Claims for Patent: 9,896,432

Summary for Patent: 9,896,432

Title:	Somatostatin modulators and uses thereof
Abstract:	Described herein are compounds that are somatostatin modulators, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in the treatment of conditions, diseases, or disorders that would benefit from modulation of somatostatin activity.
Inventor(s):	Jian Zhao, Sangdon Han, Sun Hee Kim, Shimiao Wang, Yunfei ZHU
Assignee:	Crinetics Pharmaceuticals Inc
Application Number:	US15/647,758
Patent Claims:	1. A compound that has the structure of Formula (AIIb), or a pharmaceutically acceptable salt, solvate, diastereomeric mixture, or individual enantiomers thereof: wherein: each Ra and Rb is independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted monocyclic carbocycle, unsubstituted or substituted monocyclic heterocycle, —CN, —OH, —OR14, —CO2R15, —CH2CO2R15, —C(═O)N(R15)2, —CH2C(═O)N(R15)2, —N(R15)2, —CH2N(R15)2, —CH(CF3)N(R15)2, —NR15C(═O)R14, —CH2NR15C(═O)R14, —SR14, —S(═O)R14, —SO2R14, —SO2N(R15)2 or —C(═NOR15)R15; m is 1 or 2; n is 0, 1 or 2; or if one Ra and one Rb are on adjacent atoms then the adjacent Ra and Rb groups are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic carbocycle or an unsubstituted or substituted 5- or 6-membered monocyclic heterocycle; RB is an unsubstituted or substituted ring B that is an unsubstituted or substituted phenyl or an unsubstituted or substituted pyridinyl, wherein if the ring B is substituted then the ring B is substituted with p Rc and q Rd; each Rc and Rd is independently hydrogen, halogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted monocyclic carbocycle, unsubstituted or substituted monocyclic heterocycle, —CN, —OH, —OR14, —C(═O)R15, —OC═O)R15, —CO2R15, —CH2CO2R15, —C(═O)N(R15)2, —OC(═O)N(R15)2, —NR15C(═O)N(R15)2, —NR15C(═O)OR14, —NR15C(═O)NR15OR14, —C(═O)NR15OR15, —CH2C(═O)N(R15)2, —N(R15)2, —CH2N(R15)2, —CH(CF3)N(R15)2, —NR15C(═O)R14, —CH2NR15C(═O)R14, —SR14, —S(═O)R14, —SO2R14, —SO2N(R15)2, —C(═NOR15)R15, —N(R15)SO2R14, —C(═O)NR15S(═O)2R14, —S(═O)2NR15C(═O)R14, —C(═NR15)N(R15)2, —NR15C(═NR15)N(R15)2, —NR15C(═CR14R15)N(R15)2, —C(═O)NR15C(═NR15)N(R15)2 or, —C(═O)NR15C(═CR14R15)N(R15)2; p is 1 or 2; q is 0, 1 or 2; or if one Rc and one Rd are on adjacent atoms of ring B then the adjacent Rc and Rd groups are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic carbocycle or an unsubstituted or substituted 5- or 6-membered monocyclic heterocycle; Re is hydrogen, halogen, C1-C4alkyl, C1-C4fluoroalkyl, —CN, OH, or —OR14; each Rf is independently hydrogen, halogen, C1-C4alkyl, C1-C4fluoroalkyl, —CN, —OH, or —OR14; R1 and R2 are independently hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6 heteroalkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C3-C6cycloalkyl or substituted or unsubstituted C2-C6heterocycloalkyl; or R1 and R2 are taken together with the nitrogen atom to which they are attached to form ring C that is an unsubstituted or substituted N-containing C2-C8heterocycloalkyl; R5 is selected from the group consisting of