阅读说明：本技术 趋化因子cxcr4受体调节剂及其相关用途 (Chemokine CXCR4 receptor modulators and uses related thereto ) 是由 D·C·廖塔 艾德加斯·杰科斯 罗伯特·詹姆斯·威尔逊 阮辉煌 米歇尔·博拉·金 劳伦斯· 于 2018-02-21 设计创作，主要内容包括：本公开内容涉及趋化因子CXCR4受体调节剂及其相关用途。该受体调节剂可以被配制以形成包含所公开的化合物或其药学上可接受的盐或前药的药物组合物。该组合物可以被用于控制CXCR4相关的状况,通常是预防或治疗病毒感染、异常细胞增殖、视网膜退化(retinal degeneration)、炎性疾病,或作为免疫刺激剂或免疫抑制剂,或用于控制癌症并且可以与另一种活性成分诸如抗病毒剂或化学治疗剂一起施用。(The present disclosure relates to chemokine CXCR4 receptor modulators and uses related thereto. The receptor modulators can be formulated to form pharmaceutical compositions comprising the disclosed compounds, or pharmaceutically acceptable salts or prodrugs thereof. The compositions may be used to control CXCR4 related conditions, typically to prevent or treat viral infections, abnormal cell proliferation, retinal degeneration (retinal degeneration), inflammatory diseases, or as immunostimulants or immunosuppressants, or to control cancer and may be administered with another active ingredient such as an antiviral or chemotherapeutic agent.)

1. A compound of formula (I) or a salt thereof,

Wherein RA1 is optionally substituted heterocyclyl, wherein the substituents are selected from one or more and the same or different RX 1; RA2 is hydrogen or alkyl; RB is selected from the group comprising alkyl, optionally substituted aminoalkyl and optionally substituted heterocyclyl; wherein the substituents on RA2 are selected from one or more and the same or different RX 1; RC is hydrogen, optionally substituted alkyl or optionally substituted heterocyclyl; and RX1 is selected from the group comprising alkyl, cycloalkyl, halogen, methoxy and trifluoromethyl.

2. The compound of claim 1, wherein RA1 is selected from:

RB is selected from the group comprising: methyl, RC is selected from the group comprising: H. CH2RY2, CH ═ CHCH2RY2, OCH2CH2RY2, NHRY2, N (RY2)2, RY2 are selected from the group comprising: H. OH, F, CH3, CH2CH3, CH2OCH3, CH2F, CF3, NH2, wherein the substituent RY2 is individually and independently monosubstituted or disubstituted onto RX2 where appropriate; and RX1 is selected from the group comprising methyl, ethyl, ethylene, propyl, cyclopropyl, fluoro, chloro, methoxy and trifluoromethyl.

3. the compound of claim 1, wherein RA1 is selected from the group comprising:

4. The compound of claim 1, selected from the group comprising:

5. A compound of formula (II) or a salt thereof,

Wherein RD is H or alkyl, RE is methyl, isopropyl or amino substituted carbocyclyl; RF is an optionally substituted heterocyclyl; wherein the substituents for RF are selected from one or more and the same or different RX 2; and RX2 is optionally substituted aryl, optionally substituted heterocyclyl or optionally substituted amino and wherein the substituents for RX2 are selected from one or more and the same or different RY 2; and RY2 is selected from the group comprising: methyl, ethyl, isopropyl, cyclopropyl, oxetane, amino, dimethylamino, methylpiperazine, pyridine, pyridylmethyl, pyrimidine and trifluoromethylbenzene; provided that when RD is H and RE is CH3, then RF is not:

6. The compound of claim 5, wherein RE is selected from the group comprising:

CH3, RF selected from the group comprising:

RX2 is selected from the group comprising:

CHR、CH＝CHCHR、OCHCHR、NHR、N(R)、

RY2 is selected from the group comprising: H. OH, F, CH3, CH2CH3, CH2OCH3, CH2F, CF3, NH2, wherein the substituent RY2 may be monosubstituted or disubstituted individually and independently to RX2, where appropriate; and RZ is H or CH3 and W is CH or N.

7. The compound of claim 5, wherein RF is selected from the group comprising:

8. The compound of claim 5, selected from the group comprising:

9. A compound of formula (III) or a salt thereof,

Wherein RG is an optionally substituted alkene, an optionally substituted carbocyclyl, an optionally substituted aryl, an optionally substituted heterocyclyl or an optionally substituted quaternary carbon which may be E or Z; x is C or N, and RH is hydrogen or heterocyclyl when X is C, or RH is absent when X is N.

10. The compound of claim 9, wherein RG is selected from the group comprising:

Wherein Y is H, alkyl or halogen; RI is selected from the group comprising H, NH2, halogen and CH2NHRJ, and in the case of carbocyclic rings, aryl and heterocyclic RI optionally include one or more and the same or different substituents for each ring; and the RJ is selected from the group comprising:

H. Or RG is alkyl linking the attached NMe to tetrahydroquinoline; and RH is H, CH2RY2, CH ═ CHCH2RY2, OCH2CH2RY2, NHRY2, N (RY2)2, RY2 selected from the group comprising: H. OH, F, CH3, CH2CH3, CH2OCH3, CH2F, CF3, NH2,

Wherein the substituent RY2 may be singly and independently mono-or disubstituted when X is C onto RX2, or RY2 is absent when X is N, as appropriate.

11. The compound of claim 9, wherein RG is selected from the group comprising:

and a CH2CH2 group linking NCH3 to tetrahydroquinoline.

12. the compound of claim 9, selected from the group comprising:

13. A compound of formula (IV) or a salt thereof,

Wherein ring A is a heteroaromatic ring system with or without a fused benzene ring system, RK is C1 to C6 alkyl, and Z is CH, NH, N or S.

14. The compound of claim 13, wherein ring a is selected from the group comprising:

15. The compound of claim 13, selected from the group comprising:

16. A pharmaceutical composition comprising a compound as claimed in any one of claims 1, 5, 9 or 13, including salts and prodrugs thereof, and a pharmaceutically acceptable excipient, diluent or carrier.

17. The pharmaceutical composition of claim 16, comprising the compound in greater than 60%, 70%, 80%, 90%, 95%, 98% diastereomeric or enantiomeric excess.

18. use of a compound of any one of claims 1, 5, 9 or 13 in the manufacture of a medicament for treating a CXCR4 related condition including viral infection, abnormal cell proliferation, retinal degeneration, inflammatory disease, or as an immunostimulant or immunosuppressant.

19. the use of claim 18, wherein the viral infection is an HIV infection.

20. A pharmaceutical composition comprising a compound according to any one of claims 1, 5, 9 or 13 and another active ingredient selected from antiviral agents or chemotherapeutic agents.

21. A CXCR4 antagonist comprising the compound of any one of claims 1, 5, 9, or 13 in combination with a CCR5 antagonist.

22. A method of treating or preventing a viral infection, comprising administering to a subject in need thereof a pharmaceutical composition comprising a compound of any one of claims 1, 5, 9, or 13, optionally in combination with another active ingredient.

23. The method of claim 22, wherein the subject is at risk for, exhibits symptoms of, or is diagnosed with a viral infection.

24. A method of treating or preventing cancer, the method comprising administering to a subject in need thereof a pharmaceutical composition comprising a compound of any one of claims 1, 5, 9, or 13, optionally in combination with another active ingredient.

25. The method of claim 24, wherein the subject is at risk for, exhibits symptoms of, or is diagnosed with cancer.