1,4-dihydropyridine compounds

Sambongi Y, Nitta H, Ichihashi K, Futai M, Ueda I (2002) A novel water-soluble Hantzsch 1,4-dihydropyridine compound that functions in biological processes through NADH regeneration. J Org Chem 67 3499-3501... 

Ohsumi K, Sekiyama T, Nakagawa R, Tsuji T, Morinaga Y, Ohishi K (1994) 1,4-dihydropyridine compounds useful as reverse resistance agents. US Patent 5 292 757... 

Peglion JL, Aasssi G, Pierre A, Kraus-Berthier L, Guilbaud N, Vilaine JP (1995) 1,4-Dihydropyridine compounds. US Patent 5 389 644... 

The structural features leading to optimal activity of the 1,4-dihydropyridines have been studied in detail. This group comprises the largest number of calcium channel blocking drugs and the individual compounds vary both in potency and selectivity. 1,4-Dihydropyridine compounds have been developed which show agonist effects at the calcium channel. 

A process is described to improve the reproduction quality of multiply exposable negatively tonable light-sensitive reproduction materials containing at least one 1,4-dihydropyridine compound, wherein the light-sensitive layer is treated with a strong acid before the imagewise exposure. Appl. November 12,1986. 

The most common type of Ca channel in smooth muscle is the L-channel. It belongs, as do all known channels, to the same family of channels as the Na channel of nerve and skeletal muscle, and has a conductance of about 20pS. A cardinal characteristic of the L-channel is its affinity for and sensitivity to a number of dihydropyridine compounds. These drugs can affect the probability of L-chan-nels being open. The inhibitory members (e.g., nifedipine) of this group of drugs decrease the L-channel open-time probability, while the excitatory members, (e.g., BAY-K 8644), increase the open-time probability. The implication here is that the... 

Carroll, W. A., Chen, Y., Drizin, I., Kerwin, J. F., Moore, J. L. (Abbott Laboratories) Cyclopentanone dihydropyridine compounds useful as potassium channel openers, W00051986. 

Hopf, F.W., Reddy, P., Hong, J., and Steinhardt, R.A., 1996a, A capacitative calcium current in cultured skeletal muscle cells is mediated by the calcium-specific leak channel and inhibited by dihydropyridine compounds, J Biol Chem, 271, pp 22358-22367. 

Tanaka H, Shigenobu K (2000) AHC-52, a dihydropyridine compound with chloride current-blocking and cardioprotective activities. Cardiovasc Drug Rev 18 93-102... 

Zhou X, MacDiarmid J, Coburn RA, Morris ME (2005) Pharmacokinetics and bioavailability of a newly synthesized dihydropyridine compound with multidrug resistance reversal activity. Biopharm Drug Dispos 26 279-285... 

Miyajima M, Yamaguchi Y, Tsunematsu T, Toshihisa O. Pharmaceutical composition of dihydropyridine compound. United States Patent No. 4,983,593 1989. 

Kass RS and Arena JP, Influence of pHo on calcium channel block by amlodipine, a charged dihydropyridine compound. Implications for location of the dihydropyridine receptor, /. Gen. Physiol, 93(6), 1109-1127 (1989). NB Although the pRg is repeatedly stated as 8.6, no experimental detail is given, nor any reference. The paper also claims an estimated pK value of <3.5 for nisoldipine (ref Hugenholtz PC and Meyer J (eds.), Nisoldipine, Springer-Verlag, Berlin, 3-348 (1987). 

Cascade reactions of substituted 1,2,4-triazines are of great interest as simple ways to a dramatic increase in molecular complexity, from planar 1,2,4-triazine unit into a polycyclic system. Indeed, in this multistep process, the diallylamine and cyclopentanone react first in situ to give the corresponding enamine, which undergoes an inverse electron demand cycloaddition reaction with 1,2,4-triazine to give an intermediate dihydropyridine compound. A spontaneous intramolecular Diels-Alder reaction between the allyl moiety and the dihydropyridine gives the tetracyclic compound (Scheme 99) <2004JA12260>. 

Scheme 2 Proposed reaction pathways between dihydropyridine compounds (PyH2) used as NADH model compounds and quinone derivatives.

Abele, Werner (E. I. Du Pont de Nemours and Company). November 9,1982. A nonsilver photosensitive reproduction element which comprises a support bearing a layer of a photosensitive composition which comprises (1) at least one thermoplastic binder, (2) a photosensitive system consisting essentially of (a) a hexaarylbiimidazole compound and (b) a dihydropyridine compound and optionally (3) a plasticizer, and (4) a thioamide, thiolactam or thiocarbanilic acid ester of the formula... 

When pyridine is treated with zinc dust and acetic anhydride, a type of reductive coupling occurs and the product is diacetyltetrahydrodipyridyl (I) this undergoes a curious change on heating yielding pyridine and a new diacetyl compound, 1 4 diacetyl 1 4-dihydropyridine (II). The latter is reduced by zinc and acetic acid to 4-ethylpyridine (III). 

