CN105037471B - A kind of steroid antivirotic - Google Patents
A kind of steroid antivirotic Download PDFInfo
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- CN105037471B CN105037471B CN201510219163.3A CN201510219163A CN105037471B CN 105037471 B CN105037471 B CN 105037471B CN 201510219163 A CN201510219163 A CN 201510219163A CN 105037471 B CN105037471 B CN 105037471B
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- 150000003431 steroids Chemical class 0.000 title claims abstract description 34
- 230000002155 anti-virotic effect Effects 0.000 title abstract description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 23
- 150000003839 salts Chemical class 0.000 claims abstract description 15
- 150000002611 lead compounds Chemical class 0.000 claims abstract description 5
- -1 steroid compound Chemical class 0.000 claims abstract description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
- 239000004593 Epoxy Substances 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 230000003637 steroidlike Effects 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 230000002265 prevention Effects 0.000 claims description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 150000003254 radicals Chemical class 0.000 claims description 6
- XXJGBENTLXFVFI-UHFFFAOYSA-N 1-amino-methylene Chemical compound N[CH2] XXJGBENTLXFVFI-UHFFFAOYSA-N 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 150000001721 carbon Chemical group 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 2
- 239000000651 prodrug Substances 0.000 abstract description 9
- 229940002612 prodrug Drugs 0.000 abstract description 9
- 241000725643 Respiratory syncytial virus Species 0.000 abstract description 6
- 239000003443 antiviral agent Substances 0.000 abstract description 6
- 230000002401 inhibitory effect Effects 0.000 abstract description 5
- 238000011160 research Methods 0.000 abstract description 4
- 239000012453 solvate Substances 0.000 abstract description 4
- 241000711504 Paramyxoviridae Species 0.000 abstract description 3
- 239000004480 active ingredient Substances 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 5
- 231100000816 toxic dose Toxicity 0.000 description 5
- 238000007614 solvation Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 206010061603 Respiratory syncytial virus infection Diseases 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 0 CC(C)CCC[C@@](C)C(CC1)[C@@](C)(CCC([C@](C[C@@]2*)C[C@]3C[C@]2OC(C)=O)C2=CC3=*)[C@@]12O Chemical compound CC(C)CCC[C@@](C)C(CC1)[C@@](C)(CCC([C@](C[C@@]2*)C[C@]3C[C@]2OC(C)=O)C2=CC3=*)[C@@]12O 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 206010035664 Pneumonia Diseases 0.000 description 2
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 208000030303 breathing problems Diseases 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 229960000329 ribavirin Drugs 0.000 description 2
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- KBIWNQVZKHSHTI-UHFFFAOYSA-N 4-n,4-n-dimethylbenzene-1,4-diamine;oxalic acid Chemical compound OC(=O)C(O)=O.CN(C)C1=CC=C(N)C=C1 KBIWNQVZKHSHTI-UHFFFAOYSA-N 0.000 description 1
- DULFKFJFGWGBJG-LFDAGRPUSA-N CC(C)CCC[C@@H](C)C(CC1)[C@@](C)(CC2)C1C(C[C@H]1O)C2[C@@](C)(CC/C(/C2)=[O]\C(C)=O)[C@@]12O Chemical compound CC(C)CCC[C@@H](C)C(CC1)[C@@](C)(CC2)C1C(C[C@H]1O)C2[C@@](C)(CC/C(/C2)=[O]\C(C)=O)[C@@]12O DULFKFJFGWGBJG-LFDAGRPUSA-N 0.000 description 1
- ASLRQFJAZSHQDD-OTGRGDJWSA-N CC(C)[C@@H](C)/C=C/[C@@H](C)C([C@H](C1)OC(C)=O)[C@@](C)(C[C@@H]2O)C1C([C@H]1C)C2[C@@](C)(CCC(C2)=C)[C@H]2C1=O Chemical compound CC(C)[C@@H](C)/C=C/[C@@H](C)C([C@H](C1)OC(C)=O)[C@@](C)(C[C@@H]2O)C1C([C@H]1C)C2[C@@](C)(CCC(C2)=C)[C@H]2C1=O ASLRQFJAZSHQDD-OTGRGDJWSA-N 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Natural products OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- GXFIJNNOECYQOJ-UHFFFAOYSA-N [2-[1-(1-methylpyrazol-4-yl)indol-4-yl]oxy-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound CN1N=CC(=C1)N1C=CC2=C(C=CC=C12)OC1=NC(=CC(=C1)CN)C(F)(F)F GXFIJNNOECYQOJ-UHFFFAOYSA-N 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 231100001134 median toxic concentration Toxicity 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0005—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring the nitrogen atom being directly linked to the cyclopenta(a)hydro phenanthrene skeleton
- C07J41/0011—Unsubstituted amino radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0005—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring the nitrogen atom being directly linked to the cyclopenta(a)hydro phenanthrene skeleton
- C07J41/0016—Oximes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
- C07J41/0055—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0005—Oxygen-containing hetero ring
- C07J71/001—Oxiranes
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a kind of steroid antivirotic, wherein steroid compound has structure shown in Formulas I：
Description
Technical field
The invention belongs to medicinal chemistry art, is related to a kind of steroid antivirotic.More particularly to one kind to the viscous disease of pair
The Respiratory Syncytial Virus(RSV) (RSV) of malicious section has the steroid antivirotic of extremely strong inhibitory activity.
