4-alkenyl and 4-alkynyl phenethylamine derivatives and related compounds with modified dom-like action

A method of changing neurotransmission, including the steps of:

• administering a pharmaceutically effective amount of composition to a mammal of a compound represented by FIG. 1A-1E,
• characterized in that R□1 and R□2 are, independently and in any combination, chosen from the group consisting of hydrogen, deuteron, methyl, ethyl, deuterated methyl (D1-D3), or deuterated ethyl (D1-D5), and
• further characterized in that R1, R2 and R3 are, independently and in any combination, chosen from the group consisting of hydrogen, deuteron, and/or fluorine;
• or
• C1-C3 branched or unbranched alkyl with the alkyl optionally and independently substituted with F1-F7 fluorine and/or D1-D7 deuteron substituents;
• or
• C3-C6 cycloalkyl optionally and independently substituted with one or more substituents such as F1-F15 fluorine and/or D1-D15 deuteron and/or C1-C2 alkyl;
• or
• (C3-C6 cycloalkyl)-C1-C2 branched or unbranched alkyl optionally and independently substituted with one or more substituents such as F1-F15 fluorine and/or D1-D15 deuteron and/or C1-C2 alkyl;
• or
• C2-C5 branched or unbranched alkenyl with E or Z or cis or trans double bond configuration, where any of the carbons of the branched or unbranched alkenyl substituent is optionally substituted independently and in any combination with one or more C1-C2 alkyl, with F1-F13 fluorine, with D1-D13 deuteron, with C2 alkenyl or with aryl or heteroaryl bearing no up to any number of ether, thioether, halogen, alkyl, fluorinated alkyl, alkenyl, alkynyl or nitrogen-containing substituents;
• or
• C2-C5 branched or unbranched alkynyl where any of the carbons of the branched or unbranched alkynyl substituent is optionally substituted independently and in any combination with one or more C1-C2 alkyl, with F1-F11 fluorine, with D1-D11 deuteron, with C2 alkenyl or with aryl or heteroaryl bearing no up to any number of ether, thioether, halogen, alkyl, fluorinated alkyl, alkenyl, alkynyl or nitrogen-containing substituents, any halogen or a nitrogen-containing substituent such as CN or NO2;
• and
• further characterized in that R4 is chosen from the group consisting of hydrogen, deuteron, or fluorine;
• or
• C1-C3 branched or unbranched alkyl with the alkyl optionally and independently substituted with F1-F7 fluorine and/or D1-D7 deuteron substituents;
• or
• C3-C6 cycloalkyl optionally and independently substituted with one or more substituents such as F1-F15 fluorine and/or D1-D15 deuteron and/or C1-C2 alkyl;
• or
• (C3-C6 cycloalkyl)-C1-C2 branched or unbranched alkyl optionally and independently substituted with one or more substituents such as F1-F15 fluorine and/or D1-D15 deuteron and/or C1-C2 alkyl;
• or
• C2-C5 branched or unbranched alkenyl with E or Z or cis or trans double bond configuration, where any of the carbons of the branched or unbranched alkenyl substituent is optionally substituted independently and in any combination with one or more C1-C2 alkyl, with F1-F13 fluorine, with D1-D13 deuteron, with C2 alkenyl or with aryl or heteroaryl bearing no up to any number of ether, thioether, halogen, alkyl, fluorinated alkyl, alkenyl, alkynyl or nitrogen-containing substituents;
• or
• C2-C5 branched or unbranched alkynyl where any of the carbons of the branched or unbranched alkynyl substituent is optionally substituted independently and in any combination with one or more C1-C2 alkyl, with F1-F11 fluorine, with D1-D11 deuteron, with C2 alkenyl or with aryl or heteroaryl bearing no up to any number of ether, thioether, halogen, alkyl, fluorinated alkyl, alkenyl, alkynyl or nitrogen-containing substituents, any halogen or a nitrogen-containing substituent such as CN;
• and
• further characterized in that R5 is chosen from the group consisting of fluorine, chlorine, bromine, and iodine;
• or
• SF5;
• or
• C2-C5 branched or unbranched alkyl with the alkyl optionally and independently substituted with F1-F11 fluorine and/or D1-D11 deuteron substituents or C1 alkyl substituted with F1-F3 and/or D1-D3 deuteron substituents;
• or
• C3-C6 cycloalkyl optionally and independently substituted with one or more substituents such as F1-F15 fluorine and/or D1-D15 deuteron and/or C1-C5 alkyl;
