100303-76-2

Upstream product

• 674-82-8 4-methyleneoxetan-2-one 
• 100-49-2 cyclohexylmethyl alcohol 
• 5394-63-8 2,2,6-trimethyl-4H-1,3-dioxin-4-one 
• 42490-66-4 2,2,6-trimethyl-4H-1,3-dioxin-4-one 

Downstream Products

• 103785-65-5 2,6-Dimethyl-4-(2-nitro-phenyl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-cyclohexylmethyl ester 5-methyl ester 
• 1025976-98-0 3-Oxo-2-[1-(2-phenyl-3H-imidazol-4-yl)-meth-(Z)-ylidene]-butyric acid cyclohexylmethyl ester 
• 1224680-48-1 cyclohexylmethyl 1-(2,4-dimethyoxybenzyl)-4-(3-methoxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate 
• 418799-00-5 cyclohexylmethyl 4-(4-hydroxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate 
• 1224681-34-8 cyclohexylmethyl 4-(2-hydroxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate 
• 1224680-61-8 cyclohexylmethyl 4-(3-methoxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate 
• 1224680-38-9 cyclohexylmethyl 4-(3-hydroxyphenyl)-1,6-dimethyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate 
• 330674-26-5 cyclohexylmethyl 4-(3-methoxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate 
• 1345674-66-9 dicyclohexylmethyl-1,4-dihydro-2,6-dimethyl-4-[2-methylthio-1-(phenylamino)-1H-imidazole-5-yl]-3,5-pyridinedicarboxylate 
• 1345674-81-8 iso-propyl, cyclohexylmethyl-1,4-dihydro-2,6-dimethyl-4-[2-methylthio-1-(phenylamino)-1H-imidazole-5-yl]-3,5-pyridinedicarboxylate 
• 1342884-99-4 di(cyclohexylmethyl) 4-(4-chloro-1H-imidazol-5-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate 
• 103772-84-5 2,6-Dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-cyclohexylmethyl ester 5-methyl ester 

Relevant academic research and scientific papers

Spirolactones from Dirhodium(II)-Catalyzed Diazo Decomposition with Regioselective Carbon-Hydrogen Insertion

Dirhodium(II) caprolactamate, Rh2(cap)4, catalyzes diazo decomposition of cycloalkylmethyl diazoacetates which form spirolactones in moderate to high yield by insertion into a tertiary carbon-hydrogen bond.Similar results are obtained with diazoacetates derived from tetrahydropyran-2-methanol and tetrahydrofurfuryl alcohol but not from cyclopropylmethanol.With tetrahydrofuran-3-ylmethyl diazoacetate, Rh2(cap)4 catalysis promotes δ-lactone formation via insertion into the oxygen-activated secondary C-H bond instead of γ-lactone formation by carbene insertion into the unactivated tertiary C-H bond.However, when both 1,5- and 1,6-positions are activated for insertion by adjacent oxygen atoms, as in (2,2-dimethyl-1,3-dioxolan-4-yl)methyl diazoacetate, five-membered ring formation occurs exclusively in Rh2(cap)4-catalyzed reactions, whereas use of dirhodium(II) acetate leads to both insertion products.

NEW ANALOGS AS ANDROGEN RECEPTOR AND GLUCOCORTICOID RECEPTOR MODULATORS

The present invention relates to novel dihydropyridine derivatives of formula (I): as modulators of nuclear receptors selected from androgen receptor and glucocorticoid receptor, to processes for their preparation, to pharmaceutical compositions comprising said compounds and to the use of said for manufacturing a medicament for the treatment of pathological conditions or diseases that can improve by modulation of androgen receptor and/or glucocorticoid receptor, selected from cancer, metastasizing cancers, benign prostate hyperplasia, polycystic ovary syndrome (PCOS), hair loss, hirsutism, acne, hypogonadism, muscle wasting diseases, cachexia, Cushing's syndrome, anti-psychotic drug induced weight gain, obesity, post-traumatic stress disorder and alcoholism.

