RAS inhibitors

Abstract

This disclosure deals with macrocyclic compounds that can inhibit the Ras protein, as well as pharmaceutical compositions and protein conjugates thereof, and their use in the treatment of cancer.

Claims

1. Formula I: 【Chemistry 1】 A compound having the structure thereof, or a pharmaceutically acceptable salt thereof [in the formula, Q is a 7- to 12-membered bicyclic arylene that can be optionally substituted, a 7- to 12-membered bicyclic arylene that can be optionally substituted, or a 7- to 12-membered bicyclic heterocyclylene that can be optionally substituted, where the first ring in Q is bonded to X, and the second ring in Q is bonded to A. X is a bond; fluoro, -CN, -C １ ~C ３ alkyl, and -O-C １ ~C ３ alkyl, and is optionally substituted by one to three substituents independently selected from: linear C １ ~C ３ alkylene; -O-; -S(O) ０－２ -; ＊ -CH ２ -O-; ＊ -CH ２ -S(O) ０－２ -; ＊ -O-CH ２ -; or ＊ -CH ２ -S(O) ０－２ -, where the formula " ＊ " represents the portion of X attached to -C(R ７ )(R ８ )- Y is -O-, -NH-, or -N(C １ ~C ３ Alkyl)-, R ３ C is replaced by any choice. １ ~C ６ Alkyl, optionally substituted C ３ ~C ６ Cycloalkyl, optionally substituted C ６ ~C １０ It is a 3- to 11-membered heterocycline that is substituted with an aryl or optionally substituted, W is 【Chemistry 2】 And, During the ceremony, Ring A1 is a 4- to 8-membered cycloalkyl or a 4- to 8-membered heterocycline. W １ is -N(R ２０ )-, -O-, or -C(R ２０ａ ) (Caution ２０ｂ ) - and Each R Ａ Each of these is independently a halo, cyano, hydroxyl, optionally substituted amino, and optionally substituted C. １ ~C ６ Heteroalkyl or optionally substituted C １ ~C ３ It is alkyl, r is 0, 1, 2, 3, or 4. R １７ If present, C is optionally replaced. １ ~C ６ Heteroalkylene or optionally substituted C １ ~C ６ It is alkylene, R １８ If present, C is optionally replaced. １ ~C ４ It is alkylene, R １９ C is replaced by any choice. １ ~C ６ Heteroalkylenes, C by optional substitution １ ~C ６ Alkilen, -NH-, or -N (C which is replaced by any choice) １ ~C ６ Alkyl) or saturated nitrogen-containing 3- to 8-membered heterocycline, R ２０ is hydrogen or -C １ ~C ３ Is it alkyl? R ２０ However, one R Ａ They, together with the atoms bonded to them and any intervening atoms, form an optionally substituted 5- to 8-membered heterocycline that is condensed or spiro-condensed with ring A, or R ２０ However, R １８ Any methylene unit in, or R １９ Together with any methylene unit, the atoms bonded to them, and any intervening atoms, they form optionally substituted 5- to 8-membered heterocyclines. R ２０ａ and R ２０ｂ Each of them independently consists of hydrogen or -C １ ~C ３ Alkyl or R ２０ａ and R ２０ｂ However, together with the carbon atoms bonded to them, they form a 3- to 6-membered cycloalkyl ring. R １６ is O, S, N-CN, or N-O-C １ ~C ３ It is alkyl, WH is, 【Transformation 3】 And, Each R ２２ C is independently substituted with hydrogen, cyano, or of any choice. １ ~C ３ Alkyl, or optionally substituted, 4- to 7-membered saturated heterocycline, or R ２２ However, R １７ Or R １９ Any of these, together with the atoms bonded to them and any intervening atoms, form a 5- to 8-membered ring system which is optionally substituted. R ２３ C is a hydrogen atom that can be optionally substituted. １ ~C ３ A saturated heterocycline with 4 to 7 members, which is alkyl or optionally substituted. R ２４ C is a hydrogen atom that can be optionally substituted. １ ~C ３ Alkyl, or optionally substituted, 4- to 7-membered saturated heterocycline, or R ２４ However, R １７ Or R １９ Any of these, together with the atoms bonded to them and any intervening atoms, form a 5- to 8-membered ring system which is optionally substituted. A is C optionally substituted ２ ~C ４ alkylene, C optionally substituted １ ~C ４ heteroalkylene, or C optionally substituted ２ ~C ４ is alkenylene, 3- to 6-membered cycloalkylene optionally substituted, 3- to 6-membered hetero cycloalkylene optionally substituted, 6-membered arylene optionally substituted, or 5- to 10-membered heteroarylene optionally substituted L has the structure of formula VIIa or VIIb, 【Chemistry 4】 z is 0, 1, or 2. X ９ -NR Ｌ６ -, -C(O)-, or -S(O) ２ - and R Ｌ１ 、 R Ｌ２ 、 R Ｌ３ 、 R Ｌ４ 、 R Ｌ４ 、 R Ｌ５ 、 and R Ｌ６ each is independently hydrogen, halogen, hydroxyl, optionally substituted C １ - C ６ alkyl, optionally substituted C ２ - C ６ alkenyl, optionally substituted C ２ - C ６ alkynyl, optionally substituted C １ - C ６ heteroalkyl, or optionally substituted C ３ - C ８ cycloalkyl, or any two of R Ｌ１ 、 R Ｌ２ 、 R Ｌ３ 、 R Ｌ４ 、 R Ｌ４ 、 R Ｌ５ 、 and R Ｌ６ together with the atoms to which they are attached and any intervening atoms form an optionally substituted C ３ - C ８ cycloalkyl or 3 - to 8 - membered heterocyclyl, Here, L is 【Transformation 5】 It does not have the structure, or Optionally, L is 【Transformation 6】 Instead, R ３ C is replaced by any choice. １ ~C ６ Alkyl, optionally substituted C ３ ~C ６ Cycloalkyl, optionally substituted C ６ It is a 3- to 7-membered heterocycline that is substituted with an aryl or optionally substituted, R １０ C is substituted with hydrogen, halogen, or optionally. １ ~C ３ Alkyl or optionally substituted C １ ~C ３ It is heteroalkyl, R ７ C is substituted with hydrogen, halogen, or of any choice. １ ~C ３ It is alkyl, R ８ C is substituted with hydrogen, halogen, -OH, -CN, or optionally. １ ~C ３ Heteroalkyl, optionally substituted C １ ~C ３ Alkyl, optionally substituted C ２ ~C ６ Alkenyl, C which can be optionally replaced. ２ ~C ６ Alkinyl, C, which can be optionally replaced. ６ ~C １０ Aryl, optionally substituted 4- to 8-membered heteroaryls, optionally substituted C ３ ~C ６ It is a cycloalkyl group, or a 3- to 7-membered heterocycline that is optionally substituted, or R ７ and R ８ Together, =CH ２ , C which is replaced by any choice ３ ~C ６ They form cycloalkyl groups or saturated heterocyclines with 3 to 7 members, or R ８ However, the ring atom in Q, R ７ Together with the carbon atoms bonded to it and X, it forms a 4- to 9-membered saturated or unsaturated heterocycline that is condensed with Q. R ６ is hydrogen or -CH ３ And, Each R ５ C is independently substituted with halogens, of optional choice. １ ~C ３ Alkyl or optionally substituted C １ ~C ３ It is a haloalkyl, p is 0, 1, 2, or 3, where, (i) The compound is 【Transformation 7】 not; or (ii) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, and the two Rs together Ｌ１ The substituent forms a spirocyclopropyl, and W is 【Transformation 8】 If that is the case, Q is C １－４ Neither alkyl-substituted 1-ethyl-indole-2,5-diyl nor indole-2,5-diyl; or (iii) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, and the two R Ｌ１ The substituent forms a spirocyclopropyl, and W is 【Chemistry 9】 If Q is halogen, C １－４ Alkyl and C １－４ Alkoxy [C] １－４ Alkyl and the C １－４ Alkoxy compounds are halogens, OH groups, and C groups, respectively. １－３ Alkyl and C １－３ Alkoxy (C) １－３ Alkyl and the C １－３ Alkoxy are deuterium, halogen, OH, methyl, methoxy, and OCF, respectively. ３ (Optionally substituted by one, two, or three substituents independently selected from) (Optionally substituted by one, two, or three substituents independently selected from) Not 1-ethyl-2,5-indole-diyl; or (iv) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, and together R Ｌ１ and R Ｌ２ However, it forms a condensed cyclopropyl, and W is 【Chemistry 10】 If that is the case, Q is C １－４ Alkyl-substituted 1-ethyl-2,5-indole-diyl or 2,5-indole-diyl; or (v) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, and together R Ｌ１ and R Ｌ２ However, it forms a condensed cyclopropyl, and W is 【Chemistry 11】 If that is the case, Q is C １－４ It is alkyl-substituted 1-ethyl-2,5-indole-diyl or 2,5-indole-diyl; or (vi) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, and together R Ｌ１ and R Ｌ２ However, it forms a condensed cyclopropyl, and W is 【Chemistry 12】 If Q is halogen, C １－４ Alkyl and C １－４ Alkoxy [C] １－４ Alkyl and the C １－４ Alkoxy compounds are halogens, OH groups, and C groups, respectively. １－３ Alkyl and C １－３ Alkoxy (C) １－３ Alkyl and the C １－３ Alkoxy are deuterium, halogen, OH, methyl, methoxy, and OCF, respectively. ３ (Optionally substituted by one, two, or three substituents independently selected from) (Optionally substituted by one, two, or three substituents independently selected from) Not 1-ethyl-2,5-indole-diyl; or (vii) A is -hydroxybenzene-3,5-diyl or optionally substituted phenylene, and the two Rs together Ｌ１ When the substituent forms a spirocyclopropyl group, W is 【Chemistry 13】 not; or (viiii) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, and together with R Ｌ１ and R Ｌ２ However, when condensed cyclopropyl is formed, W is 【Chemistry 14】 not; or (ix) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, and WH is 【Chemistry 15】 And the two R's that are together Ｌ１ If the substituent forms a spirocyclopropyl or spirocycloalkyl group, A1 is methyl or C １－４ Not 1,4-piperazine-diyl, optionally substituted with alkyl; or (x) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, and WH is 【Chemistry 16】 And together with R Ｌ１ and R Ｌ２ However, when forming a condensed cyclopropyl or condensed cycloalkyl group, A1 is methyl or C １－４ [Not 1,4-piperazine-diyl, but optionally substituted with alkyl.]