hydrogen, halogen, —OH, —OR14, —SR14, —S(═O)R14, —S(═O)2R14, —N(R15)2, —CN, —C(═O)OR15, —C(═O)N(R15)2, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6heteroalkyl, and unsubstituted or substituted C1-C6fluoroalkyl; or R2 and R5 are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 4-7 membered saturated N-containing heterocyclic ring; each R14 is independently selected from unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C10cycloalkyl, substituted or unsubstituted C2-C10heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl; each R15 is independently selected from hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6heteroalkyl, unsubstituted or substituted C3-C10cycloalkyl, substituted or unsubstituted C2-C10heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl; or two R15 on the same N atom are taken together with the N atom to which they are attached to form an unsubstituted or substituted N-containing heterocycle; wherein each substituted alkyl, substituted fluoroalkyl, substituted heteroalkyl, substituted carbocycle, and substituted heterocycle is substituted with one or more Rs groups independently selected from the group consisting of halogen, C1-C6alkyl, monocyclic carbocycle, monocyclic heterocycle, —CN, —OR16, —CO2R16, —C(═O)N(R16)2, —N(R16)2, —NR16C(═O)R17, —SR16, —S(═O)R17, —SO2R17, or —SO2N(R16)2; each R16 is independently selected from hydrogen, C1-C6alkyl, C1-C6heteroalkyl, C3-C6cycloalkyl, C2-C6heterocycloalkyl, phenyl, benzyl, 5-membered heteroaryl and 6-membered heteroaryl; or two R16 groups are taken together with the N atom to which they are attached to form a N-containing heterocycle; each R17 is independently selected from C1-C6alkyl, C1-C6heteroalkyl, C3-C6cycloalkyl, C2-C6heterocycloalkyl, phenyl, benzyl, 5-membered heteroaryl and 6-membered heteroaryl. 2. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, diastereomeric mixture, or individual enantiomers thereof, wherein: Re is hydrogen, F, Cl, Br, —CH3, —CH2CH3, —CH2F, —CHF2, —CF3, —CN, —OH, —OCH3, —OCH2CH3, or —OCF3; each Rf is independently hydrogen, F, Cl, Br, —CH3, —CH2CH3, —CH2F, —CHF2, —CF3, —CN, —OH, —OCH3, —OCH2CH3, or —OCF3. 3. The compound of claim 2, or a pharmaceutically acceptable salt, solvate, diastereomeric mixture, or individual enantiomers thereof, wherein: each Ra is independently hydrogen, halogen, unsubstituted or substituted C1-C4alkyl, unsubstituted or substituted C1-C4fluoroalkyl, unsubstituted or substituted C1-C4heteroalkyl, —CN, —OH, —OR14, —CO2R15, —CH2CO2R15, —C(═O)N(R15)2, —CH2C(═O)N(R15)2, —N(R15)2, —CH2N(R15)2, —CH(CF3)N(R15)2, —NR15C(═O)R14, —CH2NR15C(═O)R14, —SR14, —S(═O)R14, —SO2R14, —SO2N(R15)2 or; and each Rb is independently hydrogen, halogen, unsubstituted or substituted C1-C4alkyl, unsubstituted or substituted C1-C4fluoroalkyl, unsubstituted or substituted C1-C4heteroalkyl, —CN, —OH, or —O-(unsubstituted or substituted C1-C4alkyl). 