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Chemical Compound Review

Compound 21     (E)-3-[4-(3,4- dichlorophenyl)phenyl]-N...

Synonyms: AC1NSM29
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Disease relevance of Compound 21


High impact information on Compound 21

  • In particular, compound 21 [N-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-4-piperidinecarboxamide, BMS-387032], has been identified as an ATP-competitive and CDK2-selective inhibitor which has been selected to enter Phase 1 human clinical trials as an antitumor agent [3].
  • Compound 21, with a bioavailability of 20-30% after oral administration and a half-life estimated to 4 h in rat, induces outgrowth of neurite cells, stimulates p42/p44(mapk), enhances in vivo duodenal alkaline secretion in Sprague-Dawley rats, and lowers the mean arterial blood pressure in anesthetized, spontaneously hypertensive rats [4].
  • Synthesis and subsequent sodium channel evaluation of compound 21 (predicted IC50 = 9 microM, actual IC50 = 9 microM), a good binder to the sodium channel, established that the intact hydantion ring is not necessary for efficient binding to this site [5].
  • Among the analogs prepared, some, e.g., compound 21, were equipotent to compound 5 with respect to 5-HT1A effects [6].
  • Compound 21 also shows very weak partial agonism of PI turnover (< or = 5% of NKA maximum) which makes this the most potent member of a new class of NKA ligands: psi(CH2NR)9-NKA4-10 analogues which potently antagonize NKA binding and possess minimal partial agonist activity [7].

Chemical compound and disease context of Compound 21


Biological context of Compound 21

  • Another derivative, 1,2-di(4-amidino-2-benzofuranyl)ethane (compound 21), proved to be a highly effective inhibitor of the overall blood clotting process [9].
  • Moreover, chmronic exposure to lethal doses of compound 21 resulted in massive nuclear fragmentation, evocative of mitotic catastrophe with minour amounts of apoptosis only [10].
  • Furthermore, unlike olomoucine, compound 21 was effective upon short exposure (LD50= 25.3 microM, 2-h contact) [10].
  • With the noticeable exception of pronounced lengthening of the S-phase transit by 21 applied during early-S in synchronized HeLa cells, and in striking contrast with earlier reports on studies using plant or echinoderm cells. olomoucilnc and compound 21 were unable to reversibly arrest cell cycle progression in asynchronous growing HeLa cells [10].

Anatomical context of Compound 21

  • Among all the derivatives, compound 21 was found to be a potent human chymase inhibitor with no inhibitory activity against human leukocyte cathepsin G [11].
  • Compound 21 showed a moderate activity (EC50 ranging from 2.3 to 5.8 micrograms/ml) against different HIV-1 strains (IIIB, RF, NDK, and an AZT-resistant strain) in different cell lines (MT-4 and C-8166 cells), while it was cytotoxic at 77.7 micrograms/ml, resulting in a selectivity index of 34 [2].

Associations of Compound 21 with other chemical compounds

  • An X-ray crystal structure of compound (21) confirms that the spirocyclic amine does not cause distortion away from the chair conformation of the cyclohexane ring [12].
  • Modeling guided design of quinazolinone compound 21 led to a potency enhancement of greater than 200-fold compared to human growth hormone secretagogue affinity of a screening lead 4 [13].
  • Enzyme potency against Chek1 was optimized by the incorporation of a hydroxymethyl triazole moiety in compound 21 (Chek1 IC(50)=0.30nM) that was shown by X-ray crystallography to displace one of three highly conserved water molecules in the HI region of the ATP-binding cleft [14].
  • Optimal inhibitory activity against CDK5, CDK1 and CDK2, with IC50 values of 0.16, 0.45 and 0.65 microM, respectively, was obtained with compound 21 containing a (2R)-pyrrolidin-2-yl-methanol substituent at the C-2 and a 3-iodobenzylamino group at the C-6 of the purine [10].

Gene context of Compound 21

  • Only compound 21 showed an estrogen receptor binding affinity exceeding that of metahexestrol (15 and 10%, respectively) [15].
  • Compound 21 showed an affinity 18,000 times greater for AChE than for BuChE [16].
  • Incorporation of nonreactive polar functionalities at the C- and N-termini of renin inhibitors led to the development of a subnanomolar compound (21) with millimolar solubility [17].
  • Compound 21 was a competitive inhibitor of OSC, whereas 17 and 19 were noncompetitive inhibitors, and showed a biphasic time-dependent inactivation of OSC, their apparent binding constants being 250 microM and 213 microM, respectively [18].


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