Med Chem Exam 1

Front 1

Induction and resonance withdrawers

Back 1

nitro, ester, aldehyde, ketone, sulfinyl, sulfone

Front 2

Ortho/Para resonance and induction effects

Back 2

induction is only an issue in ortho

Front 3

Induction versus resonance

Back 3

Resonance will be the stronger of the two except when the attached is a halogen. Induction trumps resonance donation in a halogen.

Front 4

Resonance electron donator

Back 4

1st atom attached to the pi electron system has a lone pair in an sp3 orbital and isn't attached to a withdrawing group.

Front 5

Examples of resonance electron donators

Back 5

alcohol, ether, amines, sulfhydryl, sulfides

Front 6

-Is

Back 6

Inductive electron withdrawing group. Includes heteroatoms and cations.

Front 7

Examples of -Is

Back 7

nitro, sulfoxide, sulfinyl, ester, aldehyde, ketone, alcohol, ether, amine, quat ammonium

Front 8

+Is

Back 8

Inductive electron donating group. 2 types: alkyl groups and anions

Front 9

What factors can keep an acid base incompatibility from occuring?

Back 9

1. the acid and base reactants have enough polar groups to keep them in solution after reaction
2. dilute concentration
3. pH buffered so that they remain h2o soluble and ionized

Front 10

Arrhenius acid/base

Back 10

acid is a proton donor, base is a hydroxide donor

Front 11

Lowry-Bronsted

Back 11

acid is a proton donor, base is a proton acceptor

Front 12

Lewis acid/base

Back 12

acid is an electrophile, accepts an electron pair.
base is a nucleophile, donates an electron pair

Front 13

Basic salt

Back 13

free acid reacted w/ a metal hydroxide. ph-pka=log i/u

Front 14

Acid salt

Back 14

free base reacted with an organic or inorganic acid. ph-pka=log u/i

Front 15

Unionized neutral functional groups

Back 15

aldehyde, ketone, ester, amide, alcohol, tertiary sulfonamide, tertiary imide

Front 16

Phospholipase A

Back 16

effector of the second messenger arachidonic acid

Front 17

Phospholipase C

Back 17

effector of the second messengers IP3, DAG, and Ca2+

Front 18

cGMP

Back 18

second messenger of guanylate cyclase and phosphodiesterase

Front 19

cAMP

Back 19

second messenger of adenylate cyclase

Front 20

Ternary complex

Back 20

Receptor, ligand, and G protein. Intracellular amino acids attract G protein to bind after ligand induces conformational change. Message is received by G protein in this instant.

Front 21

GPCR of Gs versus Gi

Back 21

Gs has a long carboxy terminus and a short 3rd intracellular loop. Gi is the opposite.

Front 22

Example of Gs

Back 22

adrenergic receptors

Front 23

Example of Gi

Back 23

muscarinic and adrenergic receptors

Front 24

Gt

Back 24

Effector: phosphodiesterase
stimulates cGMP degrading

Front 25

Go

Back 25

Effector: ion channels
inhibit Ca2+

Front 26

Gq

Back 26

Effector: phospholipase C
stimulates IP3, DAG, Ca2+

Front 27

Gi

Back 27

Effector: adenylate cyclase
reduces cAMP production

Front 28

Gs

Back 28

Effector: adenylate cyclase
increases cAMP production

Front 29

GPCR carboxy terminus

Back 29

Intracellular domain. ARG in 2nd loop activates intracellular receptor to attract G protein to 3rd loop for binding to another ARG after LEU in membrane triggers it.

Front 30

LEU residue in GPCR

Back 30

In helix 2 of transmembrane portion. Conformational change with ligand binding turns on ARG switch in intracellular domain. Critical to ternary complex formation.

Front 31

GPCR transmembrane domain

Back 31

Substrates actually bind to embedded residue and must be lipophilic enough to do this. Receptor is amphiphilic. Passes membrane 7 times.

Front 32

GPCR receptor amino acids

Back 32

PRO scattered throughout, ASP helix 3, SER helix 5, PHE helix 6, LEU helix 2

Front 33

PRO in receptor

Back 33

Form a pocket for ligand binding

Front 34

ASP in receptor

Back 34

anionic, binding site for cations

Front 35

SER in receptor

Back 35

hydrogen bonds

Front 36

PHE in receptor

Back 36

binds aromatic rings (van der waal's)

Front 37

GPCR amino terminus

Back 37

Extracellular domain. Regulate receptor conformation and overall function. ASN and CYS are key.