4. The compound of claim 2, or a pharmaceutically acceptable salt, solvate, diastereomeric mixture, or individual enantiomers thereof, wherein: each Ra is independently hydrogen, halogen, unsubstituted or substituted C1-C4alkyl, unsubstituted or substituted C1-C4fluoroalkyl, unsubstituted or substituted C1-C4heteroalkyl, —CN, —OH, —OR14, —CO2R15, —CH2CO2R15, —C(═O)N(R15)2, —CH2C(═O)N(R15)2, —N(R15)2, or —CH2N(R15)2; and each Rb is independently hydrogen, halogen, unsubstituted or substituted C1-C4alkyl, unsubstituted or substituted C1-C4heteroalkyl, —CN, or —O-(unsubstituted or substituted C1-C4alkyl). 5. The compound of claim 2, or a pharmaceutically acceptable salt, solvate, diastereomeric mixture, or individual enantiomers thereof, wherein: each Ra is independently hydrogen, F, Cl, Br, —CH3, —CH2CH3, —CH2CH2CH3, —CH(CH3)2, —CH2CH2CH2CH3, —CH2CH(CH3)2, —CH(CH3)(CH2CH3), —C(CH3)3, —CH2OH, —CH2CN, —CH2F, —CHF2, —CF3, —CN, —OH, —OCH3, —OCH2CH3, —OCF3, —CH2CH2OH, —CO2H, —CO2CH3, —CO2CH2CH3, —CH2CO2H, —CH2CO2CH3, —CH2CO2CH2CH3, —C(═O)NH2, —C(═O)NHCH3, —C(═O)N(CH3)2, —CH2C(═O)NH2, —CH2C(═O)NHCH3, —CH2C(═O)N(CH3)2, —NH2, —NHCH3, —N(CH3)2, —CH2NH2, —CH2NHCH3, or —CH2N(CH3)2; each Rb is independently hydrogen, F, Cl, Br, —CH3, —CH2CH3, —CH2CH2CH3, —CH(CH3)2, —CH2CH2CH2CH3, —CH2CH(CH3)2, —CH(CH3)(CH2CH3), —C(CH3)3, —CH2OH, —CH2CN, —CH2F, —CHF2, —CF3, —CN, —OH, —OCH3, —OCH2CH3, or —OCF3. 6. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, diastereomeric mixture, or individual enantiomers thereof, wherein: each Rc is independently hydrogen, halogen, unsubstituted or substituted C1-C4alkyl, unsubstituted or substituted C1-C4fluoroalkyl, —CN, —OH, —OR14, —CO2R15, —CH2CO2R15, —C(═O)N(R15)2, —NR15C(═O)NR15OR14, —C(═O)NR15OR15, —CH2C(═O)N(R15)2, —N(R15)2, —CH2N(R15)2, —CH(CF3)N(R15)2, —NR15C(═O)R14, —CH2NR15C(═O)R14, —SR14, —S(═O)R14, —SO2R14, —SO2N(R15)2, or N(R15)SO2R14; and Rd is independently hydrogen, halogen, unsubstituted or substituted C1-C4alkyl, unsubstituted or substituted C1-C4fluoroalkyl, unsubstituted or substituted monocyclic 4-7-membered heterocycle, —CN, —OH, —O-(unsubstituted or substituted C1-C4alkyl), —O-(unsubstituted or substituted C1-C4heteroalkyl), —C(═O)R15, —OC(═O)R15, —CO2R15, —CH2CO2R15, —C(═O)N(R15)2, —OC(═O)N(R15)2, —NR15C(═O)N(R15)2, —NR15C(═O)OR14, —NR15C(═O)NR15OR14, —C(═O)NR15OR15, —CH2C(═O)N(R15)2, —N(R15)2, —CH2N(R15)2, —CH(CF3)N(R15)2, —NR15C(═O)R14, —CH2NR15C(═O)R14, —SO2N(R15)2, —C(═NOR15)R15, —N(R15)SO2R14, —C(═O)NR15S(═O)2R14, —S(═O)2NR15C(═O)R14, or —C(═NR15)N(R15)2; or if one Rc and one Rd are on adjacent atoms of ring B then the adjacent Rc and Rd groups are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic carbocycle or an unsubstituted or substituted 5- or 6-membered monocyclic heterocycle. 7. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, diastereomeric mixture, or individual enantiomers thereof, wherein: each Rc is independently hydrogen, F, Cl, Br, —CH3, —CH2CH3, —CH2CH2CH3, —CH(CH3)2, —CH2CH2CH2CH3, —CH2CH(CH3)2, —CH(CH3)(CH2CH3), —C(CH3)3, —CH2OH, —CH2CN, —CH2F, —CHF2, —CF3, —CN, —OH, —OCH3, —OCH2CH3, —OCF3, —CO2H, —CO2CH3, —CO2CH2CH3, —CH2CO2H, —CH2CO2CH3, —CH2CO2CH2CH3, —C(═O)NH2, —C(═O)NHCH3, —C(═O)NHOCH3, —C(═O)N(CH3)2, —SO2N(CH3)2, —C(═NOH)H, —C(═NOCH3)H, —CH2C(═O)NH2, —CH2C(═O)NHCH3, —CH2C(═O)N(CH3)2, —NH2, —NHCH3, —N(CH3)2, —NHCO2CH3, —NHSO2CH3, —CH2NH2, —CH2NHCH3, —CH2N(CH3)2, CH(CF3)NH2, azetidinyl, or