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Details

Stereochemistry ACHIRAL
Molecular Formula C18H21N5O3
Molecular Weight 355.391
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of HC-030031

SMILES

CC(C)C1=CC=C(NC(=O)CN2C=NC3=C2C(=O)N(C)C(=O)N3C)C=C1

InChI

InChIKey=HEQDZPHDVAOBLN-UHFFFAOYSA-N
InChI=1S/C18H21N5O3/c1-11(2)12-5-7-13(8-6-12)20-14(24)9-23-10-19-16-15(23)17(25)22(4)18(26)21(16)3/h5-8,10-11H,9H2,1-4H3,(H,20,24)

HIDE SMILES / InChI

Molecular Formula C18H21N5O3
Molecular Weight 355.391
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

HC-030031 is a substituted theophylline derivative. Potent and selective TRPA1 inhibitor. HC-030031 inhibits human and rat TRPA1 with IC50 of 6.2 and 7.6 uM, respectively. It is selective against several TRP channels (IC50 >10 or 20 uM). HC-030031 can block both inward and outward currents elicited by AITC or formalin rapidly and reversibly and also blocks the activation of TRPA1 by N-methylmaleimide and by electrophillic prostaglandins. It does not block currents mediated by TRPV1, TRPV3, TRPV4 hERG, or NaV1.2 channels. HC-030031 exhibited efficacy in CFA, SNL, and other pain models. HC-030031 was shown to attenuate cold hyperalgesia in CFA (inflammatory), spared never injury (SNI, neuropathic), and paclitaxelmediated cold hyperalgesia. Also HC-030031 was found to decrease heat hyperalgesia in the paclitaxel model of chemotherapy-induced neuropathic pain.In an ovalbumin-induced mouse asthma model, gene KO and treatment with HC-030031 reduced the induction of cytokines, chemokines, neurotransmitters, as well as leukocyte infiltration and airway hyperactivity. Furthermore, HC-030031 and genetic deletion of mast cells attenuated itch-scratching behaviors. In oxazolone-induced contact dermatitis models, TRPA1 KO and HC-030031 decreased pro-inflammatory cytokines, T cell infiltration, dermatitis score, and edema, indicating that TRPA1 may play a central role in inflammation and pruritus.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
6.2 µM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
Unknown
Primary
Unknown

PubMed

Sample Use Guides

In Vivo Use Guide
Mice: HC-030031 was injected i.c.v. (30 nmol in 2 uL, 5 min i.c.v. min before the behavioural test or administered p.o. at doses of 30, 100 and 300 mg/kg, by employing a gavage needle, in a volume of 10 mL/kg, 90 (p.o.) min before the behavioural test
Route of Administration: Other
In Vitro Use Guide
The long-lasting facilitation of respiratory rhythm was partially antagonized by the TRPA1 antagonist HC-030031 (10 uM) in brainstem-spinal cord preparations from newborn rats .
Substance Class Chemical
Record UNII
MU78VFH9C7
Record Status Validated (UNII)
Record Version