2. Formula IIa: 【Chemistry 17】 A compound having the structure of [formula], or a pharmaceutically acceptable salt thereof [wherein the formula, the dotted line represents 0, 1, 2, 3, or 4 non-adjacent double bonds] A is replaced by C by choice. ２ ~C ４ Alkylene, C is optionally substituted. １ ~C ４ Heteroalkylenes, C by optional substitution ２ ~C ４ Alkenylene, optionally substituted 3- to 6-membered cycloalkylene, optionally substituted 3- to 6-membered heterocycloalkylene, optionally substituted 6-membered arylene, or optionally substituted 5- to 10-membered heteroarylene. B is either absent or -CH(R ９ ) -, > C = CR ９ R ９’ , or >CR ９ R ９’ (In the formula, carbon is -N(R) １１ (bonded to the carbonyl carbon of C(O)-), optionally substituted 3- to 6-membered cycloalkylenes, optionally substituted 3- to 6-membered heterocycloalkylenes, optionally substituted 6-membered arylenes, or optionally substituted 5- to 6-membered heteroarylenes. G is replaced by C by choice. １ ~C ４ Alkylene, C is optionally substituted. １ ~C ４ Alkenylene, C is optionally substituted. １ ~C ４ Heteroalkylene, -C(O)O-CH(R ６ ) - (In the formula, the second C is -C(R ７ R ８ )-bonded),-C(O)NH-CH(R ６ ) - (In the formula, the second C is -C(R ７ R ８ ) - which is bound to, and C which is optionally replaced. １ ~C ４ These are heteroalkylenes, or 3- to 8-membered heteroarylenes. L １ It is a linker, W stands for hydrogen, cyanoacrylate, and S(O). ２ R', optionally substituted amino, optionally substituted amide, optionally substituted C １ ~C ４ Alkoxy, C is optionally substituted. １ ~C ４ Hydroxyalkyl, optionally substituted C １ ~C ４ aminoalkyl, optionally substituted C １ ~C ４ Haloalkyl, optionally substituted C １ ~C ４ Alkyl, optionally substituted C １ ~C ４ Guanidinoalkyl, C ０ ~C ４ Alkyl, optionally substituted 3- to 11-membered heterocycloalkyl, optionally substituted 3- to 8-membered cycloalkyl, or optionally substituted 3- to 8-membered heteroaryl, L has the structure of formula VIIa or VIIb, [Chemistry 18] z is 0, 1, or 2. X ９ -NR Ｌ６ -, -C(O)-, or -S(O) ２ - and R Ｌ１ , R Ｌ２ , R Ｌ３ , R Ｌ４ , R Ｌ４ , R Ｌ５ , and R Ｌ６ Each of these can be independently substituted with hydrogen, halogen, hydroxyl, or C of any choice. １ ~C ６ Alkyl, optionally substituted C ２ ~C ６ Alkenyl, C which can be optionally replaced. ２ ~C ６ Alkinyl, or C as optionally replaced. １ ~C ６ It is heteroalkyl, or R Ｌ１ , R Ｌ２ , R Ｌ３ , R Ｌ４ , R Ｌ４ , R Ｌ５ , and R Ｌ６ Any two of these atoms, along with the atoms bonded to them and any intervening atoms, are optionally substituted. ３ ~C ８ Forming cycloalkyl or 3- to 8-membered heterocyclines, Here, L is 【Chemistry 19】 It does not have the structure, or Optionally, L is 【Chemistry 20】 Instead, X １ C is replaced by any choice. １ ~C ２ Alkylene, NR, O, or S(O) ｑ And, X ２ is O or NH, X ３ is N or CH, q is 0, 1, or 2. R is a C atom that can be substituted with hydrogen, cyano, or of any choice. １ ~C ４ Alkyl, optionally substituted C ２ ~C ４ Alkenyl, C which can be optionally replaced. ２ ~C ４ Alkinyl, C(O)R', C(O)OR', C(O)N(R') ２ , S(O)R', S(O) ２ R', or S(O) ２ N(R') ２ And, Each R ’ C is independently substituted with hydrogen or of any choice. １ ~C ４ It is alkyl, Y １ is C, CH, or N, Y ２ , Y ３ , Y ４ , and Y ７ They are independently C or N, Y ５ CH, CH ２ , or N, Y ６ C(O), CH, CH ２ , or N, R １３ C is a cyano, which can be optionally replaced. １ ~C ６ Alkyl, optionally substituted C １ ~C ６ It may be a heteroalkyl, optionally substituted 3- to 6-membered cycloalkyl, optionally substituted 3- to 6-membered cycloalkenyl, optionally substituted 3- to 6-membered heterocycloalkyl, optionally substituted 6- to 10-membered aryl, or optionally substituted 5- to 10-membered heteroaryl, or R １３ and R ２ However, when combined with the atoms bonded to them, they form optionally substituted 3- to 14-membered heterocycloalkyl groups. R ２ C is either absent or optionally substituted with hydrogen. １ ~C ６ Alkyl, optionally substituted C ２ ~C ６ Alkenyl, C which can be optionally replaced. ２ ~C ６ The alkynyl, optionally substituted 3- to 6-membered cycloalkyl, optionally substituted 3- to 14-membered heterocycloalkyl, optionally substituted 6-membered aryl, and optionally substituted 5- to 10-membered heteroaryl are available. R １４ is absent, or R ２ and R １４ However, when combined with the atoms bonded to them, they form optionally substituted 3- to 8-membered cycloalkyl groups or optionally substituted 3- to 14-membered heterocycloalkyl groups. R １５ This is a methyl molecule that is either absent, hydrogen, a halogen, a cyano, or optionally substituted with one to three halogens. R ５ is hydrogen, or a halogen, cyano, hydroxyl, or C １ ~C ４ C is optionally substituted by heteroalkyl groups. １ ~C ４ It is alkyl, cyclopropyl, or cyclobutyl. R ６ R is either hydrogen or methyl, ７ C is substituted with hydrogen, halogen, or of any choice. １ ~C ３ It is alkyl, or R ６ and R ７ However, when combined with the carbon atoms bonded to them, they form optionally substituted 3- to 6-membered cycloalkyl groups or optionally substituted 3- to 7-membered heterocycloalkyl groups. R ８ C is substituted with hydrogen, halogen, hydroxyl, cyano, or any other element. １ ~C ３ Heteroalkyl, optionally substituted C １ ~C ３ Alkyl, optionally substituted C ２ ~C ６ Alkenyl, C which can be optionally replaced. ２ ~C ６ Alkynyl, optionally substituted 3- to 8-membered cycloalkyl, optionally substituted 3- to 14-membered heterocycloalkyl, optionally substituted 5- to 10-membered heteroaryl, or optionally substituted 6- to 10-membered aryl, or R ７ and R ８ However, when combined with the carbon atoms bonded to them, C=CR ７’ R ８’ ;C=N(OH), C=N(OC １ ~C ３ Forming alkyl, C=O, C=S, C=NH, or optionally substituted 3- to 6-membered cycloalkyl groups, or optionally substituted 3- to 7-membered heterocycloalkyl groups, R ７ａ and R ８ａ These are independently substituted with hydrogen, halogen, or C of any choice. １ ~C ３ It is either alkyl or combined with a carbon bonded to it to form a carbonyl group. R ７’ C is substituted with hydrogen, halogen, or of any choice. １ ~C ３ It is alkyl, R ８’ C is substituted with hydrogen, halogen, hydroxyl, cyano, or any other element. １ ~C ３ Heteroalkyl, optionally substituted C １ ~C ３ Alkyl, optionally substituted C ２ ~C ６ Alkenyl, C which can be optionally replaced. ２ ~C ６ Alkynyl, optionally substituted 3- to 8-membered cycloalkyl, optionally substituted 3- to 14-membered heterocycloalkyl, optionally substituted 5- to 10-membered heteroaryl, or optionally substituted 6- to 10-membered aryl, or R ７’ and R ８’ However, when combined with the carbon atoms bonded to them, they form optionally substituted 3- to 6-membered cycloalkyl groups or optionally substituted 3- to 7-membered heterocycloalkyl groups. R ９ C is substituted with hydrogen, fluoro, or of any choice. １ ~C ６ Alkyl, optionally substituted C １ ~C ６ It is a heteroalkyl group, a 3- to 6-membered cycloalkyl group that can be optionally substituted, or a 3- to 7-membered heterocycloalkyl group that can be optionally substituted, or R ９ And L, together with the atoms bonded to them, forms a 3- to 14-membered heterocycloalkyl group that is optionally substituted. R ９’ C is substituted with hydrogen or of any choice. １ ~C ６ It is alkyl, or R ９ and R ９’ However, when combined with atoms bonded to them, they form 3- to 6-membered cycloalkyl or 3- to 6-membered heterocycloalkyl groups. R １０ C is substituted with hydrogen, halogen, hydroxyl, or optionally. １ ~C ３ Heteroalkyl or optionally substituted C １ ~C ３ It is alkyl, R １０ａ is hydrogen or halogen, R １１ C is substituted with hydrogen or optionally. １ ~C ３ It is alkyl, R ２１ C is substituted with hydrogen or optionally. １ ~C ３ It is alkyl, and here, (i) The compound is 【Chemistry 21-1】 【Chemistry 21-2】 not; or (ii) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, and the two Rs together Ｌ１ The substituent forms spirocyclopropyl, L １ However, -N(CH ３ )C(O)- or -N(CH ３ ) C(O)CH ２ N(CH ３ ) - and B is -CH(R ９ )-(wherein, R ９ If (is is isopropyl or cyclopentyl), then W is neither 3-cyclopropylaziridin-2-yl, nor 3-phenyltetrahydrofuran-2-yl, nor optionally substituted aziridin-2-yl, nor optionally substituted tetrahydrofuran-2-yl; or (iii) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, and the two R Ｌ１ The substituent forms spirocyclopropyl, L １ However, -N(CH ３ )C(O)- or -N(CH ３ ) C(O)CH ２ N(CH ３ ) - and B is -CH(R ９ )-(wherein, R ９ C １－６ If W is alkyl or a 3- to 6-membered cycloalkyl, then W is neither 3-cyclopropylaziridin-2-yl, nor 3-phenyltetrahydrofuran-2-yl, nor an optionally substituted aziridin-2-yl, nor an optionally substituted tetrahydrofuran-2-yl; or (iv) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, and together R Ｌ１ and R Ｌ２ However, it forms a condensed cyclopropyl that is optionally substituted, L １ However, -N(CH ３ )C(O)- or -N(CH ３ ) C(O)CH ２ N(CH ３ ) - and B is -CH(R ９ )-(wherein, R ９ If (is is isopropyl or cyclopentyl), then W is neither 3-cyclopropylaziridin-2-yl, nor 3-phenyltetrahydrofuran-2-yl, nor optionally substituted aziridin-2-yl, nor optionally substituted tetrahydrofuran-2-yl; or (v) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, and together R Ｌ１ and R Ｌ２ However, it forms a condensed cyclopropyl that is optionally substituted, L １ However, -N(CH ３ )C(O)- or -N(CH ３ ) C(O)CH ２ N(CH ３ ) - and B is -CH(R ９ )-(wherein, R ９ C １－６ If W is alkyl or a 3- to 6-membered cycloalkyl, then W is neither 3-cyclopropylaziridin-2-yl, nor 3-phenyltetrahydrofuran-2-yl, nor an optionally substituted aziridin-2-yl, nor an optionally substituted tetrahydrofuran-2-yl; or (vi) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, and the two Rs together Ｌ１ The substituents are optionally substituted to form a spirocyclopropyl, L １ However, -N(CH ３ )C(O)- or -N(CH ３ ) C(O)CH ２ N(CH ３ ) - and R １４ B is absent, and B is -CH(R ９ )-(wherein, R ９ If R is isopropyl or cyclopentyl, ２ C is also substituted with ethyl by choice. １－６ Not alkyl; or (vii) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, and together R Ｌ１ and R Ｌ２ However, it forms a condensed cyclopropyl that is optionally substituted, L １ However, -N(CH ３ )C(O)- or -N(CH ３ ) C(O)CH ２ N(CH ３ ) - and R １４ B is absent, and B is -CH(R ９ )-(wherein, R ９ If R is isopropyl or cyclopentyl, ２ C is also substituted with ethyl by choice. １－６ Not alkyl; or (viiii) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, and the two Rs together Ｌ１ When the substituents form a spirocyclopropyl which can be optionally substituted, ２ C is replaced by any choice. ２ ~C ６ Alkenyl, C which can be optionally replaced. ２ ~C ６ Alkinyl, optionally substituted 3- to 6-membered cycloalkyl, optionally substituted 3- to 14-membered heterocycloalkyl, optionally substituted 6-membered aryl, optionally substituted 5- to 10-membered heteroaryl; or (ix) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, and together with R Ｌ１ and R Ｌ２ However, when a condensed cyclopropyl is formed by optional substitution, R ２ C is replaced by any choice. ２ ~C ６ Alkenyl, C which can be optionally replaced. ２ ~C ６ Alkinyl, optionally substituted 3- to 6-membered cycloalkyl, optionally substituted 3- to 14-membered heterocycloalkyl, optionally substituted 6-membered aryl, optionally substituted 5- to 10-membered heteroaryl; or (x) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, and the two Rs together Ｌ１ When the substituents form a spirocyclopropyl which can be optionally substituted, ２ and R １４ These combine with the atoms bonded to them to form optionally substituted 3- to 8-membered cycloalkyl groups or optionally substituted 3- to 14-membered heterocycloalkyl groups; or (xi) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, and together with R Ｌ１ and R Ｌ２ However, when a condensed cyclopropyl is formed by optional substitution, R ２ C is replaced by any choice. ２ ~C ６ Alkenyl, C which can be optionally replaced. ２ ~C ６ [Alkynyl, optionally substituted 3- to 6-membered cycloalkyl, optionally substituted 3- to 14-membered heterocycloalkyl, optionally substituted 6-membered aryl, optionally substituted 5- to 10-membered heteroaryl].