Front 38

CYS in amino terminus

Back 38

disulfide bridge links 2 from 1st and 2nd extracellular loops. provides rigidity and is critical to function

Front 39

ASN in amino terminus

Back 39

key sites for glycosylation, which regulates conformation and receptor function

Front 40

G protein

Back 40

Free in cell until ligand bonds receptor and throws the ARG switch attracting it. Ternary complex forms, GDP splits off, GTP binds. Mg2+ dependent process.

Front 41

G protein subunits

Back 41

alpha, beta, gamma. alpha loses affinity for beta and gamma when GTP binds.

Front 42

alpha subunit

Back 42

carries message to effector. when message transferred gtpase activity hydrolyzes GTP to GDP to shut off.

Front 43

Steps in GPCR

Back 43

drug-receptor-G protein-effector-biochemical activity

Front 44

Bioisoster of COO-

Back 44

SO2NH-

Front 45

Bioisosters of O

Back 45

CH2

Front 46

Bioisosters of S

Back 46

CH2CH2

Front 47

Bioisosters of C=O

Back 47

C=N, C=C, S=O, C=S

Front 48

Bioisosters of OH

Back 48

NH and SH

Front 49

Bioisosters of Cl

Back 49

Br and CF3

Front 50

Bioisosters of C=C

Back 50

NH2

Front 51

Bioisosters of cyclohexane

Back 51

cyclopentane

Front 52

Bioisosters of benzene

Back 52

pyridine and thiophene

Front 53

Bioisosters

Back 53

Functional groups w/similar electronic and steric properties. Exchanging them results in similar biological activity and retained affinity.

Front 54

Hydrophobic interactions

Back 54

driving force is increase in entropy in water and whle system. carbon rich, lipophilic alkyl chains, alicyclic rings, aromatic rings. weakest interaction

Front 55

van der waals

Back 55

induced dipole-induced dipole, pi stacking. distance dependent

Front 56

pi stacking

Back 56

2 aromatic rings approach, p electrons on one move to the other side to avoid the electrons on the other. a dipole is induced. the flat molecules stack.

Front 57

common unionized groups in an ion-dipole bond

Back 57

carbonyl, amino, imino, hydroxy, ethers, sulfhydryl

Front 58

groups in ion-ion bonds

Back 58

protonated amines (cationic), quat ammonium (cationic), carboxylate anions, primary and secondary sulfonamides (anionic), secondary imides (anionic)

Front 59

amino acid residues in receptors that react with anionic drugs

Back 59

ARG,LYS, HIS

Front 60

amino acid residues in receptors that react with cationic drugs

Back 60

ASP, GLU

Front 61

Optically active compounds

Back 61

+ dextrorotatory, rotates polarized light to the right
- levorotatory, rotates polarized light to the left

Front 62

Major difference between diastereomers and entantiomers

Back 62

enantiomers are identical in physical and chemical properties (mp, bp,solubility)Diastereomers aren't.

Front 63

Diastereomers

Back 63

2 or more stereocenters in a molecule. n^2 number. R,R and R,S and S,R and S,S etc.

Front 64

Enantiomers

Back 64

non-superimposable mirror images. R and S or R,R and S,S etc.

Front 65

E

Back 65

2 highest priority groups on the opposite sides of a double bond. when there are more than just 2 groups

Front 66

Z

Back 66

2 highest priority groups on the same side of the double bond. when there are more than 2 groups

Front 67

Aniline

Back 67

N is conjugated to the ring but not a part of the ring or its aromaticity. weakly basic

Front 68

DNA based receptors

Back 68

Antibiotic anti-cancer drugs insert themselves into uncoiled DNA
Nitrogen mustard anticancer agents bind DNA
Steroid hormones

Front 69

Steroid hormones

Back 69

bind HRE (hormone responsive elements) in cell nucleus. first bind receptor in cytosol and the whole complex enters nucleus and binds HRE

Front 70

Tyrosine kinase receptor

Back 70

phosphorylates OH on TYR of other enzymes & proteins. extracellular amino terminus has cysteine disulfide bridge. glycosylation. autophosphorylation of TYR on the kinase activates it.

Front 71

Calcium channel blockers

Back 71

bind inactivated calcium ion channel in vascular smooth muscle. stabilizes it to inhibit Ca2+ flow for an antianginal, antihypertensive effect. verapamil and diltiazem interact w/ open channels for antiarrhythmic and cardiodepressant action

Front 72

imides

Back 72

secondary is acidic
tertiary is neutral

Front 73

sulfonamides

Back 73

primary and secondary are acidic. tertiary neutral

Front 74

amino acids that participate in ion-ion bonds

Back 74

ASP (anionic), GLU (anionic), ARG(cationic), LYS (cationic), HIS (cationic)