Background technology
Respiratory Syncytial Virus(RSV) (respiratory syncytial virus pneumonia, abbreviation syncytial virus,
RSV, also belong to Paramyxoviridae), it is a kind of RNA virus, belongs to Paramyxoviridae.Rsv infection can trigger pneumonia and a variety of lower breathings
Tract disease, the annual whole world at least 3,000,000 infants are admitted to hospital because of the infection of RSV viruses, wherein at least there is 160,000 people death,
Therefore RSV is also referred to as children killer (Science, 2013,342,546-547).Currently without can be applied to clinic vaccine,
Ribavirin (ribavirin) be it is unique be applied to clinical chemotherapeutic agent (J.Med.Chem.2008,51,875-
896).In summary, developing the medicine of disease caused by prevention and/or treatment rsv infection turns into the task of top priority.
The content of the invention
It is an object of the invention to provide a kind of steroid antiviral drugs, wherein steroid has structure shown in formula I：
R in Formulas I1For C5-10Alkyl, C5-10Alkenyl, wherein described alkyl or alkenyl optionally by one or more OH, OAc,
CH2OAc, oxo base (=O, i.e., forming carbonyl with bonded carbon), methylol, C1-3Alkyl substitutes, or described alkyl or alkenyl
In two adjacent carbon atoms and oxygen atom form epoxy radicalsR2To R11It is each independently selected from H, OH, NH2、CH2NH2、
CN、CH(CN)2, oximido (=N-OH), OAc, oxo base (=O, i.e., with bonded carbon formed carbonyl), or on steroidal parent nucleus it is adjacent
Carbon atom forms epoxy radicals with oxygen atomWherein " --- -- " represents singly-bound or is not present,Represent to point to paper
Key in faceOr the key outside sensing paper
Wherein C5-10The preferred C of alkyl6Alkyl, further preferablyC5-10The preferred C of alkenyl5-6Alkenyl, enter one
Step is preferredDescribed alkyl or alkenyl is optional
By one or more OH, OAc, CH2It is OAc, oxo base (=O, i.e., forming carbonyl with bonded carbon), methylol, methyl, ethyl, different
Two adjacent carbon atoms form epoxy radicals with oxygen atom in propyl group, or described alkyl or alkenyl
The present invention provides at least contains 1 OH, further preferred steroid on the preferred steroidal parent nucleus of steroid of Formulas I structure
At least contain 2 OH on body parent nucleus；Contain at least three oxygen atom in further preferred Formulas I structure.
Type I compound is selected from following compounds：
The steroid of Formulas I structure of the present invention can obtain (such as chemical combination by organic synthesis or natural extraction
Thing 1-37 is known synthesis or extraction product), it can also be obtained by carrying out simple structural modification to natural extraction compound.
The steroid of Formulas I structure of the present invention is not non-including that can not be obtained by the modification of this area conventional chemical
Known steroidal.
The present invention also provides the stereoisomer of steroid of Formulas I structure, geometric isomer, dynamic isomer, molten
Agent compound, its prodrug or its pharmaceutically acceptable salt.
The present invention provides a kind of antivirotic, it is characterised in that comprising Formulas I structure steroid, its stereoisomer,
It is any one or several as effective in geometric isomer, dynamic isomer, solvate, prodrug or its pharmaceutically acceptable salt
Composition.Also contain pharmaceutic adjuvant, such as pharmaceutically acceptable carrier, diluent or excipient in the antivirotic.
The present invention provides a kind of antivirotic, it is characterised in that comprising Formulas I structure steroid, its stereoisomer,
Any one or several, Yi Jiqi in geometric isomer, dynamic isomer, solvate, prodrug or its pharmaceutically acceptable salt
His antiviral drugs.Also contain pharmaceutic adjuvant, such as pharmaceutically acceptable carrier, diluent or figuration in the antivirotic
Agent.
Antivirotic provided by the invention can be solid pharmaceutical preparation or liquid preparation, preferred tablet, capsule, freeze-dried powder
Agent, injection.
The present invention provides Formulas I structure steroid, its stereoisomer, geometric isomer, dynamic isomer, solvation
Any one or several purposes in antiviral drugs is prepared in thing, prodrug or its pharmaceutically acceptable salt.