3. Equation IIb: 【Chemistry 22】 A compound having the structure of [formula], or a pharmaceutically acceptable salt thereof [wherein the formula, the dotted line represents 0, 1, 2, 3, or 4 non-adjacent double bonds] A is replaced by C by choice. ２ ~C ４ Alkylene, C is optionally substituted. １ ~C ４ Heteroalkylenes, C by optional substitution ２ ~C ４ Alkenylene, optionally substituted 3- to 6-membered cycloalkylene, optionally substituted 3- to 6-membered heterocycloalkylene, optionally substituted 6-membered arylene, or optionally substituted 5- to 10-membered heteroarylene. B is either absent or -CH(R ９ ) -, > C = CR ９ R ９’ , or >CR ９ R ９’ (In the formula, carbon is -N(R) １１ (bonded to the carbonyl carbon of C(O)-), optionally substituted 3- to 6-membered cycloalkylenes, optionally substituted 3- to 6-membered heterocycloalkylenes, optionally substituted 6-membered arylenes, or optionally substituted 5- to 6-membered heteroarylenes. G is replaced by C by choice. １ ~C ４ Alkylene, C is optionally substituted. １ ~C ４ Alkenylene, C is optionally substituted. １ ~C ４ Heteroalkylene, -C(O)O-CH(R ６ ) - (In the formula, the second C is -C(R ７ R ８ )-bonded),-C(O)NH-CH(R ６ ) - (In the formula, the second C is -C(R ７ R ８ ) - which is bound to, and C which is optionally replaced. １ ~C ４ These are heteroalkylenes, or 3- to 8-membered heteroarylenes. L １ It is a linker, W is a crosslinking group comprising carbodiimide, oxazoline, thiazoline, chloroethylurea, chloroethylthiourea, chloroethylcarbamate, chloroethylthiocarbamate, aziridine, trifluoromethyl ketone, boronic acid, boronic acid ester, N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), iso-EEDQ or other EEDQ derivatives, epoxide, oxazolium, or glycar. L has the structure of formula VIIa or VIIb, 【Chemistry 23】 z is 0, 1, or 2. X ９ -NR Ｌ６ -, -C(O)-, or -S(O) ２ - and R Ｌ１ , R Ｌ２ , R Ｌ３ , R Ｌ４ , R Ｌ４ , R Ｌ５ , and R Ｌ６ Each of these can be independently substituted with hydrogen, halogen, hydroxyl, or C of any choice. １ ~C ６ Alkyl, optionally substituted C ２ ~C ６ Alkenyl, C which can be optionally replaced. ２ ~C ６ Alkinyl, or C as optionally replaced. １ ~C ６ It is heteroalkyl, or R Ｌ１ , R Ｌ２ , R Ｌ３ , R Ｌ４ , R Ｌ４ , R Ｌ５ , and R Ｌ６ Any two of these atoms, along with the atoms bonded to them and any intervening atoms, are optionally substituted. ３ ~C ８ Forming cycloalkyl or 3- to 8-membered heterocyclines, Here, L is 【Chemistry 24】 It does not have the structure, or Optionally, L is 【Chemistry 25】 Instead, X １ C is replaced by any choice. １ ~C ２ Alkylene, NR, O, or S(O) ｑ And, X ２ is O or NH, X ３ is N or CH, q is 0, 1, or 2. R is a C atom that can be substituted with hydrogen, cyano, or of any choice. １ ~C ４ Alkyl, optionally substituted C ２ ~C ４ Alkenyl, C which can be optionally replaced. ２ ~C ４ Alkinyl, C(O)R', C(O)OR', C(O)N(R') ２ , S(O)R', S(O) ２ R', or S(O) ２ N(R') ２ And, Each R ’ C is independently substituted with hydrogen or of any choice. １ ~C ４ It is alkyl, Y １ is C, CH, or N, Y ２ , Y ３ , Y ４ , and Y ７ They are independently C or N, Y ５ CH, CH ２ , or N, Y ６ C(O), CH, CH ２ , or N, R １３ C is a cyano, which can be optionally replaced. １ ~C ６ Alkyl, optionally substituted C １ ~C ６ It may be a heteroalkyl, optionally substituted 3- to 6-membered cycloalkyl, optionally substituted 3- to 6-membered cycloalkenyl, optionally substituted 3- to 6-membered heterocycloalkyl, optionally substituted 6- to 10-membered aryl, or optionally substituted 5- to 10-membered heteroaryl, or R １３ and R ２ However, when combined with the atoms bonded to them, they form optionally substituted 3- to 14-membered heterocycloalkyl groups. R ２ C is either absent or optionally substituted with hydrogen. １ ~C ６ Alkyl, optionally substituted C ２ ~C ６ Alkenyl, C which can be optionally replaced. ２ ~C ６ Alkinyl, optionally substituted 3- to 6-membered cycloalkyl, optionally substituted 3- to 7-membered heterocycloalkyl, optionally substituted 6-membered aryl, optionally substituted 5- or 6-membered heteroaryl, R １４ is absent, or R ２ and R １４ However, when combined with the atoms bonded to them, they form optionally substituted 3- to 8-membered cycloalkyl groups or optionally substituted 3- to 14-membered heterocycloalkyl groups. R １５ This is a methyl molecule that is either absent, hydrogen, a halogen, a cyano, or optionally substituted with one to three halogens. R ５ is hydrogen, or a halogen, cyano, hydroxyl, or C １ ~C ４ C is optionally substituted by heteroalkyl groups. １ ~C ４ It is alkyl, cyclopropyl, or cyclobutyl. R ６ R is either hydrogen or methyl, ７ C is substituted with hydrogen, halogen, or of any choice. １ ~C ３ It is alkyl, or R ６ and R ７ However, when combined with the carbon atoms bonded to them, they form optionally substituted 3- to 6-membered cycloalkyl groups or optionally substituted 3- to 7-membered heterocycloalkyl groups. R ８ C is substituted with hydrogen, halogen, hydroxyl, cyano, or any other element. １ ~C ３ Heteroalkyl, optionally substituted C １ ~C ３ Alkyl, optionally substituted C ２ ~C ６ Alkenyl, C which can be optionally replaced. ２ ~C ６ Alkynyl, optionally substituted 3- to 8-membered cycloalkyl, optionally substituted 3- to 14-membered heterocycloalkyl, optionally substituted 5- to 10-membered heteroaryl, or optionally substituted 6- to 10-membered aryl, or R ７ and R ８ However, when combined with the carbon atoms bonded to them, C=CR ７’ R ８’ ;C=N(OH), C=N(OC １ ~C ３ Forming alkyl, C=O, C=S, C=NH, or optionally substituted 3- to 6-membered cycloalkyl groups, or optionally substituted 3- to 7-membered heterocycloalkyl groups, R ７ａ and R ８ａ These are independently substituted with hydrogen, halogen, or C of any choice. １ ~C ３ It is either alkyl or combined with a carbon bonded to it to form a carbonyl group. R ７’ C is substituted with hydrogen, halogen, or of any choice. １ ~C ３ It is alkyl, R ８’ C is substituted with hydrogen, halogen, hydroxyl, cyano, or any other element. １ ~C ３ Heteroalkyl, optionally substituted C １ ~C ３ Alkyl, optionally substituted C ２ ~C ６ Alkenyl, C which can be optionally replaced. ２ ~C ６ Alkynyl, optionally substituted 3- to 8-membered cycloalkyl, optionally substituted 3- to 14-membered heterocycloalkyl, optionally substituted 5- to 10-membered heteroaryl, or optionally substituted 6- to 10-membered aryl, or R ７’ and R ８’ However, when combined with the carbon atoms bonded to them, they form optionally substituted 3- to 6-membered cycloalkyl groups or optionally substituted 3- to 7-membered heterocycloalkyl groups. R ９ C is substituted with hydrogen, fluoro, or of any choice. １ ~C ６ Alkyl, optionally substituted C １ ~C ６ It is a heteroalkyl group, a 3- to 6-membered cycloalkyl group that can be optionally substituted, or a 3- to 7-membered heterocycloalkyl group that can be optionally substituted, or R ９ And L, together with the atoms bonded to them, forms a 3- to 14-membered heterocycloalkyl group that is optionally substituted. R ９’ C is substituted with hydrogen or of any choice. １ ~C ６ It is alkyl, or R ９ and R ９’ However, when combined with atoms bonded to them, they form 3- to 6-membered cycloalkyl or 3- to 6-membered heterocycloalkyl groups. R １０ C is substituted with hydrogen, halogen, hydroxyl, or optionally. １ ~C ３ Heteroalkyl or optionally substituted C １ ~C ３ It is alkyl, R １０ａ is hydrogen or halogen, R １１ C is substituted with hydrogen or optionally. １ ~C ３ It is alkyl, R ２１ C is substituted with hydrogen or optionally. １ ~C ３ It is alkyl, and here, (i) The compound is 【Chemistry 26】 not; or (ii) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, W is 3-cyclopropylaziridin-2-yl or optionally substituted aziridine, and the two Rs together Ｌ１ When the substituent forms spirocyclopropyl, R ２ Even with ethyl, C １－６ Not alkyl; or (iii) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, W is 3-cyclopropylaziridin-2-yl or optionally substituted aziridine, and together R Ｌ１ and R Ｌ２ However, when condensed cyclopropyl is formed, R ２ Even with ethyl, C １－６ Not alkyl; or (iv) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, and the two Rs together Ｌ１ If the substituent forms spirocyclopropyl, W is neither 3-cyclopropylaziridin-2-yl nor an optionally substituted aziridine; or (v) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, and together with R Ｌ１ and R Ｌ２ However, when forming a condensed cyclopropyl, W is neither 3-cyclopropylaziridin-2-yl nor an optionally substituted aziridine; or (vi) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, W is 3-cyclopropylaziridin-2-yl or optionally substituted aziridine, and the two Rs together Ｌ１ When the substituent forms spirocyclopropyl, L １ is -N(CH ３ ) C(O)CH ２ N(CH ３ ) C(O)- not; or (vii) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, W is 3-cyclopropylaziridin-2-yl or optionally substituted aziridine, and together R Ｌ１ and R Ｌ２ However, when condensed cyclopropyl is formed, L １ is -N(CH ３ ) C(O)CH ２ N(CH ３ ) Not C(O)-].

