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US 2010/0075920 A1Published application
Small molecule stimulators of neuronal growth
AssigneeCalifornia Institute of Technology
InventorsLinda C. Hsieh-Wilson, Sarah E. Tully, Ross Mabon, Cristal I. Gama
Life of this patent
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Abstract
Provided herein are small molecule stimulators of neuronal growth, their preparation, and their use for treatment of neurological disorders. In one embodiment, provided herein are methods of treatment, prevention, or amelioration of a variety of medical conditions associated with neurological disorders using the compounds and compositions provided herein.
Claims18
-57. (canceled)
A method of modulating neuronal growth, said method comprising contacting a cell with an effective amount of a compound of the following formula:
- or a pharmaceutically acceptable derivative thereof, wherein each of R1, R2, R3, and R4 are independently selected as follows:
- (i) R1 and R2 are each independently selected from sulfate, phosphate and carboxylate;
- and R3 and R4 are hydrogen;
- (ii) R3 and R4 are each independently selected from sulfate, phosphate, carboxylate;
- and R1 and R2 are hydrogen;
- (iii) R1, R2 and R3 are each independently selected from sulfate, phosphate, carboxylate;
- and R4 is hydrogen;
- (iv) R1, R2, and R4 are each independently selected from sulfate, phosphate, carboxylate;
- and R3 is hydrogen;
- (v) R2 and R4 are each independently selected from sulfate, phosphate, carboxylate;
- and R1 and R3 are hydrogen;
- (vi) R1 is selected from sulfate, phosphate, carboxylate;
- and R2, R3, and R4 are hydrogen;
- (vii) R2 is selected from sulfate, phosphate, carboxylate;
- and R1, R3, and R4 are hydrogen;
- (viii) R3 is selected from sulfate, phosphate, carboxylate;
- and R1, R2, and R4 are hydrogen;
- or
- (ix) R4 is selected from sulfate, phosphate, carboxylate;
- and R1, R2, and R3 are hydrogen;
- with the provisos that (a) when R1 is sulfate, then R2 is other than H;
- (b) when R2 is sulfate then R1 is other than H;
- and R5 is selected from optionally substituted alkyl and optionally substituted alkenyl;
- and n is 0-100.
21 more elements
A method of inducing growth of a differentiated neural stem cell comprising contacting a neural stern cell with an effective amount of a compound of the following formula:
- or a pharmaceutically acceptable derivative thereof, wherein each of R1, R2, R3, and R4 are independently selected as follows:
- (i) R1 and R2 are each independently selected from sulfate, phosphate and carboxylate;
- and R3 and R4 are hydrogen;
- (ii) R3 and R4 are each independently selected from sulfate, phosphate, carboxylate;
- and R1 and R2 are hydrogen;
- (iii) R1, R2 and R3 are each independently selected from sulfate, phosphate, carboxylate;
- and R4 is hydrogen;
- (iv) R1, R2, and R4 are each independently selected from sulfate, phosphate, carboxylate;
- and R3 is hydrogen;
- (v) R2 and R4 are each independently selected from sulfate, phosphate, carboxylate;
- and R1 and R3 are hydrogen;
- (vi) R1 is selected from sulfate, phosphate, carboxylate;
- and R2, R3, and R4 are hydrogen;
- (vii) R2 is selected from sulfate, phosphate, carboxylate;
- and R1, R3, and R4 are hydrogen;
- (viii) R3 is selected from sulfate, phosphate, carboxylate;
- and R1, R2, and R4 are hydrogen;
- or
- (ix) R4 is selected from sulfate, phosphate, carboxylate;
- and R1, R2, and R3 are hydrogen;
- with the provisos that (a) when R1 is sulfate, then R2 is other than H;
- (b) when R2 is sulfate then R1 is other than H;
- and R5 is selected from optionally substituted alkyl and optionally substituted alkenyl;
- and n is 0-100.