Design and synthesis of new 1,4-dihydropyridines containing 4(5)-chloro-5(4)-imidazolyl substituent as a novel calcium channel blocker

New analogues of nifedipine, in which the ortho-nitro phenyl group at position 4 has been replaced by 4(5)-chloro-5(4)-imidazolyl substituent and which are able to interact with the receptor by hydrogen binding were designed, synthesized, and evaluated as calcium channel antagonists. The designed dihydropyridines were synthesized using the Hantzsch condensation and evaluated as calcium channel antagonists using the high K+ contraction of guineapig ileal longitudinal smooth muscle. A docking study was performed using the AutoDock4 program, and QSAR equations were obtained using multilinear regression. Our computational studies indicated that the oxygen of the ester (O10) and the N3′ of the imidazole ring form a hydrogen bonding interaction with the NH of HIS 363 and NH of LYS354, respectively, and that the sum of the BEHp5 and RDF075p are the most significant descriptors. The results of calcium channel antagonist evaluation demonstrated that increasing the chain length in C3 and C5 ester substituents increased activity. The most potent compound was the bis-phenylpropyl ester (5l) derivative, in that it was more active than the reference drug nifedipine and that the bis-phenylethyl ester (5k) derivative had comparable activity with nifedipine. The present research revealed that the 4(5)-chloro-5(4)-imidazolyl moiety is a bioisoster of o-nitrophenyl in nifedipine and provided novel dihydropyridines with more activity as calcium channel antagonists.

Lipophilic 4-imidazoly-1,4-dihydropyridines: Synthesis, calcium channel antagonist activity and protection against pentylenetetrazole-induced seizure

A group of alkyl, cycloalkyl and aryl ester analogs of nifedipine, in which the o-nitrophenyl group at position 4 is replaced by a 2-phenyl-4(5)-imidazolyl substituent, were synthesized and evaluated as calcium channel antagonist using the high K+ contraction of guinea-pig ileal longitudinal smooth muscle, and the activity of 5a-d, 8b and 8f against pentylenetetrazole (PTZ)-induced seizure was assessed. The results for symmetrical esters showed that lengthening of the methylene chain in C3 and C5 ester substituents increased activity. When increasing of the length is accompanied by increasing the hindrance, the activity decreased. In contrast to symmetrical derivatives, comparison of the activities of asymmetrical esters showed that increasing the length of the methylene chain was accompanied by a decrease in their activity. The results demonstrate that 8a was more active, and 5c and 8f were similar in effect to that of the reference drug nifedipine. The time-course of anticonvulsant effect on PTZ-induced seizure threshold of said compounds was assessed and showed that increasing the lipophilicity decreases the time needed for maximum effect. Mice treated with intraperitoneal injection of 25 mg/kg of these derivatives all exhibited increase seizure threshold as compared with control.

Synthesis and calcium-channel antagonist activity of 4-imidazolyl-1,4-dihydropyridines

The o-nitrophenyl group at position 4 of dihydropyridine of nifedipine analogues was replaced by 1-methylimidazole. These compounds were evaluated as calcium-channel antagonists using the high K+ contraction of guinea-pig ileal longitudinal smooth muscle. The results for the symmetrical esters showed that increasing the length of methylene chain of ester more than 3 units decreases activity. For cyclic esters, cyclopropylmethyl ester was more active than cyclohexylmethyl ester. Our results revealed two compounds with activities similar to the reference drug nifedipine; the symmetrical cyclopropylmethyl ester, and the asymmetrical phenethyl ethyl derivatives were the most potent antagonists tested.

Synthesis and calcium-channel antagonist activity of nifedipine analogues containing nitroimidazolyl substituent in guinea-pig ileal smooth muscle

Alkyl, cycloalkyl or aryl ester analogues of nifedipine, in which the ortho-nitrophenyl group at position 4 is replaced by 1-methyl-5-nitro-2-imidazolyl substituent, were synthesized and evaluated as calcium-channel antagonists using the high K+ contraction of guinea-pig ileal longitudinal smooth muscle. The results for the symmetrical esters showed that increasing the length of methylene chain (n > 2) decreases activity. The relative activity profile for asymmetrical esters was cyclopentyl > cyclohexyl > cyclopropyl. Comparison of esters having the same methylene space showed that the cyclohexyl compounds were more active than the corresponding phenyl derivatives. In addition, asymmetrical esters possessing one R2 substituent (methyl > ethyl) indicated that increasing the length of methylene chain in the R1-substituent decreased activity. Our results demonstrate that several compounds were more active than the reference drug nifedipine. The symmetrical cyclohexyl ester (n = 0) and the asymmetrical (R1 = cyclohexyl, R2 = Me, n = 0) derivatives were the most potent antagonists tested.