4. Formula IIc: 【Chemistry 27】 A compound having the structure of [formula], or a pharmaceutically acceptable salt thereof [wherein the formula, the dotted line represents 0, 1, 2, 3, or 4 non-adjacent double bonds] A is replaced by C by choice. ２ ~C ４ Alkylene, C is optionally substituted. １ ~C ４ Heteroalkylenes, C by optional substitution ２ ~C ４ Alkenylene, optionally substituted 3- to 6-membered cycloalkylene, optionally substituted 3- to 6-membered heterocycloalkylene, optionally substituted 6-membered arylene, or optionally substituted 5- to 10-membered heteroarylene. B is either absent or -CH(R ９ ) -, > C = CR ９ R ９’ , or >CR ９ R ９’ (In the formula, carbon is -N(R) １１ (bonded to the carbonyl carbon of C(O)-), optionally substituted 3- to 6-membered cycloalkylenes, optionally substituted 3- to 6-membered heterocycloalkylenes, optionally substituted 6-membered arylenes, or optionally substituted 5- to 6-membered heteroarylenes. G is replaced by C by choice. １ ~C ４ Alkylene, C is optionally substituted. １ ~C ４ Alkenylene, C is optionally substituted. １ ~C ４ Heteroalkylene, -C(O)O-CH(R ６ ) - (In the formula, the second C is -C(R ７ R ８ )-bonded),-C(O)NH-CH(R ６ ) - (In the formula, the second C is -C(R ７ R ８ ) - which is bound to, and C which is optionally replaced. １ ~C ４ These are heteroalkylenes, or 3- to 8-membered heteroarylenes. L １ It is a linker, W is a crosslinking group, which includes vinyl ketones, vinyl sulfones, inones, haloacetyls, or alkynyl sulfones. L has the structure of formula VIIa or VIIb, 【Chemistry 28】 z is 0, 1, or 2. X ９ -NR Ｌ６ -, -C(O)-, or -S(O) ２ - and R Ｌ１ , R Ｌ２ , R Ｌ３ , R Ｌ４ , R Ｌ４ , R Ｌ５ , and R Ｌ６ Each of these can be independently substituted with hydrogen, halogen, hydroxyl, or C of any choice. １ ~C ６ Alkyl, optionally substituted C ２ ~C ６ Alkenyl, C which can be optionally replaced. ２ ~C ６ Alkinyl, or C as optionally replaced. １ ~C ６ It is heteroalkyl, or R Ｌ１ , R Ｌ２ , R Ｌ３ , R Ｌ４ , R Ｌ４ , R Ｌ５ , and R Ｌ６ Any two of these atoms, along with the atoms bonded to them and any intervening atoms, are optionally substituted. ３ ~C ８ Forming cycloalkyl or 3- to 8-membered heterocyclines, Here, L is 【Chemistry 29】 It does not have the structure, or Optionally, L is 【Transformation 30】 Instead, X １ C is replaced by any choice. １ ~C ２ Alkylene, NR, O, or S(O) ｑ And, X ２ is O or NH, X ３ is N or CH, q is 0, 1, or 2. R is a C atom that can be substituted with hydrogen, cyano, or of any choice. １ ~C ４ Alkyl, optionally substituted C ２ ~C ４ Alkenyl, C which can be optionally replaced. ２ ~C ４ Alkinyl, C(O)R', C(O)OR', C(O)N(R') ２ , S(O)R', S(O) ２ R', or S(O) ２ N(R') ２ And, Each R ’ C is independently substituted with hydrogen or of any choice. １ ~C ４ It is alkyl, Y １ is C, CH, or N, Y ２ , Y ３ , Y ４ , and Y ７ They are independently C or N, Y ５ CH, CH ２ , or N, Y ６ C(O), CH, CH ２ , or N, R １３ C is a cyano, which can be optionally replaced. １ ~C ６ Alkyl, optionally substituted C １ ~C ６ It may be a heteroalkyl, optionally substituted 3- to 6-membered cycloalkyl, optionally substituted 3- to 6-membered cycloalkenyl, optionally substituted 3- to 6-membered heterocycloalkyl, optionally substituted 6- to 10-membered aryl, or optionally substituted 5- to 10-membered heteroaryl, or R １３ and R ２ However, when combined with the atoms bonded to them, they form optionally substituted 3- to 14-membered heterocycloalkyl groups. R ２ C is either absent or optionally substituted with hydrogen. １ ~C ６ Alkyl, optionally substituted C ２ ~C ６ Alkenyl, C which can be optionally replaced. ２ ~C ６ Alkinyl, optionally substituted 3- to 6-membered cycloalkyl, optionally substituted 3- to 7-membered heterocycloalkyl, optionally substituted 6-membered aryl, optionally substituted 5- or 6-membered heteroaryl, R １４ is absent, or R ２ and R １４ However, when combined with the atoms bonded to them, they form optionally substituted 3- to 8-membered cycloalkyl groups or optionally substituted 3- to 14-membered heterocycloalkyl groups. R １５ This is a methyl molecule that is either absent, hydrogen, a halogen, a cyano, or optionally substituted with one to three halogens. R ５ is hydrogen, or a halogen, cyano, hydroxyl, or C １ ~C ４ C is optionally substituted by heteroalkyl groups. １ ~C ４ It is alkyl, cyclopropyl, or cyclobutyl. R ６ R is either hydrogen or methyl, ７ C is substituted with hydrogen, halogen, or of any choice. １ ~C ３ It is alkyl, or R ６ and R ７ However, when combined with the carbon atoms bonded to them, they form optionally substituted 3- to 6-membered cycloalkyl groups or optionally substituted 3- to 7-membered heterocycloalkyl groups. R ８ C is substituted with hydrogen, halogen, hydroxyl, cyano, or any other element. １ ~C ３ Heteroalkyl, optionally substituted C １ ~C ３ Alkyl, optionally substituted C ２ ~C ６ Alkenyl, C which can be optionally replaced. ２ ~C ６ Alkynyl, optionally substituted 3- to 8-membered cycloalkyl, optionally substituted 3- to 14-membered heterocycloalkyl, optionally substituted 5- to 10-membered heteroaryl, or optionally substituted 6- to 10-membered aryl, or R ７ and R ８ However, when combined with the carbon atoms bonded to them, C=CR ７’ R ８’ ;C=N(OH), C=N(OC １ ~C ３ Forming alkyl, C=O, C=S, C=NH, or optionally substituted 3- to 6-membered cycloalkyl groups, or optionally substituted 3- to 7-membered heterocycloalkyl groups, R ７ａ and R ８ａ These are independently substituted with hydrogen, halogen, or C of any choice. １ ~C ３ It is either alkyl or combined with a carbon bonded to it to form a carbonyl group. R ７’ C is substituted with hydrogen, halogen, or of any choice. １ ~C ３ It is alkyl, R ８’ C is substituted with hydrogen, halogen, hydroxyl, cyano, or any other element. １ ~C ３ Heteroalkyl, optionally substituted C １ ~C ３ Alkyl, optionally substituted C ２ ~C ６ Alkenyl, C which can be optionally replaced. ２ ~C ６ Alkynyl, optionally substituted 3- to 8-membered cycloalkyl, optionally substituted 3- to 14-membered heterocycloalkyl, optionally substituted 5- to 10-membered heteroaryl, or optionally substituted 6- to 10-membered aryl, or R ７’ and R ８’ However, when combined with the carbon atoms bonded to them, they form optionally substituted 3- to 6-membered cycloalkyl groups or optionally substituted 3- to 7-membered heterocycloalkyl groups. R ９ C is substituted with hydrogen, fluoro, or of any choice. １ ~C ６ Alkyl, optionally substituted C １ ~C ６ It is a heteroalkyl group, a 3- to 6-membered cycloalkyl group that can be optionally substituted, or a 3- to 7-membered heterocycloalkyl group that can be optionally substituted, or R ９ And L, together with the atoms bonded to them, forms a 3- to 14-membered heterocycloalkyl group that is optionally substituted. R ９’ C is substituted with hydrogen or of any choice. １ ~C ６ It is alkyl, or R ９ and R ９’ However, when combined with atoms bonded to them, they form 3- to 6-membered cycloalkyl or 3- to 6-membered heterocycloalkyl groups. R １０ C is substituted with hydrogen, halogen, hydroxyl, or optionally. １ ~C ３ Heteroalkyl or optionally substituted C １ ~C ３ It is alkyl, R １０ａ is hydrogen or halogen, R １１ C is substituted with hydrogen or optionally. １ ~C ３ It is alkyl, R ２１ C is substituted with hydrogen or optionally. １ ~C ３ It is alkyl, and here, (i) The compound is 【Chemistry 31】 not; or (ii) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, and the two Rs together Ｌ１ When the substituent forms a spirocyclopropyl group and W is a vinyl ketone, R ２ Even with ethyl, C １－６ Not alkyl; or (iii) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, and together R Ｌ１ and R Ｌ２ However, if condensed cyclopropyl is formed and W is a vinyl ketone, then R ２ Even with ethyl, C １－６ Not alkyl; or (iv) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, and the two Rs together Ｌ１ If the substituent forms spirocyclopropyl, then W is not a vinyl ketone; or (v) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, and together with R Ｌ１ and R Ｌ２ However, if condensed cyclopropyl is formed, W is not a vinyl ketone; or (vi) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, W is a vinyl ketone, and the two Rs together Ｌ１ When the substituent forms a spirocyclopropyl or spirocycloalkyl group, L １ teeth, 【Chemistry 32】 Other than; or (vii) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, W is a vinyl ketone, and together R Ｌ１ and R Ｌ２ However, when forming a condensed cyclopropyl or condensed cycloalkyl, L １ teeth, 【Transformation 33】 Other than; or (viiii) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, W is a vinyl ketone, and the two Rs together Ｌ１ When the substituent forms a spirocycloalkyl group, L １ C is one, two, or three independently selected C １－６ Optionally substituted with alkyl groups 【Transformation 34】 not; or (ix) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, W is a vinyl ketone, and together R Ｌ１ and R Ｌ２ However, when a condensed cycloalkyl group is formed, L １ C is one, two, or three independently selected C １－６ Optionally substituted with alkyl groups 【Chemistry 35】 isn't it].