21 more elements
A method of treating a symptom associated with a neurological disorder comprising administering to a subject in need thereof an effective amount of a compound of the following formula:
- or a pharmaceutically acceptable derivative thereof, wherein each of R1, R2, R3, and R4 are independently selected as follows:
- (i) R1 and R2 are each independently selected from sulfate, phosphate and carboxylate;
- and R3 and R4 are hydrogen;
- (ii) R3 and R4 are each independently selected from sulfate, phosphate, carboxylate;
- and R1 and R2 are hydrogen;
- (iii) R1, R2 and R3 are each independently selected from sulfate, phosphate, carboxylate;
- and R4 is hydrogen;
- (iv) R1, R2, and R4 are each independently selected from sulfate, phosphate, carboxylate;
- and R3 is hydrogen;
- (v) R2 and R4 are each independently selected from sulfate, phosphate, carboxylate;
- and 121 and R3 are hydrogen;
- (vi) R1 is selected from sulfate, phosphate, carboxylate;
- and R2, R3, and R4 are hydrogen;
- (vii) R2 is selected from sulfate, phosphate, carboxylate;
- and R1, R3, and R4 are hydrogen;
- (viii) R3 is selected from sulfate, phosphate, carboxylate;
- and R1, R2, and R4 are hydrogen;
- or
- (ix) R4 is selected from sulfate, phosphate, carboxylate;
- and R1, R2, and R3 are hydrogen;
- with the provisos that (a) when R1 is sulfate, then R2 is other than H;
- (b) when R2 is sulfate then R1 is other than H;
- and R5 is selected from optionally substituted alkyl and optionally substituted alkenyl;
- and n is 0-100.
21 more elements
A method of modulating the activity of a growth factor comprising contacting a cell with an effective amount a compound comprising:
- or a pharmaceutically acceptable derivative thereof, wherein each of R1, R2, R3, and R4 are independently selected as follows:
- (i) R1 and R2 are each independently selected from sulfate, phosphate and carboxylate;
- and R3 and R4 are hydrogen;
- (ii) R3 and R4 are each independently selected from sulfate, phosphate, carboxylate;
- and R1 and R2 are hydrogen;
- (iii) R1, R2 and R3 are each independently selected from sulfate, phosphate, carboxylate;
- and R4 is hydrogen;
- (iv) R1, R2, and R4 are each independently selected from sulfate, phosphate, carboxylate;
- and R3 is hydrogen;
- (v) R2 and R4 are each independently selected from sulfate, phosphate, carboxylate;
- and R1 and R3 are hydrogen;
- (vi) R1 is selected from sulfate, phosphate, carboxylate;
- and R2, R3, and R4 are hydrogen;
- (vii) R2 is selected from sulfate, phosphate, carboxylate;
- and R1, R3, and R4 are hydrogen;
- (viii) R3 is selected from sulfate, phosphate, carboxylate;
- and R1, R2, and R4 are hydrogen;
- or
- (ix) R4 is selected from sulfate, phosphate, carboxylate;
- and R1, R2, and R3 are hydrogen;
- with the provisos that (a) when R1 is sulfate, then R2 is other than H;
- (b) when R2 is sulfate then R1 is other than H;
- and R5 is selected from optionally substituted alkyl and optionally substituted alkenyl;
- and n is 0-100.
21 more elements
A method for screening for a modulator of neuronal growth, wherein the method comprises:
- contacting a cultured neuron with a candidate modulator of the following formula:
- or a pharmaceutically acceptable derivative thereof, wherein each of R1, R2, R3, and R4 are independently selected as follows:
- (i) R1 and R2 are each independently selected from sulfate, phosphate and carboxylate;
- and R3 and R4 are hydrogen;
- (ii) R3 and R4 are each independently selected from sulfate, phosphate, carboxylate;
- and R1 and R2 are hydrogen;
- (iii) R1, R2 and R3 are each independently selected from sulfate, phosphate, carboxylate;
- and R4 is hydrogen;
- (iv) R1, R2, and R4 are each independently selected from sulfate, phosphate, carboxylate;
- and R3 is hydrogen;
- (v) R2 and R4 are each independently selected from sulfate, phosphate, carboxylate;
- and R1 and R3 are hydrogen;
- (vi) R1 is selected from sulfate, phosphate, carboxylate;
- and R2, R3, and R4 are hydrogen;
- (vii) R2 is selected from sulfate, phosphate, carboxylate;
- and R1, R3, and R4 are hydrogen;
- (viii) R3 is selected from sulfate, phosphate, carboxylate;
- and R1, R2, and R4 are hydrogen;
- or
- (ix) R4 is selected from sulfate, phosphate, carboxylate;
- and R1, R2, and R3 are hydrogen;
- with the provisos that (a) when R1 is sulfate, then R2 is other than H;
- (b) when R2 is sulfate then R1 is other than H;
- and R5 is selected from optionally substituted alkyl and optionally substituted alkenyl;
- and n is 0-100;
- (b) determining a percent increase in mean axon length of the contacted neuron and a percent increase in mean axon length of a corresponding untreated neuron;
- and
- (c) comparing the percent increase in mean axon length of the contacted neuron to the percent increase in mean axon length of the corresponding untreated neuron;
- wherein the modulator yields a difference in percent increase in mean axon length of the contacted neuron as compared to the untreated neuron.
26 more elements
Dependencies are inferred from the claim text.