganate and hydrogen peroxide, and the bromine and p-nitrobenzyl groups were removed by hydrogenolysis to give potassium 2 beta-(benzoyloxy)methyl 2 alpha-methylpenam-3 alpha-carboxylate 1,1-dioxide. A series of related compounds, including the pivaloyl, methoxybenzoyl, p-fluorobenzoyl, and p-aminobenzoyl derivatives, were prepared in a similar way. All of these compounds were potent beta-lactamase inhibitors in vitro against the TEM beta-lactamase from Klebsiella pneumoniae A22695 and Bacteroides fragiles A22695 but less active against the beta-lactamase from Staphylococcus aureus A9606. All compounds when administered orally in a 1:1 combination with amoxicillin did not show any significant protection of mice infected with S. aureus A9606. 2 beta-(Bromomethyl)-2 alpha-methylpenam-3 alpha-carboxylic acid was prepared and reacted with silver nitrate to give the nitrate ester. Oxidation with potassium permanganate and catalytic reduction afforded 2 beta-(hydroxymethyl)-2 alpha-methylpenam-3 alpha-carboxylic acid 1,1-dioxide. 2 beta-(Bromomethyl)-2 alpha-methylpenam-3 alpha-carboxylic acid 1,1-dioxide was found to be a strong beta-lactamase inhibitor, while the 2 beta-hydroxymethyl compound showed only weak beta-lactamase-inhibiting properties.

Amoxicillin↗
PubMed1987

Pyrroloisoquinoline antidepressants. 2. In-depth exploration of structure-activity relationships.

A series of pyrrolo[2,1-a]isoquinolines, and related compounds, were examined for antidepressant-like activity, by virtue of their antagonism of tetrabenazine-induced ptosis and sedation, and inhibition of biogenic amine uptake. Thus, we have identified some of the most potent antagonists of TBZ-induced ptosis and some of the most potent inhibitors of the uptake of dopamine, norepinephrine, and serotonin (in rat brain synaptosomes) ever reported. Compounds of particular note, in this regard, are 52b, 29b, 22b, and 48b, respectively. Biological activity was chiefly manifested by the trans isomeric class. Also, through resolution of four compounds, 7b, 24b, 37b, and 48b, biological activity was found to be associated with the (+) enantiomer subgroup (salts measured at 589 nm in MeOH), corresponding to the 6S, 10bR absolute configuration for 7b, 37b, and 48b, and the 6R,10bR configuration for 24b. An X-ray determination on (+)-24b X HBr established its absolute configuration; configurations for the other compounds were verified by enantiospecific synthesis starting with (+)-(R)-2-phenylpyrrolidine. Regarding the pendant phenyl ring, diverse substitution patterns were investigated. Those substitutions that were particularly unfavorable were 3',4',5'-trimethoxy (20b), 2',3',4',5',6'-pentafluoro (34b), 2'-trifluoromethyl (38b), 3',5'-bis(trifluoromethyl) (42b), 4'-n-butyl (44b), 2'-cyano (47b), 4'-methylsulfonyl (50b), and 2'-carboxy (58b). Exceedingly potent compounds, in one way or another, were 10b-12b, 22b, 23b, 25b, 28b, 29b, 33b, 45b, 48b, 51b-53b. The pattern of aromatic substitution had a strong impact on selectivity in the uptake tests (NE vs. DA vs. 5-HT). Activity was significantly diminished by methyl substitution of 7b at the 5 (65, 66), 6 (61b), or 10b (60b) position, by changing the phenyl group of 7b to cyclohexyl (67b), benzyl (68b), or H (72), by moving the phenyl group of 7b to the 5 (69) or 10b (70) position, by expansion of ring B to an azepine (78b), and by modification of ring C to an azetidine (77b), piperidine (75b), or azepine (74b). The interaction of selected analogues with various CNS receptors is reported. Little affinity was shown for the muscarinic cholinergic receptor, suggesting a lack of anticholinergic side effects. Interestingly, 24b and 33b displayed a high affinity for the serotonin-2 receptor, analogous to mianserin and clomipramine. After the body of data was reviewed, derivatives 24b and 48b were chosen for advanced development.

Animals↗
PubMed2000

Synthesis and evaluation of 17-aliphatic heterocycle-substituted steroidal inhibitors of 17alpha-hydroxylase/C17-20-lyase (P450 17).