5. Formula III: 【Transformation 36】 A compound having the structure of [formula], or a pharmaceutically acceptable salt thereof [wherein A is optionally substituted with a 3- to 6-membered cycloalkylene, optionally substituted with a 3- to 6-membered heterocycloalkylene, optionally substituted with a 6-membered arylene, optionally substituted with a 5- to 6-membered heteroarylene, optionally substituted with C] ２ ~C ４ Alkylene, C is optionally substituted. １ ~C ４ Heteroalkylene or optionally substituted C ２ ~C ４ It is alkenylene, Y ８ teeth, 【Chemistry 37】 And, W is hydrogen, C １ ~C ４ Alkyl, optionally substituted C １ ~C ３ The heteroalkyl group is a 3- to 10-membered heterocycloalkyl group that can be optionally substituted, a 3- to 10-membered cycloalkyl group that can be optionally substituted, a 6- to 10-membered aryl group that can be optionally substituted, or a 5- to 10-membered heteroaryl group that can be optionally substituted. L has the structure of formula VIIa or VIIb, 【Transformation 38】 z is 0, 1, or 2. X ９ -NR Ｌ６ -, -C(O)-, or -S(O) ２ - and R Ｌ１ , R Ｌ２ , R Ｌ３ , R Ｌ４ , R Ｌ４ , R Ｌ５ , and R Ｌ６ Each of these can be independently substituted with hydrogen, halogen, hydroxyl, or C of any choice. １ ~C ６ Alkyl, optionally substituted C ２ ~C ６ Alkenyl, C which can be optionally replaced. ２ ~C ６ Alkinyl, or C as optionally replaced. １ ~C ６ It is heteroalkyl, or R Ｌ１ , R Ｌ２ , R Ｌ３ , R Ｌ４ , R Ｌ４ , R Ｌ５ , and R Ｌ６ Any two of these atoms, along with the atoms bonded to them and any intervening atoms, are optionally substituted. ３ ~C ８ Forming cycloalkyl or 3- to 8-membered heterocyclines, or combined R Ｌ１ and R Ｌ２ However, it forms a bond, Here, L is 【Chemistry 39】 It does not have the structure, or Optionally, L is 【Chemistry 40】 Instead, X ４ and X ５ Each is independent of CH ２ , CH (CH ３ ) or NH, R １３ C is replaced by any choice. １ ~C ６ Alkyl, optionally substituted C １ ~C ６ The heteroalkyl group is a 3- to 6-membered cycloalkyl group that can be optionally substituted, a 3- to 6-membered cycloalkenyl group that can be optionally substituted, a 3- to 15-membered heterocycloalkyl group that can be optionally substituted, a 6- to 10-membered aryl group that can be optionally substituted, or a 5- to 10-membered heteroaryl group that can be optionally substituted. R ２ C is a hydrogen atom that can be optionally substituted. １ ~C ６ Alkyl, optionally substituted C ２ ~C ６ Alkenyl, C which can be optionally replaced. ２ ~C ６ Alkynyl, optionally substituted 3- to 6-membered cycloalkyl, optionally substituted 3- to 7-membered heterocycloalkyl, optionally substituted 6-membered aryl, optionally substituted 5- or 6-membered heteroaryl, R １０ is hydrogen, hydroxy, optionally substituted C １ to C ６ alkoxy, optionally substituted C １ to C ３ alkyl, optionally substituted C １ to C ６ heteroalkyl, or optionally substituted 3- to 10-membered heterocycloalkyl, and R ７ and R ８ each independently is selected from fluoro or CH ３ or R ７ and R ８ combine with the atoms to which they are attached to form a 3-member cycloalkyl, where (i) The compound is not one of those listed in Table 2 (E10-E52) and Table 5; or (ii) A is thiazole-2,4-diyl and the two Rs together Ｌ１ When the substituent forms spirocyclopropyl, R ２ C is replaced by any choice. １－６ Not alkyl; or (iii) A is thiazole-2,4-diyl and the two Rs together Ｌ２ When the substituent forms spirocyclopropyl, R ２ C is replaced by any choice. １－６ Not alkyl; or (iv) A is thiazole-2,4-diyl and together with R Ｌ１ and R Ｌ２ However, when a condensed cyclopropyl is formed by optional substitution, R ２ C is replaced by any choice. １－６ Not alkyl; or (v) A is thiazole-2,4-diyl and together with R Ｌ１ and R Ｌ２ However, when forming a bond, R ２ C is replaced by any choice. １－６ Not alkyl; or (vi) A is thiazole-2,4-diyl and together with R Ｌ１ and R Ｌ２ However, when condensed cyclobutyl is formed, R ２ C is replaced by any choice. １－６ Not alkyl; or (vii) A is thiazole-2,4-diyl and R Ｌ１ and R Ｌ３ However, when cross-linked cyclobutyl is formed together with the atoms bonded to them, R ２ C is replaced by any choice. １－６ Not alkyl; or (viiii) A is thiazole-2,4-diyl and R Ｌ１ and R Ｌ３ However, when W forms a cross-linked cyclobutyl with the atoms bonded to them, W is not a optionally substituted cyclopropyl.