pyrrolidinyl; each Rd is independently hydrogen, F, Cl, Br, —CH3, —CH2CH3, —CH2CH2CH3, —CH(CH3)2, —CH2CH2CH2CH3, —CH2CH(CH3)2, —CH(CH3)(CH2CH3), —C(CH3)3, —CH2OH, —CH2CN, —CH2F, —CHF2, —CF3, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, —CN, —OH, —OCH3, —OCH2CH3, —OCF3, —OCH2OCH3, —OCH2OCH2CH3, —OCH2CH2OH, —C(═O)NHOCH3, —C(═NOH)H, —C(═NOCH3)H, —CH2C(═O)NH2, —NH2, NHCO2CH3, NHSO2CH3, NH(C═O)NHCH3, NH(C═O)NHOCH3, or CH(CF3)NH2; or if one Rc and one Rd are on adjacent atoms of ring B then the adjacent Rc and Rd groups are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5- or 6-membered monocyclic heterocycle. 8. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, diastereomeric mixture, or individual enantiomers thereof, wherein: each Ra is independently hydrogen, F, Cl, Br, —CH3, —CHF, —CHF2, —CF3, —CN, —OH, —OCH3, —OCF3, or —CH2CH2OH; each Rb is independently hydrogen, F, Cl, Br, —CH3, —CHF, —CHF2, —CF3, —CN, —OCH3, or —OCF3; each Rc is independently hydrogen, F, Cl, Br, —CH3, —CHF, —CHF2, —CF3, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, —CN, —OH, —OCH3, —OCF3, —NH2, —C(═O)NH2, —CONHCH3, —C(═NOH)H, —C(═NOCH3)H, —SO2CH3, —SO2N(CH3)2, azetidinyl, or pyrrolidinyl; each Rd is independently hydrogen, F, Cl, Br, —CH3, —CH2F, —CHF2, —CF3, —CN, —OH, —OCH3, —OCF3, —OCH2OCH3, —CH2OH, —OCH2CH2OH, —C(═O)NH2, —C(═O)NHOCH3, —NH2, —NHCO2CH3, —NH(C═O)NHOCH3, or CH2(C═O)NH2; or if one Rc and one Rd are on adjacent atoms of ring B then the adjacent Rc and Rd groups are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 5-membered monocyclic heterocycle. 9. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, diastereomeric mixture, or individual enantiomers thereof, wherein: R1 hydrogen; R2 is hydrogen, unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted C1-C6fluoroalkyl, unsubstituted or substituted C3-C6cycloalkyl or substituted or unsubstituted C2-C6heterocycloalkyl; or R1 and R2 are taken together with the nitrogen atom to which they are attached to form ring C that is an unsubstituted or substituted N-containing C2-C6heterocycloalkyl; R5 is selected from the group consisting of hydrogen, halogen, —OH, —OR14, —S(═O)2R14, —N(R15)2, —CN, —C(═O)OR15, —C(═O)N(R15)2, unsubstituted or substituted C1-C6alkyl, and unsubstituted or substituted C1-C6fluoroalkyl; or R2 and R5 are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted 4- to 7-membered saturated N-containing heterocyclic ring. 10. The compound of claim 1, or a pharmaceutically acceptable salt, solvate, diastereomeric mixture, or individual enantiomers thereof, wherein: 11. The compound of claim 10, or a pharmaceutically acceptable salt, solvate, diastereomeric mixture, or individual enantiomers thereof, wherein: R1 hydrogen; R2 is hydrogen, —CH3, —CH2CH3, —CH2CH2OH, —CH2CH2OCH3, CH2CH2F, —CH2CH2NH2, —CH2CH2NHCH3, —CH2CH2N(CH3)2, —CH2CH2CH3, —CH(CH3)2, cyclopropyl, —CH2CH2CH2F, CH2CH2CH2OH, CH2CH2CH2OCH3, —CH2CH2CH2CH3, —CH2CH(CH3)2, —CH(CH3)(CH2CH3), —C(CH3)3, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl, tetrahydrofuranyl, or