- NEUROACTIVE STEROIDS AND COMPOSITIONS AND METHODS THEREOF
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The invention provides novel neuroactive steroids and pharmaceutical compositions thereof, as well as methods of their preparation and use, in therapy of various diseases and conditions, for example, various neurological or brain diseases.
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Paragraph 00209
(2021/06/11)
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- TETRAZOLONE SUBSTITUTED STEROIDS AND USE THEREOF
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The present disclosure relates to compounds of formula (AI), (I), (AII), and (II), or a pharmaceutically acceptable salt, solvate, stereoisomer, or tautomer thereof, a pharmaceutical composition comprising a compound of formula (AI), (I), (AII), and (II), and use thereof, wherein R2, R3, R4, R5, R6, R7, R10, R11a, R11b, R12, R16, R19a, R19b, and R20 are described herein. Such compounds are envisioned useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, movement disorders, convulsive disorders, schizophrenin spectrum disorders, disorders of memory and/or cognition, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular diseases, substance abuse disorders and/or withdrawal syndromes, or tinnitus etc.
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Paragraph 443; 445-446
(2020/07/31)
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- Steroid compound, application and preparation method thereof
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The invention relates to a steroid compound, an application and a preparation method thereof. The compounds are expected to be capable of effectively treating neuropsychiatric diseases, and have goodactive efficacy, pharmacokinetic (PK) performance, oral
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Paragraph 0059-0061
(2020/07/24)
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- C17, C20, AND C21 SUBSTITUTED NEUROACTIVE STEROIDS AND THEIR METHODS OF USE
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Described herein are neuroactive steroids or a pharmaceutically acceptable salt thereof. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. Also provided are pharmaceutical compositions comprising a compound described herein and methods of use and treatment, e.g., such as for inducing sedation and/or anesthesia.
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Page/Page column 193; 194; 207; 208
(2018/03/25)
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- Neuroactive Steroids. 2. 3α-Hydroxy-3β-methyl-21-(4-cyano-1H-pyrazol-1′-yl)-19-nor-5β-pregnan-20-one (SAGE-217): A Clinical Next Generation Neuroactive Steroid Positive Allosteric Modulator of the (γ-Aminobutyric Acid)A Receptor
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Certain classes of neuroactive steroids (NASs) are positive allosteric modulators (PAM) of synaptic and extrasynaptic GABAA receptors. Herein, we report new SAR insights in a series of 5β-nor-19-pregnan-20-one analogues bearing substituted pyrazoles and triazoles at C-21, culminating in the discovery of 3α-hydroxy-3β-methyl-21-(4-cyano-1H-pyrazol-1′-yl)-19-nor-5β-pregnan-20-one (SAGE-217, 3), a potent GABAA receptor modulator at both synaptic and extrasynaptic receptor subtypes, with excellent oral DMPK properties. Compound 3 has completed a phase 1 single ascending dose (SAD) and multiple ascending dose (MAD) clinical trial and is currently being studied in parallel phase 2 clinical trials for the treatment of postpartum depression (PPD), major depressive disorder (MDD), and essential tremor (ET).
- Martinez Botella, Gabriel,Salituro, Francesco G.,Harrison, Boyd L.,Beresis, Richard T.,Bai, Zhu,Blanco, Maria-Jesus,Belfort, Gabriel M.,Dai, Jing,Loya, Carlos M.,Ackley, Michael A.,Althaus, Alison L.,Grossman, Scott J.,Hoffmann, Ethan,Doherty, James J.,Robichaud, Albert J.
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p. 7810 - 7819
(2017/10/06)
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- COMPOSITIONS AND METHODS FOR TREATING CNS DISORDERS
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Described herein are neuroactive steroids of the Formula (II) : or a pharmaceutically acceptable salt thereof; wherein A, R1, R2a, R2b, R3a, R3b, R4a, R4b, R5, R6 and ----- are as defined herein. Such compounds are envisioned, in certain embodiments, to behave as GABA modulators. The present invention also provides pharmaceutical compositions comprising a compound of the present invention and methods of use and treatment, e. g., such for inducing sedation and/or anesthesia.