6. Formula IV: 【Chemistry 41】 A compound having the structure of the formula, or a pharmaceutically acceptable salt thereof [wherein A is an optionally substituted 3- to 6-membered heterocycloalkylene, an optionally substituted 3- to 6-membered cycloalkylene, an optionally substituted 6-membered arylene, or an optionally substituted 5- to 10-membered heteroarylene] L １ It is a linker, L has the structure of formula VIIa or VIIb, 【Chemistry 42】 z is 0, 1, or 2. X ９ -NR Ｌ６ -, -C(O)-, or -S(O) ２ - and R Ｌ１ , R Ｌ２ , R Ｌ３ , R Ｌ４ , R Ｌ４ , R Ｌ５ , and R Ｌ６ Each of these can be independently substituted with hydrogen, halogen, hydroxyl, or C of any choice. １ ~C ６ Alkyl, optionally substituted C ２ ~C ６ Alkenyl, C which can be optionally replaced. ２ ~C ６ Alkinyl, or C as optionally replaced. １ ~C ６ It is heteroalkyl, or R Ｌ１ , R Ｌ２ , R Ｌ３ , R Ｌ４ , R Ｌ４ , R Ｌ５ , and R Ｌ６ Any two of these atoms, along with the atoms bonded to them and any intervening atoms, are optionally substituted. ３ ~C ８ Forming cycloalkyl or 3- to 8-membered heterocyclines, Here, L is 【Chemistry 43】 It does not have the structure, or Optionally, L is 【Chemistry 44】 Instead, W is a crosslinking group, which includes vinyl ketones, vinyl sulfones, inones, or alkynyl sulfones. R １ This is hydrogen, optionally substituted 3- to 10-membered heterocycloalkyl groups, or optionally substituted C １ ~C ６ It is heteroalkyl, R ２ C is replaced by any choice. １ ~C ６ It is alkyl, R ３ is optionally substituted C １ -C ６ alkyl or optionally substituted C １ -C ３ heteroalkyl, (i) The compound is 【Chemistry 45】 not; or (ii) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, and the two Rs together Ｌ１ When the substituent forms a spirocyclopropyl group and W is a vinyl ketone, R ２ is not ethyl; or (iii) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, and together R Ｌ１ and R Ｌ２ However, if condensed cyclopropyl is formed and W is a vinyl ketone, then R ２ is not ethyl; or (iv) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, and the two Rs together Ｌ１ If the substituent forms spirocyclopropyl, then W is not a vinyl ketone; or (v) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, and together with R Ｌ１ and R Ｌ２ However, if condensed cyclopropyl is formed, W is not a vinyl ketone; or (vi) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, W is a vinyl ketone, and the two Rs together Ｌ１ When the substituent forms a spirocyclopropyl or spirocycloalkyl group, L １ teeth, 【Chemistry 46】 Other than; or (vii) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, W is a vinyl ketone, and together R Ｌ１ and R Ｌ２ However, when forming a condensed cyclopropyl or condensed cycloalkyl, L １ teeth, 【Chemistry 47】 not; or (viiii) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, W is a vinyl ketone, and the two Rs together Ｌ１ When the substituent forms a spirocyclopropyl or spirocycloalkyl group, L １ C is one, two, or three independently selected C １－６ Optionally substituted with alkyl groups 【Chemistry 48】 not; or (ix) A is 1-hydroxybenzene-3,5-diyl or optionally substituted phenylene, W is a vinyl ketone, and the two Rs together Ｌ１ and R Ｌ２ However, when forming a condensed cyclopropyl or condensed cycloalkyl, L １ C is one, two, or three independently selected C １－６ Optionally substituted with alkyl groups 【Chemistry 49】 isn't it].

7. Formula V: [Transformation 50] A compound having the structure of the formula, or a pharmaceutically acceptable salt thereof [wherein A is an optionally substituted 3- to 6-membered heterocycloalkylene, an optionally substituted 3- to 6-membered cycloalkylene, an optionally substituted 6-membered arylene, or an optionally substituted 5- to 10-membered heteroarylene] L has the structure of formula VIIa or VIIb, 【Chemistry 51】 z is 0, 1, or 2. X ９ -NR Ｌ６ -, -C(O)-, or -S(O) ２ - and R Ｌ１ , R Ｌ２ , R Ｌ３ , R Ｌ４ , R Ｌ４ , R Ｌ５ , and R Ｌ６ Each of these can be independently substituted with hydrogen, halogen, hydroxyl, or C of any choice. １ ~C ６ Alkyl, optionally substituted C ２ ~C ６ Alkenyl, C which can be optionally replaced. ２ ~C ６ Alkinyl, or C as optionally replaced. １ ~C ６ It is heteroalkyl, or R Ｌ１ , R Ｌ２ , R Ｌ３ , R Ｌ４ , R Ｌ４ , R Ｌ５ , and R Ｌ６ Any two of these atoms, along with the atoms bonded to them and any intervening atoms, are optionally substituted. ３ ~C ８ Forming cycloalkyl or 3- to 8-membered heterocyclines, Here, L is 【Chemistry 52】 It does not have the structure, or Optionally, L is 【Chemistry 53】 Instead, W is a crosslinking group containing aziridine, epoxide, carbodiimide, oxazoline, thiazoline, chloroethylurea, chloroethylthiourea, chloroethylcarbamate, chloroethylthiocarbamate, trifluoromethyl ketone, boronic acid, boronic acid ester, N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), iso-EEDQ or other EEDQ derivatives, oxazolium, or glycar. X ６ CH ２ or O, m is either 1 or 2. n is either 0 or 1, R １ These are 3- to 10-membered heterocycloalkyl groups that are substituted with hydrogen or optionally. R ２ C is replaced by any choice. １ ~C ６ It is alkyl.

8. Formula VI: 【Chemistry 54】 A compound having the structure of the formula, or a pharmaceutically acceptable salt thereof [wherein A is an optionally substituted 3- to 6-membered heterocycloalkylene, an optionally substituted 3- to 6-membered cycloalkylene, an optionally substituted 6-membered arylene, or an optionally substituted 5- to 10-membered heteroarylene] L has the structure of formula VIIa or VIIb, 【Transformation 55】 Optionally, L is 【Transformation 56】 Instead, z is 0, 1, or 2. X ９ -NR Ｌ６ -, -C(O)-, or -S(O) ２ - and R Ｌ１ , R Ｌ２ , R Ｌ３ , R Ｌ４ , R Ｌ４ , R Ｌ５ , and R Ｌ６ Each of these can be independently substituted with hydrogen, halogen, hydroxyl, or C of any choice. １ ~C ６ Alkyl, optionally substituted C ２ ~C ６ Alkenyl, C which can be optionally replaced. ２ ~C ６ Alkinyl, or C as optionally replaced. １ ~C ６ It is heteroalkyl, or R Ｌ１ , R Ｌ２ , R Ｌ３ , R Ｌ４ , R Ｌ４ , R Ｌ５ , and R Ｌ６ Any two of these atoms, along with the atoms bonded to them and any intervening atoms, are optionally substituted. ３ ~C ８ Forming cycloalkyl or 3- to 8-membered heterocyclines, X ６ , X ７ , and X ８ Each is independent of CH ２ CHF, CF ２ C=O or O is selected, m is either 1 or 2. n is either 0 or 1, R １ C is a hydrogen atom that can be optionally substituted. １ ~C ６ Heteroalkyl groups, or optionally substituted 3- to 10-membered heterocycloalkyl groups, R ２ C is replaced by any choice. １ ~C ６ It is alkyl, R ３ C is replaced by any choice. １ ~C ６ Alkyl, optionally substituted C １ ~C ６ A heteroalkyl group, a optionally substituted 3- to 6-membered cycloalkyl group, or an optionally substituted heterocycloalkyl group. Here, each hydrogen atom is independently and arbitrarily isotope-enriched with deuterium.