tetrahydropyranyl; or R1 and R2 are taken together with the nitrogen atom to which they are attached to form ring C that is an unsubstituted or substituted azetidinyl, unsubstituted or substituted pyrrolidinyl, unsubstituted or substituted piperidinyl, unsubstituted or substituted morpholinyl, unsubstituted or substituted thiomorpholinyl, unsubstituted or substituted piperazinyl, or unsubstituted or substituted azepanyl; R5 is hydrogen, F, Cl, Br, —OH, —OCH3, —NH2, —NHCH3, —N(CH3)2, —OCH2CH3, —OCF3, —CH3, —CH2CH3, —CH2F, —CHF2, —CF3, —CN, —C(═O)OCH3, —C(═O)NH2, —C(═O)NHCH3, or —C(═O)N(CH3)2; or R2 and R5 are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted monocyclic 4- to 7-membered heterocyclic ring selected from unsubstituted or substituted azetidinyl, unsubstituted or substituted pyrrolidinyl, unsubstituted or substituted piperidinyl, unsubstituted or substituted morpholinyl, unsubstituted or substituted thiomorpholinyl, unsubstituted or substituted piperazinyl, or unsubstituted or substituted azepanyl. 12. The compound of claim 1, wherein the compound has the following structure of Formula (AVb), or a pharmaceutically acceptable salt, solvate, diastereomeric mixture, or individual enantiomers thereof: 13. The compound of claim 12, wherein the compound of Formula (AVb) has the one of the following structures, or a pharmaceutically acceptable salt, solvate, diastereomeric mixture, or individual enantiomers thereof: 14. The compound of claim 12, or a pharmaceutically acceptable salt, solvate, diastereomeric mixture, or individual enantiomers thereof, wherein: R1 hydrogen; R2 is hydrogen, methyl, ethyl, 2-fluoroethyl, 2-hydroxyethyl, 2-methoxyethyl, n-propyl, i-propyl, cyclopropyl, 3-fluoropropyl, 3-methoxypropyl, n-butyl, i-butyl, sec-butyl, cyclobutyl, or tert-butyl, or oxetanyl; R5 is hydrogen, F, Cl, Br, —OH, —OCH3, —NH2, —NHCH3, —N(CH3)2, —OCH2CH3, —OCF3, —CH3, —CH2CH3, —CH2F, —CHF2, —CF3, —CN, —C(═O)OCH3, —C(═O)NH2, —C(═O)NHCH3, or —C(═O)N(CH3)2; or R2 and R5 are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted monocyclic 4- to 7-membered heterocyclic ring selected from unsubstituted or substituted azetidinyl, unsubstituted or substituted pyrrolidinyl, unsubstituted or substituted piperidinyl, unsubstituted or substituted morpholinyl, unsubstituted or substituted thiomorpholinyl, unsubstituted or substituted piperazinyl, or unsubstituted or substituted azepanyl. 15. The compound of claim 12, or a pharmaceutically acceptable salt, solvate, diastereomeric mixture, or individual enantiomers thereof, wherein: R1 hydrogen; R2 is hydrogen, methyl, ethyl, 2-fluoroethyl, 2-hydroxyethyl, 2-methoxyethyl, n-propyl, i-propyl, cyclopropyl, 3-fluoropropyl, 3-methoxypropyl, n-butyl, i-butyl, sec-butyl, cyclobutyl, tert-butyl, or oxetanyl; R5 is hydrogen, F, Cl, Br, —OH, —OCH3, —NH2, —NHCH3, —N(CH3)2, —OCH2CH3, —OCF3, —CH3, —CH2CH3, —CH2F, —CHF2, —CF3, —CN, —C(═O)OCH3, —C(═O)NH2, —C(═O)NHCH3, or —C(═O)N(CH3)2; or R2 and R5 are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted monocyclic 4- to 7-membered heterocyclic ring selected from unsubstituted or substituted azetidinyl, unsubstituted or substituted pyrrolidinyl, unsubstituted or substituted piperidinyl, unsubstituted or substituted morpholinyl, unsubstituted or substituted thiomorpholinyl, unsubstituted or substituted piperazinyl, or unsubstituted or substituted azepanyl. 