PMID- 6716398
OWN - NLM
STAT- MEDLINE
DCOM- 19840618
LR  - 20190709
IS  - 0022-2623 (Print)
IS  - 0022-2623 (Linking)
VI  - 27
IP  - 5
DP  - 1984 May
TI  - Synthesis of pyridine derivatives of L-phenylalanine as antisickling reagents.
PG  - 596-600
AB  - Several bicyclic agents composed of L-phenylalanine coupled to various pyridines 
      were synthesized: 2-, 3-, and 4-(L- phenylalanylamino )pyridine. All three 
      compounds at 3 mM gave positive morphological antisickling effects on homozygous 
      SS cells under reduced O2 tension. Studies on two of these compounds, 2- and 
      3-(L- phenylalanylamino )pyridine, showed that these agents increase the 
      deoxy-HbS solubility ratio, Cs/ Cs0 , by 14% at 20 mM. Observed changes in the 
      mean corpuscular hemoglobin concentration (MCHC) values of treated cells ranged 
      from 4% at 1.3 mM to 15% at 5.6 mM in compound concentration. Very minor lytic 
      activity was found for treated cells, indicating water uptake is responsible for 
      changes in the MCHC. Further, exposure of sickle cells to a 3 mM concentration of 
      these agents also increased by 6- to 7-fold cellular deformability of a treated 
      erythrocyte population as compared to an untreated one at the same total O2 
      saturation of 47%. These agents demonstrate the potential of bicyclic compounds 
      composed of a common constituent, L-Phe, in the development toward a viable 
      therapeutic agent.
FAU - Altman, J
AU  - Altman J
FAU - Gorecki, M
AU  - Gorecki M
FAU - Wilchek, M
AU  - Wilchek M
FAU - Votano, J R
AU  - Votano JR
FAU - Rich, A
AU  - Rich A
LA  - eng
GR  - N01-BH-1-3000/BH/FDA HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Med Chem
JT  - Journal of medicinal chemistry
JID - 9716531
RN  - 0 (Antisickling Agents)
RN  - 0 (Hemoglobin, Sickle)
RN  - 0 (Indicators and Reagents)
RN  - 0 (deoxyhemoglobin, sickle)
SB  - IM
MH  - Anemia, Sickle Cell/blood
MH  - Antisickling Agents/*chemical synthesis
MH  - Erythrocytes/drug effects
MH  - Hemoglobin, Sickle/metabolism
MH  - Humans
MH  - Indicators and Reagents
MH  - Solubility
MH  - Structure-Activity Relationship
EDAT- 1984/05/01 00:00
MHDA- 1984/05/01 00:01
CRDT- 1984/05/01 00:00
PHST- 1984/05/01 00:00 [pubmed]
PHST- 1984/05/01 00:01 [medline]
PHST- 1984/05/01 00:00 [entrez]
AID - 10.1021/jm00371a007 [doi]
PST - ppublish
SO  - J Med Chem. 1984 May;27(5):596-600. doi: 10.1021/jm00371a007.