9. Formula VIIIa: 【Chemistry 57】 A compound having, or a pharmaceutically acceptable salt thereof [wherein, The dotted lines represent 0, 1, 2, 3, or 4 non-adjacent double bonds. L has the structure of formula VIIa or VIIb, 【Chemistry 58】 z is 0, 1, or 2. X ９ -NR Ｌ６ -, -C(O)-, or -S(O) ２ - and R Ｌ１ , R Ｌ２ , R Ｌ３ , R Ｌ４ , R Ｌ４ , R Ｌ５ , and R Ｌ６ Each of these can be independently substituted with hydrogen, halogen, hydroxyl, or C of any choice. １ ~C ６ Alkyl, optionally substituted C ２ ~C ６ Alkenyl, C which can be optionally replaced. ２ ~C ６ Alkinyl, C, which can be optionally replaced. １ ~C ６ Heteroalkyl or optionally substituted C ３ ~C ８ It is either cycloalkyl or R Ｌ１ , R Ｌ２ , R Ｌ３ , R Ｌ４ , R Ｌ４ , R Ｌ５ , and R Ｌ６ Any two of these atoms, along with the atoms bonded to them and any intervening atoms, are optionally substituted. ３ ~C ８ Forming cycloalkyl or 3- to 8-membered heterocyclines, Here, L is 【Chemistry 59】 It does not have the structure, or Optionally, L is 【Transformation 60】 Instead, A is replaced by C by choice. ２ ~C ４ Alkylene, C is optionally substituted. １ ~C ４ Heteroalkylenes, or C as optionally substituted. ２ ~C ４ It is alkenylene, G is replaced by C by choice. １ ~C ４ Alkylene, C is optionally substituted. １ ~C ４ Alkenylene, C is optionally substituted. １ ~C ４ Heteroalkylene, -C(O)O-CH(R ６ ) - (In the formula, the second C is -C(R ７ R ８ )-bonded),-C(O)NH-CH(R ６ ) - (In the formula, the second C is -C(R ７ R ８ ) - which is bound to, and C which is optionally replaced. １ ~C ４ These are heteroalkylenes or 3- to 8-membered heteroarylenes. swIp (switch I / P-loop) is an organic moiety that non-covalently binds to both the switch I binding pocket of the Ras protein and residue 12 or 13 of the loop. X ３ is N or CH, Y １ is C, CH, or N, Y ２ , Y ３ , Y ４ , and Y ７ They are independently C or N, Y ５ CH, CH ２ , or N, Y ６ C(O), CH, CH ２ , or N, R １ C is a cyano, which can be optionally replaced. １ ~C ６ Alkyl, optionally substituted C １ ~C ６ It is a heteroalkyl, optionally substituted 3-6 membered cycloalkyl, optionally substituted 3-6 membered cycloalkenyl, optionally substituted 3-6 membered heterocycloalkyl, optionally substituted 6-10 membered aryl, or optionally substituted 5-10 membered heteroaryl, or R １ and R ２ However, when combined with the atoms bonded to them, they form a 3- to 14-membered heterocycloalkyl group which can be optionally substituted. R ２ C is either absent or optionally substituted with hydrogen. １ ~C ６ Alkyl, optionally substituted C ２ ~C ６ Alkenyl, C which can be optionally replaced. ２ ~C ６ The alkynyl, optionally substituted 3- to 6-membered cycloalkyl, optionally substituted 3- to 7-membered heterocycloalkyl, optionally substituted 6-membered aryl, optionally substituted 5 or 6-membered heteroaryl, R ３ He is absent, or R ２ and R ３ However, when combined with the atoms bonded to them, they form optionally substituted 3- to 8-membered cycloalkyl groups or optionally substituted 3- to 14-membered heterocycloalkyl groups. R ４ This is a methyl molecule that is either absent, hydrogen, a halogen, a cyano, or optionally substituted with one to three halogens. R ６ R is either hydrogen or methyl, ７ C is substituted with hydrogen, halogen, or of any choice. １ ~C ３ It is alkyl, or R ６ and R ７ However, when combined with the carbon atoms bonded to them, they form optionally substituted 3-6 membered cycloalkyl groups or optionally substituted 3-7 membered heterocycloalkyl groups. R ８ C is substituted with hydrogen, halogen, hydroxyl, cyano, or any other element. １ ~C ３ Alkoxy, C is optionally substituted. １ ~C ３ Alkyl, optionally substituted C ２ ~C ６ Alkenyl, C which can be optionally replaced. ２ ~C ６ Alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted 3-14 membered heterocycloalkyl, optionally substituted 5-10 membered heteroaryl, or optionally substituted 6-10 membered aryl, or R ７ and R ８ However, when combined with the carbon atoms bonded to them, C=CR ７’ R ８’ ;C=N(OH), C=N(OC １ ~C ３ Forming an alkyl, C=O, C=S, C=NH, or optionally substituted 3-6 member cycloalkyl, or optionally substituted 3-7 member heterocycloalkyl, R ７ａ and R ８ａ These are independently substituted with hydrogen, a halo, and C of any choice. １ ~C ３ It is either alkyl or combined with a carbon bonded to it to form a carbonyl group. R ７’ C is substituted with hydrogen, halogen, or of any choice. １ ~C ３ It is alkyl, R ８’ C is substituted with hydrogen, halogen, hydroxyl, cyano, or any other element. １ ~C ３ Alkoxy, C is optionally substituted. １ ~C ３ Alkyl, optionally substituted C ２ ~C ６ Alkenyl, C which can be optionally replaced. ２ ~C ６ Alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted 3-14 membered heterocycloalkyl, optionally substituted 5-10 membered heteroaryl, or optionally substituted 6-10 membered aryl, or R ７’ and R ８’ However, when combined with the carbon atoms bonded to them, they form optionally substituted 3-6 membered cycloalkyl groups or optionally substituted 3-7 membered heterocycloalkyl groups. R １０ is hydrogen, halo, hydroxyl, C １ ~C ３ Alkoxy, or C １ ~C ３ It is alkyl, R １０ａ [This is hydrogen or a halo.]

10. The compound has formula VIIIb, VIIIc, VIIId, VIIIe, VIIIf, or VIIIg, 【Chemistry 61】 In the formula, each time it appears, Each L independently has either formula VIIa or VIIb, 【Transformation 62】 z is 0, 1, or 2. X ９ -NR Ｌ６ -, -C(O)-, or -S(O) ２ - and R Ｌ１ , R Ｌ２ , R Ｌ３ , R Ｌ４ , R Ｌ４ , R Ｌ５ , and R Ｌ６ Each of these can be independently substituted with hydrogen, halogen, hydroxyl, or C of any choice. １ ~C ６ Alkyl, optionally substituted C ２ ~C ６ Alkenyl, C which can be optionally replaced. ２ ~C ６ Alkinyl, C, which can be optionally replaced. １ ~C ６ Heteroalkyl or optionally substituted C ３ ~C ８ It is either cycloalkyl or R Ｌ１ , R Ｌ２ , R Ｌ３ , R Ｌ４ , R Ｌ４ , R Ｌ５ , and R Ｌ６ Any two of these atoms, along with the atoms bonded to them and any intervening atoms, are optionally substituted. ３ ~C ８ Forming cycloalkyl or 3- to 8-membered heterocyclines, Here, L is 【Transformation 63】 It does not have the structure of G is replaced by C by choice. １ ~C ４ Alkylene, C is optionally substituted. １ ~C ４ Alkenylene, C is optionally substituted. １ ~C ４ Heteroalkylene, -C(O)O-CH(R ６ ) - (In the formula, the second C is -C(R ７ R ８ )-bonded),-C(O)NH-CH(R ６ ) - (In the formula, the second C is -C(R ７ R ８ ) - which is bound to, and C which is optionally replaced. １ ~C ４ These are heteroalkylenes or 3- to 8-membered heteroarylenes. Z is -C(O)- or -S(O) ２ - and Each B is independent, either absent or -NH-, -N(CH) ３ )-, -O-, -CH(R ９ ) - or > C = CR ９ R ９’ (In the formula, carbon is -N(R) １１ (bonded to the carbonyl carbon of C(O)-), optionally substituted 3- to 6-membered cycloalkylenes, optionally substituted 3- to 6-membered heterocycloalkylenes, optionally substituted 6-membered arylenes, or optionally substituted 5- to 6-membered heteroarylenes. Each L １ It is independent, absent, or a linker. Each W can independently be hydrogen, cyano, optionally substituted amino, optionally substituted amide, or optionally substituted C １ ~C ４ Alkoxy, C is optionally substituted. １ ~C ４ Hydroxyalkyl, optionally substituted C １ ~C ４ aminoalkyl, optionally substituted C １ ~C ４ Haloalkyl, optionally substituted C １ ~C ４ Alkyl, optionally substituted C １ ~C ４ Guanidinoalkyl, C ０ ~C ４ Alkyl, optionally substituted 3-11 member heterocycloalkyl, optionally substituted 3-10 member cycloalkyl, optionally substituted 6-10 member aryl, or optionally substituted 3-10 member heteroaryl. Each X ３ These are independently N or CH, X ｅ is N, CH, or CR １７ And, X ｆ is N or CH, R １２ C is replaced by any choice. １ ~C ６ C is substituted with alkyl or optionally other elements. １ ~C ６ It is heteroalkyl, R １７ C is replaced by any choice. １ ~C ６ Alkyl, optionally substituted C １ ~C ６ The heteroalkyl group is optionally substituted with a 3-6 member cycloalkyl group, optionally substituted with a 3-6 member cycloalkenyl group, optionally substituted with a 3-6 member heterocycloalkyl group, optionally substituted with a 6-10 member aryl group, or optionally substituted with a 5-10 member heteroaryl group. Each Y １ These are independently C, CH, or N. Y ２ , Y ３ , Y ４ , and Y ７ They are independently C or N, Each Y ５ CH, CH ２ , or N, Each Y ６ These are independently C(O), CH, CH ２ , or N, Each R １ The C is independently substituted with cyano by choice. １ ~C ６ Alkyl, optionally substituted C １ ~C ６ It is a heteroalkyl, optionally substituted 3-6 membered cycloalkyl, optionally substituted 3-6 membered cycloalkenyl, optionally substituted 3-6 membered heterocycloalkyl, optionally substituted 6-10 membered aryl, or optionally substituted 5-10 membered heteroaryl, or R １ and R ２ However, when combined with the atoms bonded to them, they form a 3- to 14-membered heterocycloalkyl group which can be optionally substituted. Each R ２ C is independently absent or optionally substituted with hydrogen. １ ~C ６ Alkyl, optionally substituted C ２ ~C ６ Alkenyl, C which can be optionally replaced. ２ ~C ６ The alkynyl, optionally substituted 3- to 6-membered cycloalkyl, optionally substituted 3- to 7-membered heterocycloalkyl, optionally substituted 6-membered aryl, optionally substituted 5 or 6-membered heteroaryl, Each R ３ is independent, absent, or R ２ and R ３ However, when combined with the atoms bonded to them, they form optionally substituted 3- to 8-membered cycloalkyl groups or optionally substituted 3- to 14-membered heterocycloalkyl groups. Each R ４ This is independently a methyl molecule that is absent, or optionally substituted with hydrogen, a halogen, a cyano, or one to three halogens. Each R ６ Each R is independently either hydrogen or methyl, and each R ７ C is independently substituted with hydrogen, halogen, or of any choice. １ ~C ３ It is alkyl, or R ６ and R ７ However, when combined with the carbon atoms bonded to them, they form optionally substituted 3-6 membered cycloalkyl groups or optionally substituted 3-7 membered heterocycloalkyl groups. Each R ８ C is independently substituted with hydrogen, halogen, hydroxyl, cyano, or of any choice. １ ~C ３ Alkoxy, C is optionally substituted. １ ~C ３ Alkyl, optionally substituted C ２ ~C ６ Alkenyl, C which can be optionally replaced. ２ ~C ６ Alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted 3-14 membered heterocycloalkyl, optionally substituted 5-10 membered heteroaryl, or optionally substituted 6-10 membered aryl, or R ７ and R ８ However, when combined with the carbon atoms bonded to them, C=CR ７’ R ８’ ;C=N(OH), C=N(OC １ ~C ３ Forming an alkyl, C=O, C=S, C=NH, or optionally substituted 3-6 member cycloalkyl, or optionally substituted 3-7 member heterocycloalkyl, R ７ａ and R ８ａ These are independently substituted with hydrogen, a halo, and C of any choice. １ ~C ３ It is either alkyl or combined with a carbon bonded to it to form a carbonyl group. R ７’ C is substituted with hydrogen, halogen, or of any choice. １ ~C ３ It is alkyl, R ８’ C is substituted with hydrogen, halogen, hydroxyl, cyano, or any other element. １ ~C ３ Alkoxy, C is optionally substituted. １ ~C ３ Alkyl, optionally substituted C ２ ~C ６ Alkenyl, C which can be optionally replaced. ２ ~C ６ Alkynyl, optionally substituted 3-8 membered cycloalkyl, optionally substituted 3-14 membered heterocycloalkyl, optionally substituted 5-10 membered heteroaryl, or optionally substituted 6-10 membered aryl, or R ７’ and R ８’ However, when combined with the carbon atoms bonded to them, they form optionally substituted 3-6 membered cycloalkyl groups or optionally substituted 3-7 membered heterocycloalkyl groups. Each R ９ These are independently hydrogen, F, and C which can be substituted by any choice. １ ~C ６ Alkyl, optionally substituted C １ ~C ６ A heteroalkyl group, a optionally substituted 3- to 6-membered cycloalkyl group, or an optionally substituted 3- to 7-membered heterocycloalkyl group. R ９ And L, together with the atoms bonded to them, form optionally substituted 3- to 14-membered heterocycloalkyl groups. Each R ９’ C is independently substituted with hydrogen or of any choice. １ ~C ６ It is alkyl, Each R １０ These are independently hydrogen, halo, hydroxyl, and C. １ ~C ３ Alkoxy, or C １ ~C ３ It is alkyl, R １０ａ is hydrogen or halo, R １１ is hydrogen or C １ ~C ３ A compound according to claim 9, which is alkyl, or a pharmaceutically acceptable salt thereof.