In the search for potent inhibitors of P450 17, the key enzyme in androgen biosynthesis, a series of steroidal inhibitors were synthesized and tested toward rat and human P450 17. Small aliphatic heterocycles (aziridine, oxirane, thiirane, diaziridine, diazirine, azetidine) were introduced into the 17beta-position of anstrost-5-en-3beta-ol. After identifying that aziridine is the most suitable functional group to coordinate with the heme iron, modifications of the steroidal skeleton were performed for further optimization. A wide range of inhibitory potencies toward P450 17 were found for the 21 test compounds. The most potent inhibitors toward the human and rat enzyme were aziridine compounds 3 (IC(50) rat: 0.21 microM, K(i) = 3 nM; IC(50) human: 0.54 microM, K(i) = 8 nM), 5 (IC(50) rat: 0.43 microM, K(i) = 7 nM; IC(50) human: 0.29 microM, K(i) = 4 nM), and 8 (21R:21S = 1:1; IC(50) rat: 0.53 microM, K(i) = 9 nM; IC(50) human: 0.40 microM, K(i) = 6 nM) which were more potent than the reference ketoconazole (IC(50) rat: 67 microM; IC(50) human: 0.74 microM). The inhibitory potency depends markedly on the stereochemistry at C20 of the inhibitors. This effect is more pronounced for the rat enzyme. Tested for selectivity, the highly potent inhibitors show poor inhibitory activity toward P450 arom, P450 scc, P450 TxA(2), and 5alpha-reductase. Tested for in vivo activity, 3 and 8 (0.019 mmol/kg) decreased the plasma testosterone concentration in rats by 81% and 84% after 2 h.

Androstenols↗
PubMed2002

Metal-mediated carbonyl-1,3-butadien-2-ylation by 1,4-bis(methanesulfonyl)-2-butyne or 1,4-dibromo-2-butyne in aqueous media: asymmetric synthesis of 3-substituted 3-hydroxy-beta-lactams.

Metal-mediated 1,3-butadien-2-ylation reactions between 1,4-dibromo-2-butyne or 1,4-bis(methanesulfonyl)-2-butyne and optically pure azetidine-2,3-diones were investigated in aqueous media, offering a convenient asymmetric entry to the potentially bioactive 3-substituted 3-hydroxy-beta-lactam moiety. The diastereoselectivity of the addition reaction was controlled by the bulky chiral auxiliary at C4. However, while the regioselectivity of the process was full, the chemical yield of the addition was a function of the nature of both the metal reagent and the system solvent as well. In addition, 2-azetidinone-tethered 1,3-butadienes can easily be transformed into other functionalities via Diels-Alder reaction.

Journal Article↗
PubMed2004

Theoretical analysis of Lewis basicity based on local electron-donating ability. Origin of basic strength of cyclic amines.

It has been experimentally established that the proton affinities (PA), as well as the solution basicities (pK(BH)(+)), of aziridine derivatives are much smaller than those of the corresponding pyrrolidines and piperidines, though the basic strength of azetidines is close to those of pyrrolidines and piperidines. A simple idea of dependence of the basic strength on bond angles seems to be invalid. Because the basicity of cyclic amines is a fundamental property in organic chemistry, we revisited this topic in order to clarify quantitatively the intrinsic origin of the strength of Lewis basicity of the relevant amines, in particular, based on the local electron-donating ability of the amine nitrogen atoms evaluated in terms of the localized reactive hybrid orbital (RHO) concept. In the cases of representative N-substituents such as hydrogen, methyl, and phenyl groups, the electron-donating energy level of the nitrogen center, obtained by maximizing a kind of superdelocalizability, was shown to be correlated with the magnitudes of experimental and calculated gas-phase proton affinities. The present results strongly support the view that the C-N-C bond angle, i.e., angle strain, in the cyclic amines is not the major source of the difference in strength of basicity of these amines, but rather, the degree of pyramidalization around the nitrogen atom has a significant impact on the electron-donating ability of the nitrogen lone-pair orbital.

Journal Article↗
PubMed2006

Aqueous N-heterocyclization of primary amines and hydrazines with dihalides: microwave-assisted syntheses of N-azacycloalkanes, isoindole, pyrazole, pyrazolidine, and phthalazine derivatives.

[reactions: see text] The synthesis of nitrogen-containing heterocycles from alkyl dihalides (ditosylates) and primary amines and hydrazines via a simple and efficient cyclocondensation in an alkaline aqueous medium that occurs under microwave irradiation is described. This improved greener synthetic methodology provides a simple and straightforward one-pot approach to the synthesis of a variety of heterocycles, such as substituted azetidines, pyrrolidines, piperidines, azepanes, N-substituted 2,3-dihydro-1H-isoindoles, 4,5-dihydropyrazoles, pyrazolidines, and 1,2-dihydrophthalazines.

Alkanes↗