• or
• (C3-C6 cycloalkyl)-C1-C2 branched or unbranched alkyl optionally and independently substituted with one or more substituents such as F1-F15 fluorine and/or D1-D15 deuteron and/or C1-C5 alkyl;
• or
• a nitrogen-containing substituent such as CN or NO2;
• or
• C2-C5 branched or unbranched alkoxy with the alkoxy optionally and independently substituted with F1-F11 fluorine and/or D1-D11 substituents, or C1 alkoxy substituted with F1-F3 and/or D1-D3 deuteron substituents;
• or
• C3-C6 cycloalkyloxy optionally and independently substituted with one or more substituents such as F1-F11 fluorine and/or D1-D11 substituents and/or C1-C5 alkyl;
• or
• (C3-C6 cycloalkyl)-C1-C2 branched or unbranched alkoxy optionally and independently substituted with one or more substituents such as F1-F15 fluorine and/or D1-D15 and/or C1-C5 alkyl;
• or
• C2-C5 branched or unbranched alkenyloxy with E or Z vinylic, cis or trans allylic, E or Z allylic or other double bond position in relation to the attached ether function, where any of the carbons of the branched or unbranched alkenyloxy substituent is optionally substituted independently with one or more C1-C5 alkyl, and/or with F1-F9 fluorine and/or with D1-D9 deuteron substituents;
• or
• C3-C5 branched or unbranched alkynyloxy, where any of the carbons of the alkynyloxy substituent is optionally substituted independently with one or more C1-C5 alkyl, and/or with F1-F9 fluorine and/or with D1-D9 deuteron substituents;
• or
• C3-C5 branched or unbranched alkylthio with the alkylthio group optionally and independently substituted with F1-F11 fluorine and/or D1-D11 substituents, or C1-C2 alkylthio substituted with F1-F5 and/or D1-D5 deuteron substituents;
• or
• C3-C6 cycloalkylthio optionally and independently substituted with one or more substituents such as F1-F11 fluorine and/or D1-D11 substituents and/or C1-C5 alkyl;
• or
• (C3-C6 cycloalkyl)-C1-C2 branched or unbranched alkylthio optionally and independently substituted with one or more substituents such as F1-F15 fluorine and/or D1-D15 and/or C1-C5 alkyl;
• or
• C2-C5 branched or unbranched alkenylthio with E or Z vinylic, cis or trans allylic, E or Z allylic or other double bond position in relation to the attached thioether function, where any of the carbons of the branched or unbranched alkenylthio substituent is optionally substituted independently with one or more C1-C5 alkyl, and/or with F1-F9 fluorine and/or with D1-D9 deuteron substituents;
• or
• C3-C5 branched or unbranched alkynylthio, where any of the carbons of the alkynylthio substituent is optionally substituted independently with one or more C1-C5 alkyl, and/or with F1-F9 fluorine and/or with D1-D9 deuteron substituents,
• and further characterized in that any non-protic hydrogen can be replaced by a deuteron or a fluorine in any combination;
• increasing serotonin 5-HT2A and 5-HT2C receptor interaction in the mammal;
• and
• inducing psychoactive effects.

A method of treating a patient having adverse reactions to psychedelics, including the steps of:

• administering a pharmaceutically effective amount of composition to the patient of a compound represented by FIG. 1A-1E,
• characterized in that R□1 and R□2 are, independently and in any combination, chosen from the group consisting of hydrogen, deuteron, methyl, ethyl, deuterated methyl (D1-D3), or deuterated ethyl (D1-D5), and
• further characterized in that R1, R2 and R3 are, independently and in any combination, chosen from the group consisting of hydrogen, deuteron, and/or fluorine;
• or
• C1-C3 branched or unbranched alkyl with the alkyl optionally and independently substituted with F1-F7 fluorine and/or D1-D7 deuteron substituents;
• or
• C3-C6 cycloalkyl optionally and independently substituted with one or more substituents such as F1-F15 fluorine and/or D1-D15 deuteron and/or C1-C2 alkyl;
• or
• (C3-C6 cycloalkyl)-C1-C2 branched or unbranched alkyl optionally and independently substituted with one or more substituents such as F1-F15 fluorine and/or D1-D15 deuteron and/or C1-C2 alkyl;
• or