16. The compound of claim 12, or a pharmaceutically acceptable salt, solvate, diastereomeric mixture, or individual enantiomers thereof, wherein: Ra is hydrogen, F, Cl, Br, —CH3, —CH2F, —CHF2, —CF3, —CN, —OH, —OCH3, —OCF3, —CH2OH or —CH2CH2OH; Rb is hydrogen, F, Cl, Br, —CH3, —CH2F, —CHF2, —CF3, —CN, —OH, —OCH3, or —OCF3; each Rc is independently hydrogen, F, Cl, Br, —CH3, —CH2F, —CHF2, —CF3, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, —CN, —OH, —OCH3, —OCF3, —NH2, —C(═O)NH2, —C(═NOH)H, —C(═NOCH3)H, —SO2CH3, —SO2N(CH3)2, azetidinyl, or pyrrolidinyl; each Rd is independently hydrogen, F, Cl, Br, —CH3, —CH2F, —CHF2, —CF3, —CN, —OH, —OCH3, —OCF3, —OCH2OCH3, —CH2OH, —OCH2CH2OH, —C(═O)NH2, —C(═O)NHOCH3, —NH2, —NHCO2CH3, —NH(C═O)NHOCH3, or —CH2(C═O)NH2; Re is hydrogen, F, Cl, Br, —CH3, —CH2F, —CHF2, —CF3, —CN, —OH, —OCH3, or —OCF3; R1 hydrogen; R2is hydrogen; R5 is hydrogen, F, Cl, Br, —OH, —OCH3, —NH2, —NHCH3, —N(CH3)2, —OCH2CH3, —OCF3, —CH3, —CH2CH3, —CH2F, —CHF2, —CF3, —CN, —C(═O)OCH3, —C(═O)NH2, —C(═O)NHCH3, or —C(═O)N(CH3)2; or R2 and R5 are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted monocyclic 6-membered heterocyclic ring selected from unsubstituted or substituted piperidinyl, unsubstituted or substituted morpholinyl, unsubstituted or substituted thiomorpholinyl, or unsubstituted or substituted piperazinyl. 17. The compound of claim 12, or a pharmaceutically acceptable salt, solvate, diastereomeric mixture, or individual enantiomers thereof, wherein: Ra is hydrogen, F, Cl, —CH3, —CF3, —CN, —OH, —CH2OH, —CH2CH2OH, —OCH3, or —OCF3; Rb is hydrogen, F, Cl, —CH3, —CF3, —CN, —OH, —OCH3, or —OCF3; each Rc is independently hydrogen, F, Cl, —CH3, —CF3, —CN, —OH, —NH2, —OCH3, —OCF3, ——C(═O)NH2, —C(═NOH)H , or —C(═NOCH3)H; each Rd is independently hydrogen, F, Cl, —CH3, —CF3, —CN, —OH, —NH2, —OCH3, —OCF3; R1 hydrogen; R2 is hydrogen; R5 is hydrogen; or R2 and R5 are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted morpholinyl. 18. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt, solvate, diastereomeric mixture, or individual enantiomers thereof, and at least one pharmaceutically acceptable excipient. 19. A method of modulating somatostatin receptor subtype 2 (SSTR2) activity in a mammal comprising administering a compound of claim 1, or a pharmaceutically acceptable salt, solvate, diastereomeric mixture, or individual enantiomers thereof, to the mammal. 20. A method of treating acromegaly, a neuroendocrine tumor, pain, or combinations thereof, in a mammal comprising administering a compound of claim 1, or a pharmaceutically acceptable salt, solvate, diastereomeric mixture, or individual enantiomers thereof, to the mammal in need thereof.