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Page/Page column 78
(2016/06/14)
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- NEUROACTIVE STEROIDS, COMPOSITIONS, AND USES THEREOF
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Provided herein are 19-nor C3, 3-disubstituted steroids of Formula (I) : and pharmaceutically acceptable salts thereof; wherein R1, R2, R3, and R4are as defined herein, and A is a heteroaryl ring system comprising 3 or 4 nitrogens as defined herein. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, schizophrenia spectrum disorders, convulsive disorders, disorders of memory and/or cognition, movement disorders, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular diseases, substance abuse disorders and/or withdrawal syndromes, and tinnitus.
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Page/Page column 67; 68
(2015/12/17)
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- 19-NOR C3,3-DISUBSTITUTED C21-N-PYRAZOLYL STEROIDS AND METHODS OF USE THEREOF
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Provided herein are 19-nor C3,3-disubstituted C21-pyrazolyl steroids of Formula (I), and pharmaceutically acceptable salts thereof; wherein-, R1, R2, R3a, R3b, R4a, R4b, R5, R6, and R7are as defined herein. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, schizophrenia spectrum disorders, convulsive disorders, disorders of memory and/or cognition, movement disorders, personality disorders, autism spectrum disorders, pain, traumatic brain injury, vascular diseases, substance abuse disorders and/or withdrawal syndromes, and tinnitus.
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Page/Page column 85
(2014/11/11)
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- 19-NOR NEUROACTIVE STEROIDS AND METHODS OF USE THEREOF
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Provided herein are 3,3-disubstituted19-nor-steroidal compounds according to Formula(I): and pharmaceutical compositions thereof. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions,for example, treatment of sleep disorders, mood disorders,schizophrenia spectrum disorders, disorders of memory and/or cognition, movement disorders,personality disorders,autism spectrum disorders, pain,traumatic brain injury, vascular diseases,substance abuse disorders and/or withdrawal syndromes, tinnitus, status epilepticus.
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Page/Page column 82; 83
(2014/11/11)
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- 19-NOR NEUROACTIVE STEROIDS AND METHODS OF USE THEREOF
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Provided herein are 3,3-disubstituted 19-nor-steroidal compounds according to Formula (I): and pharmaceutical compositions thereof. Such compounds are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, schizophrenia spectrum disorders, disorders of memory and/or cognition, movement disorders, personality disorders, autism spectrum disorders, pain,traumatic brain injury, vascular diseases, substance abuse disorders and/or withdrawal syndromes, tinnitus, and status epilepticus.
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Page/Page column 98
(2014/11/11)
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- 19-NOR C3,3-DISUBSTITUTED C21-C-BOUND HETEROARYL STEROIDS AND METHODS OF USE THEREOF
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Provided herein are19-nor C3,3-disubstituted steroids of Formula (I): and pharmaceutically acceptable salts thereof; wherein, ??, R1, R2, R3a, R3b, R4a, and R 4bare as defined herein, and A
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Page/Page column 81
(2014/11/11)
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- 3,3 DISUBSTITUTED 19-NOR PREGNANE COMPOUNDS, COMPOSITIONS, AND USES THEREOF
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Provided herein are 3,3-disubstituted 19-nor- steroidal compounds according to Formula (I) and (III): where R1,R2, R3, R3', R4, R6a, R6a, R11a, and R11b are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of CNS-related conditions, for example, treatment of sleep disorders, mood disorders, insomnia, anxiety, depression, traumatic brain injury (TBI), stress, and epilepsy.