• C2-C5 branched or unbranched alkenyl with E or Z or cis or trans double bond configuration, where any of the carbons of the branched or unbranched alkenyl substituent is optionally substituted independently and in any combination with one or more C1-C2 alkyl, with F1-F13 fluorine, with D1-D13 deuteron, with C2 alkenyl or with aryl or heteroaryl bearing no up to any number of ether, thioether, halogen, alkyl, fluorinated alkyl, alkenyl, alkynyl or nitrogen-containing substituents;
• or
• C2-C5 branched or unbranched alkynyl where any of the carbons of the branched or unbranched alkynyl substituent is optionally substituted independently and in any combination with one or more C1-C2 alkyl, with F1-F11 fluorine, with D1-D11 deuteron, with C2 alkenyl or with aryl or heteroaryl bearing no up to any number of ether, thioether, halogen, alkyl, fluorinated alkyl, alkenyl, alkynyl or nitrogen-containing substituents, any halogen or a nitrogen-containing substituent such as CN or NO2;
• and
• further characterized in that R4 is chosen from the group consisting of hydrogen, deuteron, or fluorine;
• or
• C1-C3 branched or unbranched alkyl with the alkyl optionally and independently substituted with F1-F7 fluorine and/or D1-D7 deuteron substituents;
• or
• C3-C6 cycloalkyl optionally and independently substituted with one or more substituents such as F1-F15 fluorine and/or D1-D15 deuteron and/or C1-C2 alkyl;
• or
• (C3-C6 cycloalkyl)-C1-C2 branched or unbranched alkyl optionally and independently substituted with one or more substituents such as F1-F15 fluorine and/or D1-D15 deuteron and/or C1-C2 alkyl;
• or
• C2-C5 branched or unbranched alkenyl with E or Z or cis or trans double bond configuration, where any of the carbons of the branched or unbranched alkenyl substituent is optionally substituted independently and in any combination with one or more C1-C2 alkyl, with F1-F13 fluorine, with D1-D13 deuteron, with C2 alkenyl or with aryl or heteroaryl bearing no up to any number of ether, thioether, halogen, alkyl, fluorinated alkyl, alkenyl, alkynyl or nitrogen-containing substituents;
• or
• C2-C5 branched or unbranched alkynyl where any of the carbons of the branched or unbranched alkynyl substituent is optionally substituted independently and in any combination with one or more C1-C2 alkyl, with F1-F11 fluorine, with D1-D11 deuteron, with C2 alkenyl or with aryl or heteroaryl bearing no up to any number of ether, thioether, halogen, alkyl, fluorinated alkyl, alkenyl, alkynyl or nitrogen-containing substituents, any halogen or a nitrogen-containing substituent such as CN;
• and
• further characterized in that R5 is chosen from the group consisting of fluorine, chlorine, bromine, and iodine;
• or
• SF5;
• or
• C2-C5 branched or unbranched alkyl with the alkyl optionally and independently substituted with F1-F11 fluorine and/or D1-D11 deuteron substituents or C1 alkyl substituted with F1-F3 and/or D1-D3 deuteron substituents;
• or
• C3-C6 cycloalkyl optionally and independently substituted with one or more substituents such as F1-F15 fluorine and/or D1-D15 deuteron and/or C1-C5 alkyl;
• or
• (C3-C6 cycloalkyl)-C1-C2 branched or unbranched alkyl optionally and independently substituted with one or more substituents such as F1-F15 fluorine and/or D1-D15 deuteron and/or C1-C5 alkyl;
• or
• a nitrogen-containing substituent such as CN or NO2;
• or
• C2-C5 branched or unbranched alkoxy with the alkoxy optionally and independently substituted with F1-F11 fluorine and/or D1-D11 substituents, or C1 alkoxy substituted with F1-F3 and/or D1-D3 deuteron substituents;
• or
• C3-C6 cycloalkyloxy optionally and independently substituted with one or more substituents such as F1-F11 fluorine and/or D1-D11 substituents and/or C1-C5 alkyl;
• or
• (C3-C6 cycloalkyl)-C1-C2 branched or unbranched alkoxy optionally and independently substituted with one or more substituents such as F1-F15 fluorine and/or D1-D15 and/or C1-C5 alkyl;
• or
• C2-C5 branched or unbranched alkenyloxy with E or Z vinylic, cis or trans allylic, E or Z allylic or other double bond position in relation to the attached ether function, where any of the carbons of the branched or unbranched alkenyloxy substituent is optionally substituted independently with one or more C1-C5 alkyl, and/or with F1-F9 fluorine and/or with D1-D9 deuteron substituents;
• or
• C3-C5 branched or unbranched alkynyloxy, where any of the carbons of the alkynyloxy substituent is optionally substituted independently with one or more C1-C5 alkyl, and/or with F1-F9 fluorine and/or with D1-D9 deuteron substituents;
