Therapeutic aminoindane compounds and compositions
AssigneeAwakn LS Europe Holdings Limited
InventorsDavid Nutt, Alan Borthwick
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Abstract
The present invention discloses therapeutic compounds of the aminoindane class, including certain short-acting ester and lactone derivatives, and pharmaceutical compositions made therewith, as well as methods of their use in the treatment of alcohol and other substance use disorders, behavioral addictions, and CNS and mental health disorders, and for the improvement of mental health and psychological functioning.
Claims112
A compound having a structure of Formula (I):
- wherein any one of R1, R2, or R3 is:
- with the others of R1, R2, and R3 both being hydrogen (H);
- and wherein R4 is either H or —OR5;
- wherein each R5 is independently any of H, alkyl, aryl, arylalkyl, —(CH2)mZ(CH2)mCH3, or —(CH2)mRcyc, and each m is independently between 0-4;
- wherein each Z is independently, and in either orientation, —O—, —C═C—, —NH—, —NHNH—, —ONH—, —CONH—, —CH(NH2)—, —S—, —S(O)—, —SO2—, —CHF—, and —CF2—;
- wherein each Rcyc is independently an aryl or heteroaryl, said aryl or heteroaryl selected from the class consisting of phenyl, naphthyl, naphthalenyl, indolyl, thiophenyl, pyridyl, pyridinyl, pyrimidinyl, furyl, furanyl, tetrahydrofuranyl, pyrrolyl, oxazolyl, thiazolyl, pyrazolyl, isoxazolyl, imidazolyl, isothiazolyl, oxadiazolyl, triazolyl, thiadiazolyl, pyridazinyl, pyrazinyl, triazinyl, indolyzinyl, isoindolyl, benzofuranyl, dihydro benzofuranyl, benzoyl, benzoxazolyl, methylenedioxyphenyl, isobenzofuranyl, benzothiophenyl, benzoxazolyl, indazolyl, benzthiazolyl, benzimidazolyl, quinolinyl, isoquinolinyl, purinyl, quinolizinyl, cinnolinyl, phthalyl, quinoxalinyl, napthyridinyl, pteridinyl, and quinazolinyl;
- and wherein one or more hydrogen atoms of said aryl or heteroaryl are optionally and independently replaced with any of:
- (a) halogen, (b) C1-7 alkyl, (c) hydroxy, (d) methoxy, (e) isopropoxy, (f) ethoxy, (g) hydroxymethyl, (h) hydroxypropyl, (i) tert-butyl, (j) n-butyl, (k) sec-butyl, (l) isobutyl, (m) acetamide, (n) carbamoyl, (o) —CN, (p) —COOH, (q) —NO2, (r) —S(O)2OH, (s) —S(O)CH3, (t) —S(O)2CH3, (u) —OR6, or (v) —SR6;
- wherein R6 is hydrogen or C1-7 alkyl;
- or alternatively, where R3 is
- R5 is joined to the benzene ring at an R4 position adjacent to the R3 to form a lactone ring.
The compound of any one of the preceding claims, wherein each R5 is independently H, —CH3, or —CH2CH3.
The compound of any one of the preceding claims, wherein the compound is classified as highly soluble in PBS pH 7.4.
The compound of any one of the preceding claims, wherein the compound is classified as highly permeable, as determined by a MDR1-MDCKII permeability assay.
The compound of any one of the preceding claims, wherein the compound is not determined to be a substrate for P-glycoprotein, as determined in the presence of a P-glycoprotein inhibitor or in mock MDCKII cells.
The compound of any one of the preceding claims, wherein the clearance rate of the compound is greater than the clearance rate of MDMA, as determined in human liver microsomes.
The compound of any one of the preceding claims, wherein the half-life of the compound is shorter than the half-life of MDMA, as determined by a pharmacokinetic study in vitro or in vivo.
The compound of any one of the preceding claims, wherein the compound stimulates release of a monoamine neurotransmitter and inhibits the function of a monoamine transporter.
The compound of any one of the preceding claims, wherein the compound stimulates release of a monoamine neurotransmitter or inhibits the function of a monoamine transporter.
A compound for use in modulating neurotransmission, wherein modulating neurotransmission treats a substance use disorder, a behavioral addiction, or a mental health disorder.
A pharmaceutical composition, comprising a compound having the structure of any of:
- and a pharmaceutically acceptable carrier, diluent, or excipient.
A unit dosage form, comprising the compound having the structure of any of.
A method for modulating neurotransmission in a mammal, comprising administering to the mammal a therapeutically effective amount of the compound, composition, or unit dosage form of any of the foregoing claims.
A method for modulating neurotransmission in a subject, comprising administering to the subject a compound having the structure of any of.
A method of treating a medical condition in a mammal in need of such treatment, the method comprising administering the compound having the structure of any of:
A method of reducing the symptoms of a substance use disorder, a behavioral addiction, or a mental health disorder in a human, the method comprising administering the compound having the structure of any of:
Dependencies are inferred from the claim text.