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Paragraph 00320
(2013/04/25)
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- 4-(3′α15′β-dihydroxy-5′β-estran- 17′β-yl)furan-2-methyl alcohol: An anti-digoxin agent with a novel mechanism of action
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The synthesis and some pharmacological properties of 4-(3′α- 15′β-dihydiOxy-5β-estran-17′β9-yl)furan-2-methyl alcohol (16) have been described. The compound was synthesized by reacting a synthetic 3α-benzyloxy-5β-estr-15-en-17-one with the ethylene acetal
- Deutsch, Joseph,Jang, Huang G.,Mansur, Nura,Ilovich, Ohad,Shpolansky, Uri,Galili, Dana,Feldman, Tomer,Rosen, Haim,Lichtstein, David
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p. 600 - 606
(2007/10/03)
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- 19-norbufalin derivatives, their preparation and pharmaceutical compositions containing them
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A 19-norbufalin derivative compound of formula (I) and isomers pharmaceutically acceptable salts thereof. Compounds of formula (I) are Na+,K+-ATPase inhibitors and can be used in the treatment of cardiac and/or vascular malfunction,
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- Neurosteroid analogues. 4. The effect of methyl substitution at the C-5 and C-10 positions of neurosteroids on electrophysiological activity at GABA(A) receptors
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A series of analogues of the neuroactive steroids 3α-hydroxy-5α- pregnan-20-one and 3α-hydroxy-5β-pregnan-20-one were studied to elucidate the mode of binding of 5α- and 5β-reduced steroids to steroid binding sites on GABA(A) receptors. Analogues which were either 3α-hydroxy-20-ketosteroids or 3α-hydroxysteroid-17β-carbonitriles and which contained various methyl group substitution patterns at C-5 and C-10 were prepared. Evaluations utilized whole-cell patch clamp electrophysiological methods carried out on cultured rat hippocampal neurons, and the results obtained with the rigid 17β-carbonitrile analogs were analyzed using molecular modeling methods. The molecular modeling results provide a rationale for the observation that the configuration of the hydroxyl group at C-3 is a greater determinant of anesthetic potency than the configuration of the A,B ring fusion at C-5. The electrophysiological results identify steric restrictions for the space that can be occupied in 5α- and 5β-reduced steriod modulators of GABA(A) recepters in the regions of space proximate to the steroid C-5, C-10, and possibly C-4 positions. This information is useful for the development of nonsteroidal analogues that can modulate GABA(A) receptors via interactions at steroid binding sites.
- Han, Mingcheng,Zorumski, Charles F.,Covey, Douglas F.
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p. 4218 - 4232
(2007/10/03)
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- Synthesis of 5β,17α-19-norpregn-20-yne-3β,17-diol and of 5β,17α-19-norpregn-20-yne-3α,17-diol, human metabolites of norethindrone
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A convenient synthesis of both 5β, 17α-19-norpregn-20-yne-3β,17-diol (1) and 5β,17α-19-norpregn-20-yne-3α, 17-diol (2) in multigram quantities from estr-4-ene-3, 17-dione is reported. Full characterization of these often-cited human melaholites of norethindrone is presented for the first time.
- Curts, Stephen W.,Wren, Douglas L.,Cooper, Gary F.
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- Stereochemistry of the Palladium-catalyzed Hydrogenation of 3-Oxo-4-ene Steroids. V. A Kinetic Study in Basic and Acidic Media
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Effects of the β-methyl group at C-10 and some oxygen functions (=O, OH, OAc) at C-11, C-17, and C-20 on the rates of hydrogenation of 3-oxo-4-ene steroids have been studied with palladium catalyst in pyridine or THF/HBr as solvent.In contrast to the hydrogenation in pyridine, the rate in THF/HBr was greatly depressed by the presence of 10β-methyl group.The reactivity of the steroids was enhanced by the oxygen functions, in particular, by 11, 17-dioxo group.The effects of the substituents are discussed from a mechanistic consideration based on the obtained results.
- Nishimura, Shigeo,Momma, Yasuhiro,Kawamura, Hideo,Shiota, Michio
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p. 780 - 783
(2007/10/02)
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- Microbiological Transformations. XVI. Transformation of 5α- and 5β-Dihydro, and 1- and 6-Dehydro Derivatives of Testosterone and Androstenedione by Means of Rhodotorula mucilaginosa Strain
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The following transformation of 5α- and 5β-dihydro derivatives of testosterone and androstenedione by means of Rhodotorula mucilaginosa has been observed: reduction of the carbonyl group on C-3 to both possible alcohols in the 5α-series and only to one alcohol (3α) in the 5β-series.In the transformation of 1- and 6-dehydro derivatives of testosterone and androstenedione, reduction in ring A was completely inhibited.The carbonyl or hydroxy groups at C-17 in both series of substrates underwent interconversion.
- Draczynska, Bozena,Tlomak, Elzbieta,Dmochowska-Gladysz, Jadwiga,Siewinski, Antoni
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