• or
• C3-C5 branched or unbranched alkylthio with the alkylthio group optionally and independently substituted with F1-F11 fluorine and/or D1-D11 substituents, or C1-C2 alkylthio substituted with F1-F5 and/or D1-D5 deuteron substituents;
• or
• C3-C6 cycloalkylthio optionally and independently substituted with one or more substituents such as F1-F11 fluorine and/or D1-D11 substituents and/or C1-C5 alkyl;
• or
• (C3-C6 cycloalkyl)-C1-C2 branched or unbranched alkylthio optionally and independently substituted with one or more substituents such as F1-F15 fluorine and/or D1-D15 and/or C1-C5 alkyl;
• or
• C2-C5 branched or unbranched alkenylthio with E or Z vinylic, cis or trans allylic, E or Z allylic or other double bond position in relation to the attached thioether function, where any of the carbons of the branched or unbranched alkenylthio substituent is optionally substituted independently with one or more C1-C5 alkyl, and/or with F1-F9 fluorine and/or with D1-D9 deuteron substituents;
• or
• C3-C5 branched or unbranched alkynylthio, where any of the carbons of the alkynylthio substituent is optionally substituted independently with one or more C1-C5 alkyl, and/or with F1-F9 fluorine and/or with D1-D9 deuteron substituents, and further characterized in that any non-protic hydrogen can be replaced by a deuteron or a fluorine in any combination;
• and
• avoiding adverse effects present with psychedelics.

A method of changing neurotransmission of an individual, including the steps of:

• administering a pharmaceutically effective amount of composition to the individual of a compound represented by FIG. 1A-1E,
• characterized in that R□1 and R□2 are, independently and in any combination, chosen from the group consisting of hydrogen, deuteron, methyl, ethyl, deuterated methyl (D1-D3), or deuterated ethyl (D1-D5), and
• further characterized in that R1, R2 and R3 are, independently and in any combination, chosen from the group consisting of hydrogen, deuteron, and/or fluorine;
• or
• C1-C3 branched or unbranched alkyl with the alkyl optionally and independently substituted with F1-F7 fluorine and/or D1-D7 deuteron substituents;
• or
• C3-C6 cycloalkyl optionally and independently substituted with one or more substituents such as F1-F15 fluorine and/or D1-D15 deuteron and/or C1-C2 alkyl;
• or
• (C3-C6 cycloalkyl)-C1-C2 branched or unbranched alkyl optionally and independently substituted with one or more substituents such as F1-F15 fluorine and/or D1-D15 deuteron and/or C1-C2 alkyl;
• or
• C2-C5 branched or unbranched alkenyl with E or Z or cis or trans double bond configuration, where any of the carbons of the branched or unbranched alkenyl substituent is optionally substituted independently and in any combination with one or more C1-C2 alkyl, with F1-F13 fluorine, with D1-D13 deuteron, with C2 alkenyl or with aryl or heteroaryl bearing no up to any number of ether, thioether, halogen, alkyl, fluorinated alkyl, alkenyl, alkynyl or nitrogen-containing substituents;
• or
• C2-C5 branched or unbranched alkynyl where any of the carbons of the branched or unbranched alkynyl substituent is optionally substituted independently and in any combination with one or more C1-C2 alkyl, with F1-F11 fluorine, with D1-D11 deuteron, with C2 alkenyl or with aryl or heteroaryl bearing no up to any number of ether, thioether, halogen, alkyl, fluorinated alkyl, alkenyl, alkynyl or nitrogen-containing substituents, any halogen or a nitrogen-containing substituent such as CN or NO2;
• and
• further characterized in that R4 is chosen from the group consisting of hydrogen, deuteron, or fluorine;
• or
• C1-C3 branched or unbranched alkyl with the alkyl optionally and independently substituted with F1-F7 fluorine and/or D1-D7 deuteron substituents;
• or
• C3-C6 cycloalkyl optionally and independently substituted with one or more substituents such as F1-F15 fluorine and/or D1-D15 deuteron and/or C1-C2 alkyl;
• or
• (C3-C6 cycloalkyl)-C1-C2 branched or unbranched alkyl optionally and independently substituted with one or more substituents such as F1-F15 fluorine and/or D1-D15 deuteron and/or C1-C2 alkyl;
• or