11. L is formula VIIa, formula VIIa-1, formula VIIa-2, formula VIIa-3, formula VIIa-4, formula VIIa-5, formula VIIa-6, formula VIIb, formula VIIb-1, formula VIIb-2, or 【Chemistry 64】 It has a structure, 【Transformation 65】 In the formula, X ９ However, -NR Ｌ６ - or X ９ However, it is either -C(O)- or X ９ However, S(O) ２ - The compound according to any one of claims 1 to 10, or a pharmaceutically acceptable salt thereof.

12. A compound according to any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof, wherein z is 0, or z is 1, or z is 2.

13. R Ｌ１ However, is it hydrogen, or R Ｌ１ However, C is replaced by an optional choice. １ ~C ６ Alkyl or R Ｌ１ However, it is either methyl, ethyl, or trifluoromethyl, or R Ｌ１ However, C is replaced by an optional choice. １ ~C ６ It is heteroalkyl, or R Ｌ１ However, is it methoxy or ethoxy, or R Ｌ１ However, C is replaced by an optional choice. ２ ~C ６ It is either alkinyl or R Ｌ１ A compound according to any one of claims 1 to 12, wherein the compound is ethinyl, or a pharmaceutically acceptable salt thereof.

14. R Ｌ２ However, is it hydrogen, or R Ｌ２ However, is it halogen, or R Ｌ２ A compound according to any one of claims 1 to 13, or a pharmaceutically acceptable salt thereof, wherein the compound is fluoro.

15. R Ｌ３ However, is it hydrogen, or R Ｌ３ However, C is replaced by an optional choice. １ ~C ６ Alkyl or R Ｌ３ A compound according to any one of claims 1 to 14, wherein the compound is methyl, or a pharmaceutically acceptable salt thereof.

16. R Ｌ４ However, is it hydrogen, or R Ｌ１ and R Ｌ４ These combine to form C, which is replaced by arbitrary selection. ４ Forms a cycloalkyl group, or R Ｌ１ and R Ｌ３ These combine to form C, which is replaced by arbitrary selection. ４ Forms a cycloalkyl group, or R Ｌ１ and R Ｌ３ These combine to form C, which is replaced by arbitrary selection. ５ Forms a cycloalkyl group, or Two R's Ｌ１ These combine to form C, which is replaced by arbitrary selection. ３ ~C ６ Forms a cycloalkyl group, or R Ｌ１ and R Ｌ２ These combine to form C, which is replaced by arbitrary selection. ３ ~C ６ A compound according to any one of claims 1 to 15 that forms a cycloalkyl group, or a pharmaceutically acceptable salt thereof.

17. L, 【Chemical Formula 66】 is, or L, 【Transformation 67】 A compound according to any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof.

18. R Ｌ６ However, C is replaced by an optional choice. １ ~C ６ Alkyl or R Ｌ６ A compound according to any one of claims 1 to 17, wherein the compound is methyl, or a pharmaceutically acceptable salt thereof.

19. R Ｌ５ However, is it hydrogen, or R Ｌ５ However, C is replaced by an optional choice. １ ~C ６ Alkyl or R Ｌ５ However, C is replaced by an optional choice. ３ ~C ８ It is either cycloalkyl or has two R's Ｌ５ These combine to form C, which is replaced by arbitrary selection. ３ ~C ８ A compound according to any one of claims 1 to 18 that forms a cycloalkyl group, or a pharmaceutically acceptable salt thereof.

20. A is a 3- to 6-membered heterocycloalkylene that can be optionally substituted, a 6-membered arylene that can be optionally substituted, or a 5- to 10-membered heteroarylene that can be optionally substituted, or A is a six-membered arrine that is optionally substituted, or A, 【Transformation 68】 is, or Is A a 3- to 6-membered heterocycloalkylene that is substituted by choice? A, 【Transformation 69】 is, or A is a 5-membered to 10-membered heteroarylene that is optionally substituted, or A, 【Transformation 70】 A compound according to any one of claims 1 to 19, or a pharmaceutically acceptable salt thereof.

21. R ２ The compound according to any one of claims 2 to 20, wherein the compound is ethyl or haloethyl, or a pharmaceutically acceptable salt thereof.

22. R ３ However, C is replaced by an optional choice. １ ~C ６ A compound according to any one of claims 1 and 6 to 21, which is alkyl, or a pharmaceutically acceptable salt thereof.

23. The compounds listed in Table 1, or their pharmaceutically acceptable salts.

24. A pharmaceutical composition comprising a compound according to any one of claims 1 to 23, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

25. A method for treating cancer in a subject requiring cancer treatment, the method comprising administering to the subject a therapeutically effective amount of a compound according to any one of claims 1 to 23, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 24. At will, whether the cancer is pancreatic cancer, colorectal cancer, non-small cell lung cancer, or endometrial cancer. Or, optionally, the cancer contains a Ras mutation, or The method further optionally comprises administering an additional anticancer agent, wherein the additional anticancer agent is an EGFR inhibitor, a second Ras inhibitor, a SHP2 inhibitor, a SOS1 inhibitor, a Raf inhibitor, a MEK inhibitor, an ERK inhibitor, a PI3K inhibitor, a PTEN inhibitor, an AKT inhibitor, an mTORC1 inhibitor, a BRAF inhibitor, a PD-L1 inhibitor, a PD-1 inhibitor, a CDK4 / 6 inhibitor, a HER2 inhibitor, or a combination thereof.

26. A method for treating a Ras protein-related disorder in a subject requiring treatment for the Ras protein-related disorder, comprising administering to the subject a therapeutically effective amount of a compound according to any one of claims 1 to 23, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 24, wherein optionally the Ras protein is K-Ras, or The method further optionally comprises administering an additional anticancer agent, wherein the additional anticancer agent is an EGFR inhibitor, a second Ras inhibitor, a SHP2 inhibitor, a SOS1 inhibitor, a Raf inhibitor, a MEK inhibitor, an ERK inhibitor, a PI3K inhibitor, a PTEN inhibitor, an AKT inhibitor, an mTORC1 inhibitor, a BRAF inhibitor, a PD-L1 inhibitor, a PD-1 inhibitor, a CDK4 / 6 inhibitor, a HER2 inhibitor, or a combination thereof.

27. A method for inhibiting intracellular Ras protein, comprising contacting the cells with an effective amount of the compound described in any one of claims 1 to 23, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition described in claim 24. Optionally, whether the Ras protein is K-Ras, Or, optionally, the cells are cancer cells, and optionally, the cancer cells are pancreatic cancer cells, colorectal cancer cells, non-small cell lung cancer cells, or endometrial cancer cells, or The method further optionally comprises administering an additional anticancer agent, wherein the additional anticancer agent is an EGFR inhibitor, a second Ras inhibitor, a SHP2 inhibitor, a SOS1 inhibitor, a Raf inhibitor, a MEK inhibitor, an ERK inhibitor, a PI3K inhibitor, a PTEN inhibitor, an AKT inhibitor, an mTORC1 inhibitor, a BRAF inhibitor, a PD-L1 inhibitor, a PD-1 inhibitor, a CDK4 / 6 inhibitor, a HER2 inhibitor, or a combination thereof.

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