Specialtyydmines. Some substituted nitrogenous compounds can provide similar benefits. Esters of 2-aminocrotonate and bis-2-aminocrotonate, and appropriately substituted dihydropyridines, eg, 3,5-his-lauryloxycarhoxy-2,6-dimethyl-1,4-dihydropyridine [37044-66-7] and... 

The basic metal salts and soaps tend to be less cosdy than the alkyl tin stabilizers for example, in the United States, the market price in 1993 for calcium stearate was about 1.30— 1.60, zinc stearate was 1.70— 2.00, and barium stearate was 2.40— 2.80/kg. Not all of the coadditives are necessary in every PVC compound. Typically, commercial mixed metal stabilizers contain most of the necessary coadditives and usually an epoxy compound and a phosphite are the only additional products that may be added by the processor. The requited costabilizers, however, significantly add to the stabilization costs. Typical phosphites, used in most flexible PVC formulations, are sold for 4.00— 7.50/kg. Typical antioxidants are bisphenol A, selling at 2.00/kg Nnonylphenol at 1.25/kg and BHT at 3.50/kg, respectively. Pricing for ESO is about 2.00— 2.50/kg. Polyols, such as pentaerythritol, used with the barium—cadmium systems, sells at 2.00, whereas the derivative dipentaerythritol costs over three times as much. The P-diketones and specialized dihydropyridines, which are powerful costabilizers for calcium—zinc and barium—zinc systems, are very cosdy. These additives are 10.00 and 20.00/kg, respectively, contributing significantly to the overall stabilizer costs. Hydrotalcites are sold for about 5.00— 7.00/kg. 

In this paper the electtode anodic reactions of a number of dihydropyridine (DHP) derivatives, quantum-chemical calculations of reactions between DHP cation-radicals and electrochemiluminescers anion-radicals (aromatic compounds) and DHP indirect ECL assay were investigated. The actuality of this work and its analytical value follow from the fact that objects of investigation - DHP derivatives - have pronounced importance due to its phaiTnacology properties as high effective hypertensive medical product. 

Analogous to DPNH (144-146), 1,4-dihydropyridines (147) act as reducing agents. For instance, the conversion of aromatic nitro compounds to amines (148) and reduction of enones to ketones (749) has been achieved. 

The Hantzsch pyridine synthesis involves the condensation of two equivalents of a 3-dicarbonyl compound, one equivalent of an aldehyde and one equivalent of ammonia. The immediate result from this three-component coupling, 1,4-dihydropyridine 1, is easily oxidized to fully substituted pyridine 2. Saponification and decarboxylation of the 3,5-ester substituents leads to 2,4,6-trisubstituted pyridine 3. 

Once formed, 7 and 8 undergo a Michael reaction that gives rise to ketoenamine 9. Ring closure, to form 10, and loss of water then afforded 1,4-dihydropyridine 11. The presence of 9 and 10 could not be detected thus ring closure and dehydration were deduced to proceed faster than the Michael addition. This has the result of making the Michael addition the rate-determining step in this sequence. Conversely, if the reaction is run in the presence of a small amount of diethylamine, compounds related to 10 could be isolated. Diol 20 has been isolated in an unique case (R = CFb). Attempts to dehydrate this compound under a variety of conditions were unsuccessful. Stereoelectronic effects related to the dehydration may be the cause. In related heterocyclic ring formations, it has been determined that dehydration (20 —> 10) is about 10 times slower than diol formation (19 —> 20). Therefore, one would expect 20 to... 

Subsequent to Hantzsch s communication for the construction of pyridine derivatives, a number of other groups have reported their efforts towards the synthesis of the pyridine heterocyclic framework. Initially, the protocol was modified by Beyer and later by Knoevenagel to allow preparation of unsymmetrical 1,4-dihydropyridines by condensation of an alkylidene or arylidene P-dicarbonyl compound with a P-amino-a,P-unsaturated carbonyl compound. Following these initial reports, additional modifications were communicated and since these other methods fall under the condensation approach, they will be presented as variations, although each of them has attained the status of named reaction . 

Reaction of lithiated allene with methoxymethyl isothiocyanate afforded 107, after trapping with methyl iodide. The newly formed 107 isomerizes under mild conditions to triene 108. This compound is ideally setup to experience an electrocyclization to dihydropyridine 109. Heating in the presence of acid facilitates aromatization of 109 to pyridines 110. 

Stereocontrolled Additions to Dihydropyridines and Tetrahydropyridines Access to N-Heterocyclic Compounds Related to Natural Products... 

The [2 + 2] cycloaddition reaction of A -benzyl-l,4-dihydropyridine 34b with acrylonitrile, followed by catalytic reduction gave two pairs of diastereoisomeric amides 36 and 37 with a low diastereomeric excess, probably due to the large distance between the asymmetric center and the site of acrylonitrile attack. Compounds 36 and 37 were resolved into the four individual diastereoisomers (ca 5% for compound 36 and 15% for 37) [97JCR(M)321], Irradiation of 1,4-dibenzyl-1,4,5,6-tetrahydropyridine 38 in the presence of 29 gave two stereoisomers. 

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