• C2-C5 branched or unbranched alkenyl with E or Z or cis or trans double bond configuration, where any of the carbons of the branched or unbranched alkenyl substituent is optionally substituted independently and in any combination with one or more C1-C2 alkyl, with F1-F13 fluorine, with D1-D13 deuteron, with C2 alkenyl or with aryl or heteroaryl bearing no up to any number of ether, thioether, halogen, alkyl, fluorinated alkyl, alkenyl, alkynyl or nitrogen-containing substituents;
• or
• C2-C5 branched or unbranched alkynyl where any of the carbons of the branched or unbranched alkynyl substituent is optionally substituted independently and in any combination with one or more C1-C2 alkyl, with F1-F11 fluorine, with D1-D11 deuteron, with C2 alkenyl or with aryl or heteroaryl bearing no up to any number of ether, thioether, halogen, alkyl, fluorinated alkyl, alkenyl, alkynyl or nitrogen-containing substituents, any halogen or a nitrogen-containing substituent such as CN;
• and
• further characterized in that R5 is chosen from the group consisting of fluorine, chlorine, bromine, and iodine;
• or
• SF5;
• or
• C2-C5 branched or unbranched alkyl with the alkyl optionally and independently substituted with F1-F11 fluorine and/or D1-D11 deuteron substituents or C1 alkyl substituted with F1-F3 and/or D1-D3 deuteron substituents;
• or
• C3-C6 cycloalkyl optionally and independently substituted with one or more substituents such as F1-F15 fluorine and/or D1-D15 deuteron and/or C1-C5 alkyl;
• or
• (C3-C6 cycloalkyl)-C1-C2 branched or unbranched alkyl optionally and independently substituted with one or more substituents such as F1-F15 fluorine and/or D1-D15 deuteron and/or C1-C5 alkyl;
• or
• a nitrogen-containing substituent such as CN or NO2;
• or
• C2-C5 branched or unbranched alkoxy with the alkoxy optionally and independently substituted with F1-F11 fluorine and/or D1-D11 substituents, or C1 alkoxy substituted with F1-F3 and/or D1-D3 deuteron substituents;
• or
• C3-C6 cycloalkyloxy optionally and independently substituted with one or more substituents such as F1-F11 fluorine and/or D1-D11 substituents and/or C1-C5 alkyl;
• or
• (C3-C6 cycloalkyl)-C1-C2 branched or unbranched alkoxy optionally and independently substituted with one or more substituents such as F1-F15 fluorine and/or D1-D15 and/or C1-C5 alkyl;
• or
• C2-C5 branched or unbranched alkenyloxy with E or Z vinylic, cis or trans allylic, E or Z allylic or other double bond position in relation to the attached ether function, where any of the carbons of the branched or unbranched alkenyloxy substituent is optionally substituted independently with one or more C1-C5 alkyl, and/or with F1-F9 fluorine and/or with D1-D9 deuteron substituents;
• or
• C3-C5 branched or unbranched alkynyloxy, where any of the carbons of the alkynyloxy substituent is optionally substituted independently with one or more C1-C5 alkyl, and/or with F1-F9 fluorine and/or with D1-D9 deuteron substituents;
• or
• C3-C5 branched or unbranched alkylthio with the alkylthio group optionally and independently substituted with F1-F11 fluorine and/or D1-D11 substituents, or C1-C2 alkylthio substituted with F1-F5 and/or D1-D5 deuteron substituents;
• or
• C3-C6 cycloalkylthio optionally and independently substituted with one or more substituents such as F1-F11 fluorine and/or D1-D11 substituents and/or C1-C5 alkyl;
• or
• (C3-C6 cycloalkyl)-C1-C2 branched or unbranched alkylthio optionally and independently substituted with one or more substituents such as F1-F15 fluorine and/or D1-D15 and/or C1-C5 alkyl;
• or
• C2-C5 branched or unbranched alkenylthio with E or Z vinylic, cis or trans allylic, E or Z allylic or other double bond position in relation to the attached thioether function, where any of the carbons of the branched or unbranched alkenylthio substituent is optionally substituted independently with one or more C1-C5 alkyl, and/or with F1-F9 fluorine and/or with D1-D9 deuteron substituents;
• or
• C3-C5 branched or unbranched alkynylthio, where any of the carbons of the alkynylthio substituent is optionally substituted independently with one or more C1-C5 alkyl, and/or with F1-F9 fluorine and/or with D1-D9 deuteron substituents, and further characterized in that any non-protic hydrogen can be replaced by a deuteron or a fluorine in any combination;
• and
• changing neurotransmission in the individual.