The present invention provides Formulas I structure steroid, its stereoisomer, geometric isomer, dynamic isomer, solvation
It is any one or several in thing, prodrug or its pharmaceutically acceptable salt to prepare the medicine for the treatment of and/or prevention breathing problem
In application.
The present invention provides Formulas I structure steroid, its stereoisomer, geometric isomer, dynamic isomer, solvation
It is any one or several in thing, prodrug or its pharmaceutically acceptable salt to prepare treatment and/or the prevention disease as caused by RSV
Application in medicine.
The present invention provides Formulas I structure steroid, its stereoisomer, geometric isomer, dynamic isomer, solvation
In thing, prodrug or its pharmaceutically acceptable salt in any one or several researchs as antiviral drugs lead compound should
With；Preferably as the purposes of lead compound in the medicine of research treatment and/or prevention breathing problem；Further preferred conduct
The purposes of lead compound in the medicine of research treatment and/or the prevention disease as caused by RSV.
Term " pharmaceutically acceptable salt " refers to the addition of atoxic inorganic or organic acid and/or alkali in the present invention
Salt, reference can be made to " Salt selection for basic drugs ", Int.J.Pharm. (1986), 33,201-217.It is inorganic
Or the preferred hydrochloric acid of organic acid, sulfuric acid, phosphoric acid, maleic acid, citric acid, fumaric acid, glucuronic acid, formic acid, acetic acid, ethanedioic acid,
Succinic acid etc..
Term " geometric isomer " refers to when R1 contains double bond in Formulas I structure in the present invention, including double bond is two kinds of Z, E
The compound of geometric configuration.
Embodiment
For the ease of a further understanding of the present invention, examples provided below has done more detailed description to it.But
It is that these embodiments only are not used for limiting the scope of the present invention or implementation principle, reality of the invention for being better understood from inventing
The mode of applying is not limited to herein below.
The antiviral activity of the steroid (by taking compound 1-37 as an example) of structure shown in formula I of the present invention
The compounds of this invention is to the inhibitory activity of Respiratory Syncytial Virus(RSV) (RSV) according to document：Zhang,Y.J.；Stein,
D.A.；Fan,S.M.；Wang,K.Y.；Kroeker,A.D.；Meng,X.J.；Iversen,P.L.；Matson,
D.O.Vet.Microbiol.2006,117 (2-4), 117-129 or Grassauer, A.；Weinmuellner,R.；
Meier,C.；Pretsch,A.；Prieschl-Grassauer,E.；Described in Unger, H., Virol.J.2008,5,107.
Method tested, or can according in the prior art other tested similar to method reported in the literature.
As a result show, test compound (1-37) is respectively provided with significant inhibitory action to RSV, its medium effective concentration
(EC50) at 0.05 to 3 μM, and median toxic concentration (TC50) at 20-100 μM, press down malicious index (TI)=TC50/EC50Up to
300, it is seen that formula I structures steroid, its stereoisomer, geometric isomer, dynamic isomer, solvate,
Prodrug or its pharmaceutically acceptable salt can be used for preparing anti-rsv infection medicine.The activity knot of the compounds of this invention is listed in table 1
Fruit.
Inhibitory activity of the compounds of this invention of table 1 (1-37) to Respiratory Syncytial Virus(RSV) (RSV).
" A " represents that compound concentration is 0.05-1 μM (being free of 1 μM) in table 1, and " B " represents that compound concentration is 1-10 μM
(being free of 10 μM), " C " represent that compound concentration is 10-20 μM (being free of 20 μM), and " D " represents that compound concentration is 20-30 μM；“+
+++ " represent TC50/EC50Between 200~300, " +++ " represents TC50/EC50Between 100-200, " ++ " represents TC50/EC50
Between 50-100.
Explanation：It is related to the not unique situation of compound spatial configuration in active testing, the compound used during test is it
The mixture of any configuration or the mixing of several configuration equal proportions in a variety of configurations, by taking compound 5 as an example, it has two kinds of configurations：Active testing result in table 1 is compound 5-1 and 5-2 grade ratio
The activity of example mixture, for another example in the active testing of compound 6, actual measurement compound is：
Bibliography is all incorporated as in this application in all documents that the present invention refers to, just as each document quilt
It is individually recited as with reference to such.In addition, it is to be understood that after the above of the present invention has been read, those skilled in the art
The present invention can be made various changes or modifications, these equivalent form of values equally fall within what the application appended claims were limited
Scope.
