The present invention relates to agonists of the 5-HT.sub.2A serotonin receptors and their medical uses. In one aspect the invention relates to 5-HT.sub.2A agonists of formula (I). In second aspect, the invention relates to selective 5-HT.sub.2A agonists of formula (II). In another aspect, the invention relates to mixed 5-HT.sub.2A/5-HT.sub.2C agonists of formula (III). In yet another aspect, the invention relates to 5-HT.sub.2A agonists for use in the treatment of a depressive disorder, more particular a 5-HT.sub.2A agonist for the use in the treatment of treatment-resistant depression.

The present invention relates to agonists of the 5-HT.sub.2A serotonin receptors and their medical uses. In one aspect the invention relates to 5-HT.sub.2A agonists of formula (I). In second aspect, the invention relates to selective 5-HT.sub.2A agonists of formula (II). In another aspect, the invention relates to mixed 5-HT.sub.2A/5-HT.sub.2C agonists of formula (III). In yet another aspect, the invention relates to 5-HT.sub.2A agonists for use in the treatment of a depressive disorder, more particular a 5-HT.sub.2A agonist for the use in the treatment of treatment-resistant depression.

The invention provides compounds of Formula (I), or pharmaceutically acceptable salts thereof: ##STR00001## The compounds, compositions, methods and kits of the invention are useful for the treatment of pain, itch, and neurogenic inflammation.

The invention relates to a process for the preparation of compounds of formula (I), which are useful intermediates in the synthesis of Upadacitinib and structurally related compounds, by using Weinreb amide (III), or an equivalent thereof, as key intermediate.

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The invention relates to a process for the preparation of compounds of formula (I), which are useful intermediates in the synthesis of Upadacitinib and structurally related compounds, by using Weinreb amide (III), or an equivalent thereof, as key intermediate.

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Provided are compounds of Formula (II) or a pharmaceutically acceptable salt thereof, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, and p are as defined herein. Also provided is a pharmaceutically acceptable composition comprising a compound of Formula (II), or a pharmaceutically acceptable salt thereof. Also provided are methods of using a compound of Formula (II), or a pharmaceutically acceptable salt thereof.

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Provided are compounds of Formula (II) or a pharmaceutically acceptable salt thereof, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, and p are as defined herein. Also provided is a pharmaceutically acceptable composition comprising a compound of Formula (II), or a pharmaceutically acceptable salt thereof. Also provided are methods of using a compound of Formula (II), or a pharmaceutically acceptable salt thereof.

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The present disclosure details various lipids, compositions, and/or methods of optimized systems and delivery vehicles for the delivery of nucleic acid sequences, polypeptides or peptides for use in vaccinating against infectious agents.

The present disclosure details various lipids, compositions, and/or methods of optimized systems and delivery vehicles for the delivery of nucleic acid sequences, polypeptides or peptides for use in vaccinating against infectious agents.

Compounds of formula (I) wherein: X is —O—, —S(O).sub.r—, —CH.sub.2—, or —NR—, wherein r is 0, 1, or 2; X.sup.1, X.sup.2, and X.sup.5 are each independently CR.sup.7 or N; one of X.sup.3 or X.sup.4 is C and is attached by a single bond to -L-, and the other is CR.sup.7 or N, provided that no more than three of X.sup.1, X.sup.2, X.sup.3, X or X.sup.5 are N; Ring A is monocyclic C.sub.5-6scycloalkyl or a 5- to 6-membered monocyclic heterocyclyl comprising from 1 to 5 heteroatoms independently selected from N, S, or O; wherein Ring A is further optionally substituted with from 1 to 3 R.sup.4; provided that Ring A is not morpholinyl, thiomorpholinyl or tetrahydro-2H-pyranyl; L is a bond, —O—, —NR—, —S(O).sub.n—, —CH.sub.2—, or —C(O)—, wherein n is 0, 1, or 2; 1 2 L.sup.1 is an C.sub.1-8alkylene, C.sub.3-scycloalkylene, —CH.sub.2-L.sup.2-, or a 3- to 8-membered heterocyclylene comprising 1 to 5; R.sup.1 is C.sub.6-20alkyl or a monocyclic C.sub.3-8cycloalkyl; wherein said C.sub.3-8cycloalkyl is substituted with at least one R.sup.6 and may be optionally substituted with from 1 to 5 additional R.sup.6 substituents, wherein R.sup.6 for each occurrence is independently selected; and R.sup.2 is —C(O)OR.sup.3, —C(O)N(R.sup.3)—S(O).sub.2R.sup.3, —S(O).sub.2OR.sup.3, —C(O)NHC(O)R.sup.3, —Si(O)OH, —B(OH).sub.2, —N(R.sup.3)S(O).sub.2R.sup.3, —S(O).sub.2N(R.sup.3).sub.2, —O—P(O)(OR.sup.3).sub.2, or —P(O)(OR.sup.3).sub.2, —CN, —S(O).sub.2NHC(O)R.sup.3, —C(O)NHS(O).sub.2R3, —C(O)NHOH, —C(O)NHCN, —CH(CF.sub.3)OH, —C(CF.sub.3).sub.2OH, or a selected heteroaryl or heterocyclyl; and pharmaceutically acceptable salts thereof, can modulate the activity of one or more SIP receptors and/or the activity of autotaxin (ATX). ##STR00001##