Claims (18)
1. a kind of Formulas I structure steroid, its stereoisomer, geometric isomer, dynamic isomer or its can pharmaceutically connect
Any one or several purposes in the medicine for preparing treatment and/or the prevention disease as caused by RSV in the salt received；Wherein Formulas I
Structure steroid is：
Wherein R1For C5-10Alkyl, C5-10Alkenyl, wherein described alkyl or alkenyl optionally by one or more OH, OAc,
CH2OAc, oxo base (=O, i.e., forming carbonyl with bonded carbon), methylol, C1-3Alkyl substitutes, or described alkyl or alkenyl
In two adjacent carbon atoms and oxygen atom form epoxy radicalsR2To R11It is each independently selected from H, OH, NH2、CH2NH2、CN、
CH(CN)2, oximido (=N-OH), OAc, oxo base (=O, i.e., forming carbonyl with bonded carbon), or adjacent carbons is former on steroidal parent nucleus
Son forms epoxy radicals with oxygen atomWherein " --- -- " represents singly-bound or is not present,Represent to point in paper
KeyOr the key outside sensing paperThe C5-10Alkenyl is selected from
2. the purposes described in claim 1, it is characterised in that C5-10The preferred C of alkyl6Alkyl.
3. the purposes described in claim 2, it is characterised in that C6Alkyl is preferred
4. the purposes described in claim any one of 1-3, it is characterised in that described alkyl or alkenyl is optionally one or more
OH、OAc、CH2OAc, oxo base (=O, i.e., forming carbonyl with bonded carbon), methylol, methyl, ethyl, isopropyl, or it is described
Alkyl or alkenyl in two adjacent carbon atoms and oxygen atom form epoxy radicals
5. a kind of Formulas I structure steroid, its stereoisomer, geometric isomer, dynamic isomer or its can pharmaceutically connect
Any one or several use in the lead compound for preparing treatment and/or the prevention disease as caused by RSV in the salt received
On the way；Wherein Formulas I structure steroid is：Wherein R1For C5-10Alkyl, C5-10Alkene
Base, wherein described alkyl or alkenyl is optionally by one or more OH, OAc, CH2OAc, oxo base (=O, i.e., with bonded carbon shape
Into carbonyl), methylol, C1-3Alkyl substitutes, or two adjacent carbon atoms form epoxy with oxygen atom in described alkyl or alkenyl
BaseR2To R11It is each independently selected from H, OH, NH2、CH2NH2、CN、CH(CN)2, oximido (=N-OH), OAc, oxo
Base (=O, i.e., forms carbonyl) with bonded carbon, or adjacent carbon atom forms epoxy radicals with oxygen atom on steroidal parent nucleus
Wherein " --- -- " represents singly-bound or is not present,Represent to point to the key in paperOr the key outside sensing paperThe C5-10Alkenyl is selected from
6. the purposes described in claim 5, it is characterised in that C5-10The preferred C of alkyl6Alkyl.
7. the purposes described in claim 6, it is characterised in that C6Alkyl is preferred
8. the purposes described in claim any one of 5-7, it is characterised in that described alkyl or alkenyl is optionally one or more
OH、OAc、CH2OAc, oxo base (=O, i.e., forming carbonyl with bonded carbon), methylol, methyl, ethyl, isopropyl, or it is described
Alkyl or alkenyl in two adjacent carbon atoms and oxygen atom form epoxy radicals
9. the purposes described in any one of claim 1-3,5-7, it is characterised in that the preferred steroid of steroid of the Formulas I structure
At least contain 1 OH on body parent nucleus.
10. the purposes described in claim 4, it is characterised in that the preferred steroidal parent nucleus of steroid of the Formulas I structure is up to
Contain 1 OH less.
11. the purposes described in claim 8, it is characterised in that the preferred steroidal parent nucleus of steroid of the Formulas I structure is up to
Contain 1 OH less.
12. the purposes described in claim 9, it is characterised in that the further preferred steroidal of steroid of the Formulas I structure is female
At least contain 2 OH on core.
13. the purposes described in claim any one of 10-11, it is characterised in that the steroid of the Formulas I structure is further
It is preferred that at least contain 2 OH on steroidal parent nucleus.
14. the purposes described in any one of claim 1-3,5-7, it is characterised in that the steroid of the Formulas I structure enters one
Contain at least three oxygen atom in step preferred formula I structures.
15. the purposes described in claim 4, it is characterised in that the further preferred Formulas I structure of steroid of the Formulas I structure
In contain at least three oxygen atom.
16. the purposes described in claim 8, it is characterised in that the further preferred Formulas I structure of steroid of the Formulas I structure
In contain at least three oxygen atom.
17. the purposes described in claim 1, it is characterised in that the steroid of the structure shown in formula I is selected from following compounds：
18. in compound 16,18,28,31,32 or its pharmaceutically acceptable salt it is any one or several prepare treatment and/or
Prevent the purposes in the medicine of the disease as caused by RSV, it is characterised in that the structure of compound 16,18,28,31,32 is as follows：
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| FR3108504B1 (en) * | 2020-03-30 | 2023-03-31 | Biophytis | Phytoecdysones and their derivatives for their use in the treatment of respiratory function alterations during a viral infection |
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